Treating Obesity 2012 by Ashville Media Group

TREATING OBESITY

Issue 1 // 2012

Original research and articles relating to obesity in Ireland

A TIME FOR ACTION Battling the causes and effects of obesity

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rev Cholestagel A4 Ad:Layout 1

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• A bile acid sequestrant (resin) 625mg film coated tablets • Indicated as an adjunctive therapy to diet in adults with primary hypercholesterolaemia either - With a statin for patients inadequately controlled on a statin alone or - As monotherapy when a statin is considered inappropriate or not well tolerated • Can also be used in combination with ezetimibe, with or without a statin in adult patients with primary hypercholesterolaemia - This includes patients with familial hypercholesterolaemia • Recommended dose: in combination with a statin with or without ezetimibe: 4-6 tablets daily (maximum dose 3 tablets taken twice daily or 6 tablets taken once daily) . Cholestagel Summary of Product Characteristics

Made in Waterford Marketing Authorisation Holder: Genzyme Europe B.V., Goomieer 10, NL-1411 DD Naarden.The Netherlands. EU/1/03/268/001-004 Further information is available from: Sanofi, 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com Tel.: (01) 4035600 Please refer to the Summary of Product Characteristics which can be found on IPHA @ http://www.medicines.ie/ before prescribing. Date of Preparation: June 2012

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Bene

CONTENTS 040

049 07 09 015 019 022 029 034

054 A Letter from the Editor

034 038

Addressing Arthritis

040

The Struggle Against Psoriasis

045

Arthritis and the Role of Obesity

049

Reducing the Risk

054

The Cancer Diet

The Effect of Obesity on Cholesterol Recent studies show a link between obesity and cholesterol metabolism. Words: Prof Gerald H. Tomkin

Defeating Diabetes St Vincent’s consultant endocrinologist and physician Professor Donal O’Shea discusses the link between diabetes and obesity, new treatments and why educating the public on prevention is so important.

A Time to Act We cannot succeed in the fighter against obesity without leadership at Government level. Words: Barry Dempsey, CEO, Irish Heart Foundation

Better Than Cure? What can be done to reduce Ireland’s obesity levels? Words: Dr Angie Brown & Maureen Mulviill

Breathe Easy CEO of the Asthma Society of Ireland, Sharon Cosgrove, speaks about how obesity can exacerbate asthma symptoms and what the organisation are doing to raise awareness of the dangers.

Broadcasting Better Health Should the Broadcasting Authority of Ireland restrict the advertising of certain foods to children? Words: Dr Francis Finucane

Rising obesity levels have coincided with a rise in the number of Irish people suffering with arthritis. Words: John Church, CEO Arthritis Ireland

As the obesity epidemic worsens, treating conditions like psoriasis and psoriatic arthritis is become increasingly urgent. Words: Prof Oliver Fitzgerald

Studies show that obesity is detrimental to the treatment of many forms of arthritis. Words: Geraldine McCarthy, MD

With the number of Irish cancer victims set to spike over the next two decades, preventing the illness is of increasing importance. Words: John McCormack, CEO, Irish Cancer Society

With incidences of cancer increasing worldwide, more and more research funds are being channelled into tackling its causes. Words: Prof John Reynolds

Editor: Dean Van Nguyen Managing Editor: Ruairi Kavanagh Sub Editor: Kirsty Tobin

Ashville Media Group Old Stone Building Blackhall Green Dublin 7

Design: Maria O’Rourke, Tara O’Reilly Production Manager: Leonard Wilson Production: Rebecca McNamee

Tel: 0 1 432 2200 Fax: 01 672 7100 Email: info@ashville.com

Sales Director: Paul Clemenson Publisher: Michael Quigley

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NEW Milk with added plant sterols can help reduce cholesterol Avonmore Milk has launched New Heart Active, the first Irish cholesterol reducing milk with plant sterols. “Irish people have really embraced foods with added plant sterols and understand that they can have a big impact on reducing cholesterol levels. But it’s important people understand that in order to get the full cholesterol lowering benefits, they must consume the recommended amount of 1.5g to 2.4g of plant sterols every day.” Dr. Nina Byrnes.

Raised cholesterol a health concern

Coronary heart disease is one of the leading causes of death in Ireland (1). High cholesterol is one of the risk factors as it causes fatty deposits to build up in the arteries making it harder for the heart to pump blood around the body. The most recent survey on lifestyles, attitudes and nutrition in Ireland (SLAN Report, 2007) showed that 82% of adults aged 45+ years had raised cholesterol (> 5mmol/L) (2). One way to help maintain a healthy heart is to keep cholesterol at a healthy level.

A healthy cholesterol level (3). Cholesterol Healthy levels mmol/l Total cholesterol LDL cholesterol HDL cholesterol

no greater than 5 no greater than 3 greater than 1

What are plant sterols?

Plant sterols are naturally found in a range of plant sources such as vegetables, vegetable oils, nuts, grains, seeds and legumes, but not in large enough quantities to have an affect on cholesterol. There is strong scientific evidence that plant sterols can help lower unhealthy LDL cholesterol, a major risk factor for heart disease if consumed as part of a heart healthy diet and active lifestyle (4).

How do plant sterols work?

Plant sterols are similar to cholesterol in structure and work by mimicking cholesterol and competing with it for absorption in the intestine. When plant sterols travel through the digestive tract, they partially block real cholesterol from being absorbed into the bloodstream. The end result is that the body retains less cholesterol because more is being excreted. Over time this can lead to lower total levels of LDL blood cholesterol. *Please see footnote for information on use

Footnote Plant sterols have been shown to lower cholesterol. High cholesterol is a risk factor for developing coronary heart disease. Heart disease has multiple risk factors, altering one may or may not have a beneficial effect. This product is exclusively for people with high cholesterol. If you are on cholesterol lowering medicine consult your doctor before use. The benefits of plant sterols are achieved by consuming 1.5 – 2.4g daily; consuming more than 3g per day should be avoided. A reduction of 7-10% can be achieved in 2 to 3 weeks. Consume as part of a healthy balanced diet rich in fruit and vegetables to maintain carotenoid levels. This product may not be suitable for pregnant or breastfeeding women, or children under 5 years old. ‘This newsletter is for health professional information only and is not for wider distribution.’

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Many people not getting the full benefits of Plant Sterols Research carried out by Avonmore reveals that in general, the Irish population is “cholesterol aware” with 76% of people over 40 stating that they have had their cholesterol level tested at least once and 43% of these getting it checked regularly.(5) The research also revealed that consuming cholesterol reducing products is the most popular method employed by Irish people to manage their cholesterol, with almost 70% of over 40’s consuming them. But worryingly only 36% of these people are using the products as recommended daily and as a result the majority are not receiving the full benefits. Over a third of people consuming these products say they forget to take them every day, and nearly 1 in 5 find it difficult to consume the right amount. In order to get the full benefits of plant sterols, the recommended amount of between 1.5g and 2.4g should be consumed every day.(4) 0%

Reasons why Irish people not consuming recommended amount of plant sterols every day

I forget to eat/drink them regularly It’s difficult to eat/drink the correct amount the packet says will reduce my cholesterol

40%

37% 17%

Introducing New Avonmore Heart Active milk

Avonmore is making it easier to put plant sterols into the daily routine with the introduction of Avonmore Heart Active with added plant sterols. Irish consumers are one of the highest per capita consumers of milk in the world. Now they can get cholesterol reducing plant sterols in one of the things they consume every day, simply by switching from regular milk to new Avonmore Heart Active.

What are the benefits of Avonmore Heart Active Milk with added plant sterols?

Consuming 2-3 glasses (250ml per glass) of Avonmore Heart Active Milk with added plant sterols daily will provide the recommended 1.5–2.4g of plant sterols to produce the cholesterol lowering benefit (helping reduce cholesterol by 7%-10% over 2-3 weeks). Avonmore Heart Active Milk is made using 1% fat milk which makes it lower in fat than many low fat milks (which contains 1.5% fat), helping to make an important reduction to total fat intake over time. It tastes just like standard low fat milk, and can be used in exactly the same way; as a drink, in cereal, and in tea and coffee. Milk is a staple food in Ireland so adding plant sterols to Avonmore Heart Active Milk is a good way to incorporate plant sterols into a daily routine, especially as it is recommended that plant sterols are consumed every day to ensure the cholesterol lowering effect is optimised.

For more information check out our website

www.avonmoreheartactive.ie

References (1) Health in Ireland - Key Trends- Department of Health and Children (2009). (2) Surveys of lifestyles, attitudes and nutrition in Ireland. SLAN (2007) (3) Nutrition Guidelines for Heart Health- Irish Heart Foundation (2007). (4) Plant Sterols and Blood Cholesterol. Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies. The EFSA Journal (2008) 781, 1-12. (5) Research carried out on behalf of Avonmore, January 2012 Sample 1,000 adult consumers.

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The 1st GLIPTIN (DPP-4 inhibitor) with efficacy and safety data in elderly patients ≥75 years of age1

Let GALVUS slow down the sugar train ®

GALVUS® ABBREVIATED PRESCRIBING INFORMATION. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentations: Galvus 50 mg tablet. Each tablet contains 50 mg of vildagliptin and 47.82 mg of the excipient lactose. Indications: For the treatment of type 2 diabetes mellitus. As monotherapy, in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance. As dual oral therapy, in combination with metformin, in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin; with a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of a sulphonylurea and for whom metformin is inappropriate due to contraindications or intolerance; with a thiazolidinedione, in patients with insufficient glycaemic control and for whom the use of a thiazolidinedione is appropriate. Dosage and Administration: When used as monotherapy or in dual combination with metformin or thiazolidinedione 100mg daily, administered in two divided doses of one 50 mg in the morning and one 50 mg in the evening. In dual combination with sulphonylurea, 50 mg once daily in the morning. Galvus can be administered with or without a meal. Doses greater than 100 mg are not recommended. In patients with moderate or severe renal impairment or with end-stage renal disease (ESRD), the recommended dose of Galvus is 50 mg once daily. Galvus is not recommended for use in patients less than 18 years old. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions/Warnings: Galvus should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Galvus should be used with caution in patients with ESRD on haemodialysis. Galvus is not recommended in patients with hepatic impairment, including patients with pre-treatment ALT or AST >3x the ULN. Liver function tests should be performed prior to treatment, initiation, at three month intervals during the first year and periodically thereafter. Should an increase in AST or ALT of 3xULN or greater persist, withdrawal of Galvus therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Galvus.Vildagliptin is not recommended in patients with NYHA functional class III-IV. Routine monitoring of diabetic patients for skin disorders such as blistering or ulceration is recommended. Patients should be informed that persistent, severe abdominal pain is the characteristic symptom of acute pancreatitis. If pancreatitis is suspected, vildagliptin and other potentially suspect medicinal products should be discontinued. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Pregnancy and Lactation: Galvus should not be administered during pregnancy or lactation. Interactions: Vildagliptin has a low potential for drug interactions. No clinically relevant interactions with other antidiabetics (glyburide, pioglitazone, metformin), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin. As with other oral antidiabetic medicines, the hypoglycaemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics. Adverse Reactions: Vildagliptin: Common: dizziness. Uncommon: headache, constipation, arthralgia, hypoglycaemia, oedema peripheral. Rare: angiodema, hepatic dysfunction (including hepatitis). Not known: Pancreatitis. Combination with metformin: Common: tremor, headache, dizziness, nausea, hypoglycaemia. Uncommon: fatigue. Combination with sulfonylurea: Common: tremor, headache, dizziness, asthenia, hypoglycaemia. Uncommon: constipation. Combination with thiazolidinedione: Common: weight increase, oedema peripheral. Uncommon: headache, asthenia, hypoglycaemia. For further information regarding adverse reactions, please refer to the Summary of Product Characteristics. Pack Size: Blister packs of 56 (4 x 14) tablets. Legal Category: POM. Marketing Authorisation Number: EU/1/07/414/005. Marketing Authorisation Holder: Novartis Europharm Limited, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom. Date of Revision of API Text: February 2012. Full prescribing information, including SmPC is available from: Novartis Ireland Limited, Beech House, Beech Hill Office Campus, Clonskeagh, Dublin 4. Tel: 01 260 1255 or at www.medicines.ie EUCREAS® ABBREVIATED PRESCRIBING INFORMATION. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentations: Eucreas 50 mg/ 850 mg film-coated tablet. Eucreas 50 mg/1000 mg film-coated tablet. Each 50 mg/850 mg film-coated tablet contains 50 mg of vildagliptin and 850 mg metformin hydrochloride. Each 50 mg/1000 mg film-coated tablet contains 50 mg of vildagliptin and 1000 mg metformin hydrochloride. Indications: Eucreas is indicated in the treatment of type 2 diabetes mellitus patients who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone or who are already treated with the combination of vildagliptin and metformin as separate tablets. Dosage and Administration: The recommended daily dose should be based on the patient’s current regimen of vildagliptin and /or metformin hydrochloride. The usual dose is 50 mg/850 mg or 50 mg/1000 mg twice daily one tablet in the morning and the

A_W Galvus TOJ DPS 4270612.indd 1 TreatingObesity.indd

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2.5 OVE R P M A PE RIE TIEN ILLIO NC T N E W YEA OR RS LD W

IDE 2

POWERFUL EFFICACY YOU CAN SEE3

other in the evening. Eucreas should be taken with or just after food. Doses of vildagliptin greater than 100 mg are not recommended. Patients ≥ 65 taking Eucreas should have their renal function monitored regularly, Eucreas is not recommended in patients ≥75 years. Eucreas is not recommended for use in patients less than 18 years old. For use in renal or hepatic impairment, see contraindications and precautions below or refer to the SmPC for more information. Contraindications: Hypersensitivity to vildagliptin or metformin hydrochloride or to any of the excipients. Diabetic ketoacidosis or diabetic pre-coma. Renal failure or renal dysfunction defined as creatinine clearance < 60 ml/min. Acute conditions with the potential to alter renal function e.g. dehydration, severe infection, shock or intravascular administration of iodinated contrast agents. Acute or chronic disease which may cause tissue hypoxia e.g. cardiac or respiratory failure, recent myocardial infarction, shock. Hepatic impairment. Acute alcohol intoxication, alcoholism. Lactation. Precautions/Warnings: Eucreas should not be used in patients with type 1 diabetes. Due to the risk of lactic acidosis, renal function should be monitored at least once yearly in patients with normal renal function and at least two to four times/year in patients with serum creatinine at the upper limit of normal and in elderly patients. Eucreas is not recommended in patients with hepatic impairment, including patients with pre-treatment ALT or AST >3x the ULN. LFT’s should be performed prior to treatment, initiation, at three month intervals during the first year and periodically thereafter. Should an increase in AST or ALT of 3x ULN or greater persist, withdrawal of Eucreas therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Eucreas. Vildagliptin should be used with caution in patients with congestive heart failure of New York Heart Association (NYHA) functional class I-II and is not recommended in patients with NYHA functional class III-IV. Metformin is contraindicated in patients with heart failure, therefore Eucreas is contraindicated in this population. Routine monitoring of diabetic patients for skin disorders such as blistering or ulceration is recommended. Patients should be informed that persistent, severe abdominal pain is the characteristic symptom of acute pancreatitis. If pancreatitis is suspected, vildagliptin and other potentially suspect medicinal products should be discontinued. As Eucreas contains metformin, treatment should be discontinued 48 hours before elective surgery with general anaesthesia and not usually resumed earlier than 48 hours afterwards. The IV administration of iodinated contrast agents can lead to renal failure. Therefore due to metformin active ingredient, Eucreas should be discontinued prior to or at the time of the test and not reinstituted until 48 hours afterwards and only after renal function has been re-evaluated and found to be normal. Pregnancy and Lactation: Eucreas should not be administered during pregnancy or lactation. Interactions: Vildagliptin has a low potential for drug interactions. No clinically relevant interactions with other antidiabetics (glyburide, pioglitazone, metformin), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin. Interactions with Metformin hydrochloride that are not recommended include alcohol, cationic active substances e.g. cimetidine and intravascular administration of iodinated contrast media. Caution is advised when using metformin hydrochloride with medicines tending to produce hyperglycaemic activity e.g. glucocorticoids, beta agonists and diuretics. The dose of antihyperglycaemic medicinal products may need to be adjusted in combination with ACE inhibitors. Adverse Reactions: Vildagliptin: Common: dizziness. Uncommon: headache, constipation, arthralgia, hypoglycaemia, oedema peripheral. Rare: angiodema, hepatic dysfunction (including hepatitis). Not known: Pancreatitis. Metformin: Very common: Nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. Common: metallic taste. Very rare: decrease of vitamin B12 absorption and lactic acidosis, liver function test abnormalities or hepatitis. Combination vildagliptin with metformin: Common: tremor, headache, dizziness, nausea, hypoglycaemia. Uncommon: fatigue. Pack Size: Blister packs of 60 (6 x 10) tablets. Legal Category: POM. Marketing Authorisation Numbers: EU/1/07/425/003, 009. Marketing Authorisation Holder: Novartis Europharm Limited, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom. Date of Revision of API Text: December 2011. Full prescribing information, including SmPC is available from: Novartis Ireland Limited, Beech House, Beech Hill Office Campus, Clonskeagh, Dublin 4. Tel: 01 260 1255 or at www.medicines.ie References. 1. Schweizer A, Dejager S, Foley JE, Shao Q, Kothny W. Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ≥75 years: a pooled analysis from a database of clinical trials. Diabetes Obes Metab. 2011; 13 (1): 55-64. 2. Global IMS data 2012. 3. Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care. 2007; 30 (4): 890-895. Date of Preparation: February 2012. NO0212086

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It’s time to change your ideas about ORENCIA® ORENCIA® has similar efﬁcacy in RF-positive and RF-negative patients over 12 months.1

ORENCIA® is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA), in combination with methotrexate, in adult patients who have responded inadequately to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDS), including methotrexate (MTX) or a Tumour Necrosis Factor (TNF) – alpha inhibitor. ORENCIA® (abatacept) PRESCRIBING INFORMATION See Summary of Product Characteristics before prescribing. PRESENTATION: 250mg powder for concentrate for solution for IV infusion containing 250mg abatacept per vial. Each ml contains 25mg of abatacept, after reconstitution. INDICATION: Rheumatoid arthritis: Treatment of moderate to severe active rheumatoid arthritis (RA), in combination with methotrexate, in adult patients who have responded inadequately to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) or a Tumour Necrosis Factor (TNF) -alpha inhibitor. A reduction in the progression of joint damage and improvement of physical function has been demonstrated during combination treatment with abatacept and methotrexate. Polyarticular juvenile idiopathic arthritis (pJIA): treatment of moderate to severe active pJIA in paediatric patients six years of age and older who have had an insufficient response to other DMARDs including at least one TNF inhibitor. DOSAGE: Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of RA. Adult and elderly patients weighing < 60kg: 500mg (2 vials). Patients weighing ≥ 60kg ≤ 100kg: 750mg (3 vials). Patients weighing > 100kg: 1000mg (4 vials). Treatment of pJIA: Paediatric patients, 6 to 17 years of age, weighing less than 75 kg: 10 mg/kg. paediatric patients weighing 75 kg or more: to be administered adult dosage, not exceeding a maximum dose of 1,000 mg. See SmPC for details of reconstitution and administration as a 30 minute IV infusion. After initial administration, Orencia should be given at 2 and 4 weeks, then every 4 weeks thereafter. Consider therapeutic alternatives if there is no response within 6 months. Use in children below 6 years of age is not recommended. CONTRAINDICATIONS: Hypersensitivity to the active substance or excipients. Severe and uncontrolled infections such as sepsis and opportunistic infections. WARNINGS AND PRECAUTIONS: Infections: Treatment should not be initiated in patients with active infections until infections are controlled. Caution should be exercised when considering the use in patients with a history of recurrent infections, in patients with underlying conditions which may predispose them to infection or in patients on concomitant immunosuppressive therapy. Any patient who develops a new infection should be closely monitored and Orencia should be discontinued if a patient develops a serious infection. Screening for tuberculosis and hepatitis B should be performed prior to therapy. Monitor for signs of infection when transitioning from a TNF-antagonist to Orencia. Treatment with immunosuppressive therapy may be associated with progressive multifocal leukoencephalopathy (PML). ORENCIA treatment should be discontinued if neurological symptoms suggestive of PML occur, and appropriate diagnostic measures initiated. Allergic Reactions: Caution in patients with a history of allergic reactions.Orencia should be discontinued if a patient develops serious allergic or anaphylactic reaction. Malignancies: The potential role of abatacept in the development of malignancies is unknown, see SmPC. Elderly: Caution should be used when treating elderly patients due to a higher incidence of infections and malignancies in this patient group. Autoimmune processes: Theoretical risk of deterioration in autoimmune disease. Immunisation: Live vaccines should not be given concurrently or within 3 months of discontinuation of Orencia. It is recommended that patients with pJIA be brought up to date with all immunisations in agreement with current immunisation guidelines, prior to initiating ORENCIA therapy. Blood Glucose Tests: False elevations on day of infusion can occur, see SmPC. DRUG INTERACTIONS: Concomitant therapy of Orencia with a TNF inhibitor is not recommended. No major safety issues were identified with the use of Orencia in combination with sulfasalazine, hydroxychloroquine or leflunomide. PREGNANCY AND LACTATION: Do not use in pregnancy unless clearly necessary. Women should use contraception and not breast-feed during treatment and up to 14 weeks after last dose. UNDESIRABLE EFFECTS: in adult placebo-controlled trials the following adverse drug reactions were reported Very Common (≥ 1/10): upper respiratory tract infection; Common (≥ 1/100 to < 1/10) Hypertension, flushing, increased blood pressure, headache, paraesthesia, conjunctivitis, abnormal LFTs, dizziness, cough, abdominal pain, diarrhoea, nausea, dyspepsia, mouth ulceration, aphthous stomatitis, vomiting, rash, alopecia, pruritus, leukopenia, pain in extremity, fatigue, asthenia, infections including LRTIs, UTIs, herpes simplex, rhinitis, pneumonia, influenza Uncommon (≥ 1/1,000 to < 1/100): tooth infection, onychomycosis, herpes zoster, sepsis, musculoskeletal infections, skin abcess, pyelonephritis, basal cell carcinoma, skin papilloma, thrombocytopenia, hypersensitivity, depression, anxiety, sleep disorder, migraine, dry eye, reduced visual acuity, vertigo, palpitations, tachycardia, bradycardia, hypotension, hot flush, vasculitis, decreased blood pressure, bronchospasm, wheezing, dyspnea, gastritis, increased tendency to bruise, dry skin, urticaria, psoriasis, arthralgia, amenorrhea, menorrhagia, influenza-like illness, weight increase. Rare: Bacteraemia, gastrointestinal infection, lymphoma, malignant lung neoplasm, throat tightness. In COPD patients, a greater percentage of abatacept than placebo-treated patients developed a serious adverse reactions. In paediatric patients with pJIA, adverse reactions were similar in type and frequency to those seen in adults except: Common (≥ 1/100 to < 1/10): upper respiratory tract infection (including sinusitis, nasopharyngitis and rhinitis), otitis (media and externa), haematuria, pyrexia. See SmPC for further details. LEGAL CATEGORY: POM. MARKETING AUTHORISATION NUMBER: EU/1/07/389/001, 1 vial pack MARKETING AUTHORISATION HOLDER: Bristol-Myers Squibb Pharma EEIG, Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex UB8 1DH FURTHER INFORMATION FROM: Bristol-Myers Squibb Pharmaceuticals, South County Business Park, Leopardstown, Dublin 18. Tel: 1-800-749-749 or medical.information@bms.com DATE OF PREPARATION: March 2012 1. Sibilia J et al. Abatacept plus MTX treatment confers similar clinical efficacy in rheumatoid factor negative and positive patients in the AIM trial. 24th French Society of Rheumatology (SFR) Conference 2011, 11-14 December, Paris, France. In Press. © 2012 Bristol-Myers Squibb Company Date of preparation: June 2012 427IE12PM011 IROC-K0004

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Treating Obesity a Letter from the editor

Dear reader, To tackle obesity is to tackle thousands of years of human evolution. Before food was pre-packaged and plentiful, our earliest ancestors ate as much as they could to nurture their growing brains, fuel their high-levels of physical activity and ensure that they could maximise the amount of time needed between meals, just in case the next scrap of food wasn’t easily come by. It’s these instincts – instilled by evolution and preserved by natural selection – that have ensured the survival of our species. For example, early man had to endure famines and shortages of food, so our bodies were equipped to store fat in order to survive long periods without eating. These psychological traits and physical attributes are still evident today. So while the nutritional quality of our food and our activity levels may have both decreased, our bodies still behave like those of our ancestors. And it’s that dangerous combination that has led to the obesity epidemic. Medical science continues to improve year after year, but the number of people suffering from heart disease, arthritis and other afflictions is creeping up, while in the case of the US, life expectancy is falling drastically. Something is very wrong here. Treating Obesity has accepted papers from experts on some of the most prominent diseases and afflictions linked to obesity. In these pages we will examine the damaging effects being overweight or obese can have on the human body, the treatments available for patients suffering from these afflictions, and discuss how obesity can be prevented. I would like to thank all of our contributors, as well as the Diabetes Federation, the Irish Heart Foundation, the Asthma Society of Ireland, Arthritis Ireland and The Irish Cancer Society for their invaluable input, without which this publication could not have happened. Dean Van Nguyen Editor

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FOR PATIENTS WITH HYPERCHOLESTEROLEMIA NOT AT LDL-C GOAL ON STATIN MONOTHERAPY5

AN EFFECTIVE LDL-C TREATMENT, FUELLED BY DUAL POWER1-4

TreatingObesity.indd 8

therapy with simvastatin and lipid modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and when the dose of either medicinal product is increased. Caution should be used when treating Chinese patients with INEGY (particularly doses of 10/40 mg or higher) co administered with lipid modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin. Because the risk of myopathy with statins is dose-related, the use of INEGY 10/80 mg with lipid modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin is not recommended in Chinese patients. It is unknown whether there is an increased risk of myopathy in other Asian patients treated with simvastatin co-administered with lipid modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin. Patients on fusidic acid and INEGY should be closely monitored. Temporary suspension of INEGY treatment may be considered. Liver enzymes: Perform liver function tests before treatment and thereafter when clinically indicated. Patients titrated to the 10/80 mg dose should receive an additional test prior to titration, 3 months after titration to the 10/80 mg dose, and periodically thereafter (e.g., semi-annually) for the first year of treatment. Pay special attention to patients who develop elevated serum transaminase levels. Use cautiously in patients who consume substantial quantities of alcohol. Hepatic insufficiency: Not recommended in patients with moderate or severe hepatic insufficiency. Paediatric (10 to 17 Years of Age) Patients Efficacy and safety of ezetimibe co-administered with simvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys (Tanner stage II or above) and in girls who were at least one year post-menarche. In this limited controlled study, there was generally no detectable effect on growth or sexual maturation in the adolescent boys or girls, or any effect on menstrual cycle length in girls. However, the effects of ezetimibe for a treatment period > 33 weeks on growth and sexual maturation have not been studied (see sections 4.2 and 4.8) The safety and efficacy of ezetimibe co-administered with doses simvastatin above 40mg daily have not been studied in paediatric patients 10 to 17 years of age. Ezetimibe has not been studied in patients younger than 10 years of age or in pre-menarchal girls. (See sections 4.2 and 4.8.) The long-term efficacy of therapy with ezetimibe in patients below 17 years of age to reduce morbidity and mortality in adulthood has not been studied. Interstitial lung disease: Cases of interstitial lung disease have been reported with some statins, including simvastatin, especially with long term therapy. Presenting features can include dyspnoea, non productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, INEGY therapy should be discontinued. Other interactions: Cholestyramine: Concomitant cholestyramine administration decreased the mean AUC of total ezetimibe approximately 55%. The incremental low density lipoprotein cholesterol (LDL C) reduction due to adding INEGY to cholestyramine may be lessened by this interaction. Anticoagulants: If INEGY is added to warfarin, another coumarin anticoagulant or fluindione the INR should be appropriately monitored. Prothrombin time should be determined before starting INEGY and frequently enough to ensure that no significant alteration of prothrombin time occurs. Fibrates: concomitant use not recommended. *The 10/10mg tablet is not marketed in Ireland. This dose can be met by co-administering 10 mg of each of ezetimibe and simvastatin. SIDE EFFECTS The frequencies of adverse events are ranked according to the following: Very common (≥ 1/10), Common ≥ 1/100, < 1/10), Uncommon (≥ 1/1000, < 1/100), Rare (≥ 1/10,000, < 1/1000), Very Rare (< 1/10,000) including isolated reports. Investigations: ALT and/or AST increased; blood CK increased. Musculoskeletal and connective tissue disorders: Common: myalgia. Laboratory Values In co-administration trials, the incidence of clinically important elevations in serum transaminases (ALT and/or AST ≥3 X ULN, consecutive) was 1.7% for patients treated with INEGY. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment. Clinically important elevations of CK (≥10 X ULN) were seen in 0.2% of the patients treated with INEGY. Post-marketing Experience: The following additional adverse reactions have been reported in post-marketing use with INEGY or during clinical studies or post-marketing use with one of the individual components. Blood and lymphatic system disorders: thrombocytopaenia; anaemia. Nervous system disorders: peripheral neuropathy; memory impairment. Respiratory, thoracic and mediastinal disorders: cough; dyspneoa, interstitial lung disease. Gastrointestinal disorders: constipation; pancreatitis; gastritis. Skin and subcutaneous tissue disorders: alopecia; erythema multiforme; hypersensitivity reactions, including rash, urticaria, anaphylaxis, angio-oedema. Musculoskeletal, connective tissue disorders: muscle cramps; myopathy/rhabdomyolysis (see section 4.4). Metabolism and nutrition disorders: decreased appetite. Vascular disorders: hot flush; hypertension. General disorders and administration site conditions: pain. Hepato-biliary disorders: hepatitis/jaundice; hepatic failure; cholelithiasis; cholecystitis. Reproductive system and breast disorders: erectile dysfunction. Psychiatric disorders: depression Paediatric (10 to 17 years of age) Patients In a study involving adolescent (10 to 17 years of age) patients with heterozygous familial hypercholesterolaemia (n = 248), elevations of ALT and/or AST (≥3X ULN, consecutive) were observed in 3% (4 patients) of the ezetimibe/simvastatin patients compared to 2% (2 patients) in the simvastatin monotherapy group; these figures were respectively 2% (2 patients) and 0% for elevation of CPK (≥ 10X ULN). No cases of myopathy were reported. This trial was not suited for comparison of rare adverse drug reactions. Laboratory Values: elevated alkaline phosphatase, liver function test abnormal. The following additional adverse events have been reported with some statins: sleep disturbances, including nightmares; memory loss, sexual dysfunction. PACKAGE QUANTITIES 28 Tablets Marketing Authorisation number: 10/20 mg: PA 1091/4/2 10/40 mg: PA 1091/4/3 10/80 mg: PA 1091/4/4 Marketing Authorisation holder: MSD-SP Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK POM Date of review: October 2011 © Merck Sharp & Dohme Limited, 2011. All rights reserved. (WS026) Additional prescribing information is available on www.medicines.ie or on request from MSD Pelham House, South County Business Park, Leopardstown, Dublin 18. Date of preparation: November 2011 References: 1. Bays HE, Davidson MH, Massaad R, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE study). Am J Cardiol. 2011. doi:10.1016/j.amjcard.2011.03.079. 2. Leiter LA, Bays H, Conard S, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008;102(11):1495–1501. 3. Stein E, Stender S, Mata P, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004;148(3):447–455. 4. Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004;26(11):1758–1773. 5. INEGY Summary of Product Characteristics.

Pelham House, South County Business Park, Leopardstown, Dublin 18.

CARD-1018896-0000

INEGY® ezetimibe/simvastatin ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before Prescribing PRESENTATION Tablets containing 10 mg ezetimibe and 20, 40 or 80 mg of simvastatin. USES As adjunctive therapy to diet in: Hypercholesterolaemia: in primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use is appropriate: • patients not appropriately controlled with a statin alone • patients already treated with a statin and ezetimibe INEGY contains ezetimibe and simvastatin. Simvastatin (20-40 mg) has been shown to reduce the frequency of cardiovascular events. A beneficial effect of INEGY or ezetimibe on cardiovascular morbidity and mortality has not yet been demonstrated. Homozygous Familial Hypercholesterolaemia (HoFH): Patients may also receive adjunctive treatments (e.g., low-density lipoprotein [LDL] apheresis). DOSAGE AND ADMINISTRATION For oral administration, with or without food. The tablet should not be split. Put patients on an appropriate lipid lowering diet and continue during treatment. Hypercholesterolaemia The dosage range is 10/10 mg/day* through 10/80 mg/day in the evening. The typical dose is 10/20 mg/day or 10/40 mg/day given as a single dose in the evening. The 10/80 mg dose is only recommended in patients with severe hypercholesterolaemia and high risk for cardiovascular complications who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks. Consider the patient’s low-density lipoprotein cholesterol (LDL C) level, coronary heart disease risk status, and response to current cholesterol-lowering therapy when starting therapy or adjusting the dose. Individualise the dose based on the known efficacy of the various dose strengths of INEGY and the response to the current cholesterol-lowering therapy. Make any adjustments at intervals of not less than 4 weeks. Homozygous Familial Hypercholesterolaemia The recommended dosage is 10/40 mg/day or 10/80 mg/day in the evening. May be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis). Coadministration with other medicines: Bile acid sequestrants: dosing should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant. Amiodarone, verapamil or lipid-lowering doses (≥1 g/day) of niacin: the dose should not exceed 10/20 mg/day. Ciclosporin or danazol: the dose should not exceed 10/10 mg/day*. Diltiazem or amlodipine: do not exceed 10/40 mg unless clinical benefit outweighs increased risk of myopathy and rhabdomyolysis. Use in elderly: no dosage adjustment required. Use in children and adolescents: Initiation of treatment must be performed under review of a specialist. Adolescents ≥ 10 years (pubertal status: boys Tanner Stage II and above and girls who are at least one year post-menarche): The clinical experience in paediatric and adolescent patients (aged 10-17 years old) is limited. The recommended usual starting dose is 10/10 mg once a day in the evening. The recommended dosing range is 10/10 to a maximum of 10/40 mg/day (see sections 4.4 and 5.2). Children < 10 years: INEGY is not recommended for use in children below age 10 due to insufficient data on safety and efficacy (see section 5.2). The experience in pre-pubertal children is limited. Use in hepatic impairment: no dosage adjustment required in mild hepatic insufficiency (Child Pugh score 5 to 6). Not recommended in patients with moderate (Child Pugh score 7 to 9) or severe (Child Pugh score >9) liver dysfunction. Use in renal impairment: no dosage adjustment required in moderate renal insufficiency. If treatment in patients with severe renal insufficiency (creatinine clearance ≤30 ml/min) is deemed necessary, implement dosages above 10/10 mg/day* cautiously. CONTRAINDICATIONS Hypersensitivity to ezetimibe, simvastatin, or to any of the excipients. Pregnancy and lactation. Active liver disease or unexplained persistent elevations in serum transaminases. Concomitant administration of potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (e.g. nelfinavir) and nefazodone). PRECAUTIONS Myopathy/Rhabdomyolysis: In post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin concomitantly with ezetimibe. However, rhabdomyolysis has been reported very rarely with ezetimibe monotherapy and very rarely with the addition of ezetimibe to other agents known to be associated with increased risk of rhabdomyolysis. Simvastatin, like other HMG-CoA reductase inhibitors, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above 10 X the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and very rare fatalities have occurred. The risk of myopathy/rhabdomyolysis is dose related for simvastatin. CK measurement: CK should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CK increase. If CK levels are significantly elevated at baseline (>5 X ULN), measure levels again within 5 to 7 days. Before treatment: Advise all patients starting therapy, or in whom the dose is being increased, of the risk of myopathy and to report promptly any unexplained muscle pain, tenderness or weakness. Exercise caution in patients with pre-disposing factors for rhabdomyolysis. Measure CK level before starting treatment in the following: elderly (age >65 years); female gender; renal impairment; uncontrolled hypothyroidism; personal or familial history of hereditary muscular disorders; previous history of muscular toxicity with a statin or fibrate; alcohol abuse. In these situations, clinical monitoring is recommended. If a patient has previously experienced a muscle disorder on a fibrate or a statin, initiate treatment with caution. If CK levels are significantly elevated at baseline (>5 X ULN), treatment should not be started. Whilst on treatment: If muscle pain, weakness or cramps occur measure CK levels and stop treatment if found to be significantly elevated (>5 X ULN). If muscular symptoms are severe even if CK levels are <5 X ULN, consider discontinuation. Discontinue if myopathy is suspected for any other reason. If symptoms resolve and CK levels return to normal, then re-introduction of INEGY or another statin-containing product may be considered at the lowest dose and with close monitoring. A higher rate of myopathy has been observed in patients titrated to the 80 mg dose of simvastatin. Periodic CK measurements are recommended as they may be useful to identify subclinical cases of myopathy. There is no assurance that such monitoring will prevent myopathy. Stop therapy temporarily a few days prior to elective major surgery and when any major medical or surgical condition supervenes. Measures to reduce the risk of myopathy caused by interactions: The risk of myopathy and rhabdomyolysis is significantly increased by concomitant use with potent inhibitors of CYP3A4 (such as itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (e.g. nelfinavir), nefazodone, whose concomitant use is contra-indicated), as well as ciclosporin, danazol and gemfibrozil. If treatment with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin or telithromycin is unavoidable, suspend therapy with INEGY during the course of treatment. The risk of myopathy and rhabdomyolysis is also increased by concomitant use of other fibrates, lipid-lowering doses (≥1 g/day) of niacin or by concomitant use of fluconazole, amiodarone or verapamil with higher doses of INEGY. The risk is increased by concomitant use of diltiazem or amlodipine is used with INEGY 10 mg/80 mg. The risk of myopathy including rhabdomyolysis may be increased by concomitant administration of fusidic acid with INEGY. Concomitant intake with grapefruit juice should be avoided. Do not exceed 10/10 mg* daily in patients receiving concomitant medication with ciclosporin or danazol. Weigh the benefits of the combined use with ciclosporin or danazol carefully against the potential risks of these combinations. Monitor ciclosporin concentrations in patients receiving INEGY and ciclosporin. The combined use of INEGY at doses higher than 10/20 mg daily with amiodarone, verapamil or lipid-lowering doses (≥ 1 g/day) of niacin or at doses higher than 10/40 mg daily with diltiazem or amlodipine should be avoided unless the clinical benefit outweighs the increased risk of myopathy. Rare cases of myopathy/rhabdomyolysis have been associated with concomitant administration of HMG-CoA reductase inhibitors and lipid modifying doses (≥ 1 g/day) of niacin (nicotinic acid), either of which can cause myopathy when given alone. Physicians contemplating combined

13/09/2012 12:04:09

Treating Obesity The Effect of Obesity on Cholesterol

The Effect of Obesity on Cholesterol Recent studies show a link between obesity and cholesterol metabolism. Words: Prof Gerald H. Tomkin

ecoming a television star is never easy. If you are a chef weighing 18.5 stone (114kg), are of limited height at 5ft 7in (170cm), and have hypercholesterolemia, hypertension and diabetes, it might seem impossible. And yet the advent of the reality show – the successor to the soap on television – has brought stardom to someone with these very characteristics. The chef in question found that the task of dealing with his obesity was difficult until his involvement with TV programme Operation Transformation led to more than 1 million viewers supporting him in his efforts. His reduction in weight of almost five stone over an eight-week period led to incredulity and stardom. His cholesterol fell from 5.5 mmol/l to 3.3 mmol/l – and his LDL cholesterol from 3.54 to 1.86 – while his HDL remained stable at 1.06 vs 1.07mmol/l and his fasting triglycerides fell from 2.06 to 0.82mmol/l.

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These results demonstrate the link between obesity and cholesterol metabolism, and merit an explanation. The low-cholesterol diet (it is inevitable that such a weight reduction program would involve a reduction in dietary cholesterol) plays only a small part. Patients get so upset if not warned that changing diet without calorie restriction leads to, at most, 15 CARD-1018896-0000

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TreatingObesity.indd 9

per cent cholesterol reduction. Cholesterol enters the body through absorption and synthesis. This seems to be determined genetically, and it has been shown that the high synthesisers and low absorbers do best on statin therapy. Ezetimibe, which inhibits cholesterol absorption, also reduces cholesterol by about 10 to 15 per cent and works best in the high absorbers and low synthesisers. The reason why cholesterol restriction without calorie restriction has so little impact is because the body has a wonderful ability to maintain cholesterol within a very narrow band and, hence, inhibition of absorption by diet or ezetimibe results in an increase in de novo cholesterol synthesis. Vice versa, inhibition of de novo synthesis

by a statin up-regulates cholesterol absorption. Therefore, our reality TV star did not reduce his cholesterol to such an extent solely by reducing cholesterol intake. Cholesterol is carried by the solubilising lipoproteins in the circulatory system. The major cholesterol carrying particle is LDL. However, LDL turnover is rather slow and cumbersome – taking four days to complete its processes – rather like a slow jumbo jet that takes so long to load and unload its passengers and accompanying baggage. On the other hand, the chylomicron, which is the postprandial particle that transports fat and cholesterol, has a very fast halflife that is measured in minutes rather than days. The amount of cholesterol

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13/09/2012 12:04:16

FOR PATIENTS WITH HYPERCHOLESTEROLEMIA NOT AT LDL-C GOAL ON STATIN MONOTHERAPY5

POWERFUL LDL-C TREATMENT, FUELLED BY DUAL ACTION1-4

TreatingObesity.indd 10

fenofibrate, adverse reactions were usually mild and transient. The overall incidence of side effects was similar between ‘Ezetrol’ and placebo. Similarly, the discontinuation rate due to adverse experiences was comparable between ‘Ezetrol’ and placebo. The following common (≥1/100, <1/10) drug-related adverse experiences were reported in patients taking ‘Ezetrol’ (N=2396) and at a greater incidence than placebo (N=1159) or in patients treated with Ezetrol coadministered with a statin (N=11308) and at a greater incidence than statin administered alone (N=9361): or co-administered with fenofibrate: ‘Ezetrol’ administered alone: General disorders and administration site condition: fatigue. Gastro-intestinal disorders: abdominal pain, diarrhoea and flatulence. ‘Ezetrol’ co-administered with a statin: Investigations: ALT and/or AST increased. Nervous system disorders: headache. Musculoskeletal and connective tissue disorders: myalgia. ‘Ezetrol’ co-administered with fenofibrate: Gastrointestinal disorders: abdominal pain (common). Laboratory values. In controlled clinical monotherapy trials, the incidence of clinically important elevations in serum transaminases (ALT and/or AST ≥3 X ULN, consecutive) was similar between ‘Ezetrol’ (0.5%) and placebo (0.3%). In co-administration trials, the incidence was 1.3% for patients treated with ‘Ezetrol’ co-administered with a statin and 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, returning to baseline after discontinuation of therapy or with continued treatment. In clinical trials, CPK >10 X ULN was reported for 4 of 1,674 (0.2%) patients administered ‘Ezetrol’ alone vs 1 of 786 (0.1%) patients administered placebo, and for 1 of 917 (0.1%) patients co-administered ‘Ezetrol’ and a statin vs 4 of 929 (0.4%) patients administered a statin alone. There was no excess of myopathy or rhabdomyolysis associated with ‘Ezetrol’ compared with the relevant control arm (placebo or statin alone). In a study involving adolescent (10 to 17 years of age) patients with heterozygous familial hyperchlolesterolaemia (n = 248), elevations of ALT and/or AST (≥3X ULN, consecutive) were observed in 3% (4 patients) of the ezetimibe/simvastatin patients compared to 2% (2 patients) in the simvastatin monotherapy group; these figures were respectively 2% (2 patients) and 0% for elevation of CPK (≥ 10X ULN). No cases of myopathy were reported. This trial was not suited for comparison of rare adverse drug reactions. Post-marketing experience. The following additional adverse reactions have been reported in post marketing experience. Because these adverse experiences have been identified from spontaneous reports, their true frequencies are not known and cannot be estimated. Blood and lymphatic system disorders: thrombocytopaenia. Nervous system disorders: dizziness; paraesthesia. Respiratory, thoracic and mediastinal disorders: dyspnoea. Gastrointestinal disorders: pancreatitis; constipation. Skin and subcutaneous tissue disorders: erythema multiforme. Musculoskeletal and connective tissue disorders: myalgia; myopathy/rhabdomyolysis. General disorders and administration site conditions: asthenia. Immune system disorders: hypersensitivity, including rash, urticaria, anaphylaxis and angio-oedema. Hepatobiliary disorders: hepatitis; cholelithiasis; cholecystitis. Psychiatric disorders: depression. PACKAGE QUANTITIES 28 Tablets. Legal Category: POM. Marketing Authorisation number: PA 1091/1/1. Marketing Authorisation holder: MSD-SP Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK. Date of review: March 2010. ® denotes registered trademark of MSP Singapore Company, LLC © Merck Sharp & Dohme Limited, 2010 All rights reserved. API.EZE.(II/33) Additional information is available on www.medicines.ie. or on request from MSD Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland. Date Or Preparation: October 2011 References: 1. Bays HE, Davidson MH, Massaad R, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE study). Am J Cardiol. 2011. doi:10.1016/j.amjcard.2011.03.079. 2. Leiter LA, Bays H, Conard S, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008;102(11):1495–1501. 3. Stein E, Stender S, Mata P, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004;148(3):447–455. 4. Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, doubleblind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004;26(11):1758–1773. 5. EZETROL Summary of Product Characteristics.

Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland

10-12-EZT-2011-IRL-5018-J

EZETROL® ezetimibe ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics (SPC) before Prescribing PRESENTATION 10 mg Tablet containing 10 mg of ezetimibe. USES As adjunctive therapy to diet in: Primary hypercholesterolaemia: For co-administration with an HMG-CoA reductase inhibitor (statin) for patients with primary (heterozygous familial and non-familial) hypercholesterolaemia not appropriately controlled with a statin alone. Monotherapy: For use in patients with primary (heterozygous familial and non-familial) hypercholesterolaemia in whom a statin is considered inappropriate or is not tolerated. Homozygous Familial Hypercholesterolaemia (HoFH): For co-administration with a statin, for use in patients with HoFH. Patients may also receive adjunctive treatments (e.g. LDL apheresis). Homozygous sitosterolaemia (phytosterolaemia): For use in patients with homozygous familial sitosterolaemia. A beneficial effect of Ezetrol on cardiovascular morbidity and mortality has not yet been demonstrated. DOSAGE AND ADMINISTRATION For oral administration. Put patients on an appropriate lipid-lowering diet and continue during treatment. Recommended dose is one ‘Ezetrol’ 10 mg tablet daily, administered at any time of the day, with or without food. When added to a statin, either continue with the indicated usual initial dose of that particular statin or the already established higher statin dose. Consult the statin dosage instructions. Co-administration with bile acid sequestrants: Dosing should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant. Use in paediatric patients: Initiation of treatment must be performed under review of a specialist. Adolescents ≥ 10 years): no dosage adjustment is required. The clinical experience in paediatric and adolescents patient (aged 10- 17 years old) is however limited. Children < 10 years: Ezetrol is not recommended due to insufficient data on safety and efficacy. Use in hepatic impairment. No dosage adjustment is required with mild hepatic insufficiency (Child Pugh score 5 to 6). Not recommended in patients with moderate (Child Pugh score 7 to 9) or severe (Child Pugh score >9) liver dysfunction. CONTRA-INDICATIONS Hypersensitivity to any component. When co-administered with a statin, refer to the SPC for that particular medicinal product. ‘Ezetrol’ co-administered with a statin during pregnancy and lactation. ‘Ezetrol’ coadministered with a statin in patients with active liver disease or unexplained persistent elevations in serum transaminases. PRECAUTIONS Liver enzymes: When co-administered with a statin, perform liver function tests at initiation of therapy and according to the SPC for that particular medicinal product. Skeletal muscle: In post-marketing experience with ‘Ezetrol’, myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin concomitantly with ‘Ezetrol. However, rhabdomyolysis has been reported very rarely with ‘Ezetrol’ monotherapy and very rarely with the addition of ‘Ezetrol’ to other agents known to be associated with increased risk of rhabdomyolysis. If myopathy is suspected based on muscle symptoms or is confirmed by a creatinine phosphokinase (CPK) level >10 times the ULN, immediately discontinue ‘Ezetrol’, any statin, and any of these other agents. Advise all patients starting therapy with ‘Ezetrol’ of the risk of myopathy and to report promptly any unexplained muscle pain, tenderness or weakness Hepatic insufficiency: Not recommended in patients with moderate or severe hepatic insufficiency due to the unknown effects of the increased exposure to ‘Ezetrol’. Fibrates: The safety and efficacy of co-administration have not been established. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected in a patient receiving ‘Ezetrol’ and fenofibrate, gallbladder investigations are indicated and this therapy should be discontinued. Ciclosporin: Exercise caution when initiating ‘Ezetrol’ in patients taking ciclosporin and monitor ciclosporin concentrations. Warfarin, another coumarin anticoagulant or fluindione: Monitor the International Normalised Ratio (INR) if taken together with ‘Ezetrol’. Excipient: ‘Ezetrol’ tablets contain lactose: do not use in patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Interactions (studies have only been performed in adults): Cholestyramine: Concomitant cholestyramine administration decreased the mean AUC of total ‘Ezetrol’ approximately 55%. The incremental low-density lipoprotein cholesterol (LDL-C) reduction due to adding ‘Ezetrol’ to cholestyramine may be lessened by this interaction. Fibrates: Possible risk of cholelithiasis and gallbladder disease upon co-administration of fenofibrate with ‘Ezetrol’. Statins: No clinically significant pharmacokinetic interactions were seen upon co-administration with atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, or rosuvastatin. Pregnancy and lactation: ‘Ezetrol’ co-administered with a statin is contra-indicated during pregnancy and lactation, refer to the SPC for that particular statin. Pregnancy: ‘Ezetrol’ should be given to pregnant women only if clearly necessary. No clinical data are available on the use of ‘Ezetrol’ during pregnancy. Lactation: ‘Ezetrol’ is contra-indicated. Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, when driving vehicles or operating machines, it should be taken into account that dizziness has been reported. SIDE EFFECTS Refer to SPC for complete information on side effects. Clinical Studies In clinical studies where ‘Ezetrol’ was administered alone or with a statin or with

13/09/2012 12:04:18

Treating Obesity The Effect of Obesity on Cholesterol

Obesity and hyperinsulinaemia with insulin resistance often go hand-inhand, particularly if the obesity is central. The LDL receptor is insulin sensitive. Thus, in insulin resistance and diabetes, a high cholesterol level will improve somewhat following exercise, weight reduction and improvements in blood sugar. Drugs that improve insulin resistance – such as metformin and pioglitazone – also improve cholesterol and, indeed, triglyceride. The LDL receptor is upregulated by insulin. Insulin signaling via AKT2 and mTORC1 has emerged as a key process in the regulation of hepatic lipogenesis in obese mice. The underlying mechanism involves induction of proprotein convertase subtilisin kexin type 9 (PCSK9) via mTORC1 leading to post transcriptural down-regulation of hepatic LDL receptors.

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The glucose insulin pathway is, perhaps, another story but is, nonetheless, very exciting as it involves

an understanding of how glucose stimulates insulin secretion in the beta cell and how insulin stimulates glucose disposal in all other cells. A few years ago, PKCs were all the rage and an editorial in Diabetologia on The Rising Star of PKC started with the sentence: “In the pubs of Ireland there is talk of little else”. PKCs are involved in insulin signaling and glucose transport but another pathway – in particular, a pathway involved in glucose disposal in exercise – is signaled by AKT2. Thus, the understanding that AKT2 is also involved in cholesterol lowering through its effect on the LDL receptor is another link in the chain between dyslipidaemia and hyperglycaemia in diabetes (and, of course, supports the idea of diabetes mellitus being re-named diabetes lipidus). mTORC1 would appear to be downstream of PKCδ and decreases HNF1α, a key regulator of insulin signaling. Of course, polymorphism of this gene is one cause of maturity onset diabetes of the young (MODY – AKA monogenic diabetes).

The excitement of this new information is borne out of the fact that, apart from offering a better understanding of the control mechanism for the receptor, it opens up new avenues for pharmacological intervention. An example of translational science at its best might one day be the discovery of antibodies that inhibit PCSK9. PCSK9 is the gene which regulates recycling of the LDL receptor, diverting it to the lysosomal compartment for degradation. PCSK9 binds tightly to the LDL receptor and channels it towards the lysosomal compartment for degradation, resulting in decreased LDL receptor numbers and increased plasma LDL levels. An interesting loss of function polymorphism of PCSK9 increases the number of LDL receptors and increases LDL removal from the plasma, thereby reducing LDL levels. There is strong evidence that

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in the particle is small, with it mostly consisting of triglycerides. It might be considered like a supersonic jet, delivering as much cholesterol over a four-day period as the bulky LDL particle. The presence of chylomicrons is vastly increased in the systems of obese patients, due not only to the increased dietary load but, also, since a fatty liver has limited ability to clear the particles efficiently, to delay in clearance. VLDL, the transporter of triglyceride from the liver, has an intermediate amount of cholesterol in the particle and an intermediate rate of clearance. In obese patients, particles are increased in an effort to improve fat transport from the liver. Once the particle has deposited the triglyceride it becomes LDL. LDL is cleared via the LDL receptor in the liver.

011

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Treating Obesity The Effect of Obesity on Cholesterol

PCSK9 and LDLR transcription are both activated by cellular cholesterol depletion via sterol regulatory element binding protein-2 (SREBP-2). This notion is supported by human studies that plasma PCSK9 concentration is increased with statin. It has been shown that fibrates significantly increase circulating PCSK9 levels. Thus an inhibitor of PCSK9 would be a useful addition to statin and fibrate therapy.

©thinkstockphotos.com_istockphoto

Dramatic lowering of LDL cholesterol has been described in non-human primates using monoclonal antibodies (mAB) against PCSK9, and the New England Journal of Medicine has recently reported on a clinical trial of mAB against PCSK9. This trial showed up to 65 per cent reduction in LDL cholesterol in healthy volunteers. These experiments were repeated in patients with familial hypercholesterolaemia – who were already on atorvastatin – and the results were similar to those of the healthy volunteers. The authors found a good correlation between reduction in free PCSK9 and reduction in LDL cholesterol. They demonstrated that the drug had an additive rather than synergistic effect,

TreatingObesity.indd 12

as the mean reductions were similar between normal and FH patients when administered alone or with atorvastatin. This result was to be expected since atorvastatin increases hepatic LDL receptor activity by enhancing production of LDL receptors, whereas the antibody decreases the degradation of receptors. There was a significant increase in HDL cholesterol. There was no clear evidence of drugrelated events which, perhaps, was the most important finding in the study. New block busters appear to be very hard to come by these days but, perhaps, PCSK9 inhibitors may help at least one pharmaceutical company to be optimistic, at least in the short term. For patients and practicing phycians it may help to take the burden of guilt away since so often LDL targets are not being met and in particular not being met in patients who already have had a myocardial infarction. Returning to obesity – and our chef who lost so much weight and had such a dramatic reduction in cholesterol – we should now explore the role of cholesterol absorption. Cholesterol absorption is tightly

regulated. The role of the three genes regulating cholesterol absorption in human diabetes have been defined as follows: (a) Niemann Pick C1 like1 (NPC1L1) gene has been well known since the introduction of the NPC1L1 inhibitor, Ezetimibe. In diabetes, NPC1L1 is up-regulated and cholesterol absorption is increased. It is likely that in obesity with insulin resistance, cholesterol absorption is increased, and dietary intervention combined with weight loss would have the opposite effect. (b)ABCG5 and G8 act as heterodimers to further control cholesterol absorption by excreting – back into the lumen of the bowel – absorbed cholesterol. These genes are insulin sensitive and, in diabetes, this mechanism is inhibited, further increasing cholesterol absorption. Studies in human obesity have not yet been done, but one assumes that weight reduction is associated with improvement in the ability to excrete unwanted cholesterol. Finally, (c) MTP packages triglyceride and cholesterol to form the chylomicron ,and this packaging is disturbed in diabetes and improved by insulin and blood sugar-lowering. In conclusion, new pathways have been described to explain the effect of obesity, and the benefits of weight reduction, on cholesterol. New drugs are being developed that will be more effective in lowering cholesterol. Statins lower cardiovascular mortality by up to 30 per cent, suggesting that 70 per cent of patients don’t benefit from statins. More effective cholesterol lowering may yield benefits. The field is exciting and moving very fast. But it is hard not to be impatient. Professor Gerald H. Tomkin is a consultant endocronologist and Director of Diabetes Ireland.

13/09/2012 12:04:47

® A : N EW Z N LI N LY TIO SU N G N A I O D I C TO I N - ON

Add Onglyza 5mg to metformin and regain glycaemic control.

Onglyza reduces HbA1c, PPG, FPG when added to metformin, sulphonylurea or TZD monotherapy1-5

1. 2. 3. 4. 5.

Onglyza, Summary of Product Characteristics DeFronzo RA, et al. Diabetes Care. 2009;32(9):1649-55. Data on File. SAXA 004. Bristol-Myers Squibb/AstraZeneca. Chacra AR, et al. Int J Clin Pract. 2009;63(9):1395-406. Hollander P, et al. J Clin Endocrinol Metab. Dec 2009, 94 (12): 4810-4819.

ONGLYZA® 2.5 mg & 5 mg film-coated tablets (saxagliptin). Abridged prescribing information. Consult Summary of Product Characteristics (SmPC) before prescribing. Presentation: 2.5 mg or 5 mg saxagliptin (as hydrochloride) film-coated tablets. Uses: Adults 18 and older: For Type 2 diabetes mellitus patients to improve glycaemic control in combination with diet and exercise and: Metformin, when metformin and diet and exercise alone, do not provide adequate glycaemic control; Sulphonylurea, when sulphonylurea and diet and exercise alone, do not provide adequate glycaemic control, where metformin is considered inappropriate; Thiazolidinedione, when thiazolidinedione and diet and exercise alone do not provide adequate glycaemic control and thiazolidinedione is considered appropriate; Insulin (with or without metformin), when this regimen alone, with diet and exercise, does not provide adequate glycaemic control. Dosage: Adults: 5 mg once daily as add-on therapy with or without food at any time of the day. When used in combination with a sulphonylurea or insulin, consider a lower dose of sulphonylurea or insulin to reduce the risk of hypoglycaemia. Children and Adolescents (< 18 years old): Safety and efficacy not yet established. Moderate Hepatic Impairment: Use with caution. Severe Hepatic Impairment: Not recommended. Moderate & Severe Renal Impairment: 2.5 mg once daily, caution in patients with severe renal impairment. Assessment of renal function recommended prior to initiation. End stage renal disease: Not recommended. Elderly ≥ 75 years: Use with caution. Contraindications: Hypersensitivity to saxagliptin, to any of the excipients or history of a serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and angioedema, to any dipeptidyl peptidase

TreatingObesity.indd 13

4 inhibitor. Precautions and warnings: Not for the treatment of Type 1 diabetes mellitus or diabetic ketoacidosis. Not a substitute for insulin in insulin requiring patients. Post-marketing reports of acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, discontinue Onglyza and other potentially suspect medicinal products. Resolution of pancreatitis has been observed after discontinuation of saxagliptin. If a serious hypersensitivity reaction to saxagliptin is suspected, discontinue use, assess for other potential causes, and institute alternative treatment. Contains lactose, not recommended in patients with rare hereditary galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption. No experience in cardiac failure (NYHA class III-IV) or immunocompromised patients. Recommend monitoring for evidence of skin disorders. Drug Interactions: Clinical data suggest low risk for clinically meaningful interactions with co-administered medicinal products. The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5) – refer to SmPC for information. Caution with potent CYP3A4/5 inducers as glycaemic lowering effect of Onglyza may be reduced. Pregnancy and lactation: Avoid use during pregnancy unless clearly necessary. Risk to suckling child cannot be excluded – either discontinue breast-feeding or Onglyza therapy. Fertility: The effect of saxagliptin on fertility in humans has not been studied, see SmPC. Undesirable effects: Common adverse reactions reported in add-on trials: Upper respiratory infection; urinary tract infection; gastroenteritis; sinusitis; headache; and vomiting. Add-on to metformin: Common: Nasopharyngitis. Add-on to sulphonylurea: Very Common: Hypoglycaemia Add-on to

thiazolidinedione: Common: Peripheral oedema (mild to moderate only). Adverse reactions reported in post-marketing experience: Common: Nausea, rash. Uncommon: Hypersensitivity reactions, pancreatitis, urticaria, dermatitis, pruritus. Rare: Anaphylactic reactions including anaphylactic shock, angioedema. Adverse reactions considered to be at least possibly related to Onglyza: Monotherapy: Common: Dizziness and fatigue. Initial combination with metformin: Common: Gastritis. Uncommon: Arthralgia, myalgia and erectile dysfunction. Add on to metformin: Common: Dyspepsia and myalgia. Add on to sulphonylurea: Uncommon: Fatigue, dyslipidaemia and hypertriglyceridaemia. Investigations: Small decreases in absolute lymphocyte count were observed but were not associated with clinically relevant adverse reactions. Key: Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000). Consult SmPC for a full list of undesirable effects. Legal Category: Prescription Only Medicine. Marketing authorisation number: EU/1/09/545/006 & EU/1/09/545/012. Marketing Authorisation holder: BristolMyers Squibb / AstraZeneca EEIG, Bristol-Myers Squibb House, Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex, UB8 1DH, UK. Further information is available from Bristol-Myers Squibb Pharmaceuticals, Tel + 353 (1 800) 749 749. ONGLYZA is a trademark of the Bristol-Myers Squibb / AstraZeneca group of companies. Abridged prescribing information prepared: 01-2012. 422IE12PM001. URN: 11/0558. Date of Preparation: January 2012. 422IE11PM025.

13/09/2012 12:04:48

JANUMET® targets the 3 key defects of Type 2 Diabetes to improve glycemic control1 (sitagliptin/metformin)

Increases insulin sensitivity • Metformin increases glucose uptake and utilization (greater effect in the liver than in muscle and fat)3,4

Increases insulin synthesis and release • Sitagliptin works in a glucose-dependent manner to increase active incretins, which stimulate the synthesis and release of insulin from β cells2

Decreases hepatic glucose overproduction

JANUVIA® JANUMET® Sitagliptin Sitagliptin/metformin hydrochloride ABRIDGED PRESCRIBING INFORMATION Refer to Summary of Product Characteristics (SmPC) before prescribing PRESENTATION Januvia® 25 mg, 50 mg and 100 mg film-coated tablet each containing 25 mg, 50 mg or 100 mg of sitagliptin respectively. Janumet® 50 mg/850 mg and 50 mg/1000 mg tablets each containing 50 mg sitagliptin and 850 mg or 1000 mg metformin hydrochloride. USES For patients with type 2 diabetes mellitus Januvia is indicated to improve glycaemic control: as monotherapy, • in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance as dual oral therapy in combination with • metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control • a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contra-indications or intolerance • a PPARγ agonist (i.e. a thiazolidinedione) when use of a PPARγ agonist is appropriate and when diet and exercise plus the PPARγ agonist alone do not provide adequate glycaemic control. as triple oral therapy in combination with • a sulphonylurea and metformin when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control. • a PPARγ agonist and metformin when use of a PPARγ agonist is appropriate and when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control. Januvia is also indicated as add-on to insulin (with or without metformin) when diet and exercise plus stable dosage of insulin do not provide adequate glycaemic control. Janumet: as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximal tolerated dose of metformin alone or those already being treated with the combination of sitagliptin and metformin. • in combination with a sulphonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea. • as triple combination therapy with a PPARγ agonist (i.e., a thiazolidinedione) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a PPARγ agonist. • as add-on to insulin (i.e., triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when stable dosage of insulin and metformin alone do not provide adequate glycaemic control. DOSAGE AND ADMINISTRATION Januvia – One 100 mg tablet once daily, with or without food. Janumet – The dose of antihyperglycaemic therapy with Janumet should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin. For patients not adequately controlled on metformin alone, the usual starting dose of Janumet should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken. For patients switching from co-administration of sitagliptin and metformin, Janumet should be initiated at the dose of sitagliptin and metformin already being taken. For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a sulphonylurea or with maximal tolerated dose of metformin and a PPARγ agonist or with maximal tolerated dose of metformin and insulin, the dose of Janumet should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken. All patients should continue their diet with an adequate distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet. Januvia and Janumet – In combination with a sulphonylurea or with insulin, consider a lower dose of sulphonylurea or insulin, to reduce risk of hypoglycaemia. Renal impairment: For Januvia only: When considering sitagliptin with another anti-diabetic product, its use in patients with renal impairment should be checked. Moderate impairment (CrCl ³30 to <50 mL/min), the dose is 50 mg once daily. Severe impairment (CrCl <30 mL/min) or with end-stage renal disease (ESRD), the dose is 25 mg once daily. Mild impairment, no dose adjustment. Assessment of renal function is recommended prior to initiation of Januvia and periodically thereafter. For Janumet only: Should not be used in patients with moderate or severe renal impairment (creatinine clearance < 60 ml/min). Hepatic impairment: For Januvia only – no dosage adjustment necessary for patients with mild to moderate hepatic impairment. Januvia has not been studied in patients with severe hepatic impairment. For Janumet only – do not use. Elderly < 75 years: For Januvia only – no dosage adjustment necessary. For Janumet only - use with caution as age increases. Monitoring of renal function is necessary to aid prevention of metformin-associated lactic acidosis. Elderly ≥ 75 years: Exercise care as there are limited safety data in this population. Children: not recommended below 18 years of age. CONTRA-INDICATIONS For Januvia – Hypersensitivity to active substance or excipients. For Janumet – Hypersensitivity. Diabetic ketoacidosis and diabetic pre-coma. Moderate and severe renal impairment (creatinine clearance < 60 ml/min). Acute conditions with the potential to alter renal function such as dehydration, severe infection, shock. Intravascular administration of iodinated contrast agents. Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock. Hepatic impairment. Acute alcohol intoxication, alcoholism. Lactation. PRECAUTIONS For Januvia and Janumet – General: do not use in patients with type 1 diabetes or for diabetic ketoacidosis. Pancreatitis: Post-marketing experience - spontaneously reported adverse reactions of acute pancreatitis. Inform patients of the symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin, but very rare cases of necrotizing or haemorrhagic pancreatitis and/or death have been reported. If pancreatitis is suspected, Januvia or Janumet and other potentially suspect medicinal products should be discontinued. Hypoglycaemia when used with other anti-hyperglycaemic agents: Rates of hypoglycaemia reported with sitagliptin were generally similar to rates in patients taking placebo. When sitagliptin was added to a sulphonylurea or to insulin, the incidence of hypoglycaemia was increased over that of placebo; therefore consider a lower dose of sulphonylurea or insulin to reduce the risk of hypoglycaemia when administering Janumet or Januvia. Hypersensitivity reactions: Serious hypersensitivity reactions have been reported, including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset occurred within the first 3 months after initiation of treatment with some reports occurring after the first dose. If suspected, discontinue Januvia or Janumet. For Januvia only – Renal Impairment: Lower dosages are recommended in patients with moderate and severe renal impairment, as well as in ESRD patients requiring haemodialysis or peritoneal dialysis- see Dosage. For Janumet only – Lactic acidosis and renal function: a very rare, but serious, metabolic complication can occur due to metformin accumulation. Cases

TreatingObesity.indd 14

in patients on metformin have occurred primarily in diabetic patients with significant renal failure. Reduce incidence by assessing other associated risk factors. If suspected, discontinue treatment and hospitalise patient immediately. If changes in clinical status of patients with previously controlled type 2 diabetes occurs, evaluate promptly for evidence of ketoacidosis or lactic acidosis in any patient with type 2 diabetes previously well controlled on Janumet who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness). If acidosis of either form occurs, stop Janumet immediately and initiate corrective measures. Determine serum creatinine concentrations regularly, i.e. at least once a year in patients with normal renal function and at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in elderly patients. Decreased renal function in elderly patients is frequent and asymptomatic. Exercise special caution where renal function may become impaired, e.g. when initiating antihypertensive or diuretic therapy or when starting treatment with a non-steroidal anti-inflammatory drug (NSAID). Surgery: due to metformin hydrochloride content of Janumet, discontinue treatment 48 hours before elective surgery with general, spinal or epidural anaesthesia. Do not resume earlier than 48 hours afterwards and only after renal function is normal. DRUG INTERACTIONS For Janumet only – Alcohol: avoid alcohol and medicinal products containing alcohol due to risk of lactic acidosis. Cationic agents that are eliminated by renal tubular secretion (e.g., cimetidine): these may interact with metformin by competing for common renal tubular transport systems. Consider close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment when these agents are co-administered. Iodinated contrast agents in radiological studies: intravascular administration of these agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Discontinue Janumet prior to, or at the time of the test and do not reinstitute until 48 hours afterwards, and only after renal function is found to be normal. Combination requiring precautions for use: glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust dose of the anti-hyperglycaemic medicine during therapy with, or on discontinuation of the other medicine. ACE-inhibitors: as these may decrease the blood glucose levels, if necessary, adjust dose of the antihyperglycaemic during therapy with, or on discontinuation of the other medicine. For Januvia and Janumet – Low risk of clinically meaningful interactions with metformin and ciclosporin. Meaningful interactions would not be expected with other p-glycoprotein inhibitors. The primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8. Digoxin: sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p-glycoprotein in vivo. No dosage adjustment of digoxin is recommended, but monitor patients at risk of digoxin toxicity if the two are used together. Pregnancy and lactation: Do not use during pregnancy or breast-feeding. SIDE EFFECTS Refer to SmPC for complete information on side effects There have been no therapeutic clinical trials conducted with Janumet tablets however Janumet is bioequivalent to co-administered sitagliptin and metformin. The following adverse reactions reported from both clinical trials and post-marketing experience using the following conversion: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000). Sitagliptin only: Common: hypoglycaemia, headache, upper respiratory tract infection, nasopharyngitis, osteoarthritis and pain in extremity. Uncommon: dizziness, constipation. Metformin only: Clinical Trial Data and Post-marketing data: Very common: gastro-intestinal symptoms; Common: metallic taste; Very rare: urticaria, erythema; pruritis; lactic acidosis; vitamin B12 deficiency; liver function disorders, hepatitis. Sitagliptin with metformin: Common: nausea; Uncommon: somnolence; upper abdominal pain, diarrhoea, blood glucose decreased. Sitagliptin with a sulphonylurea: Common: hypoglycaemia. Sitagliptin with metformin and a sulphonylurea: Very common: hypoglycaemia; Common: constipation. Sitagliptin with a PPARg agent (pioglitazone): Common: hypoglycaemia, flatulence, peripheral oedema. Sitagliptin with a PPARg agent (rosiglitazone) and metformin: Common: headache, cough, diarrhoea, vomiting, hypoglycaemia, peripheral oedema; Uncommon: fungal skin infection. Sitagliptin with insulin with/ without metformin: Common: headache, hypoglycaemia, influenza; Uncommon: dry mouth, constipation. Sitagliptin with metformin and insulin: Very common: hypoglycaemia; Uncommon: headache and dry mouth. Post-marketing experience additional side effects have been reported (frequency not known): hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis and exfoliative skin conditions including Stevens-Johnson syndrome (see precautions); acute pancreatitis, including fatal and non-fatal haemorrhagic and necrotizing pancreatitis (see precautions); impaired renal function, including acute renal failure (sometimes requiring dialysis); vomiting; arthralgia, myalgia. PACKAGE QUANTITIES Januvia 25 mg, 50 mg and 100 mg film-coated tablets 28 tablets Janumet 50mg/850mg and 50mg/1000mg film-coated tablets 56 tablets Marketing Authorisation Number Januvia 25 mg: EU/1/07/383/002 Janumet 50 mg/850 mg: EU/1/08/455/003 Januvia 50 mg: EU/1/07/383/008 Janumet 50 mg/1000 mg: EU/1/08/455/010 Januvia 100mg: EU/1/07/383/0014 Marketing Authorisation Holder Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK Legal Category: POM Date of review of prescribing information: December 2011. Further information is available on request from: MSD Pelham House, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. © Merck Sharp & Dohme Ireland (Human Health) Limited, 2012. All rights reserved. Date of preparation: March 2012. References: 1. Ramlo-Halsted BA, Edelman SV. The natural history of type 2 diabetes: practical points to consider in developing prevention and treatment strategies. Clin Diabetes. 2000;18(2):80–88. 2. Janumet SPC available at www.medicines.ie. 3. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574–579. 4. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):E-25–E-33. 5. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385–411.

Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland.

DIAB-1037992-0001

• Metformin reduces glucose production in the liver (gluconeogenesis) and diminishes the breakdown of glycogen into glucose (glycogenolysis)4,5 • Sitagliptin suppresses glucagon secretion from pancreatic α cells (by enhancing active incretin levels), which results in reduced glycogen breakdown and glucose synthesis2 • By enhancing active incretin levels, sitagliptin increases insulin synthesis and release from pancreatic β cells, which helps reduce hepatic glucose overproduction2

13/09/2012 12:04:53

Treating obesity prof donal o’shea Interview

Defeating Diabetes St Vincent’s physician and consultant endocrinologist Prof Donal O’Shea discusses the link between diabetes and obesity, new treatments, and why educating the public on prevention is so important.

DIAB-1037992-0001

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Could you give me a brief synopsis of your career thus far? I qualified in medicine from UCD in 1989 and moved over to London to a training post in diabetes and obesity in 1992. [I spent] seven years over there before coming back to my current job, which is as a consultant at Vincent’s involved with the management of diabetes and obesity. I assessed the situation when I came back to Ireland and there were two big gaps. One was structured education for people with Type 1 diabetes, and we got very involved in looking at that and bringing in a structured programme – the DAFNE programme - that was in operation in the UK back to Ireland. The other was the absence of any service for obesity, which causes 80 per cent of type 2 diabetes, so we set up a service for that as well.

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TreatingObesity.indd 15

How much of a factor is body mass when it comes to getting diabetes? There are three big predictors of developing diabetes: One is your genetic tendencies – so if there is a family history of it – the second is overweight and obesity, and the third would be physical inactivity. If you

13/09/2012 12:05:09

TreatingObesity.indd 16

13/09/2012 12:05:19

Treating obesity prof donal o’shea Interview

have a genetic predisposition to Type 2 diabetes but you keep your weight normal, you will delay or maybe not even develop type-2 diabetes. Overall, 80 per cent of type-2 diabetes is caused by being overweight or obese. What do you think has caused the recent rise in obesity? What’s caused it is a combination of reduced activity from day-to-day; people are much less physically active than they were. Calorie intake overall has crept up and the type of food we’re eating is, itself, high in fat. That drives insulin resistance independent of total energy. So If you have a diet that is high in fat, you ultimately become insulin resistant. You store that fat in your muscles and that effects how your muscles work. You store that fat in your liver, and that effects how your liver works.

The advice is around healthy eating and a gradual build up of physical activity. You don’t need to go to the gym – you just need to go for a brisk walk. If you eat healthy and get active

you will turn things around if you’re overweight. The problem we’re beginning to recognise is that if you’re obese, it’s really difficult. Shifting pounds is a massive challenge. The body resists, in every way possible, weight loss. It goes into a type of shut down when you try to lose weight, and that’s a problem. So really the argument has to be about prevention and prevention in kids. Are there any recent developments in treating diabetes that you’re excited about? The two areas would be the role of gastric bypass surgery in the severely obese type 2 diabetic. There is a significant amount of research in the last year that says its very good for diabetes. In some cases the diabetes is even temporarily reversed, and we need longer follow up on that to find out how long it can be reversed for. And it’s also good for the complications of diabetes, and it’s the complications of diabetes that account for the cost. And then the other advance would be a new class of drug called the incretin family, which are based around a hormone called GLP-1. It’s a hormone that helps your insulin work better. Added to the treatments we already use, it’s effective in people with type-2 diabetes. Those are the two big advances, but I think prevention is important. If we try and treat our way out of the obesity and diabetes epidemic, it will completely bankrupt the health care system.

©thinkstockphotos.com_iStockPhoto

With so much evidence tying obesity to a lot of different afflictions, do you think there’s enough being done to educate the public, and what can we do to stem the rise in obesity levels? I recently attended the inaugural

meeting of The Association for the Study of Obesity on the Island of Ireland. I think that’s an important organisation because people have not been doing enough. There are pockets of activity. There’s interest over the summer because there’s not much else going on in the news. There’s interest in January because of everyone’s New Year’s resolutions. But what we need is week-to-week awareness of people knowing their physical activity level is good enough, knowing their weight is reasonable. Parents taking responsibility for knowing what their kids weigh, what they should weigh, and making sure their kids are physically active. The focus for prevention must be in childhood. 25 per cent of three-yearolds are overweight or obese and that is stoking up a massive problem with early type 2 diabetes for the next ten to 15 years.

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13/09/2012 12:05:24

NEW from

Reduces Total Cholesterol and LDL Cholesterol1 Helps prevent cardiovascular events in patients at risk of first event1

Ireland has a NEW King of Hearts! Abbreviated prescribing information: Torvan 10 mg/ 20 mg/ 40 mg and 80 mg Film-coated tablets. Presentation: Torvan is supplied as film-coated tablets of 10 mg/ 20 mg/ 40 mg or 80 mg of atorvastatin. Indications: Torvan is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate. Atorvastatin is also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable. Used for the prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors. Dosage: The patient should be placed on a standard cholesterol-lowering diet before receiving atorvastatin and should continue on this diet during treatment with atorvastatin. The dose should be individualized according to baseline LDL-C levels, the goal of therapy, and patient response. The usual starting dose is 10 mg once a day. Adjustment of dose should be made at intervals of 4 weeks or more. The maximum dose is 80 mg once a day. Atorvastatin is for oral administration. Each daily dose of atorvastatin is given all at once and may be given at any time of day with or without food. Contraindications: Hypersensitivity to the active substance or to any of the excipients of this medicinal product. Active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal. During pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures. Special warnings and precautions for use: Liver function tests should be performed before the initiation of treatment and periodically thereafter and in patients who develop any signs or symptoms suggestive of liver injury (monitor raised transaminase levels until they resolve). Should an increase in transaminases of greater than 3 times the upper limit of normal (ULN) persist, reduction of dose or withdrawal of atorvastatin is recommended. For patients with prior hemorrhagic stroke or lacunar infarct, the balance of risks and benefits of atorvastatin 80 mg is uncertain, and the potential risk of hemorrhagic stroke should be carefully considered before initiating treatment. Torvan should be prescribed with caution in patients with pre-disposing factors for rhabdomyolysis and a CK (creatine kinase) level should be measured before treatment. If CK levels are significantly elevated at baseline (> 5 times ULN), treatment should not be started. Patients with muscle pain, cramps, or weakness especially if accompanied by malaise or fever should have their CK levels monitored. Torvan must be discontinued if clinically significant elevation of CK levels (> 10 x ULN) occur, or if rhabdomyolysis is diagnosed or suspected. If muscular symptoms are severe and cause daily discomfort treatment discontinuation should be considered. The risk of myopathy may also be increased when administered with other medicinal products that have a potential to induce myopathy. In cases where co-administration of these medicinal products with Torvan is necessary, the benefit and the risk of concurrent treatment should be carefully considered. The concurrent use of atorvastatin and fusidic acid is not recommended, therefore, temporary suspension of atorvastatin may be considered during fusidic acid therapy. Exceptional cases of interstitial lung disease have been reported with some statins. If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued. Developmental safety in the paediatric population has not been established. Drug Interactions: CYP3A4 inhibitors, CYP3A4 inducers, Transport protein inhibitors, Gemfibrozil / fibric acid, derivatives, Ezetimibe, Colestipol, Fusidic acid, Digoxin, Oral contraceptives, Warfarin, Tipranavir, Ciclosporin, Lopinavir, Ritonavir, Clarithromycin, Saquinavir, Darunavir, Itraconazole, Fosamprenavir, Nelfinavir, Grapefruit Juice, Diltiazem, Erythromycin, Amlodipine, Cimetidine, Efavirenz, Rifampin, Gemfibrozil, Fenofibrate, Phenazone. Pregnacy and lactation: Torvan should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with atorvastatin should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant. Undesirable effects: Common side effects include: nasopharyngitis, allergic reactions, hyperglycaemia, pharyngolaryngeal pain, epistaxis, constipation, flatulence, dyspepsia, nausea, diarrhoea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function test abnormal, blood creatine kinase increased, headache, abdominal pain, alanine aminotransferase increased, blood creatine phosphokinase increased, For further undesirable effects, please refer to the SPC. Shelf Life: 18 months. Marketing Authorisation Holder: Pinewood Laboratories Ltd, Ballymacarbry, Clonmel, Co. Tipperary. Marketing Authorisation Holder Numbers(s): PA 281/150/001 - 004. This medicine is a prescription only product. Further prescribing information is available on request. Date of revision: April 2012 References: 1. Torvan Summary of Product Characteristics, April 2012 Date of preparation: April 2012

Irelandâ&#x20AC;&#x2122;s No. 1 Generic Healthcare Specialists

TreatingObesity.indd 18

13/09/2012 12:05:27

Treating Obesity IRISH HEART FOUNDATION | Message from the CEO

019

A Time to Act Why Ireland cannot succeed in the fight against obesity without leadership at government level. Words: Barry Dempsey, CEO, Irish Heart Foundation

he Irish Heart Foundation welcomes the publication of Treating Obesity. We need as many opportunities as possible to engage with stakeholders in a bid to halt the obesity epidemic in Ireland and prevent a rise in cardiovascular disease, and we need many voices to join the fight.

not reduced or in anyway lessened in terms of the risk they pose to cardiovascular health. Of particular note is that 23 per cent of ischaemic heart disease is estimated to be attributable to being overweight or obesity. This raises major concerns and challenges for the Irish Heart Foundation as we face a potential rise in the prevalence of cardiovascular risk factors, disease incidence and increased premature deaths from obesity-related CVD.

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The good news is that deaths from coronary heart disease (CHD) have halved since the 1980s. This can be

explained by a reduction of the major contributing risk factors thanks to increased health promotion and developments, and improvements in treatments and medication. Yet, despite this decline, cardiovascular disease (CVD) remains the leading cause of mortality in Ireland. More worrying is that recent analyses of trends in CHD mortality indicate a flattening of this downward trend. Analysis also shows that obesity, diabetes and physical inactivity have

TreatingObesity.indd 19

13/09/2012 12:05:42

Heart failure management has moved up a gear

Ivabradine

Twice daily

Beat better, live longer1 Procoralan: Abbreviated Prescribing Information. Please refer to Summary of Product Characteristics (SmPC) before prescribing. Presentation and composition: Procoralan 5 mg film-coated, scored tablet containing 5 mg ivabradine; Procoralan 7.5 mg film-coated tablet containing 7.5 mg ivabradine. Indication: Treatment of coronary artery disease: Symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm, who have a contraindication or intolerance for β-blockers or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is >60 bpm. Treatment of chronic heart failure: Indicated in NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥75bpm, in combination with standard therapy including beta-blocker therapy or when beta blocker therapy is contraindicated or not tolerated. Dosage and administration: Treatment of coronary artery disease: The starting dose is 5 mg orally twice daily, during meals: breakfast and dinner. The dose can be increased to 7.5mg twice daily after 3-4 weeks of treatment, depending on the therapeutic response. If heart rate decreases persistently below 50 beats per minute (bpm) at rest, treatment should be down titrated to 2.5 mg twice daily. Treatment of chronic heart failure: to be initiated only in patients with stable heart failure and preferably by a physician experienced in the management of chronic heart failure. Starting dose of ivabradine is 5 mg twice daily. After two weeks of treatment, the dose can be increased to 7.5 mg twice daily if resting heart rate is persistently above 60 bpm, or decreased to 2.5 mg twice daily if resting heart rate is persistently below 50 bpm or in case of symptoms related to bradycardia. If heart rate is between 50 and 60 bpm, the dose of 5 mg twice daily should be maintained. Treatment must be discontinued if heart rate remains below 50 bpm or symptoms of bradycardia persist. Pharmacology: Procoralan is a pure heart rate-lowering agent, acting by a selective inhibition of the cardiac pacemaker If current that controls spontaneous diastolic depolarization in the sinus node and regulates heart rate. Procoralan dose-dependently reduces heart rate, and provides a significant anti-ischaemic and anti-anginal efficacy. Contraindications: Hypersensitivity to ivabradine or any of its excipients, resting heart rate below 60 bpm prior to treatment, cardiogenic shock, acute myocardial infarction, severe hypotension (<90/50 mmHg), severe hepatic insufficiency, sick sinus syndrome, sinoatrial block, unstable or acute heart failure, pace maker dependent, unstable angina, AV block 3rd degree, co-administration with strong CYP 3A4 inhibitor. Pregnancy and lactation (in absence of data). Interactions: Combination with heart rate-reducing agents, combination with QT-prolonging medicinal products, moderate CYP 3A4 inhibitors and inducers. Precautions: cardiac arrhythmias: Ivabradine is not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function. The risk of developing atrial fibrillation may be higher in chronic heart failure patients treated with ivabradine. Chronic heart failure: Heart failure must be stable before considering ivabradine treatment. Ivabradine should be used with caution in heart failure patients with NYHA functional classification IV due to limited amount of data in this population. No data are available in patients with creatinine clearance below 15 ml/min, therefore ivabradine should be used with caution in this population. Not recommended in patients with AV-block of 2nd degree; in patients with a pre-treatment resting heart rate below 60 beats per minute; Concomitant use of ivabradine with heart rate reducing calcium channel blockers such as verapamil or diltiazem is not recommended; Not recommended immediately after a stroke since no data is available in these situations. Side effects: Luminous phenomena, bradycardia, ventricular extrasystoles, headache, dizziness, blurred vision, AV 1st degree block, uncontrolled blood pressure, angioedema, urticaria, asthenia possibly related to bradycardia and fatigue possibly related to bradycardia. Presentation: Pack of 56 tablets of Procoralan 5 mg, Pack of 56 tablets of Procoralan 7.5 mg. Legal Category: POM. Marketing Authorisation Numbers and Holders: EU/1/05/316/001-014, Les Laboratoires Servier, 30, rue Carnot, 92284 Suresnes cedex France. Date of Preparation or Last Review: February 2012. Full prescribing information is available from: Servier Laboratories, Block 2, West Pier Business Campus, Old Dunleary Road, Dun Laoghaire, Co Dublin. Tel: (01) 6638110, Fax (01) 6638120. www.servier.ie

in Ar Made

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Reference 1. Procoralan Summary of Product Characteristics February 2012. 2. Swedberg et al. for the SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2012; 376:875-885. Date of preparation: February 2012

Procoralan® is also effective for the treatment of Coronary Artery Disease1 TreatingObesity.indd 20

13/09/2012 12:05:47

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Further disimprovement is all the more likely due to increasing levels of overweight and obese children. We are now seeing children, teenagers and young adults present with risk factors like elevated cholesterol and blood pressure. In addition to this, we are seeing more and more physical inactivity, overweight and obese patients. And, as we know, an obese child is more likely to become an obese adult, perpetuating the cycle of increasing levels of diabetes and CVD risk factors, as well as leaving themselves open to other health problems and premature mortality. The statistics on childhood overweight and obesity in Ireland are alarming, and confirm that childhood obesity is the most prevalent childhood disease in the country. A quarter of Irish threeyear-olds are overweight or obese, 19

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tablet ers in n with an be to be heart must in the ment, strong is not stable

Treating Obesity IRISH HEART FOUNDATION | Message from the CEO

TreatingObesity.indd 21

per cent and 6 per cent respectively. Among nine-year olds, 19 per cent are overweight and 7 per cent are obese. 23 per cent of children aged five to 12 and 23 per cent of nine to 18-year-olds are overweight or obese. Much of this data has been published following the seminal report by the National Task Force on Obesity (NTFO). Ireland was one of the first countries to outline comprehensive recommendations on what was needed to tackle the obesity crisis addressing the main determinants of obesity and looking at social, economic and environmental factors. Despite many public calls from us here at the Irish Heart Foundation for implementation of the NTFO recommendations, there has been too little action and the overall response

021

has been dismal. Seven years on, and now more than ever, Ireland needs a political champion to drive this health issue at government level and to ensure full implementation of the recommendations. While Minister for Health Dr James Reilly has brought a lot of energy to the campaign and initiated some positive public health policy proposals on the issue, success will depend on the support of other government departments. The medical and health community need to influence public and media opinion in order to inspire public policies to reduce obesity and improve poor dietary habits. Only then can we become proactive and deliver meaningful public health policies that will make the healthy choice the easier choice by adopting such policies as a levy on sugary sweetened drinks and the display of calorie counts on menus. International consensus and evidence has identified the need to focus not just on individual approaches, but to look at policies and interventions that have an impact on a wide population. At the Irish Heart Foundation, we believe Ireland cannot succeed in the fight against obesity without leadership at government level. We urge a multisector approach led by An Taoiseach supporting the Minister for Health to show leadership across government departments, local authorities and NGOs, driving implementation of public health policies to reduce obesity, particularly in our children. As called for by the World Health Organisation in the Adelaide Statement on Health, Ireland needs to put health and well-being on the agenda in all policies across all departments and government agencies â&#x20AC;&#x201C; otherwise society and the health system will be overburdened with the impact and costs of obesity now and for years to come.

13/09/2012 12:05:53

022

Treating Obesity Better Than Cure?

Better Than Cure? What can be done to reduce Ireland’s obesity levels? Words: Dr Angie Brown & Maureen Mulvihill

Obesity leads to insulin resistance, type 2 diabetes, hypercholesterolaemia and hypertension, each of which increases the risk of developing cardiovascular disease. Sleep apnoea and arthritis are well-recognised consequences of obesity, but few are aware of the reduced life expectancy it fosters, the increased risk of various cancers and liver disease, and the psychological distress which comes from being obese. Even more concerning is the ever increasing weight of children with 26 per cent exhibiting symptoms of being overweight or obese.3 Once a child is substantially overweight, successful weight loss is difficult to achieve – as it is for adults – and requires intensive health care resources. Sadly, many studies have shown that those overweight or obese in childhood or adolescence are more likely to be overweight or obese in adulthood.4 Prevention is much preferred, for the child’s sake in terms of the social, health and economic costs that otherwise ensue. Without interventions to modify the predicted continued increase in obesity levels, all the

TreatingObesity.indd 22

benefits in reducing mortality from CVD will be lost. Obesity has been described as an unforeseen outcome of polices of increased output since the 1950s5 and as a natural response to an unnatural environment. This is often termed the obesogenic environment. Today, the big problem is unhealthy food choices – given the accessibility, range and low cost of food high in fat, sugar and salt – combined with a physical environment that has engineered activity out of our lives through the increased use of motorised transport, automated home and recreational gadgets as well as more sedentary, leisure and entertainment activities. To tackle this exponential rise in obesity rates, we urgently need to create a more supportive environment in which the healthier choice is the easier choice.

The argument for a focus on population level strategies as a solution for disease prevention was originally made by the eminent epidemiologist Geoffrey Rose,6 and that argument holds equally true where obesity is concerned. Rose identified that a small shift in the risk of disease across a whole population can lead to greater disease burden reductions, than a large shift among those persons already at high risk. This is certainly true for obesity, as successful and sustainable interventions to reduce and maintain weight loss are very difficult. Polices and actions operating at international, national and local levels influence the broader social, economic and physical determinants of people’s behaviours. Such strategies could include fiscal measures (taxation and subsidies), rules for marketing of foods,

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ith 24 per cent of the adult population obese, and 37 per cent overweight,1 the problem of excess weight is reaching epidemic proportions. Already its effects are being seen in terms of increased morbidity and even cases of mortality with a serious corresponding economic impact. A new study conservatively estimates primary healthcare costs at €17 million and secondary healthcare costs at €24m.2

13/09/2012 12:06:10

A 4 1 4 d L 8 la w m H w s a li D g P s c p P c

Atorvas Advert a4.pdf

25/05/2012

14:07

The power to reduce cardiovascular events1

ABBREVIATED PRESCRIBING INFORMATION. Product Name: Atorvas 10mg, 20mg, 40mg and 80mg Film-coated Tablets. Composition: Each film-coated tablet contains 10mg, 20mg, 40mg or 80mg atorvastatin respectively. Description: 10mg, 20mg and 40mg tablets: Light yellow, dappled, glossy, round biconvex film-coated tablets, debossed with ‘HLA 10’, ‘HLA 20’ and ‘HLA 40’ on one side respectively. 80mg tablets: Light yellow, dappled, glossy, oval biconvex film-coated tablets, debossed with ‘HLA 80’ on one side. Indication(s): Hypercholesterolaemia and prevention of cardiovascular disease. Dosage: Adults and elderly: Usual starting dose is 10mg daily with or without food. Primary hypercholesterolaemia and mixed hyperlipidaemia: 10mg daily, maintained for chronic therapy. Maximum therapeutic response seen after 4 weeks. Heterozygous familial hypercholesterolaemia: Initially 10mg daily. Adjust every 4 weeks to 40mg daily. Dose may still be increased to 80mg daily, or add a bile acid sequestrant with 40mg Atorvas as daily dose. Homozygous familial hypercholesterolaemia: Limited data available. Dose is 10mg to 80mg daily or as an adjunct to other lipid lowering treatments (i.e. LDL apheresis). Prevention of cardiovascular disease: Dose of 10mg daily may be increased to attain (LDL-) cholesterol levels in line with guidelines. Renal impairment: No adjustment of dose. Hepatic impairment: Caution. Paediatric use: Only by a specialist. Experience is limited to age group 4-17 years with severe dyslipidaemias at a starting dose of 10mg increased to 80mg daily. Contraindications: Hypersensitivity to the active or excipients. Active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit. Pregnancy, breast-feeding and women of childbearing potential not using adequate contraception. Warnings and Precautions for Use: Liver effects: Monitor liver

function tests regularly. Caution in patients with liver disease or high alcohol intake. Stroke prevention by aggressive reduction in cholesterol levels: Increase in incidence of stroke with 80mg dose in prior haemorrhagic stroke or lacunar infarct. Caution as risks and benefits of 80mg dose is uncertain. Skeletal muscle effects: In rare occasions: myalgia, myositis, myopathy that may lead to rhabdomyolysis characterised by elevated creatine kinase (CK) levels, myoglobinaemia and myoglobinuria. Caution in predisposing factors for rhabdomyolysis; measure CK levels before treatment in the following situations: renal impairment, hypothyroidism, personal or familial history of muscular disorders, previous history of muscular toxicity with a statin or fibrate, previous history of liver disease or high alcohol intake, where an increase in plasma levels may occur, such as possible interactions, special populations. Increased CK levels 5 times higher than normal and if confirmed after 5 to 7 days; unsuitable for treatment. If patients complain about muscle pain, cramps, weakness with malaise, measure CK levels and act accordingly. Caution when taking drugs that may increase plasma concentration of atorvastatin (potent inhibitors of CYP3A4 or transport proteins, e.g. ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors). Higher risk of myopathy with gemfibrozil, other fibric acid derivatives, erythromycin, niacin, ezetimbe. Adjust dose of atorvastatin if use is necessary. Interstitial lung disease: Have been reported with long term therapy, discontinue atorvastatin. Interactions: Caution: CYP3A4 inhibitors: See above if given with potent inhibitors of CYP3A4. Moderate CYP3A4 inhibitors, e.g. erythromycin, verapamil, fluconazole: Monitor patients and give lower dose of atorvastatin. CYP3A4

inducers: Lower plasma levels of atorvastatin with efavirenz, rifampicin, St John’s Wort. Transport protein inhibitors: Ciclosporin can increase systemic exposure of atorvastatin. Gemfibrocil/fibric acid derivatives, Ezetimbe: Higher risk of muscle related events. Colestipol: Lower atorvastatin plasma levels, but lipid effects were greater when given in combination. Fusidic acid: Avoid. Digoxin: Monitor as digoxin levels may increase. Oral contraceptives: Increased plasma levels of norethindrone and ethinyl estradiol. Warfarin: Monitor prothrombin time. First 4 days of an 80mg dose gave a slight decrease in prothrombin time that normalised after 15 days of atorvastatin treatment. See SPC for recommended dosage schedules in combination with other drugs. Pregnancy and Lactation: Contraindicated. Ability to Drive and Use Machinery: Negligible influence. Undesirable Effects: Nasopharyngitis, allergic reactions, hyperglycaemia, headache, constipation, pharyngolaryngeal pain, epistaxis, flatulence, dyspepsia, nausea, diarrhoea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function tests abnormal, and blood creatine kinase increased. Marketing Authorisation Holder: Rowex Ltd, Bantry, Co. Cork. Marketing Authorisation Numbers: PA 711/180/1-4. Further information and SPC are available from: Rowex Ltd, Bantry, Co. Cork. Freephone: 1800 304 400 Fax: 027 50417 E-mail rowex@rowa-pharma.ie Legal Category: Subject to medical prescription. Date of Preparation: April 2012. Ref 1: PMID:21873710. Edition 1 05/12

CCF No: 14111

Manufacturing in Ireland from our Bantry base, we believe in investing in the best medicines for your patients Medicinal products subject to prescription. Further information and SPC available from Rowex Ltd., Bantry, Co. Cork.

TreatingObesity.indd 23

13/09/2012 12:06:11

STROKE PREVENTION

The only licensed oral anticoagulant to show superior efficacy to warfarin for prevention of both ischaemic and haemorrhagic stroke – Pradaxa® 150mg b.d.1-3 Pradaxa® is licensed for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more risk factors.1,4 Pradaxa® 150mg b.d. Superior prevention of stroke and systemic embolism (p=0.0001) with similar rates of major bleeding vs warfarin.1,5,6 Pradaxa® 110mg b.d. Similar prevention of stroke and systemic embolism with significantly lower rates of major bleeding vs warfarin (p=0.003).4-6

Prescribing Information (SPAF - Ireland) PRADAXA® (dabigatran etexilate) Capsules containing 110 mg or 150 mg dabigatran etexilate (as mesilate) Action: Direct thrombin inhibitor Indication: Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more of the following risk factors: Previous stroke, transient ischemic attack, or systemic embolism (SEE); Left ventricular ejection fraction < 40 %; Symptomatic heart failure, ≥ New York Heart Association (NYHA) Class 2; Age ≥ 75 years; Age ≥ 65 years associated with one of the following: diabetes mellitus, coronary artery disease, or hypertension Dose and Administration: Renal function should be assessed by calculating CrCL prior to initiation to exclude patients with severe renal impairment (CrCL < 30 ml/min). Recommended daily dose 300 mg taken as one 150 mg capsule twice daily. Therapy should be continued long term. In case of intolerability to dabigatran, patients should be instructed to immediately consult their doctor. Elderly: Aged ≥ 80 years 220 mg taken as one 110 mg capsule twice daily; 75 – 80 years consider 220 mg taken as one 110 mg capsule twice daily. As renal impairment may be frequent in the elderly (> 75 years), assess renal function by calculating CrCL prior to initiation to exclude patients with severe renal impairment (CrCL < 30 ml/min). Renal function should also be assessed at least once a year or more frequently as needed in certain clinical situations when it is suspected that the renal function could decline or deteriorate. Patients with an increased risk of bleeding: closely monitor clinically looking for signs of bleeding or anaemia. Dose adjustment should be decided at the discretion of the physician, following assessment of the potential benefit and risk to an individual patient. A coagulation test may help identify increased risk patients. Patients with gastritis, esophagitis, or gastroesophageal reflux consider 220 mg taken as one 110 mg capsule twice daily due to the elevated risk of major gastro intestinal bleeding. Renal impairment: contraindicated in severe renal impairment (CrCL < 30 ml/ min); patients with renal impairment and a high risk of bleeding consider 220 mg taken as one 110 mg capsule twice daily. Close clinical surveillance is recommended in patients with renal impairment. As above assess renal function prior to initiation to exclude patients with severe renal impairment and assess renal function at least once a year or more frequently as needed. Concomitant verapamil 220 mg taken as one 110 mg capsule twice daily; Pradaxa and verapamil should be taken at the same time. No dose adjustment required but close clinical surveillance in patients < 50 kg. Not recommended if liver enzymes > 2 Upper Limit of Normal (ULN). If switching from Pradaxa to parenteral anticoagulant wait 12 hours after the last dose of Pradaxa; if switching from parenteral anticoagulants to Pradaxa then Pradaxa should be given 0-2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment; if switching from Pradaxa to VKA adjust the starting time of the VKA based on CrCL; if switching from VKA to Pradaxa stop VKA and give Pradaxa once INR <2.0. Cardioversion patients can stay on Pradaxa whilst being cardioverted. Not recommended aged < 18 years. Pradaxa should be swallowed whole with water, with or without food. Patients should be instructed not to open the capsule as this may increase the risk of bleeding. Contraindications: Hypersensitivity to any component; severe renal impairment (CrCL < 30 ml/min); active clinically significant bleeding; organic lesion at risk of bleeding; impairment of haemostasis; hepatic impairment or liver disease expected to have any impact on survival; concomitant systemic ketoconazole, cyclosporine, itraconazole, tacrolimus. Warnings and Precautions: Not recommended if liver enzymes > 2 ULN. Haemorrhagic risk: Close clinical surveillance (signs of bleeding or anaemia) is recommended throughout the treatment period, especially when haemorrhagic risk is increased or risk factors combined. Factors which may increase haemorrhagic risk: age ≥ 75 years; moderate renal impairment (CrCL

TreatingObesity.indd 24

30 – 50 ml/min); P-glycoprotein inhibitor co-medication; body weight < 50 kg; acetylsalicylic acid (aspirin); NSAID; clopidogrel; selective serotonin re-uptake inhibitors (SSRIs) or selective serotonin norepinephrine re-uptake inhibitors (SNRIs); diseases/ procedures associated with a risk of bleeding such as coagulation disorders, thrombocytopenia or functional platelet defects, active ulcerative GI disease, recent GI bleeding, recent biopsy or major trauma, recent ICH or brain, spinal or ophthalmic surgery, bacterial endocarditis. The measurement of dabigatran related anticoagulation may be helpful to avoid excessive high exposure to dabigatran in the presence of additional risk factors. Patients who develop acute renal failure must discontinue Pradaxa. If severe bleeding occurs, discontinue treatment and investigate the source of the bleeding. Avoid or use with caution agents which may increase the risk of haemorrhage. The use of fibrinolytic agents for the treatment of acute ischemic stroke may be considered if the patient presents with a dTT, ECT or aPTT not exceeding the ULN according to the local reference range. Avoid concomitant administration with P-gp inducers. Patients on dabigatran etexilate who undergo surgery or invasive procedures are at increased risk for bleeding therefore surgical interventions may require the temporary discontinuation of dabigatran etexilate; prescribers should consult the Summary of Product Characteristics for further information. Procedures such as spinal anaesthesia may require complete haemostatic function. The risk of spinal or epidural haematoma may be increased in cases of traumatic or repeated puncture and by the prolonged use of epidural catheters. After removal of a catheter, an interval of at least 2 hours should elapse before the administration of the first dose of dabigatran etexilate; these patients require frequent observation for neurological signs and symptoms of spinal or epidural haematoma. Treat with caution patients at high surgical mortality risk and with intrinsic risk factors for thromboembolic events. Myocardial infarction. Contains Sunset Yellow (E110) which may cause allergic reactions. Interactions: Anticoagulants and antiplatelet aggregation agents; Strong P-gp inhibitors e.g. amiodarone, quinidine, verapamil, clarithromycin coadministration (close clinical surveillance); verapamil co-administration - reduce Pradaxa dose to 220 mg (see above); not recommended for concomitant treatment posaconazole, dronedarone, protease inhibitors including ritonavir and its combinations with other protease inhibitors; avoid with P-gp inducers e.g. rifampicin, St John’s wort, carbamazepine, phenytoin; SSRIs or SNRIs. Dabigatran etexilate and dabigatran are not metabolised by cytochrome CYP450 system, therefore related medicinal product interactions not expected. Pantoprazole and other proton-pump inhibitors (PPI) were coadministered with Pradaxa in clinical trials and concomitant PPI treatment did not appear to reduce the efficacy of Pradaxa. Ranitidine administration together with Pradaxa had no clinically relevant effect on the extent of absorption of dabigatran. Fertility, pregnancy and lactation: Avoid pregnancy during treatment. Do not use in pregnancy unless clearly necessary. Discontinue breast-feeding during treatment. Undesirable effects: Most commonly reported adverse reactions are bleedings occurring in total in approximately 16.5 % in patients with atrial fibrillation treated for the prevention of stroke and SEE. Common (≥ 1/100, <1/10): anaemia; epistaxis; gastrointestinal haemorrhage; abdominal pain; diarrhoea; dyspepsia; nausea; hepatic function abnormal/liver function test abnormal; genitourological haemorrhage (150 mg). Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 110 mg 60 capsules 150 mg 60 capsules Legal category POM MA numbers: 110 mg EU/1/08/442/007 (60 capsules) 150 mg EU/1/08/442/011 (60 capsules) Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, Binger Str. 173, D-55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Additional information is available on request from Boehringer Ingelheim Ireland Ltd, Corrig Court, Corrig Road, Sandyford Business Estate, Dublin 18. Prepared in May 2012.

References: 1. Boehringer Ingelheim. Pradaxa® 150mg hard capsules Summary of Product Characteristics. 2. Patel MR, Mahaffrey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-891. 3. Patel MR, Mahaffrey KW, Garg J, et al. Supplementary appendix to Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-891. 4. Boehringer Ingelheim. Pradaxa® 110mg hard capsules Summary of Product Characteristics. 5. Connolly S, Ezekowitz MD, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-1151. 6. Connolly S, Ezekowitz MD, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010; 363:1875-1876. Date of preparation: June 2012 Job code:IRE/DBG-121334•

For more information, including an educational pack, go to www.pradaxa.ie/SPAFeducationalpack or call the Pradaxa® information line on 1850 946100

13/09/2012 12:06:13

Treating Obesity Better Than Cure?

HFSS and food production, as well as environmental and transport polices.7 A position paper on populationlevel changes which would promote cardiovascular health and prevent other chronic diseases proposes that responsibility for driving policy initiatives should be shared between politicians, Government departments – health, education, environment and finance – health professionals and providers and NGOs . They should scrutinise the balance between health and profit and, be aware of conflicts of interest with industries.8 The Irish Heart Foundation’s overreaching goal is to reduce preventable deaths and disability from cardiovascular disease. Tackling obesity is, therefore, one of its high-level targets. The causes of the increase in obesity are multifactorial and, consequently, there needs to be a multi-pronged approach, with policies being undertaken and interventions taking place on many levels. The National Task Force on Obesity Report made a very good case for populationbased strategies with over 100 recommendations.9 As a first priority, we at the Irish Heart Foundation would recommend the adoption and full implementation of this report. In addition, we would propose a number of actions that adhere to public and health agendas – they are easily implementable, supported by evidence and, in some cases, could be cost effective. As an example, a review of preventative and treatment interventions for obesity in Australia (Assessing Cost-Effectiveness [ACE] in Obesity) found eight interventions to be both health improving and

TreatingObesity.indd 25

cost saving: unhealthy food and beverage tax (10 per cent); front-ofpack traffic light nutrition labelling; reduction in advertising of junk food and beverages to children; school-based education programme to reduce television viewing; multifaceted school-based programme; including nutrition education and physical activity; school-based education programme to reduce sugar-sweetened drink consumption; family-based targeted programme for obese children; and multi-faceted targeted school-based programme.10 The Australian ACE’s prevention programme helps policy makers to select policies that are backed up with plenty of evidence and have a solid rationale, a wide reach, a low cost, and have been shown to be effective in other jurisdictions. The foundation has, for a number of years, called for a complete ban on TV advertising of foods high in fat, sugar and salt to children. We are concerned that the proposed revisions for the BAI’s Children’s Commercial Communications Code, when published, will fall short of providing adequate protection from commercial advertising, thereby missing an opportunity to implement a key legislative response that has been identified as beneficial by WHO and many other international and national public health bodies.11, 12 Fiscal measures are being considered by many Governments and are already in place in Denmark, Hungary and France. Taxation of unhealthy food is estimated to reduce CVD by about 2 per cent,13 and a 10 per cent tax or levy on sugar-sweetened drinks may lead to an 8 to 10 per cent reduction in consumption.14

025

Ideally, taxes should be used in combination with subsidies on healthier foods to mitigate the potentially negative impact of such a tax on the more disadvantaged.15 In this way, the healthy choice becomes the easier choice. The foundation welcomes the improved food labelling regulations to be introduced in 2014, which will provide standard information on the back of packs. However, despite research in Ireland, UK and Australia16-20 which showed that consumers would prefer a simplified front-of-pack label, this was not adopted by the EU. The foundation will continue to lobby for traffic light front-of-pack food labelling as a national scheme. As a prequel to this, Minister Reilly’s initiative to have calorie counts printed on menus in chain restaurants and food outlets is welcome, and is the first step in creating a framework and incentive for healthy eating standards in all education facilities, hospitals and government offices as cited in the NTFO report. The Irish Heart Foundation, supported by the HSE, is actively involved in promoting healthy menus in the workplace, with the Happy Heart Healthy Eating Awards a key feature of this ongoing process. Industry can play a vital role and has already shown positive progress in the reformulation of products, cutting down salt content. However, this needs to be expanded to reducing fat and sugar. Dietary change is not enough, though, and all of this needs to be done in combination with a physical activity programme which should to be reintegrated into day-to-day life – in the classroom, workplace and also as a large part of our active travel and leisure activities.

13/09/2012 12:06:14

026

Treating Obesity Better Than Cure?

Fiscal policies can play a powerful role in influencing changes in the environment. Subsidies to make public travel cheaper, incentives or small grants for community groups, workplaces and schools organising physical activity campaigns – each of these have a massive effect. A comprehensive paper published by the National Heart Alliance and the Irish Heart Foundation mapped out a range of changes in the physical environment which could dismantle some of the barriers to physical activity among children and young people (under 21) like introducing the lower speed limit of 30km in the proximity of all schools, with this speed limit being strictly enforced. Further, the drop off spots should be restricted to a ‘park and walk’/‘park and stride’ zone directly outside the school. Neighbourhood design in particular can have an enormous influence on health and physical activity and should provide a good range of amenities and services within easy and safe walking distance of homes. Street design should be carefully thought out to encourage exercise. Features such as shared surfaces (between pavement and road); seating, plants, and traffic calming measures are all employed to slow down traffic and favour pedestrian use. Reversing the increasingly sedentary lives we and our children live will play an important part in a multi-pronged approach required to combat the encroaching obesity epidemic. Dr Angie Brown, BSC, MB, BChir, MRCP MD is the Consultant Cardiologist and Medical Director of the Irish Heart Foundation. Maureen Mulvihill is the foundation’s Health Promotion Manager.

TreatingObesity.indd 26

1 Irish Universities Nutrition Alliance. 2011. www.iuna.net 2 Doherty, E., A. Dee, and C. O’Neill, Estimating the amount of overweight and obesity related health-care use in ROI using SLAN data. The Economic and Social Review, 2011. 43(2): pp 227-250. 3 Layte R. and C McCrory, Growing Up in Ireland: National Longitudinal Study of Children. Overweight and Obesity among 9-year-olds. Report 2. Department of Children and Youth Affairs. Dublin: Government Publications Office. 2011. 4 Singh A.S. et al, Tracking of childhood overweight into adulthood: A systematic review of the literature. Obesity Reviews, 2008. 9: pp 474-488. 5 Lang, T and G. Rayner, Obesity: a growing issue for European policy? J. Eur. Soc. Policy. 2005. http://esp.sagepub.com/cgi/ content/abstract/14/4/301 Ref Swinburn B. and G. Egger, Preventative Strategies against weight gain and obesity. Obesity Reviews, 2002. 3(4): pp 289-301. 6 Rose, G. The strategy of preventive medicine. Oxford. Oxford University Press 1992. 7 Jorgenson, T., S. Capewell, E. Prescott, Population-level changes to promote cardiovascular health. European Journal of Preventive Cardiology, 2012. http://cpr.sagepub.com/content/ early/2012/04/17/2047487312441726 8 Jahiel, R.I. and T.F. Babor, Industrial epidemics, public health advocacy and the alcohol industry: lessons from other fields. Addiction, 2007. 102(9): pp 1335-1339 9 National Taskforce on Obesity (2005) Report. Obesity The Policy challenges. Department of Health and Children. 10 Gortmaker SL, et al, Changing the future of obesity: science, policy and action. The Lancet, 2011. 378(9793): pp 838-847. 11 World Health Organisation, Set of Recommendations on the marketing of foods and non-alcoholic drinks to children. World Health Organisation, Geneva, 2010.

13 Mytton O., A. Gray, M. Rayner, et al, Could targeted food taxes improve health? J. Epidemiol. Community Health, 2007. 61(8): pp 689-694 http://jech.bmj.com/ cgi/content/full/61/8/689 14 Andreyeva,T., M.W. Long, K.D. Brownell, The impact of food prices on consumption :a systematic review of research on the price elasticity of demand for food. Am J Public Health, 2010. 100: pp 216-222 15 European Heart Network. Diet Physical Activity and CVD Prevention. www.ehn.org 16 Irish Heart Foundation, National Youth Council of Ireland, and Irish Cancer Society, Food Labelling Research. Undertaken by Red C Research and Marketing Dublin, 2011. http://www. irishheart.ie/media/pub/red_c_final_ report_4__16_11_10.pdf 17 Expert Panel Report on Front-of-Pack Labelling, Food Standards Agency, United Kingdom, May 2009: http://www.food. gov.uk/news/newsarchive/2009/may/pmp 18 Front-of-pack labelling and traffic light labelling get the green light, New South Wales Health Department, the University of Sydney and several Australian public health and consumer organizations, Australia, 2009: http://heapro. oxfordjournals.org/cgi/content/abstract/ dap012 19 Comparison between traffic light and GDA systems, Food Watch, Germany, April 2009: http://www. foodwatch.de/kampagnen__themen/ ampelkennzeichnung/vergleich_ampel___ gda/index_ger.html 20 Summary of original worldwide research from December 2006-June 2008 on consumer preference and use of frontof-pack nutrition schemes, European Heart Network, August 2008: http://www. ehnheart.org/content/ItemPublication.as p?docid=7282&level0=1455&level1=1499 21 National Heart Alliance and the Irish Heart Foundation, Building Young Hearts, 2010.

12 National Institute for Clinical Excellence, Prevention of cardiovascular disease at population level, 2010. www.nice.org.uk/ guidance/PH25

13/09/2012 12:10:15

As of May 7th, Torvacol from Clonmel Healthcare is the new name in Atorvastatin.

Torvacol

May 7th 2012. A red letter day.

Adjunct to diet in primary hypercholesterolaemia, including familial hypercholesterolaemia or combined hyperlipidaemia Adjunct to other lipid-lowering treatments in adults with homozygous, familial hypercholesterolaemia, or if such treatments are unavailable Prevents cardiovascular events in adult patients at high risk, as an adjunct to correction of other risk factors 1 Reference: 1. Summary of product characteristics

Atorvastatin

FILM-COATED TABLET 10mg 20mg 40mg 80mg

ABBREVIATED PRESCRIBING INFORMATION Torvacol 10, 20, 40 and 80 mg film-coated tablets. Each film-coated tablet contains 10 mg, 20mg, 40mg or 80mg atorvastatin (as atorvastatin calcium). Presentation: Torvacol 10 mg tablets: White to off-white, round, biconvex film-coated tablets scored on one side. Torvacol 20 mg tablets: White to off-white, oval, biconvex film-coated tablets with a score line on one side. Torvacol 40 mg tablets: White to off-white, oval, biconvex film-coated tablets with a score line on one side. Torvacol 80 mg tablets: White to off-white, oblong, biconvex film-coated tablets with score lines on both sides. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses. Indications: Adjunct to diet in primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types IIa and IIb of the Fredrickson classification). Reduces total-C and LDL-C in adults with homozygous, familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments or if such treatments are unavailable. Prevention of cardiovascular events in adult patients with a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors. Dosage: Dosage may be given at any time of day with or without food. Initially, 10 mg once a day, increase as necessary at intervals of 4 weeks or more to max. dose of 80 mg once a day. Primary hypercholesterolaemia and combined (mixed) hyperlipidaemia: Usually 10 mg once a day. Heterozygous familial hypercholesterolaemia: Initially 10 mg daily. Doses should be individualised and adjusted every 4 weeks to 40 mg daily. The dose may be increased to a max. 80 mg daily or a bile acid sequestrant plus 40 mg Torvacol once daily. Homozygous familial hypercholesterolaemia: 10 to 80 mg daily as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) in these patients or if such treatments are unavailable. Prevention of cardiovascular disease: 10 mg/day. Higher doses may be necessary. Renal impairment: No adjustment of dose is required. Hepatic impairment: Use with caution in patients with hepatic impairment. Paediatric use: Hypercholesterolaemia: Paediatric use should only be carried out by physicians experienced in the treatment of paediatric hyperlipidaemia. Patients aged 10 years and above: 10 mg per day with titration up to 20 mg per day. Not indicated in the treatment of patients below the age of 10 years. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active liver disease or unexplained persistent elevations of serum transaminases. Pregnancy, breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures. Warnings and precautions: Liver function tests should be performed before the initiation of treatment and periodically thereafter. Use with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. For patients with prior haemorrhagic stroke or lacunar infarct, the balance of risks and benefits of atorvastatin 80 mg is uncertain and the potential risk of haemorrhagic stroke should be carefully considered before initiating treatment. Torvacol may in rare occasions affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis. Prescribe with caution in patients with pre-disposing factors for rhabdomyolysis. Measure CK levels before starting statin treatment in at risk patients. In such situations, the risk of treatment should be considered in relation to possible benefit, and clinical monitoring is recommended. If CK levels are significantly elevated (> 5 x ULN) at baseline, treatment should not be started. Creatine kinase (CK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CK increase as this makes value interpretation difficult. If CK levels are significantly elevated at baseline (> 5 x ULN), remeasure levels within 5 to 7 days later to confirm results. Patients must be asked to promptly report muscle pain, cramps, or weakness especially if accompanied by malaise or fever. If such symptoms occur whilst a patient is receiving treatment with atorvastatin, measure CK levels. If levels are significantly elevated (> 5 x ULN), stop treatment. If muscular symptoms are severe and cause daily discomfort, even if the CK levels are elevated to â&#x2030;¤ 5 x ULN, treatment discontinuation should be considered. If symptoms resolve and CK levels return to normal, then re-introduction of atorvastatin or introduction of an alternative statin may be considered at the lowest dose with close monitoring. Discontinue if clinically significant elevation of CK levels (> 10 x ULN) occur, or if rhabdomyolysis is diagnosed or suspected. Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. If it is suspected a patient has developed interstitial lung disease, discontinue therapy. Contains lactose. Interactions: Atorvastatin is metabolized by CYP3A4 and is a substrate to transport proteins. Concomitant administration of medicinal products that are inhibitors of CYP3A4 or transport proteins may lead to increased plasma concentrations of atorvastatin and an increased risk of myopathy. The risk might also be increased at concomitant administration of atorvastatin with other medicinal products that have a potential to induce myopathy. Co-administration of potent CYP3A4 inhibitors should be avoided if possible. A lower maximum dose of atorvastatin should be considered and appropriate clinical monitoring of the patient is recommended when concomitantly used with moderate CYP3A4 inhibitors. Concomitant administration of atorvastatin with inducers of cytochrome P450 3A can lead to variable reductions in plasma concentrations of atorvastatin. Inhibitors of transport proteins can increase the systemic exposure of atorvastatin. The risk of muscle related events may be increased with the concomitant use of fibric acid derivatives and atorvastatin, or ezetimibe and atorvastatin. Plasma concentrations of atorvastatin and its active metabolites were lower when co-administered with colestipol. However, lipid effects were greater when Torvacol and colestipol were co-administered than when either medicinal product was given alone. Muscle related events, including rhabdomyolysis, have been reported in post-marketing experience with atorvastatin and fusidic acid given concurrently. Patients taking digoxin should be monitored appropriately. Co-administration of Torvacol with an oral contraceptive produced increases in plasma concentrations of norethindrone and ethinyl oestradiol. Prothrombin time should be determined before starting atorvastatin in patients taking coumarin anticoagulants. Fertility, pregnancy and lactation: Torvacol is contraindicated during pregnancy and lactation. Women of child-bearing potential should use appropriate contraceptive measures during treatment. Undesirable effects (common): nasopharyngitis, allergic reactions, hyperglycaemia, headache, pharyngolaryngeal pain, epistaxis, constipation, flatulence, dyspepsia, nausea, diarrhoea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function test abnormal, blood creatine kinase increased. Refer to Summary of Product Characteristics for other adverse effects and side effects affecting the paediatric population. Pack size: 28 tablets. Marketing authorisation holder: Clonmel Healthcare Ltd, Clonmel, Co. Tipperary. Marketing authorisation number: PA 126/234/1-4. Full prescribing information is available on request or go to www.clonmel-health.ie. Medicinal product subject to medical prescription. Date last revised: February 2012. 2012/ADV/ATO/029 TORVACOL IS THE CLONMEL BRAND OF ATORVASTATIN

TreatingObesity.indd 27

13/09/2012 12:10:17

Agents

Tablet

OLMESARTAN

AMLODIPINE

HYDROCHLOROTHIAZIDE

20mg

5mg

12.5mg

40mg

5mg

12.5mg

40mg

10mg

12.5mg

40mg

5mg

25mg

40mg

10mg

25mg

Konverge Plus 20 mg/5 mg/12.5 mg, 40 mg/5 mg/12.5 mg, 40 mg/10 mg/12.5 mg, 40 mg/5 mg/25 mg and 40 mg/10 mg/25 mg film-coated tablets (olmesartan medoxomil/ amlodipine [as amlodipine besilate]/hydrochlorothiazide). Prescribing information: Please consult the Summary of Product Characteristics (SmPC) for full prescribing information. Presentation: Film-coated tablets containing: 20 mg olmesartan medoxomil, 5 mg amlodipine, 12.5 mg hydrochlorothiazide or 40 mg olmesartan medoxomil, 5 mg amlodipine, 12.5 mg hydrochlorothiazide or 40 mg olmesartan medoxomil, 10 mg amlodipine, 12.5 mg hydrochlorothiazide or 40 mg olmesartan medoxomil, 5 mg amlodipine, 25 mg hydrochlorothiazide or 40 mg olmesartan medoxomil, 10 mg amlodipine, 25 mg hydrochlorothiazide. Uses: Treatment of essential hypertension. Indicated as add-on therapy in adult patients whose blood pressure is not adequately controlled on the combination of olmesartan medoxomil and amlodipine taken as dual-component formulation. Also as substitution therapy in adult patients whose blood pressure is adequately controlled on the combination of olmesartan medoxomil, amlodipine and hydrochlorothiazide, taken as a dual-component (olmesartan medoxomil and amlodipine or olmesartan medoxomil and hydrochlorothiazide) and a single-component formulation (hydrochlorothiazide or amlodipine). Dosage: Oral administration. Adults (18-65 years): Recommended dose is 1 tablet daily. Add –on therapy: administer in patients whose blood pressure is not adequately controlled on olmesartan medoxomil and amlodipine taken as dual-component combination. Step-wise titration of the dosage of the individual components recommended before changing to the triple-component combination. When clinically appropriate, direct change from dual-component combination to triple-component combination may be considered. Substitution therapy: dose to be based on the doses of the individual components of combination at time of switching. Maximum daily dose of 40 mg/10 mg/25 mg. Elderly: Caution, monitor blood pressure frequently especially at maximum dose. Extreme caution, including more frequent monitoring of blood pressure, recommended in patients aged 75 or older. Patients with mild to moderate renal impairment: Maximum dose 20 mg/5 mg/12.5 mg and monitor potassium and creatinine levels. Caution in patients with mild to moderate hepatic impairment; maximum daily dose 20 mg/5 mg/12.5 mg; monitor blood pressure and renal function closely. Children and adolescents under 18 years: Not recommended. Contra-indications: Hypersensitivity to any component, to dihydropyridine derivates or to sulfonamide-derived substances. Severe renal impairment. Refractory hypokalaemia, hypercalcaemia, hyponatraemia and symptomatic hyperuricaemia. Severe hepatic insufficiency, cholestasis or biliary obstruction. Second or third trimesters of pregnancy. Severe hypotension, shock (including cardiogenic shock), obstruction of the outflow tract of the left ventricle, haemodynamically unstable heart failure after acute myocardial infarction. Warnings and Precautions: Correct intravascular volume depletion before administering Konverge Plus or maintain close medical supervision. In patients with other conditions associated with stimulation of renin-angiotensin-aldosterone system, possible side effects include acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. Increased risk of severe hypotension and renal insufficiency in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Periodic monitoring of serum and potassium levels is recommended in patients with impaired renal function and kidney transplantation. Special caution in patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy. Not recommended in patients with primary aldosteronism. May impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required. Increases in cholesterol and triglyceride levels. Thiazides may precipitate hyperuricaemia or frank gout. Periodic determination of serum electrolytes should be performed. Can cause fluid or electrolyte imbalance (including hypokalaemia, hyponatraemia and hypochloraemic alkalosis). Risk of hypokalaemia with cirrhosis of the liver, brisk diuresis, inadequate oral intake of electrolytes, concomitant therapy with corticosteroids or ACTH. Hyperkalaemia, risk factors include renal impairment, and/or heart failure. Monitoring of serum potassium in patients at risk of hyperkalaemia is recommended. Concomitant use of potassium containing and sparing products should be undertaken with caution and potassium levels monitored frequently. May cause intermittent and slight elevation of serum calcium. Discontinue before carrying out tests for parathyroid function. May increase urinary excretion of magnesium. Dilutional hyponatraemia may occur in oedematous patients in hot weather. Not recommended for combination use with lithium. Changes in renal function in susceptible individuals with heart failure. Amlodipine associated with increased reports of pulmonary oedema. Do not initiate during pregnancy. Discontinue as soon as possible if pregnancy occurs. Photosensitivity reactions have been reported with thiazide diuretics. Excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke. Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus with the use of thiazides. The blood pressure lowering effect of olmesartan medoxomil is somewhat less in black patients than non-black patients. Interactions: Not recommended for concomitant use with lithium, drugs affecting potassium levels, caution with baclofen, NSAIDs, amifostine, other hypertensive agents, alcohol, barbiturates, narcotics, antidepressants CYP3A4 inhibitors, CYP3A4 inducers, calcium salts, cholestyramine and colestipol, digitalis glycosides, non-depolarizing skeletal muscle relaxants, anticholinergic agents, antidiabetic medicinal products, beta-blockers and diazoxide, pressor amines, medicinal products used in the treatment of gout, amantadine, cytotoxic agents, salicylates, methyldopa, ciclosporin, tetracyclines. Pregnancy and Lactation: Do not use in the first trimester and discontinue as soon as possible if pregnancy occurs. Contraindicated in second and third trimesters of pregnancy. Not recommended during lactation. Side Effects: Konverge Plus: Common (≥ 1/100 <1/10): upper respiratory tract infection, nasopharyngitis, urinary tract infection, dizziness, headache, palpitations, hypotension, diarrhoea, nausea, constipation, muscle spasm, joint swelling, pollakiuria, asthenia, peripheral oedema, fatigue, blood creatinine increased, blood urea increased, blood uric acid increased. Olmesartan: Common: urinary tract infection, hypertriglyceridaemia, hyperuricaemia, dizziness, headache, cough, bronchitis, pharyngitis, rhinitis, diarrhoea, nausea, abdominal pain, dyspepsia, gastroenteritis, arthritis, back pain, skeletal pain, haematuria, peripheral oedema, fatigue, chest pain, influenza-like symptoms, pain, blood urea increased, hepatic enzymes increased, blood creatine phosphokinase increased. Amlodipine: Common: dizziness, headache, somnolence, flushing, nausea, abdominal pain, ankle swelling, fatigue, oedema. Hydrochlorothiazide: Very common (≥1/10): hypertriglyceridaemia, hypercolesterinaemia, hyperuricaemia. Common: hypokalaemia, glycosuria, hypercalcaemia, hyperglycaemia, hypomagnesaemia, hyponatriaemia, hypochloraemia, hyperamylasaemia, confusional state, dizziness, diarrhoea, nausea, constipation, abdominal pain, meteorism, gastric irritation, vomiting, blood creatinine increased, blood urea increased. For less frequent side effects see SmPC. Pack Sizes: Blister containing 28 film-coated tablets. Legal Category: POM. Product Authorisation Numbers: PA 865/19/1-5. Product Authorisation Holder: Menarini International Operations Luxembourg S.A, 1 Avenue de la Gare, L-1611 Luxembourg. Marketed by: A. Menarini Pharmaceuticals Ireland. Further information is available on request from A. Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Co. Dublin or may be found in the SmPC. Date of Preparation: May 2012. Co-promoter: DAIICHI SANKYO IRELAND LTD., Riverside One, Sir John Rogerson Quay, Dublin 2, Ireland. Date of item: June 2012. 12Kon034

A. MENARINI

PHARMACEUTICALS IRELAND LTD

Healthcare for Life

KONVERGE_PLUS AD_A4.indd 1 TreatingObesity.indd 28

27/06/2012 12:10:21 14:39 13/09/2012

2 14:39

Treating obesity the asthma society of ireland | CEO Interview

029

BreathE Easy

Sharon Cosgrove, CEO of the Asthma Society of Ireland, speaks about how obesity can exaCerBate asthma symptoms and what the organisation are doing to raise awareness of the dangers. Obesity obviously brings great health risks, but what are the additional threats to asthma sufferers?

Do you think parents of children with asthma are sufficiently aware of extra risks it can bring to the condition?

While obese patients are no more likely to be diagnosed with asthma than non-obese patients, obesity may worsen asthma symptoms and negatively impact on levels, and quality, of exercise activity. Asthma is an inflammatory condition and it has been recognised that obesity creates a low-grade inflammatory state in the body. This releases a constant stream of inflammatory chemicals which influence asthma symptoms in terms of both severity and persistence. Furthermore, studies have shown that response to medication – particularly inhaled corticosteroid – is influenced by Body Mass Index (BMI) making asthma more difficult to control in obese patients. Obesity is also common in patients with Obstructive Sleep Apnoea and/or Gastro-oesophageal reflux, which are associated with poor asthma control.

The Asthma Society of Ireland would like to see a better parental awareness of how an increased risk of poor asthma control in children can be caused by obesity. As a sensitive subject to raise with parents, healthcare professionals can be reluctant to broach the subject of obesity. But a number of researchers agree that childhood obesity may be a significant cause of asthma development and, with levels of obesity in children on the increase, this will lead to an increased prevalence of asthma in adulthood. So we would strongly encourage healthcare professionals to sensitively raise the subject of obesity and asthma with parents when it is necessary.

TreatingObesity.indd 29

Is obesity something that has become more important on the Asthma Society’s agenda than in recent years?

CEO of the Asthma Society of Ireland, Sharon Cosgrove.

As part of our current three year strategic plan, the Asthma Society of Ireland plans to conduct a study into obesity and asthma, which will examine the impact that obesity has on asthma control as well as the impact obesity has on the development and/or progression of asthma. The outcomes of this study will feed into our campaigning and

13/09/2012 12:10:31

(mometasone furoate) For the regular treatment to control mild to moderate persistent asthma in patients aged > 12 years1

Proven Asthma Control with Once-Daily Dosing2* Easy to Use Inhaler3 Once-daily dosing may improve patient adherence4 * Some patients may be more adequately controlled on 400 micrograms daily, given in two divided doses (200 micrograms twice daily)

ASMANEX TWISTHALER 200 AND 400 MICROGRAMS INHALATION POWDER ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. Presentation: Inhalation powder for oral inhalation containing 200 or 400 micrograms mometasone furoate per inhalation. USES: Regular treatment to control persistent asthma. DOSAGE: For use in adult and adolescent patients 12 years of age and older with persistent mild to moderate asthma: the recommended starting dose for most patients is 400 micrograms once daily in the evening. Some patients may be more adequately controlled on 400 micrograms daily given in two divided doses. Dose reduction to 200 micrograms once daily in the evening may be an effective maintenance dose for some patients. Patients with severe asthma: the recommended starting dose is 400 micrograms twice daily, which is the maximum recommended dose. In patients receiving oral corticosteroids, Asmanex Twisthaler treatment will be initiated concurrently with systemic corticosteroid, which will be gradually withdrawn. Children <12 years of age: not recommended. Elderly patients >65 years: no dosage adjustment necessary. CONTRAINDICATIONS: Hypersensitivity to any of the ingredients. PRECAUTIONS AND WARNINGS: Oral candidiasis may occur, requiring appropriate treatment or discontinuation of Asmanex Twisthaler therapy. Recommended doses of Asmanex Twisthaler must not be exceeded, and must be titrated to the lowest effective dose for each individual patient at which effective control of asthma is maintained in order to reduce system effects. Patients who are transferred from systemically active corticosteroids to Asmanex Twisthaler require careful attention due to the possibility of adrenal insufficiency. During dose reduction, withdrawal symptoms such as joint and/or muscle pain, lassitude and depression may occur. During periods of stress, including trauma, surgery, or infection, or a severe asthma attack, patients transferred from systemic corticosteroids will require supplementary treatment with a short course of systemic corticosteroids. Periodic testing of adrenocortical function is recommended. Pre-existing allergic conditions may be unmasked in patients who are transferred from systemic corticosteroid therapy to Asmanex Twisthaler. Asmanex Twisthaler is not a bronchodilator and is not indicated for rapid relief of bronchospasm or asthma attacks. Patients should be instructed to contact their physician immediately when asthmatic episodes are not responsive to bronchodilators during treatment with Asmanex Twisthaler. If bronchospasm occurs immediately following dosing, immediate treatment with a bronchodilator is recommended. Asmanex should be discontinued in these patients. Use with caution, if at all, in patients with untreated active or quiescent tuberculous infections of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections or ocular herpes simplex. Patients who are potentially immunosuppressed should be warned of the risk of exposure to certain infections. A reduction of growth velocity in children or adolescents may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. It is recommended that the height of children or adolescents receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, review therapy with the aim of reducing the dose of inhaled corticosteroids if possible, to the lowest dose at which effective control of symptoms is achieved. When using inhaled corticosteroids, significant adrenal suppression may occur, especially after treatment with higher than recommended doses; however, during clinical trials there was no evidence of HPA axis suppression after prolonged treatment with Asmanex Twisthaler at doses ≤ 800 micrograms per day. Lack of response or severe exacerbation of asthma should be treated by increasing the maintenance dose and if necessary administering a systemic corticosteroid and/or antibiotic and beta-agonist therapy. Patients should be advised against abrupt discontinuation of Asmanex therapy. Asmanex Twisthaler should not be used in pregnancy or lactation unless the potential benefit justifies the potential risk to the mother, foetus or infant. INTERACTIONS: Co-administration of Asmanex Twisthaler with the potent CYP3A4 inhibitor ketoconazole causes small but marginally significant (p= 0.09) decreases in serum cortisol AUC(0-24) and there may be potential for increased systemic exposure. There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir) are co-administered. SIDE EFFECTS: The most common treatment-related undesirable effects reported in placebo-controlled clinical studies were oral candidiasis, pharyngitis, headache and dysphonia. Uncommonly reported were dry mouth, dyspepsia, weight increase and palpitations. Systemic effects of inhaled corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. Rare cases of glaucoma, increased intraocular pressure or cataracts have been reported with the use of inhaled corticosteroids. Package Quantities: Asmanex Twisthaler 200 micrograms: 1 unit of 30 or 60 metered doses. Asmanex Twisthaler 400 micrograms: 1 unit of 30 or 60 metered doses. Legal Category: Prescription only medicine Marketing Authorisation Holder: Merck Sharp & Dohme Ireland (Human Health) Limited, Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland Marketing Authorisation Numbers: Asmanex Twisthaler 200 micrograms: PA 1286/39/2 Asmanex Twisthaler 400 micrograms: PA 1286/39/3 Date of Review: September 2011 Additional perscribing information is available on www.medicines.ie or on request from MSD Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland. Date of Preparation: October 2011 Copyright © 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Whitehouse Station, NJ USA. All rights reserved. References: 1. ASMANEX Summary of Product Characteristics September 2011 2. D’Urzo A, Karpel JP, Busse WW et al. Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids. Curr Med Res Opin. 2005;21(8):1281-9 3. Wardlaw A, Larivee P, Eller J et al. Efficacy and safety of mometasone furoate dry powder inhaler vs fluticasone propionate metered-dose inhaler in asthma subjects previously using fluticasone propionate. Ann Allergy Asthma Immunol. 2004;93(1):49-55. 4. Friedman H, et al: Adherence and asthma control with mometasone furoate versus fluticasone propionate in adolescents and young adults with asthma. J Asthma;2010: Early online:1-7.

Pelham House, South County Business Park, Leopardstown, Dublin 18, Ireland

TreatingObesity.indd 30

10-12-ASM-2011-IRL-4983-J

Asmanex is not intended to be used ”on demand” as a reliever medication to treat acute symptoms.

13/09/2012 12:10:48

Treating obesity the asthma society of ireland | CEO Interview

awareness-raising work during this period as well. The Asthma Society of Ireland has updated the Asthma Control in General Practice Guidelines to include recommendations about the treatment of obese asthma patients in order to achieve improved control of their asthma. The guidelines – which were developed in partnership with the ICGP’s Quality in Practice Committee – recommend that all obese asthma patients should be counselled about the impact their obesity has on their condition and general health. It also recommends that obesity treatment plans should be included in the patient’s written asthma management plan.

There is an abundance of evidence to support the national asthma treatment guidelines’ recommendations, which advocate weight loss as a strategy to improve asthma control and other chronic conditions in people of all ages. It is important that regular exercise

and healthy diets are promoted and prescribed by healthcare practitioners for overweight and obese patients. Can you give me an overview of the Asthma Society’s last 12 months and the challenges you face over the coming years? The Asthma Society has had a very busy and exciting year. At the end of 2011, the Asthma Society of Ireland won the Irish Healthcare Award for Best Patient Organisation Project of the Year for our Asthma Demonstration Programme. We also received a commendation for Best Patient Lifestyle Education Project for our ‘Treat-not-Trigger’ allergyfriendly garden shown at the Bloom Garden Festival last year.

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10-12-ASM-2011-IRL-4983-J

Children are often targeted for education on healthier eating, but a recent study found that seniors are five times more likely to suffer from poorly controlled asthma than those of normal weight. Is enough being done to educate all age groups?

There is not enough being done to educate people in general about the health implications of being obese. An obesity epidemic is sweeping the world as people eat more and exercise less. The connection between the incidence of diabetes, Heart disease, CVD and Asthma are linked to obesity and sedentary life styles. So we collectively need to do more to tackle obesity and, consequently, reduce the prevalence of chronic diseases such as asthma.

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Treating obesity the asthma society of ireland | CEO Interview

The Asthma Demonstration Programme was completed in 2011 and formed the basis for the development of the HSE National Asthma Programme. So we continue to play a key role in the steering of the National Asthma Programme, and we continue to advocate for international best practice, represent patients and ensure that existing asthma patients are at the centre of the implementation of the National Asthma Programme. Going forward, the Asthma Society will continue to monitor the effectiveness and the standard of patient care in the role out of the National Asthma Programme and will campaign for change when we see gaps or room for improvement. We will also be working hard to support the National Asthma Programme through the provision of

“We know that there are 470,000 people in Ireland with asthma, there is on average one death per week from the disease.” the National Asthma Management Education Programme, which the Asthma Society has developed. This accredited asthma educational programme for GPs, nurses and pharmacists forms the base-line of learning for healthcare professionals treating asthma patients in Ireland. We are delighted to report that there has been a steady rise in the number of healthcare professionals completing the programme throughout the year and the Asthma Society has received expressions of interest in translating and tailoring the education programme for a number of EU and non-EU countries.

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One of the Asthma Society’s key projects this year is the development of an asthma management app for the iPhone. We are currently in the final development stages and the ‘Asthma Coach’ app will be available shortly

TreatingObesity.indd 32

to download. The Asthma Coach will allow patients to manage their asthma with the touch of a button and will include features such as a personal asthma management diary and a daily pollen forecast. We are also currently finalising the revision of the Asthma Control in General Practice Guidelines. These guidelines were locally adapted from the GINA (Global Initiative for Asthma) Guidelines, which are designed to assist healthcare professionals to improve diagnostic accuracy; assess, treat and monitor asthma, develop an asthma management plan for individual patients, optimise asthma control, and manage exacerbations in line with approved protocols. And finally, one of the biggest challenges facing the Asthma Society of Ireland in 2012 lies in trying to maintain core patient services – such as the Asthma Advice Line and the National Asthma Clinic Programme – with substantially reduced resources. We know that there are 470,000 people in Ireland with asthma and that there is, on average, one death per week from the disease. So our work to raise awareness of asthma and provide information on how to control it is an enormous importance in of work. Decreases in statutory and public funding, coupled with an increased demand for services, mean that the Asthma Society must continue to provide services for asthma patients and health care professionals with fewer resources. So our reliance on fundraising income, including membership fees, regular donations and bequests, is ever increasing.

13/09/2012 12:11:28

THE VERDICT IS IN.

EVIDENCE PROVES:

Acerycal (perindopril arginine/amlodipine besylate) Abbreviated Prescribing Information: Please refer to the summary of product characteristics before prescribing. Presentation and Composition: Each tablet contains perindopril arginine, a long-acting ACE inhibitor, and amlodipine besylate, a calcium channel blocker. Acerycal 5mg/5mg contains perindopril 5mg and amlodipine 5mg: one white rod-shaped tablet. Acerycal 5mg/10mg contains perindopril 5mg and amlodipine 10mg: one white square-shaped tablet. Acerycal 10mg/5mg contains perindopril 10mg and amlodipine 5mg: one white triangular-shaped tablet. Acerycal 10mg/10mg contains perindopril 10mg and amlodipine 10mg: one white round tablet. Indications: Acerycal is indicated as substitution therapy for treatment of essential hypertension and/or stable coronary artery disease, in patients already controlled with perindopril and amlodipine given currently at the same dose level. Dosage and administration: Oral route. One tablet daily, preferably taken in the morning and before a meal. The fixed-dose combination is not suitable for initial therapy. If a change of dosage is required, the dose of Acerycal can be modified or individual titration with free combination may be considered. Renal Impairment: Acerycal can be administered in patients with Clcr ≥60ml/min, and is not suitable for patients with Clcr < 60ml/min. Hepatic Impairment: A dosage regimen for patients with hepatic impairment has not been established. Therefore, Acerycal should be administered with caution. Children (<18y): Acerycal should not be used in children and adolescents. Contraindications: Linked to perindopril: Known hypersensitivity to perindopril or to any other ACE inhibitor, history of angioedema associated with previous ACE inhibitor therapy, hereditary or idiopathic angioedema, 2nd and 3rd trimesters of pregnancy. Linked to amlodipine: severe hypotension, hypersensitivity to amlodipine or to any other dihydropyridines, shock including cardiogenic shock, obstruction of the outflow tract of the left ventricle (high-grade aortic stenosis), unstable angina pectoris, heart failure after acute myocardial infarction (during the first 28 days), hypersensitivity to any of the excipients. Precautions: Assess renal function before and during treatment. Renovascular hypertension, surgery/anesthesia. Symptomatic hypotension is rarely seen, but is more likely to happen in volume-depleted patients, those receiving diuretics, or with the first two doses. Patients with pulmonary edema should be treated with caution. In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor. Hypersensitivity/angioedema: Angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including perindopril. Neutropenia, agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. Perindopril should be used with extreme caution in patients with collagen vascular disease, immunosupressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Renal Impairment: In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. Hepatic failure: Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis. In patients with impaired hepatic function amlodipine’s half-life is prolonged. Drug should be administered with caution and with close monitoring of liver enzymes. Hyperkaliemia: Elevations in serum potassium have been observed in some patients treated wit ACE inhibitors, including perindopril. Pregnancy and lactation: Acerycal is not recommended during the first trimester of pregnancy. Acerycal is contraindicated during the second and third trimesters of pregnancy. Acerycal is not recommended during lactation. Effect on driving: No studies on the effects of Acerycal on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur. Interactions: Concomitant use not recommended: combination therapy with lithium, potassium-sparing diuretics, potassium salts, potassium supplements, potassium-containing salt substitutes, dantrolene, estramustine and certain medicines that cause heart rhythm disorders. Other: Diuretics, sympathomimetics, gold, nonsteroidal anti-inflammatory drugs, antidiabetic agents, CYP3A4 inducers (rifampicin, hypericum perforatum, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), CYP3A4 inhibitors (itraconazole, ketoconazole), beta-blockers in heart failure, baclofen, corticosteroid, tetracosactide, alpha-blockers, amifostine, tricyclic antidepressants, antipsychotics, anesthetics, immunosuppressive agents. Undesirable effects: Common: somnolence, dizziness, headache, paraesthesia, vertigo, visual disturbances, tinnitus. Cardiovascular: paplpitations, flushing, hypotension, dyspnoea, cough, abdominal pain, nausea, vomiting, dyspepsia, dysgeusia, diarrhoea, constipation, pruritus, rash, muscle cramps, oedema, fatigue, asthenia, skin rashes. Uncommon: allergic reactions, weight changes, mood and sleep disturbances, tremor, syncope, rhinitis, bronchospasm, dry mouth, taste disturbances, quincke’s oedema, alopecia, purpura, skin discoloration, sweating, myalgia, arthralgia, back pain, increased urinary frequency, renal impairment, impotence, gynaecomastia. Very Rare: Blood test abnormalities. Risk of dehydration in the elderly and in patients suffering from heart failure. hypertonia (abnormal increase in muscle tension), swelling of the gums, hyperglycaemia. Frequency not known: hypoglycaemia, vasculitis. extrapyramidal syndrome. Presentation: Container of 30 tablets. PA 568/018/001-004. PA Holder: Les Laboratoires Servier, 50, rue Carnot 92284 Suresnes cedex France. Legal Category: POM. Date of First Authorisation: 13th June 2008. Date of Revision of the Text: December 2011. Further information available from: Servier Laboratories Ireland Ltd, Block 2, West Pier Business Campus, Old Dunleary Road, Dún Laoghaire, Co Dublin. Tel: (01) 6638110 Fax: (01) 6638120. www.servier.ie.

in Ar e d a M

klow

References: 1. Dahlöf B, Sever PS, Poulter NR, et al; ASCOT Investigators. Lancet. 2005; 366:895-906. Date of preparation: January 2012

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034

Treating Obesity Broadcasting Better Health

ÂŠthinkstockphotos.com_ Pixland

Broadcasting Better Health

Should the Broadcasting Authority of Ireland restrict the advertising of certain foods to children? Words: Dr Francis Finucane

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ecently, the Broadcasting Authority of Ireland (BAI) launched a consultation process considering how best to regulate television advertising of food to Irish children. This consultation was borne out of the context of an epidemic of childhood overweight and obesity. In its undertaking they must take account of the disparate views of stakeholders in medicine and public health and of the food and advertising industries. From an obesity physicianâ&#x20AC;&#x2122;s perspective, there are several good reasons to introduce greater regulation and restriction of food advertising to children.

Firstly, while there is uncertainty about the nature and extent of health benefits associated with restricting food advertising to children (and their parents), there is no real doubt that advertising increases consumption of the advertised product. The food industry is reluctant to accept advertising restrictions because of concerns that these will affect consumption, sales and profits. In a sense, there is unanimous agreement between proponents of advertising restriction and those in the food industry that such restriction will reduce the consumption of unhealthy foods.

13/09/2012 12:11:41

Treating Obesity Broadcasting Better Health

035

We know for certain that consumption of unhealthy food is associated with adverse health effects on a population level. The impact of restricted advertising on each individual’s health within that population is likely to be small and thus difficult to quantify in a scientific context. However, the effect on a population level is likely to be large, with a significant reduction in what is termed the ‘population attributable risk’ of obesity and being overweight. Achieving large overall health benefits (which are difficult to quantify) in the context of small individual changes is a core principal of preventative medicine.

“The reductions in food industry profits and television programming revenue are likely to be small and cannot be prioritised over the likely overall benefits to children’s health.” exists and it poses a very real threat to our children’s health. The scale of the obesity problem isn’t really disputed, but there is controversy and disagreement about the aetiological factors contributing to it and, consequently, what solutions are going to help us overcome it.

and government policy on this issue? Hardly! Putting forward their argument and influencing policy is one thing, but sometimes, when it comes to the disproportionate influence the food industry has on legislation, it feels like we’ve put Dracula in charge of the blood bank.

There is a lack of hard evidence to indicate that advertising restriction leads to weight loss in overweight children because the scientific means to conduct such an ‘experiment’ do not exist. This is a limitation of science, not of the advertising restrictions, and must not be used as a rationale to limit the introduction of feasible, pragmatic and sensible public health strategies to tackle childhood obesity. Quite simply, the absence of evidence isn’t evidence of absence of benefit. Consider the well-known example of the systematic review of parachute use to prevent death from ‘gravitational challenge’, which was published in the BMJ in 2003. Nobody has done a trial to show that parachutes protect people jumping from a plane, but we know they work.

Obesity is undeniably multifactorial. Its prevalence has increased because of changes in the environment over the last three decades. Complex genetic factors also contribute to individual obesity risk. We know that unhealthy food consumption is higher in low income areas. Children could and should be more activity in schools. Better infrastructure – such as wider cycle lanes and footpaths – would facilitate more physical activity in the population. Educating people about healthy lifestyle is critically important. And yet at the same time, if it was just about education, we’d have no fat doctors or dietitians.

Another consideration is the responsibility that the BAI has to not impose unnecessary restrictions on food marketing. However, their primary duty of care must be to the Irish children who constitute their television audience. The reductions in food industry profits and television programming revenue are likely to be small and cannot be prioritised over the likely overall benefits to children’s health. Furthermore, this strategy poses no risk to children themselves. From a public health point of view, there are no downsides here. This is an attempt to limit the amount of trash that children eat, pure and simple. Yet the slick food industry PR machine makes it about an attack on cheese and our dairy industry! They portray the initiative as ill-conceived and scientifically unsound. I met an 11 year-old girl recently with obesity-induced type 2 diabetes. Her cheese consumption wasn’t high on the agenda. In considering how advertising restriction might lead to healthier dietary behaviours in children, it’s the reductions in soft drinks, crisps and chocolate consumption that get health care professionals excited.

Advertising restrictions reduce chocolate consumption. The extent to which this would probably have an adverse effect on food company profits is directly proportional to its positive impact on population health, so the variation in enthusiasm for this restriction is entirely understandable. Nobody set out to create an obesity epidemic, but the fact is that one

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Tackling the obesity epidemic requires a multifaceted approach in the same way that reversing global warming does. Suggesting that restricting food advertising is not the solution is like Ferrari saying that taxing cars on the basis of emissions is over-simplistic. In isolation, these initiatives are futile but as part of an overall strategy, they will probably have the desired effect. Confectioners want people to eat more chocolate, which is fine, but should they be formulating legislation

13/09/2012 12:11:42

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13/09/2012 12:11:51

Treating Obesity Broadcasting Better Health

The BAI ought to apply the proposed restrictions on the timing and content of advertisements as quickly and as rigidly as possible. To some this may sound unreasonable and an extension of the ‘nanny state’. Yet we don’t compromise on our approach to children’s safety in other respects. Would we tolerate a public health approach to reduce injuries to children in cars that relied solely on parents driving carefully? Clearly not. We have stringent statutory regulation of the use of child restraints. We don’t feel the same way about protecting children from obesity. In fact,

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fat people are parodied in the media. It is one thing for a well-known journalist like Kevin Myers to write that he loathes “seeing the faces of fat children, without chins or jaws or cheekbones” in the Irish Independent. It is quite another for a national newspaper to publish such vitriol. Everybody knows that advertising restrictions will reduce the consumption of unhealthy food and beverages in children, just like belting up makes them safer in a car. Haven’t we created enough of a burden for future generations in Ireland already, without adding a reckless failure to address the obesity epidemic to their woes? In considering the many points of view the consultation process will generate and draw upon, the interests of our children need to be paramount. Our multibillion euro food industry is a powerful lobby and exerts significant influence on public health policy through entities like the Nutrition and Health Foundation. The bottom line for the food industry is profit for

shareholders. This means that there is an insurmountable conflict of interest when it comes to them influencing policy in this area, however well intentioned their contributions are. They portray attempts to influence dietary behaviour in children through legislation as churlish, scientifically unsound and even unethical. The truth is that confronting the evolving epidemic of childhood obesity in Ireland will require a multifaceted approach, and the measures proposed by the BAI are appropriate, proportionate, objective and transparent. As much as obesity is a burden on society caused by irresponsible individual behaviour, we need to see it as a burden on individuals within an irresponsible society. Legislators will need to have the courage to make difficult and unpopular decisions if we are to address this problem. Dr Francis Finucane MB MD MRCPI is a Consultant Endocrinologist at Galway University Hospital and honorary Senior Lecturer at NUI Galway.

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Those who wish to maintain the status quo in relation to food advertising for children will cite personal and parental responsibility as the key influences of lifestyle patterns and obesity risk. Of course, diet and physical activity behaviours are fundamentally important determinants of body weight. However, current public health strategies telling people to eat less and exercise more are failing. This belies a collective misunderstanding of the complex aetiology of obesity. The fact is that its rising prevalence has occurred as a result of changing environmental and idiological factors. There has always been a spectrum of fatness in humans; it is just that this spectrum has shifted to such a degree that a greater proportion of individuals now exceed the arbitrarily defined thresholds for overweight and obesity. Of course, individual variation in fatness within the population is determined by differences in behaviour, but the shift in the fatness of the whole population has occurred because of environmental and idiological change. It seems that when policy-makers consider the obesity epidemic they see too many fat people, whereas what they should be seeing is too many burgers, so to speak.

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038

Treating Obesity Arthritis Ireland | Message from the CEO

Addressing Arthritis Rising obesity levels have coincided with a rise in the number of Irish people suffering with arthritis. Words: John Church, CEO, Arthritis Ireland

t is no coincidence that an almost identical pattern emerges when a graph tracking obesity levels is compared with one plotting the incidences of arthritis in Ireland. Like obesity rates, the proportion of the population living with arthritis has been growing at an alarming rate, with more than one in five people in Ireland now living with the condition. This figure is set to rise further in the coming years with 25 per cent of adults predicted to have doctor-diagnosed arthritis by the year 2030. An ageing population is somewhat responsible for this trend, but it is not the only factor. Rising levels of obesity have also had a detrimental impact. According to figures from the Centre for Disease Control (CDC) in the US, the prevalence of obesity among adults with arthritis is on average 54 per cent higher than among people without the condition. Coupled with this, every 1kg of additional weight in overweight people adds an extra 4kg of stress to an affected joint. Arthritis Ireland is Ireland’s only organisation wholly dedicated to transforming the experience of people with arthritis and to reducing the impact of the condition on society. It is well documented that healthy living is a key part of reducing obesity levels, but it also plays an essential role in controlling arthritis and reducing the likelihood of a person developing osteoarthritis. As such, the promotion

TreatingObesity.indd 38

of healthy living – including a balanced diet and regular exercise, is a central component of all of the organisation’s support services and communications. Often it is the little things that make a big difference to people with arthritis. Difficulty with things like making a cup of tea, getting dressed or opening the front door can all add up to have a big impact on a person’s quality of life. The organisation strives to address this through educating and supporting patients and informing the general public and health professionals on all aspects of arthritis. The organisation prides

itself on providing people with the most accurate, accessible and comprehensive information available on all matters related to arthritis through the publication of a wide range of patient booklets and through the development of a diverse array of programmes and events, which focus on a variety of topics from exercise and motivation to self-management. Addressing rising obesity levels in Ireland is one of Arthritis Ireland’s core goals. We breathe the message of healthy living, focusing on a balanced diet and regular exercise, through every one of our services and resources.

A P P m i s m u t m u P c h t p e d s N m d < u a p a p d t H T

John Church, CEO, Arthritis Ireland

13/09/2012 12:12:09

Some things simply work better together Misoprostol 200 mcg Enteric coating Diclofenac Na 50 mg or 75 mg

Think Arthrotec.

Pain relief with proven protection from NSAID-induced ulcers1 Arthrotec 50® and 75® modified-release tablets Abbreviated Prescribing Information Prescribing Information Please refer to the SmPC before prescribing Arthrotec 50® and 75® modified-release tablets Presentation: White, round, biconvex, modified-release tablets with a gastro-resistant core containing 50 or 75 milligrams of diclofenac sodium surrounded by an outer mantle containing 200 micrograms misoprostol. Indications: For patients who require the nonsteroidal anti-inflammatory drug (NSAID) diclofenac together with misoprostol. The diclofenac component is indicated for the symptomatic treatment of osteoarthritis and rheumatoid arthritis. The misoprostol component is indicated for patients with a special need for prophylaxis of NSAID induced gastric and duodenal ulceration. Adult dosage: Tablets should be swallowed whole not chewed. Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. Arthrotec 50: One tablet to be taken with food, two or three times daily. Arthrotec 75: One tablet to be taken with food two times daily. Elderly/Renal Impairment/Hepatic impairment: No dose adjustment is necessary in the elderly, or in patients with hepatic impairment or mild to moderate renal impairment. Elderly patients and patients with renal or hepatic impairment should be closely monitored. Children: Safety and efficacy not established. Contraindications: Active gastric or duodenal ulceration or perforation or active gastrointestinal (or other) bleeding; use in pregnant women, women planning a pregnancy; known hypersensitivity to diclofenac, aspirin, other NSAIDs, misoprostol, other prostaglandins or any of the excipients; use in patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin /other NSAIDs; in treatment of peri-operative pain associated with coronary artery bypass graft surgery; severe renal and hepatic failure; severe heart failure. Warnings/Precautions: For full details see SmPC. Use with concomitant NSAIDs including COX-2 inhibitors should be avoided. Not for use by premenopausal women unless using effective contraception. Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. Use with caution in elderly patients and in patients with renal, cardiac or hepatic impairment. To be used only in exceptional circumstances and with close clinical monitoring in patients with advanced cardiac failure, advanced kidney failure, advanced liver disease or severe dehydration. In rare cases may cause interstitial nephritis, glomerulitis, papillary necrosis and nephrotic syndrome. Patients at greatest risk of such a reaction (careful monitoring required) are those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease. Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure. As with all NSAIDS, diclofenac/misoprostol can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. Use with careful consideration in patients with hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease and before initiating longer-term treatment of patients with risk factors for cardiovascular events. Monitor blood pressure closely during initiation and throughout the course of therapy. Data suggest that use of diclofenac, particularly at high dose (150mg daily) in long term treatment may be associated with a small increased risk of serious arterial thrombotic events (e.g. myocardial infarction or stroke) - be alert for such events even in the absence of previous cardiovascular symptoms and inform patients of the signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur. Can cause serious gastrointestinal (GI) adverse events, which can be fatal. When GI bleeding or ulceration occurs withdraw treatment. These events can occur at any time during treatment, with or without warning symptoms. Higher risk of GI events with high doses, the elderly, cardiovascular disease, concomitant aspirin, history of, or active gastrointestinal disease so use with caution and start on the lowest dose possible. May decrease platelet aggregation and prolong bleeding time. Extra supervision recommended in haemopoeitic disorders/conditions with defective coagulation or in patients with a history of cerebrovascular bleeding. Caution required in patients with ulcerative colitis or Crohn’s disease. Serious skin reactions, some of them fatal, have been reported very rarely in association with NSAID use. Patients appear to be at highest risk early in treatment (majority onset within the first month). Discontinue at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. NSAIDs may precipitate bronchospasm in patients with /history of bronchial asthma/allergic disease. Arthrotec may mask fever and thus underlying infection. All patients on long term treatment with NSAIDs should be monitored (e.g. blood counts, renal and hepatic function) as a precautionary measure. Use with caution with concomitant corticosteroids, other NSAIDs, selective serotonin-reuptake inhibitors, anti-platelet agents or anti-coagulants. Interactions: See SmPC. Pregnancy and lactation: Contraindicated in pregnancy, women planning a pregnancy. Should not be administered during breastfeeding. Driving and using machines: Patients who experience dizziness /other central nervous system disturbances should refrain from driving or operating machinery. Undesirable Effects: Very common (≥1/10): Abdominal pain, diarrhoea, nausea, dyspepsia. Common (≥1/100, <1/10): insomnia, headache, dizziness, gastritis, vomiting, flatulence, eructation, constipation, peptic ulcer, alanine aminotransferase increased, erythema multiforme, rash, pruritis blood alkaline phosphatase increased. Uncommon (≥1/1000, <1/100): thrombocytopenia, stomatitis, purpura, urticaria, menorrhagia, metrorrhagia, vaginal haemorrhage, postmenopausal haemorrhage. Rare (≥1/10,000,<1/1000): anaphylactic reaction, hepatitis, jaundice, angioedema. Frequency: Unknown (Post-marketing experience): aseptic meningitis, aplastic anaemia, agranulocytosis, haemolytic anaemia, leucopenia, hypersensitivity, anorexia, psychotic reaction, disorientation, depression, anxiety, nightmares, mood change, irritability, convulsions, memory disturbance, drowsiness, tremor, taste disturbance, paraesthesia, visual disturbances, blurred vision, tinnitus, cardiac failure, palpitations, shock, hypertension, hypotension, vasculitis, asthma, pneumonitis, dyspnoea, GI perforation, gastrointestinal bleeding, melaena, haematemesis, colitis, Crohn’s disease, oesophageal disorder, mouth ulceration, glossitis, tongue odema, dry mouth, hepatitis fulminant, aspartate aminotransferase increased, blood bilirubin increased, toxic epidermal necrolysis, Stevens-Johnson syndrome, dermatitis exfoliative, dermatitis bullous, Henoch Schonlein purpura, mucocutaneous rash, rash vesicular, photosensitivity reaction, alopecia, renal failure, acute renal failure, renal papillary necrosis, nephritis interstitial, nephrotic syndrome, proteinuria, haematuria, intra-uterine death, uterine rupture, incomplete abortion, premature baby, anaphylactoid syndrome of pregnancy, retained placenta or membranes, uterine contractions abnormal, uterine haemorrhage, birth defects, oedema, chest pain, face oedema, fatigue, pyrexia, chills, inflammation, decreased haemoglobin, uterine perforation. Data suggest that use of diclofenac, particularly at high doses (150 mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events. For all other adverse events see SmPC. Overdose: See SmPC. Packaging quantity: Arthrotec 50: Pack of 60 tablets. Arthrotec 75: Pack of 60 tablets. Marketing Authorisation number(s) and holder: Arthrotec 50: PA 0822/112/001 Arthrotec 75: PA 0822/112/002. Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24, Ireland. Legal category: S1B Further information is available on request from: Medical Information at Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK. Tel: +44 (0) 1304 616161 Date of preparation of PI: December 2011 Ref: AE 7_0 References: 1. Arthrotec SmPC December 2011. Date of preparation: January 2012. ART/2012/001

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040

Treating Obesity The Struggle against Psoriasis

The Struggle against Psoriasis As the obesity epidemic worsens, treating conditions like psoriasis and psoriatic arthritis is becoming increasingly urgent. Words: Prof Oliver Fitzgerald

walk along any Irish city street will tell you that obesity is a major medical issue in Ireland today, with the number of the overweight and obese continuing to rise. Alarmingly, more and more children are becoming dangerously overweight at progressively younger ages, indicating that we will have in decades to come a growing population of patients with weightrelated conditions, fuelled by a combination of unhealthy diet and insufficient exercise.

have not perhaps received the airing that they might warrant. Fatty tissue – known as adipose tissue – can be a reservoir of numerous cell types, among them inflammatory or immune cells which can have an adverse effect on the body’s immune-defense balance. Ergo, the more fatty tissue you have, the greater the possible contribution of immune cells or their products – known as cytokines – which

can be released into the general system. One such consequence of these cytokines can be the initiation or accentuation of inflammatory arthritis. There are several ways in which obesity can lead to underlying inflammatory arthritis. The already inflammatory component of skin may be increased in patients suffering from obesity, which can lead to conditions

The cardiovascular consequences of obesity are well known. Heart disease, blood pressure etc all play a part. But also of note are the other detrimental implications this debilitating condition can have on the human body, including ailments such as psoriasis, psoriatic arthritis and immune system complications. As we shall see, these conditions can result in significant impairment of quality of life, joint damage and disability, and accelerated atherosclerosis, each with possible dangerous consequences for sufferers. The adverse effects of obesity on the immune system have been known for some time, yet these potential dangers ©thinkstockphotos.com_istockphoto

TreatingObesity.indd 40

13/09/2012 12:12:17

Treating Obesity The Struggle against Psoriasis

It is important to note that not all inflammatory-joint diseases (notably rheumatoid arthritis) have a verifiable correlation with obesity. There is increasing evidence however that psoriatic arthritis – the second most common inflammatory joint disease – is indeed strongly associated with obesity. Psoriatic arthritis often

TreatingObesity.indd 41

such as psoriasis, but can also result in more systemic effects. For instance, obese patients have higher frequencies of insulin resistance and diabetes. Insulin – produced in the pancreas – normally suppresses the immune system, so insulin-resistance or reduced insulin production associated with obesity can curtail this suppressive effect, typically leading obese patients to develop more immunerelated conditions than those of a healthier bodyweight. Cells such as macrophages can infiltrate adipose tissue adding to the existing inflammation milieu. Obesity can lead to increased macrophage (or natural killer cell) infiltration and increased production of inflammatory cytokines such as interleukin-6 and TNFalpha. In obese individuals, there are also changes in molecules like leptin and adiponectin, which in turn can drive the development of multiple bodily disturbances in predisposed individuals. All of these pro-inflammatory molecules can drive inflammation, not only locally – resulting in conditions such as psoriasis – but also more systemically, in synovial joints for instance. The data strongly suggests that obesity has the potential to trigger many of the known inflammatory pathways that underlie inflammatory joint diseases.

041

“Psoriatic arthritis often accompanies patients afflicted with psoriasis, being found in 15-40 per cent of cases.” appears in patients afflicted with psoriasis, and is found in 15 to 40 per cent of cases. Psoriasis is a common disorder of the skin which clinically reveals itself in the form of scaly patches or plaques on extensor surfaces such as the knees and elbows, and also on the scalp. There is a strong genetic component to the development of the condition which can become quite severe, covering the entire body in some instances and can include involvement of the nails. Psoriasis affects approximately 2 to 3 per cent of the population, so it is a very common skin disease. More worryingly, psoriasis patients often develop disease aspects over and above their skin disease including joint involvement (as referred to above), axial or spinal inflammation, digital swelling (dactylitis), inflammation

of the site of attachment of ligament to bone (enthesitis), not to mention more systemic features such as obesity, metabolic syndrome and cardiovascular complications. The extended phenotype of psoriasis is such that the concept of psoriatic disease has been proposed. For many years we have known about the undeniable link between the psoriasis and obesity – obesity is common among patients with psoriasis and being overweight appears to be a primary risk factor for developing the condition. In particular, this relationship was shown in the Nurses’ Health study, a longitudinal study involving more than 116,000 female nurses in the US. Other studies show that Body Mass Index (BMI) is linked with the severity of psoriasis,

13/09/2012 12:12:29

POSITIVE RESULTS

Targeting

ABRIDGED PRESCRIBING INFORMATION (Rheumatoid Arthritis [RA] Indication Only) (For full prescribing information and use in the oncology setting, refer to the Summary of Product Characteristics [SmPC]) MABTHERA® (rituximab) 100 mg and 500 mg Concentrate for Solution for Infusion (10 mg/ml) Indications: MabThera in combination with methotrexate is indicated for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to other disease-modifying antirheumatic drugs including one or more tumour necrosis factor (TNF) inhibitor therapies. When given in combination with methotrexate (MTX), MabThera has been shown to reduce the rate of progression of joint damage (measured by x-ray) and to improve physical function. Refer to the SmPC for use in the oncology setting. Dosage and Administration (RA): MabThera is for use in adults only. Administer prepared MabThera solution as an intravenous (IV) infusion (not as an IV push or bolus) through a dedicated line, with full resuscitation facilities immediately available and under the supervision of an experienced physician. With each infusion, provide patient with a patient alert card which contains important safety information regarding potential increased risk of infections, including PML. Patients should receive and complete treatment with 100mg IV methylprednisolone 30 minutes prior to MabThera infusions to decrease the incidence and severity of infusion related reactions. Premedication (an analgesic/anti-pyretic (e.g. paracetamol) and an antihistamine (e.g diphenhydramine)) should always be administered before each infusion – refer to SmPC. Monitor for the onset of cytokine release syndrome – refer to management guidance in the SmPC. Severe reactions e.g. severe dyspnoea, bronchospasm or hypoxia require immediate interruption of infusion; mild or moderate reactions usually respond to a reduction in the rate of infusion. A course of MabThera consists of two 1000mg IV infusions, with the second infusion following two weeks after the first. Evaluate 24 weeks after previous course for need for further courses - retreat at that time if residual disease activity remains, otherwise delay until disease activity returns. Clinical response is usually achieved within 16-24 weeks of an initial treatment course. Carefully reconsider continued therapy in patients showing no evidence of therapeutic benefit within this time period. First infusion of each course: initial rate for infusion is 50mg/hr; after the first 30 minutes, it can be escalated in 50mg/hr increments every 30 minutes, to a maximum of 400mg/hr. Second infusion of each course: initial rate of 100mg/hr, and increased by 100mg/hr increments at 30 minute intervals, to a maximum of 400mg/hr. The safety and efficacy of MabThera in children has not been established. No dose adjustment required in elderly patients (aged >65 years). Contraindications (RA): Hypersensitivity to the active substance or to any of the excipients of the product or to murine proteins. Active, severe infections. Patients in a severely immunocompromised state. Severe heart failure (NYHA Class IV) or severe, uncontrolled cardiac disease. Warning and Precautions (RA): Not recommended for use in MTX-naïve patients - favourable benefit risk relationship has not been established. MabThera is associated with infusion related reactions (IRR) - premedication with a glucocorticoid (to reduce the frequency and severity of IRRs), an analgesic/anti-pyretic drug and an antihistamine should always be administered before each infusion.. Severe IRRs with fatal outcome have been reported in the post-marketing setting. Most IRR events reported in clinical trials were mild to moderate in severity. Most common symptoms were allergic reactions like headache, pruritus, throat irritation, flushing, rash, urticaria, hypertension and pyrexia. The proportion of patients experiencing any infusion reaction was generally higher following the first infusion than following the second infusion of any treatment course. Incidence of IRR decreased with subsequent courses. Closely monitor patients with pre-existing cardiac conditions and those who experienced prior cardiopulmonary adverse reactions. Refer to SmPC for management. Medicinal products for the treatment of hypersensitivity reactions, e.g. epinephrine (adrenaline), antihistamines and glucocorticoids, should be available for immediate use in the event of an allergic reaction. No data on the safety of MabThera in patients with moderate heart failure (NYHA class III) or severe, uncontrolled cardiovascular disease. Prior to MabThera treatment, consider the risk of cardiovascular complications resulting from infusion reactions in patients with a known cardiac history and those who experienced prior cardiopulmonary adverse reactions. Monitor closely during administration. Consider withholding anti-hypertensive medications 12 hours prior to the MabThera infusion. Serious infections, including fatalities, can occur during therapy with MabThera. Do not administer MabThera to patients with an active, severe infection (e.g. tuberculosis, sepsis and opportunistic infections) or severely immunocompromised patients (e.g. where levels of CD4 or CD8 are very low). Exercise caution when considering the use of MabThera in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection e.g. hypogammaglobulinaemia. Prior to initiating treatment, it is recommended that immunoglobulin levels are determined. Patients reporting signs and symptoms of infection following MabThera

therapy should be promptly evaluated and treated appropriately. Re-evaluate patients for any potential risk for infections before giving any subsequent courses of MabThera. In patients with non-Hodgkin’s lymphoma receiving MabThera in combination with cytotoxic chemotherapy, cases of fatal hepatitis B reactivation have been reported. Reactivation of hepatitis B infection has also been very rarely reported in RA patients receiving MabThera. Prior to MabThera treatment, review patient’s vaccination status and follow current immunisation guidelines. Complete vaccination at least four weeks prior to first administration of MabThera. No data concerning the use of live viral vaccines following MabThera therapy. Live virus vaccines not recommended while on MabThera or whilst peripherally B cell depleted. Patients treated with MabThera may receive non-live vaccinations - response rates may be reduced. If non live vaccines required while receiving MabThera, vaccinations should be completed at least four weeks before receiving the next course of MabThera. Concomitant use of MabThera and antirheumatic therapies other than those specified under the rheumatoid arthritis indication and posology not recommended. Insufficient data from clinical trials to fully assess the safety of sequential use of other DMARDs (including TNF inhibitors and other biologics) following therapy with MabThera. Closely monitor patients for signs of infection if biologic agents and/or DMARDs are used following MabThera therapy. Immunomodulatory drugs may increase the risk of malignancy. Based on limited experience with MabThera in RA patients, the present data do not seem to suggest any increased risk of malignancy, though the possible risk for the development of solid tumours cannot be excluded. Use of MabThera may be associated with an increased risk of Progressive Multifocal Leukoencephalopathy (PML). Monitor patients at regular intervals for any new or worsening neurological symptoms or signs that are suggestive of PML. If PML suspected, suspend further dosing until PML has been excluded. Evaluate symptoms to determine if they are indicative of neurological dysfunction, and if so, determine if symptoms suggestive of PML. Consultation with a Neurologist should be considered as clinically indicated. If unsure, consider further evaluation, including MRI scan preferably with contrast, CSF testing for JC Viral DNA and repeat neurological assessments. Be vigilant for symptoms suggestive of PML that the patient may not notice (e.g. cognitive, neurological or psychiatric symptoms). Advise patients to inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is not aware of. If a patient develops PML, the dosing of MabThera must be permanently discontinued. Very rare cases of fatal PML reported following treatment with MabThera for rheumatoid arthritis and autoimmune diseases including Systemic Lupus Erythematosus (SLE) and vasculitis. Drug Interactions (RA): Limited data on possible drug interactions with MabThera. Patients with human anti-mouse antibody or human anti-chimeric antibody (HAMA/HACA) titres may have allergic or hypersensitivity reactions when treated with monoclonal antibodies. In RA patients who received subsequent therapy with a biologic DMARD following MabThera, the rate of clinically relevant infection while on MabThera was 6.01 per 100 patient years compared to 4.97 per 100 patient years following treatment with the biologic DMARD. Fertility, Pregnancy and Lactation (RA): Do not give to a pregnant woman unless the potential benefit outweighs the potential risk. MabThera may cause B cell depletion in the foetus. Effective contraception required in women of child bearing age, both during and for 12 months following MabThera therapy. Women should not breastfeed during and for 12 months following MabThera treatment. Side Effects and Adverse Reactions (RA): Very Common ADRs (> 1/10) – upper respiratory tract infection, urinary tract infections, infusion related reactions (hypertension, nausea, rash, pyrexia, pruritis, urticaria, throat irritation, hot flush, hypotension, rhinitis, rigors, tachycardia, fatigue, oropharyngeal pain, peripheral oedema, erythema) and headache; Common ADRs (> 1/100 - < 1/10) - bronchitis, sinusitis, gastroenteritis, tinea pedis, hypercholesterolaemia, paraesthesia, migraine, dizziness, sciatica, alopecia, depression, anxiety, dyspepsia, diarrhoea, gastro-oesophageal reflux, mouth ulceration, upper abdominal pain, arthralgia/musculoskeletal pain, osteoarthritis and bursitis. Refer to SmPC for a complete listing of adverse events including post-marketing experience. Legal Category: Limited to sale and supply on prescription only. Presentations and Marketing Authorisation Numbers: 100mg of rituximab in 10ml (10mg/ml) pack of 2 vials (EU/1/98/067/001); 500mg of rituximab in 50ml (10mg/ml) pack of 1 vial (EU/1/98/067/002). Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. MabThera is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: September 2011. P08/11/11

Reference: 1. Summary of Product Characteristics 19 September 2011

TreatingObesity.indd 42

13/09/2012 12:12:31

r g d. o e l t y r s t d s f t . ). e e n I r ). e y e n c l e t a n g e y t d a, l o o b l k, s )

Treating Obesity The Struggle against Psoriasis

with severe psoriasis being more prevalent among the obese than its milder counterpart. Even worse, the effectiveness of therapeutic treatments for psoriasis appears to be impaired in obese subjects as medications such as biologic therapies appear to become more effective as patients lose weight. All of this evidence leads us to conclude that psoriasis occurs with greater severity and frequency among patients who are overweight, and that obesity can adversely affect their response to therapy. The question remains of whether obesity is a cause or a consequence of the psoriasis. The answer continues to elude us, and more studies are needed – particularly of patients with early psoriasis. Finally, some studies conducted here in Ireland have investigated the role of Glucagon-like peptide (GLP) in patients with psoriasis. It is known that treatment with liraglutide, a GLP-1 analogue, considerably improves weight and glycaemic control in people with type-2 diabetes, and that its receptor is present on innate immune cells. In a small group of psoriasis patients, GLP-1 analogue therapy lessened psoriasis severity, increased circulating invariant natural killer T cell numbers and modulated cytokine secretion. These effects may result from improvements in weight and glycaemic control as well as from direct immune effects

of GLP-1 receptor activation. Patients with psoriasis and obesity should be made aware that favorable lifestyle changes not only lower their risk of metabolic diseases – particularly diabetes – but psoriasis may be improved or even prevented if they make an active attempt to lose weight. This should certainly be an additional motivation for patients to consider restructuring their lifestyle and attempting to acquire a healthier BMI. This is certainly something that we need to focus on more with patients suffering from psoriasis. A little less clear, until recently, has been the link between obesity and psoriatic arthritis. A case-controlled study published in 2010 showed that patient-reported BMI at 18 years of age – but not current BMI – was associated with psoriatic arthritis, suggesting a link between obesity and the subsequent development of the disease. In the August 2012 issue of Annals of Rheumatic Disease there were two separate articles and an editorial published on this subject. One article describes an electronic medical records database from the UK called The Health Improvement Network (THIN), which has accrued data including BMI and the prevalence of psoriasis and psoriatic arthritis between 1995 and 2010. THIN encompasses data pertaining to a total of 75,395 patients with psoriasis, 976 of whom had psoriatic arthritis. This study demonstrated

“Two very large and independent studies have confirmed that there is an undeniable link between psoriatic arthritis and obesity in large populations of patients with psoriasis.”

TreatingObesity.indd 43

043

that the incidence rate of psoriatic arthritis increased with increasing BMI, indicating a relationship between psoriatic arthritis and being overweight. The second study – the Nurses’ Health study II, or NHS II– was published in Boston and featured 80,049 participants followed over a 14 year period between 1991 and 2005. Information was collected on BMI, weight change and central obesity, and a record was made of the diagnosis of psoriasis and psoriatic arthritis. What they found was yet more evidence to confirm a correlation between BMI and psoriatic arthritis. The risk ratio (RR) for psoriatic arthritis increased with an increase in BMI, being 1.83 for a BMI of 25-29, 3.2 for 30-34 and 6.46 for a BMI over 35. Thus, two very large and independent studies have confirmed that there is an undeniable link between psoriatic arthritis and obesity in large populations of patients with psoriasis. The exact mechanisms of this connection remain unclear, but are probably similar to those already proposed in relation to psoriasis. All of these findings are crucially important, as they demonstrate that we need to pay more attention to overweight psoriasis patients in order to reduce the likelihood of these patients developing psoriatic arthritis over the course of time. This is important if we are to reduce the prevalence of these conditions and their impact on the population over the coming decades. Professor Oliver Fitzgerald is Newman Clinical Research Professor and consultant rheumatologist at the School of Medicine & Medical Science at St. Vincent’s University Hospital and the Conway Institute at University College Dublin.

13/09/2012 12:12:31

In DMARD-IR AnD TnF-IR RA PATIenTs, In DMARD-IR AnD TnF-IR RA PATIenTs, WHEN COMBINATION WITH MTX IS NOT AN OPTION... WHEN COMBINATION WITH MTX IS NOT AN OPTION...

ROACTEMRA ROACTEMRA STANDS OUT1 STANDS OUT1

RoActemRA, in combination with methotrexate (mtX), is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease-modifying RoActemRA, in combination with methotrexate (mtX),factor is indicated for the treatment of patients, moderate to severe active rheumatoid arthritis (RA) anti-rheumatic drugs (DmARDs) or tumour necrosis (tNF) antagonists. In these RoActemRA can be given as monotherapy in adult patients who have to either inadequately to, orwith whomtX wereisintolerant to, previous therapy with one or more disease-modifying in case of intolerance mtXresponded or where continued treatment inappropriate. RoActemRA has been shown to reduce the rate of 2 anti-rheumatic drugs (DmARDs) necrosis factor antagonists. In function these patients, RoActemRA can be given as monotherapy progression of joint damageorastumour measured by X-ray and(tNF) to improve physical when given in combination with methotrexate. in case of intolerance to mtX or where continued treatment with mtX is inappropriate. RoActemRA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with methotrexate.2

ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]) RoActemra® (Tocilizumab) 20mg/ml Concentrate for Solution for Infusion Indications: (i) In combination with methotrexate (MTX), for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more DMARDs or TNF antagonists. In these patients, RoActemra can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. RoActemra has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with methotrexate. (ii) As monotherapy (in case of intolerance to MTX or where treatment with MTX is inappropriate) or in combination with MTX, for the treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients ≥ 2 years ® ABRIDGED PRESCRIBING INFORMATION (For fulltoprescribing information, refer and to the Summary of Product Dosage Characteristics [SmPC]) RoActemra (Tocilizumab) 20mg/ml Concentrate for Solution for Infusion of age, who have responded inadequately previous therapy with NSAIDs systemic corticosteroids. and Administration: Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA or sJIA and all patients should be given Patient Alert Card. Recommended posology is 8mg/kgtodiluted a final volume ofarthritis 100ml, (RA) givenwho once every weeks by iv infusion over hour. For patients > 100kg, dosesantagonists. > 800mg per infusion are not Indications: (i) In combination with the methotrexate (MTX), forRA thePatients: treatment of adult patients with moderate severeto active rheumatoid have had4an inadequate response or 1intolerance to one orweighing more DMARDs or TNF In these patients, recommended. data on dosesinabove 1.2g. Dose adjustments: interruption orMTX in some cases discontinuation of RoActemra recommended therate event raised liverofenzymes, low absolute neutrophil count (ANC) or low physical platelet count (see RoActemra can be given No as monotherapy case of intolerance to MTX or Dose wheremodification, continued treatment with is inappropriate. RoActemra has been shown to reduceinthe of of progression joint damage as measured by X-ray and to improve function 9 SmPC for details). In patients not previously with RoActemra, not to recommended in treatment patients with anMTX ANCisbelow 2 x 10 /l. Closely monitor renal in patients with moderate severe juvenile renal impairment RoActemra not been≥studied when given in combination with methotrexate. (ii) As treated monotherapy (in case ofinitiation intolerance MTX or where with inappropriate) or in combination withfunction MTX, for the treatment of active to systemic idiopathicasarthritis (sJIA)has in patients 2 yearsin these patients. No data in patients to with hepatictherapy impairment. Patients: No data in patients < 2 years of age. 8mg/kg for patientsshould ≥ 30kgbe or initiated 12mg/kgby forhealthcare patients < professionals 30kg once every 2 weeks byinivthe infusion over and 1 hour. Check patient’s at each of age, who have responded inadequately previous with sJIA NSAIDs and systemic corticosteroids. Dosage andPosology: Administration: Treatment experienced diagnosis treatment of RA orweight sJIA and all visit – refer to SmPC. In the event raised enzymes, low ANC or low plateletiscount, interrupt/discontinue RoActemra dose orgiven modify/stop concomitant other over medications appropriate. – see>SmPC details. Reduction RoActemra dose patients should be given the Patient AlertofCard. RAliver Patients: Recommended posology 8mg/kg diluted to a final volume of 100ml, once every 4 weeksMTX by ivand infusion 1 hour. where For patients weighing 100kg,fordoses > 800mg perofinfusion are not due to No laboratory studied sJIA patients.Dose Clinical improvement is generallyorseen withincases 6 weeks of starting RoActemra, reconsider continuedintherapy if noof improvement seen in thislow timeframe. Hypersensitivity to anycount component recommended. data onabnormalities doses abovenot 1.2g. Doseinadjustments: modification, interruption in some discontinuation of RoActemra recommended the event raised liver enzymes, absoluteContraindications: neutrophil count (ANC) or low platelet (see the product; active, severe infections. Warnings and Precautions: Serious (sometimes fatal) infections reported inbelow patients immunosuppressive agents including RoActemra. Do nottoinitiate patients with active infection. If serious develops SmPC forof details). In patients not previously treated with RoActemra, initiation not recommended in patients with an ANC 2 xreceiving 109/l. Closely monitor renal function in patients with moderate severeinrenal impairment as RoActemra has notinfection been studied in interrupt infection controlled. Caution insJIA patients with No history infections, or other underlying conditions may patients to < infection. Vigilance forweeks the timely of serious recommended. these patients. Notherapy data in until patients with hepatic impairment. Patients: dataofinrecurring/chronic patients < 2 years of age. Posology: 8mg/kg for patientswhich ≥ 30kg or predispose 12mg/kg for patients 30kg once every 2 by iv detection infusion over 1 hour.infection Check patient’s weight Advise at eachall patients and In parents/guardians of sJIA to contact their healthcare immediately when RoActemra symptoms suggestive of an infection appear. Screen for latent prior to starting Treat latent withfor standard therapy dose before visit – refer to SmPC. the event of raised liverpatients enzymes, low ANC or low plateletprofessional count, interrupt/discontinue dose or modify/stop concomitant MTX and otherTB medications wheretherapy. appropriate. – see TB SmPC details.anti-mycobacterial Reduction of RoActemra initiating RoActemra. Viral reactivation (e.g. hepatitis B) reported with biologic therapies for RA. Patients screening positive for hepatitis excluded from clinical trials. Events of diverticular perforations as complications of diverticulitis reported uncommonly with due to laboratory abnormalities not studied in sJIA patients. Clinical improvement is generally seen within 6 weeks of starting RoActemra, reconsider continued therapy if no improvement seen in this timeframe. Contraindications: Hypersensitivity to any component RoActemra in severe RA patients. Exercise cautionand in patients with a Serious history of intestinal ulceration or diverticulitis. patients withimmunosuppressive symptoms of complicated promptly. Serious reactions reported - may be more severe and develops potentially of the product; active, infections. Warnings Precautions: (sometimes fatal) infections reported Evaluate in patients receiving agentsdiverticulitis including RoActemra. Do nothypersensitivity initiate in patients with active infection. If serious infection in patients who have experienced hypersensitivity reactions during previous infusions even if they have received premedication with steroids and anti-histamines. Appropriate treatment be available use in the event of an anaphylactic interrupt fatal therapy until infection controlled. Caution in patients with history of recurring/chronic infections, or other underlying conditions which may predispose patients to infection. Vigilance for should the timely detectionfor ofimmediate serious infection recommended. Advise all reaction with RoActemra. If an patients anaphylactic reaction or other serious hypersensitivity/serious related reaction occurs, stop administration of RoActemra immediately and discontinue therapy with caution in patients with activebefore hepatic patients and parents/guardians of sJIA to contact their healthcare professional immediately infusion when symptoms suggestive of an infection appear. Screen for latent TB prior to starting therapy. Treat permanently. latent TB withUse standard anti-mycobacterial therapy disease or hepatic impairment. Not recommended in patients with baseline ALT or AST > 5 x ULN; use with caution in patients with ALT or AST > 1.5 x ULN. Monitor ALT and AST levels for RA and sJIA patients according to SmPC – other liver function tests including initiating RoActemra. Viral reactivation (e.g. hepatitis B) reported with biologic therapies for RA. Patients screening positive for hepatitis excluded from clinical trials. Events of diverticular perforations as complications of diverticulitis reported uncommonly with bilirubin beExercise considered whereinindicated. If raised, followofdosage recommendations in SmPC for RA and sJIA patients. Risk of neutropenia may be increased in patients previously treated with a TNF antagonist. Continued therapy not recommended in patients RoActemra in RA should patients. caution patients with a history intestinal ulceration or diverticulitis. Evaluate patients with symptoms of complicated diverticulitis promptly. Serious hypersensitivity reactions reported - may be more severe and potentially 9 3 9 who develop an ANC < 0.5 x 10 /l or platelet count < 50 x 10 /μl. In patients not previously treated with RoActemra, initiation not recommended where ANC is below 2 x 10 l. Caution in patients with low platelet count; monitor neutrophils and platelets in RA and fatal in patients who have experienced hypersensitivity reactions during previous infusions even if they have received premedication with steroids and anti-histamines. Appropriate treatment should be available for immediate use in the event of an anaphylactic sJIA patients according to SmPC. If reduced, follow dosage recommendations in SmPC for RA and sJIA patients. Elevations in lipid parameters seen - refer to SmPC. Assess lipid parameters according to SmPC, if elevated, manage patients according to local reaction with RoActemra. If an anaphylactic reaction or other serious hypersensitivity/serious infusion related reaction occurs, stop administration of RoActemra immediately and discontinue therapy permanently. Use with caution in patients with active hepatic guidelines for hyperlipidaemia. Potential for central demyelination with RoActemra currently unknown; physicians should be vigilant for symptoms of new onset disease. Immunomodulatory medicines may increase malignancy risk in RA patients. Do not give live disease or hepatic impairment. Not recommended in patients with baseline ALT or AST > 5 x ULN; use with caution in patients with ALT or AST > 1.5 x ULN. Monitor ALT and AST levels for RA and sJIA patients according to SmPC – other liver function tests including and live attenuated vaccines concurrently with RoActemra as safety not established – refer to SmPC for further details on immunisations. RA patients should have CV risk factors managed as part of usual standard of care. Not recommended for use with other bilirubin should be considered where indicated. If raised, follow dosage recommendations in SmPC for RA sJIA patients. Riskpatients of neutropenia may be increased patients treated a TNF Continued therapy not recommended into patients biological agents. Macrophage activation syndrome (MAS) is a serious life-threatening disorder thatand may develop in sJIA – RoActemra has not beeninstudied in previously patients during an with active MASantagonist. episode. Advise patients experiencing dizziness not drive or who develop an ANC <until 0.5 xdizziness 109/l or resolved. platelet count < 50 x 103/μl. In patients not per previously treated with RoActemra, initiation recommended where ANC is below 2 x 109l.by Caution in patients with low platelet count; monitor neutrophils and platelets in RAhigher and use machines Product contains 26.55mg sodium 1200mg. Drug Interactions: In RA patients,not levels of simvastatin (CYP3A4) were decreased 57% one week following a single dose of tocilizumab to levels similar to or slightly sJIA patients to SmPC. If reduced, follow dosage recommendations in which SmPC are for individually RA and sJIA patients. in lipid parameters - refer to SmPC. Assess lipid parameters according SmPC, manage patients accordingeffect. to local thanaccording those observed in healthy subjects. Monitor patients taking medicines adjusted andElevations metabolised via CYP450 3A4, seen 1A2 or 2C9 when starting or stopping RoActemra, as doses to may need iftoelevated, be increased to maintain therapeutic The guidelineseffect for hyperlipidaemia. for central demyelination RoActemra unknown; physicians for symptoms of new disease. Immunomodulatory may increase risk in RA patients. Douse notingive live of tocilizumab onPotential CYP450 enzyme activity may persistwith for several weekscurrently after stopping therapy. Refer toshould SmPC be for vigilant further details on the effects ofonset RoActemra on cytochrome CYP450. medicines Fertility, Pregnancy and malignancy Lactation: No adequate data from pregnant and live attenuated vaccines with RoActemra as safety notabortion/embryo-foetal established – refer to death SmPCatfor further on immunisations. patients have CV risk factors managed as part of usual standard of care. Not for use with other women. Animal studyconcurrently showed an increased risk of spontaneous high dose.details RoActemra should not be RA used during should pregnancy unless clearly necessary. Women of childbearing potential should userecommended effective contraception during and biologicalup agents. Macrophage activation syndrome (MAS) is a serious life-threatening disorder that may develop in sJIA patients – RoActemra has not been studied in patients during an active MAS episode. Advise patients experiencing dizziness not to drive or to 3 months after treatment. No lactation data in humans. A decision on whether to continue/discontinue breastfeeding or RoActemra therapy should be made taking into account the relative benefits to the child and mother. Side Effects and Adverse Reactions: use machines until dizziness Product 26.55mg sodium per 1200mg.orDrug Interactions: RA patients, levels of simvastatin (CYP3A4) were decreased by 57% week and following a single dose of tocilizumab levels similar-to or slightly higher RA: ADRs occurringresolved. in patients with RAcontains receiving tocilizumab as monotherapy in combination withInMTX or other DMARDs: Very Common (≥ 1/10): upper respiratory tract one infections hypercholesterolaemia. Common (≥to 1/100 - <1/10) cellulitis, pneumonia, than those observed in healthyherpes subjects. Monitor patients taking medicines which are individually adjusted andheadache, metabolised via CYP450 3A4, 1A2 or 2C9 increased, when starting or stopping RoActemra, as doses may hypertension, need to be increased to maintain therapeutic effect. The oral herpes simplex, zoster, abdominal pain, mouth ulceration, gastritis, rash, pruritus, urticaria, dizziness, hepatic transaminases weight increased, total bilirubin increased, leucopenia, neutropenia, peripheral oedema, effect of tocilizumab on CYP450 enzyme activity may persist for severalsJIA: weeks after stopping therapy. Refer to for further details on the effects of RoActemra onofcytochrome Fertility, Pregnancy Lactation: No adequatereactions data from use in pregnant hypersensitivity reactions, conjunctivitis, cough and dyspnoea. In general, the ADRs were similar to SmPC those seen in RA patients. Infections – Serious infections varicella andCYP450. otitis media reported. Infusionand reactions – Hypersensitivity requiring treatment women. Animal study showed an increased of spontaneous abortion/embryo-foetal death high dose. RoActemra not be pregnancy clearly necessary. Women of childbearing potential should use effective discontinuation occurred in < 1% ofrisk patients. Other events occurring within 24 hours ofat infusion in 16% of patientsshould included, butused wereduring not limited to rash,unless urticaria (considered serious), diarrhoea, epigastric discomfort, arthralgia and contraception during and up to 3 months after treatment. No lactation data in humans. A decision on whether to continue/discontinue breastfeeding or RoActemra therapy should be made taking into account the relative benefits to the child and mother. Side Effects and Adverse Reactions: headache. IgG – decreased levels during therapy. Other – decreases in neutrophil and platelet counts, hepatic transaminase elevations, lipid parameter increases and anti-tocilizumab antibodies observed. Refer to SmPC for a complete RA: ADRslisting occurring in patients with as monotherapy or in combination with MTX oronly. other DMARDs: Very (≥ Authorisation 1/10): upper respiratory and hypercholesterolaemia. Common (≥ 1/100 - <1/10) - cellulitis, pneumonia, of adverse events forRA RA receiving and sJIA. tocilizumab Legal Category: Limited to sale and supply on prescription Presentations andCommon Marketing Numbers: tract 80mginfections of tocilizumab in 4ml (20mg/ml) pack of 1 (EU/1/08/492/001); oral herpes simplex, herpes zoster, abdominal pain, mouth ulceration, gastritis,400mg rash, pruritus, urticaria, headache, dizziness, hepatic transaminases increased, increased, total Roche bilirubin increased,Limited, hypertension, leucopenia, peripheral oedema, 200mg of tocilizumab in 10ml (20mg/ml) pack of 1 (EU/1/08/492/003); of tocilizumab in 20ml (20mg/ml) pack of 1 (EU/1/08/492/005). Marketingweight Authorisation Holder: Registration 6 Falcon Way, Shireneutropenia, Park, hypersensitivity conjunctivitis, cough Kingdom. and dyspnoea. sJIA: Inisgeneral, the ADRs were similar those seenisinavailable RA patients. Infections – Serious infections of 3004 varicella and otitis media reported. Infusion – Hypersensitivity reactions requiring treatment Welwynreactions, Garden City, AL7 1TW, United RoActemra a registered trade mark. Furtherto information from Roche Products (Ireland) Limited, Lake Drive, Citywest, Naas Road, Dublinreactions 24. Telephone: (01) 4690700. discontinuation occurred in <Date 1% of Other events2011. occurring withinCopyright 24 hours of infusion 16% Products of patients included, limitedReferences: to rash, urticaria (considered epigastric discomfort, and of Fax: (01) 4690791. of patients. Preparation: August p27/01/12. © 2012 by in Roche (Ireland) Ltd.but All were rights not reserved. 1. Nisar MK et al. serious), The role diarrhoea, of tocilizumab monotherapy in thearthralgia management arthritis: a review. Int.therapy. J. Clin. Other Rheumatol. (2012) 7(1): 9-19. 2. SmPC. RoACTEMRA (tocilizumab) Summaryelevations, of Productlipid Characteristics, August 2011. headache.rheumatoid IgG – decreased levels during – decreases in neutrophil and platelet counts, hepatic transaminase parameter increases and anti-tocilizumab antibodies observed. Refer to SmPC for a complete listing of adverse events for RA and sJIA. Legal Category: Limited to sale and supply on prescription only. Presentations and Marketing Authorisation Numbers: 80mg of tocilizumab in 4ml (20mg/ml) pack of 1 (EU/1/08/492/001); 200mg of tocilizumab in 10ml (20mg/ml) pack of 1 (EU/1/08/492/003); 400mg of tocilizumab in 20ml (20mg/ml) pack of 1 (EU/1/08/492/005). Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. RoActemra is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: August 2011. p27/01/12. Copyright © 2012 by Roche Products (Ireland) Ltd. All rights reserved. References: 1. Nisar MK et al. The role of tocilizumab monotherapy in the management of rheumatoid arthritis: a review. Int. J. Clin. Rheumatol. (2012) 7(1): 9-19. 2. SmPC. RoACTEMRA (tocilizumab) Summary of Product Characteristics, August 2011.

TreatingObesity.indd 44

13/09/2012 12:12:37

Treating Obesity Arthritis and the role of obesity

045

Arthritis and the Role of Obesity

Studies show that obesity is detrimental to the treatment of many forms of arthritis and can even aggrAvate symptoms. Words: Geraldine McCarthy, MD

Arthritis, of course, is a broad term for many different types of joint diseases. Rheumatoid arthritis has been less well-studied from an obesity standpoint than have other forms, such as osteoarthritis. However, obesity does seem to play a role – obese rheumatoid arthritis patients seem to have higher disease activity and worse quality of life then non-rheumatoid arthritis patients, though they don’t appear to have worse joint damage.

TreatingObesity.indd 45

s physicians, we always try to point out to our patients the link between obesity and arthritis in an attempt to encourage them to lose weight when necessary. After all, obesity has been show to be a risk factor for developing arthritis. Population-based studies have consistently shown a link between being overweight, or obese, and osteoarthritis. Overweight women have nearly four times the risk of osteoarthritis than non-overweight women. For men, the risk is five times greater. Studies have shown that for a woman of average height, every 11lb weight loss corresponds to a 50 per cent reduction in the role of developing osteoarthritis. Conversely, a comparable weight gain is associated with an increased risk of later development.

13/09/2012 12:12:49

Ideal for Osteoporosis Increases Bone Mineral Density1 Vitamin D3 together with calcium, helps to protect older adults from osteoporosis2 Suitable for Diabetics Handy Pocket Packs

Great taste... ...with a hint of lemon

Presentation: Greyish white, square, chewable tablets with lemon flavour. Each Idéos® tablet contains 1250 mg of calcium carbonate (i.e. 500 mg of elemental calcium) plus 10 µg of cholecalciferol (corresponding to 400 IU of Vitamin D3). Indications: Vitamin D3 and calcium deficiency correction in the elderly. Vitamin D3 and calcium supplement in association with certain therapy for osteoporosis. Dosage and administration: For adults only. Two tablets to be chewed daily. Contraindications: Hypersensitivity to one of the constituents. Hypercalcaemia, as a result of hyperparathyroidism (primary or secondary), hypercalciuria, calcium lithiasis, tissue calcifications (nephrocalcinosis),vitamin D overdose, Myeloma and bone metastases, renal insufficiency (creatinine clearance < 20 ml/min). Idéos® tablets are also contra-indicated in patients where prolonged immobilisation is accompanied by hypercalcaemia and/or hypercalciuria. In these cases, treatment should only be resumed when the patient becomes mobile. Precautions and warnings: Calculate the total vitamin D intake in case of treatment with another drug containing this vitamin. Plasma calcium and urinary calcium determinations is important in patient monitoring therefore plasma calcium and urinary levels should be monitored regularly. In the elderly, renal function must be monitored regularly. In patients with renal failure, dosage has to be adapted accordingly to the creatinine clearance. In case of long-term treatment, the urinary calcium excretion must be monitored and treatment must be reduced or suspended if urinary calcium excretion exceeds 7.5 to 9 mmol/24 hours (300 to 360mg/24 hours). Interactions: Idéos® may impair the intestinal absorption of oral tetracyclines, etidronate, fluoride or iron. At least 3 hours should intervene between the consumption of Idéos® and these agents. With digitalis glycosides: risk of cardiac arrhythmias. Clinical surveillance is required and possibly electrocardiographic and plasma calcium monitoring are recommended. With thiazides diuretics: risk of hypercalcaemia by decreasing urinary calcium excretion. Undesirable effects: Hypercalciuria in case of prolonged treatment at high doses, exceptionally hypercalcaemia. Hypophosphataemia. Pregnancy and Lactation: Not applicable. Effects on ability to Drive and Use Machines: None. Package Quantities: Pack size 60 tablets (4 tubes of 15 tablets) PA number: 1033/1/1 MAH: LABORATOIRE INNOTECH INTERNATIONAL 22 avenue Aristide Briand 94110 Arcueil – France Date of text revision: July 2009 References: 1. Grados et al., Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Joint Bone Spine. 70 (2003) 203-208. 2. Kilbane et al., Boosting defences with vitamin D. IMT. Available from pharmacies only.

For full prescribing information contact: Fannin Ltd., Fannin House, South County Business Park, Leopardstown, Dublin 18. Tel: 01 290 7000 Fax: 01 290 7111 medinfo@fannin.ie

TreatingObesity.indd 46

FN 2012/04/002

13/09/2012 12:12:52

Gout, in particular, is a condition that is becoming more and more common. It is characterised by high levels of serum uric acid, which ultimately result in the precipitation of monosodium urate crystals in the joints. These, in turn, can cause recurrent episodes of a severely painful form of arthritis. Increased amounts of fatty tissue, whether due to the individual being obese or merely overweight, are associated with higher serum uric acid levels, which result from increased production of uric acid and reduced removal of uric acid by the kidneys. Our understanding of the role of obesity is increasing all the time as a result of ongoing research discoveries. One of these discoveries has been the identification of a group of bioactive molecules called adipokines that seem to be secreted by fatty tissue. Historically, adipose tissue was considered to be merely an energy storage depot, but now we know that it behaves as an active endocrine or paracrine organ, secreting adipokines. Adipokines can contribute to inflammation in arthritis. There are, of course, more factors than obesity involved in the development of arthritis. In osteoarthritis, for example, there is genetic predisposition, and those who may have damaged joints – for instance, as a result of past sports injuries – also increase their risk.

gout is steadily increasing as well and, while obesity isn’t in itself a cause of rheumatoid arthritis, obese patients have more systemic inflammation and a reduced quality of life. When it comes to treatment, there really isn’t a magic potion that results in weight lost, so we assess patient’s BMI and advise all overweight and obese individuals to lose weight. We emphasise the link between weight loss and exercise, and improvement in joint pain. We try to steer them away from fad diets that may lead to massive amounts of weight loss in a short time but are not sustainable. We suggest an initial weight loss goal of 10 per cent and, if possible, refer them to a dietitian.

“obese rheumatoid arthritis patients seem to have higher disease activity and worse quality of life.” Nonetheless, as the prevalence of obesity increases, we are going to continue to see a corresponding increase in the rate of osteoarthritis. The prevalence of

TreatingObesity.indd 47

047

Treating Obesity Arthritis and the role of obesity

In terms of rheumatoid arthritis, we have excellent treatments now. When patients present with a new

diagnosis of rheumatoid arthritis, our aim is that ultimately the only reason they’re aware that they still have arthritis is that they’re taking medication. We don’t always achieve this goal, but that’s what we aim for. Unfortunately, with osteoarthritis – the most common form of arthritis – we have very little at present that can slow the progression of the disease. We can prescribe medications that can reduce the symptoms of pain and stiffness, but not the joint damage. In other words, we don’t have any drugs that can definitively change the course of osteoarthritis, and that’s why weight loss is particularly important in these patients. Geraldine McCarthy MD, FRCPI graduated in medicine from University College Dublin. She was appointed consultant in Rheumatology at the Mater Misericordiae University Hospital, Dublin in 1999, where she runs a busy clinical practice and has established a clinical research program. She has been appointed Clinical Professor of Medicine at Faculty of Medicine, UCD.

13/09/2012 12:13:01

FOR THE TREATMENT OF PsA * *HUMIRA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to disease-modifying anti-rheumatic drug therapy has been inadequate.1 Full prescribing information is available upon request from Abbott Laboratories Ireland Ltd., 4051 Kingswood Drive, Citywest Business Campus, Dublin 24, Ireland. Legal category POM. Marketing Authorisation Numbers: EU/1/03/256/001-005, EU/1/03/256/007-010. Marketing Authorisation Holder: Abbott Laboratories Ltd., Maidenhead, Berkshire SL6 4XE, UK. Reference: 1. For more information on HUMIRAâ&#x20AC;&#x2122;s licensed indications, please refer to HUMIRAâ&#x20AC;&#x2122;s Summary of Product Characteristics; available on www.medicines.ie. IREHUM120094a Date of Preparation: May 2012

HUMIRA_PsA_A4 ad.indd TreatingObesity.indd 48 1

30/08/201212:13:05 12:03 13/09/2012

2 12:03

Treating Obesity Irish cancer society | Message from the CEO

049

Reducing the Risk With the number of Irish cancer victims set to spike over the next two decades, preventing the illness is of increasing importance. Words: John McCormack, CEO, Irish Cancer Society

Tackling our obesity problem is one of the ways we can help prevent some cancers. The International Agency for Research on Cancer has classified evidence of a causal link between obesity and cancer as ‘sufficient’ for cancers of the colon, female breast, (post-menopausal) uterus, kidney and oesophagus. Recently, it has been reported in the US that up to 40 per cent of oesophageal cancers are caused by obesity. One study has estimated that, in general, 7 per cent of cancers in women, and 4 per cent in men, were due to obesity. The Growing Up in Ireland survey has found that 26 per cent of nine year olds

are overweight or obese. The majority of this group come from high risk populations and, therefore, they need a very targeted response. A projection of the future health and economic burden of obesity estimated that continuation of existing trends in obesity will lead to about 500,000 additional cases of cancer in the United States by 2030. This analysis also found that, if every adult reduced their BMI by 1 per cent – which would be equivalent to a weight loss of roughly 1kg for an adult of average weight – this would prevent the increase in the number of cancer cases and actually

ancer is a serious public health problem that needs a comprehensive Government response – not just in the areas of early detection and treatment, but, increasingly, in the area of cancer prevention. The number of people who will be diagnosed with cancer is rising. The National Cancer Registry of Ireland has predicted that the number of new cancer cases will increase to 38,000 per year by 2020 and to 64,000 by 2035. The Irish Cancer Society believes that the rate of cancer can be reduced by creating an environment that makes the healthy choice the easy choice. We have made tremendous progress in diagnosing and treating cancer and now we need to focus on preventing it. We need to shift our thinking and prioritise health promotion and disease prevention once and for all.

TreatingObesity.indd 49

The Irish Cancer Society’s CEO, John McCormack.

13/09/2012 12:13:13

050

Treating obesity Irish cancer society | Message from the CEO

result in the avoidance of about 100,000 new cases of cancer. The Irish Cancer Society has highlighted to a Seanad Sub-Committee that a Government response to the issue of lifestyle should not be treated in isolation, nor should its interventions be seen as silver bullets. We have stressed that a co-ordinated, multifaceted and inclusive approach should be pursued, with decision-makers across a range of fields taking responsibility and influencing lifestyle choices. The World Cancer Research Fund says that “policy-makers and decision-makers in government, civil society, industry and the media, and employers and other actors, share responsibility for taking action, as do people as consumers and citizens”.

We need to change the language we use to talk about health. We shouldn’t be talking solely about our health services, but about the health of our people. We need to acknowledge

In the same way that Government should not be perceived as being

solely responsible for changing the population’s lifestyle choice, Government itself should not assume that reducing the cancer rate or obesity levels in Ireland is the sole responsibility of the Department of Health. It spans environmental policy, education policy, social welfare policy, economic policy and justice policy. We need to move away from the belief that health is just the responsibility of one Government Department. For this reason, we have recommended that a Cabinet Sub-Committee be established that is responsible for overseeing the co-ordinated, integrated, multi-agency, multi-faceted approach to disease prevention, cancer and lifestyle factors.

TreatingObesity.indd 50

that, as a country, Ireland is very unhealthy. Almost one quarter of our people smoke, 300,000 children are obese and up to 60 per cent of us are overweight. These shocking statistics highlight a clear need for investment in improving our health as a nation. If we don’t make this investment now, it will be very difficult to meet the cost of diseases such as cancer, heart disease and diabetes which, in many cases, are caused by obesity and other lifestyle choices. Dietary factors have been estimated to account for up to 30 per cent of cancers in western countries, and are second only to smoking as a preventable contributor of cancer. Dietary patterns change alongside a population’s evolution, but the environmental changes that have taken place over the last 100 years – including diet and physical activity patterns – are likely to have affected the risk of chronic diseases including cancer. The Minister of Health, Dr. James Reilly, has spearheaded a major initiative aimed at improving Ireland’s general standard of health. This major policy review – titled Your Health is Your Wealth – will inform care programmes, protect health, promote healthier lifestyles and improve our environment. The Irish Cancer Society believes that the initiatives resulting from the new policy framework will help drive the cancer rate down and lead to an enriched public health policy. We need to match this with changes in educational, economic and social policy. In 2005, a Government report estimated that obesity costs the State up to €4 billion per year. Therefore, dealing with the obese nation is a highly desirable requirement, given

13/09/2012 12:14:30

N P

A s c 1 r D ju p p g s o a g c in p r d c D S d m D r

Made in Ireland

New 25% Price* Lower

Difene Caps 50mg 75mg

Abbreviated prescribing information for Difene. Presentations: Difene (diclofenac sodium) 25mg and 50mg capsules containing enteric coated pellets; 75mg capsules containing 25mg enteric coated pellets combined with 50mg sustained release pellets; 100mg capsules containing 25mg enteric coated pellets combined with 75mg sustained release pellets; Suppositories of 100mg; Ampoules of 75mg/3ml. Difene Spray Gel 4%; Difene Gel 1%. Indications: Capsules and suppositories: rheumatoid arthritis (including juvenile chronic arthritis for 25mg and 50mg only), osteoarthritis, ankylosing spondylitis, psoriatic arthropathy, low back pain and acute musculoskeletal disorders including periarthritis, tendinitis, tenosynovitis, bursitis, sprains, strains, dislocations and in acute gout. Post operative pain and inflammation in orthopaedic, dental and other minor surgery. 75mg and 100mg capsules only: Relief of pain in fractures; in the management of dysmenorrhoea and associated menorrhagia. Ampoule 75mg/3ml for i.m. injection: acute exacerbation of rheumatoid arthritis and osteoarthritis, in acute back pain, acute gout, post operative pain, acute traumatic musculoskeletal disorders, fractures and renal colic. IV Infusion: Post operative pain. Difene Spray Gel 4%: local relief of pain and inflammation following acute blunt trauma of small and medium-sized joints and periarticular structures. Difene Gel 1% also includes localized forms of soft tissue rheumatism. Dosage: Adults: usual daily dose is 100 - 150mg per day. Maximum daily dose is 150mg. In elderly, dosage should be kept as low as possible. 25mg and 50mg capsules only: Children over 6 years: usual total daily dose is 1 - 3mg/kg in divided doses. Difene 25mg and 50mg t.d.s; Difene 75mg Dual Release b.d.; Difene 100mg D.R. and Suppository - once daily; Ampoule: Adults: 1-2 i.m. injections daily for maximum of 2 days. IV by infusion diluted in a minimum of 300ml of normal saline over 30 minutes. A maximum of 2 doses may be given intravenously. Difene Spray Gel 4% 4-5 sprays TDS; Difene Gel 1% 2-4g qds. Contra-indications: History of GI bleeding or perforation related to previous NSAID therapy. Active or history of recurrent peptic ulcer /

TreatingObesity.indd 51

2010 2011 €4.36 €2.83 €17.90 €13.43 *MIMS April 2011

haemorrhage. Use in patients hypersensitive to aspirin, diclofenac or other non-steroidal anti-inflammatory agents or any of the excipients which precipitate attacks of asthma, urticaria or acute rhinitis. Severe heart failure. Last trimester of pregnancy. Precautions and warnings: Use lowest effective dose for shortest duration possible. Avoid concomitant NSAIDs including COX-2s. GI bleeding, ulceration and perforation may occur with or without warning symptoms or previous history of GI events. Consider combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) for at risk patients. Patients with history of peptic ulcer, G.I. bleeding, hepatic, renal or cardiac insufficiency or bleeding diathesis or intestinal inflammation. All patients, particularly the elderly, on long term NSAID treatment should be kept under regular surveillance with monitoring of renal, cardiac and hepatic function and of haematological parameters. Pregnancy. Caution in patients with history of hypertension and congestive heart failure. High dose and long-term use may be associated with small increased risk of arterial thrombotic events. Careful consideration before use in longterm patients with cardiovascular disease or risk factors. Discontinue at first sign of skin rash, mucosal lesion or other sign of hypersensitivity. May impair female fertility. Topical formulations should only be administered onto intact skin, not on open wounds or diseased areas. Avoid contact with mucous membranes, eyes or oral use. Avoid excessive exposure to sunlight to prevent photosensitivity. Precaution with large areas of skin i.e. 600sqcm or prolonged use to avoid systemic side-effects (see below). Concomitant use with oral NSAIDs. Interactions: Co-administration of digoxin, lithium, acetylsalicylic acid, anti-diabetic agents, cyclosporin, methotrexate, quinolone antimicrobials, cardiac glycosides, anti-hypertensives, aminglycosides and probenacid. Activity of some diuretics may be inhibited and potassium retaining property increased. Concurrent use of systemic corticosteroid, NSAIDs, anti-coagulants, SSRIs or anti-platelet agents may increase the risk of G.I. bleeding and of ulceration. Topical formulations only theoretical risk.

Side-effects: G.I. disturbances and bleeding, irritability, fluid retention, rash, dizziness, hepatitis, renal dysfunction, anaphylaxis and, rarely, blood dyscrasias, bronchospasm and erythema multiforme. Topical formulations local allergic skin reactions. Photosensitivity in isolated cases. Systemic absorption is very low but possibility of systemic side effects cannot be excluded. Full details available in the SmPC. Packs: Blister pack of 56: 25mg (PA 1241/12/1), 50mg (PA 1241/12/2), 75mg D.R (PA 1241/12/3). Blister pack of 28: 100mg D.R. (PA 1241/12/4). Blister pack of 10: 100mg suppositories (PA 1241/12/7). Pack of 10 ampoules (PA1241/12/6). Difene Spray Gel 4% 25g bottle (PA 1241/12/8). Difene Gel 1% 50g (PA1241/12/5). Legal Category: Prescription only medicine. Product Authorisation Holder: Astellas Pharma Co., Ltd, 25 The Courtyard, Kilcarbery Business Park, Clondalkin, Dublin 22. Full prescribing information available on request. Difene is a registered trademark. Astellas Pharma Co., Ltd. Tel: +353 1 467 1555. Reference 1: Data on File 305769, Astellas. Date of Preparation: February 2011. Difene/03/2011/132. Created by www.mindmap.ie

13/09/2012 12:14:32

...to help your patients with type 2 diabetes achieve:1 Mean reductions in HbA1c: up to 1.50% (16 mmol/mol)1 Mean reductions in weight: up to 3.7 kg1 Improvements in SBP* from baseline1 Improvements in beta-cell function1 *SBP = Systolic Blood Pressure

Abbreviated Prescribing Information Victoza® 6 mg/ml solution for injection in pre-filled pen (liraglutide) Please refer to the Summary of Product Characteristics for full information. Victoza® 2 x 3 ml pre-filled pens. Victoza® 3 x 3 ml pre-filled pens. 1 ml of solution contains 6 mg of liraglutide. Indication: Treatment of adults with type 2 diabetes mellitus in combination with metformin or a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of metformin or sulphonylurea monotherapy; or in combination with metformin and a sulphonylurea, or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy. Dosage: Victoza® is administered once daily by subcutaneous injection and can be administered at any time independent of meals however, it is preferable that Victoza® is injected around the same time of the day. Victoza® should not be administered intravenously or intramuscularly. Recommended starting dose is 0.6 mg daily. After at least one week, the dose should be increased to a maintenance dose of 1.2 mg. Based on clinical response, after at least one week the dose can be increased to 1.8 mg to further improve glycaemic control in some patients. Daily doses higher than 1.8 mg are not recommended. When used with existing metformin therapy or in combination with metformin and thiazolidinedione therapy, the current dose of metformin and thiazolidinedione can continue unchanged. When added to existing sulphonylurea therapy or in combination with metformin and sulphonylureas, a reduction in the dose of sulphonylurea may be necessary to reduce the risk of hypoglycaemia. Victoza® can be used in the elderly (>65 years old) without dose adjustment but therapeutic experience in patients ≥75 years of age is limited. No dose adjustment is required for patients with mild renal impairment (creatinine clearance 60-90 ml/min). Due to lack of therapeutic experience Victoza® is not to be recommended for use in patients with moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min), patients with end stage renal disease, patients with hepatic impairment and children below 18 years of age. Contraindications: Hypersensitivity to the active substance or any of the excipients. Warnings and Precautions for use: Victoza® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Victoza® is not a substitute for insulin. Addition of liraglutide in patients already treated with insulin has not been evaluated and is therefore not recommended.

Limited experience in patients with congestive heart failure New York Heart Association (NYHA) class I-II and no experience in patients with NYHA class III-IV. Due to limited experience Victoza® is not recommended for patients with inflammatory bowel disease and diabetic gastroparesis. Victoza® is associated with transient gastrointestinal adverse reactions, including nausea, vomiting and diarrhoea. GLP-1 analogues have been associated with pancreatitis; patients should be informed of symptoms of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis suspected, Victoza® and other suspect medicinal products should be discontinued. Thyroid adverse events, including increased blood calcitonin, goitre and thyroid neoplasm reported in clinical trials particularly in patients with pre-existing thyroid disease. Risk of hypoglycaemia in combination with sulphonylureas; lowered by dose reduction of sulphonylurea. Signs and symptoms of dehydration, including renal impairment and acute renal failure reported with Victoza®. Patients should be advised of potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion. No studies on the effects on the ability to drive and use machines performed. Patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines, in particular when Victoza® is used in combination with a sulphonylurea. Substances added to Victoza® may cause degradation; in the absence of compatibility studies Victoza® must not be mixed with other medicinal products. Fertility, pregnancy and lactation: Victoza® should not be used during pregnancy or during breast feeding. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Victoza® should be discontinued; use of insulin is recommended instead. Apart from a slight decrease in number of live implants, animal studies did not indicate direct harmful effects with respect to fertility. Undesirable effects: During clinical trials with Victoza® the most frequently observed adverse reactions which varied according to the combination used (sulphonylurea, metformin or a thiazolidinedione) were: Very common: nausea, diarrhoea, headache when used in combination with metformin. Hypoglycaemia, nausea and diarrhoea when used with metformin and a sulphonylurea. Nausea, diarrhoea and vomiting when used with metformin and a thiazolidinedione; Common: anorexia, appetite decreased, dizziness, vomiting, dyspepsia, gastritis and injection site reactions when used in combination with metformin. Nasopharyngitis, hypoglycaemia, anorexia, nausea, diarrhoea, vomiting, dyspepsia, constipation,

1. Pratley R et al. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract 2011;65(4):397-407 Victoza® and the Apis bull logo are registered trademarks of Novo Nordisk A/S. Date of preparation: January 2012. IR/LR/0112/0012

TreatingObesity.indd 52

abdominal discomfort, injection site reactions when used in combination with a sulphonylurea. Bronchitis, anorexia, headache, vomiting, dyspepsia, abdominal pain upper, constipation, toothache when used with metformin and a sulphonylurea. Nasopharyngitis, hypoglycaemia, anorexia, appetite decreased, headache, dyspepsia, constipation, flatulance, abdominal distension, gastroesophageal reflux disease, gastroenteritis viral, fatigue, pyrexia, injection site reactions when used with metformin and a thiazolidinedione. Gastrointestinal adverse reactions are more frequent at start of therapy but are usually transient. Very few hypoglycaemic episodes observed other than with sulphonylureas. Patients >70 years or with mild renal impairment (creatinine clearance 60-90 ml/min) may experience more gastrointestinal effects. Consistent with medicinal products containing proteins/peptides, patients may develop anti-liraglutide antibodies following treatment but this has not been associated with reduced efficacy of Victoza®. Few cases reported of angioedema (0.05%) and acute pancreatitis (<0.2%). Injection site reactions usually mild. Thyroid neoplasms, increased blood calcitonin and goitres are the most frequent reported thyroid adverse events – rates per 1000 subjects years of exposure were 6.8, 10.9 and 5.4 of liraglutide treated patients in comparison with 6.4, 10.7 and 2.1 of placebo treated and 2.4, 6.0 and 1.8 of total comparator treated. The Summary of Product Characteristics should be consulted for a full list of side effects. Overdose: In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. MA numbers: Victoza® 2 x 3ml pre-filled pens EU/1/09/529/002. Victoza® 3 x 3ml pre-filled pens EU/1/09/529/003. Legal Category: POM. For complete prescribing information please refer to The Summary of Product Characteristics which is available on www.medicines.ie or by email from info@novonordisk.ie or from Medical department, Novo Nordisk Limited, 3-4 Upper Pembroke Street, Dublin 2, Ireland; www.novonordisk.ie. Date created: Dec 2011. Victoza® is a trademark of Novo Nordisk A/S. Information about adverse event reporting is available at www.imb.ie. Adverse events should be reported to the Novo Nordisk Medical department: Tel: 1850 665 665. Further Information is available from: Novo Nordisk Limited 3/4 Upper Pembroke Street Dublin 2, Ireland Tel: 01 678 5989 Fax: 01 676 3259 Lo Call: 1850 665 665 www.novonordisk.ie

13/09/2012 12:14:34

Treating Obesity Irish cancer society | Message from the CEO

In Ireland, we already tax some items to influence consumer behaviour. Tobacco and alcohol are heavily levied, but the price elasticity for demand (estimated at about -0.5) means that even though consumption decreases, revenue does not. For economists, this is an optimal outcome but, for those working in the public health space – particularly when one considers that tobacco and alcohol taxes are not ring-fenced – one must seriously ask whether the Government’s finance policy has taken priority over its health objectives. If the price of these goods was increased twenty-fold they would be unaffordable and consumption would fall. Consequently, the cancer rate would be cut considerably. But that is not in the short-term interests of the Department of Finance, and we have a situation whereby moderate price increases at Budget time are tokenistic rather than actual efforts to cut consumption. The Irish Cancer Society believes that the industries that place a significant burden on the health of our nation

TreatingObesity.indd 53

should never be perceived as a valid revenue stream for Government. These industries place a massive societal and financial burden on Ireland in terms of both chronic and fatal illnesses, and any revenue raised from it needs to be ring-fenced and reinvested to encourage people to change their behaviour permanently. It is important to note that both tobacco and alcohol are different from food in a number of different ways and therefore the implications of a tax on food will vary quite considerably. Indeed, when considering this issue at its most basic level, whether and how fiscal measures would influence food consumption behaviour and health outcomes is energetically debated by policy-makers. Food is a necessity and, therefore, it differs from alcohol and tobacco, and taxing it needs to be carefully considered. Studies from the US, France and the UK have found that low-income populations spend a greater proportion of their incomes on food than do those on higher incomes and, therefore, the taxation model must be equitable. Sweden has looked at combining a tax and a subsidy, and considered this to be a progressive approach to the taxing of foods. The US looked at a vending machine to reduce the price of low fat snacks, and this reduced the intake of the higher fat snacks. However, when the price was reduced further, there was an increase in the number and frequency of snacks consumed throughout the day. There is a fine line to be considered with the introduction of a tax on food, but it has been successfully introduced in

other countries. Within Ireland, we need to consider a model – and design it and test it – using the data, to see what would work best within this population. This is a necessary step in tackling the obesity issue. The Irish Cancer Society believes that there is a need to restrict the marketing of food and to limit exposure to advertising, particularly for children. In addition, the Irish Cancer Society wants to maintain a commitment to research on obesity and fully implemented the earlier strategy. We are at a juncture in how we tackle the obesity problem in Ireland. The policy decisions we make today will impact on the futures of our children and their relationship with food. The Irish Cancer Society considers obesity to be a critical challenge in the fight to reduce the cancer rate in Ireland, and we highlight that it is a complex problem that spans cultural, societal and financial considerations. We need to begin by admitting that we are an unhealthy nation and then work, in a collaborative way, to develop effective solutions to this growing crisis. There are a range of approaches that could be adopted but decisions on what strategy should be followed need to be taken now, and not when it’s too late.

that the number of people who are overweight is rising. Recent research by safefood found that only 40 per cent of people acknowledge that they are overweight. While there is a general awareness in Ireland of the dangers of obesity, many of those at risk felt the dangers pertained to others and not to themselves. When the Irish Cancer Society looked at the issue, we recommended that the Government consider a food tax. However, there are many complex issues around a food tax which need to be considered carefully first. These include the structure of the tax, at what point in the production line it should be levied, whether it would lead to behavioural change and whether it could actually improve health outcomes.

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Treating Obesity The Cancer Diet

THE

CANCER Diet With incidences of cancer increasing worldwide, more research funds are being channelled into tackling its causes. Words: Prof John Reynolds Geographic and socioeconomic differences in cancer trends and incidences indicate that environmental factors affect the development of cancer. Changes in cancer epidemiology over the last number of decades cannot be accounted for solely by the changing population demographics – such as increased life expectancy and increased population numbers – or by the fact that improved screening, detection and treatment methods have lead to increased numbers of people living with a cancer diagnosis. Since not enough time has elapsed in order for significant genetic changes to account for the increased cancer incidence, it has to be attributable to environmental factors. There has been an evolution in society from a hunter-gatherer structure to one which is peasantagricultural and increasingly urbanindustrialised. Doubtless, there have

TreatingObesity.indd 54

been a number of inter-related changes to body composition, physical activity, energy balance and diet, and it is these environmental changes which are thought to be the cause of the alteration in cancer epidemiology. In Ireland, the prevalence of obesity among adults has increased significantly since 1990, rising from 8 per cent to 26 per cent in men and from 13 per cent to 21 per cent in women.1 This worrying pattern shows no signs of abating as obesity rates are increasing among children and adolescents,2 and overweight children tend to become overweight adults.3 In countries where sedentary lifestyles and high-energy foods are abundant, it is easy to see how energy intake exceeds energy expended. It has been estimated that ingestion of 5 per cent more energy than is expended may result in an accumulation of 5kg adipose tissue in a single year.4 The effect that this passive overconsumption of energy and accumulation of adipose tissue has on the human body is calamitous. Epidemiological studies have demonstrated a robust link between obesity and cancer development at numerous sites – the oesophagus, pancreas, colorectum, breast (postmenopausal), endometrium

and kidney, in particular.5 The World Cancer Research Fund estimates that up to 28 per cent of gallbladder cancers, 35 per cent of pancreatic, 16 per cent of colorectal, 17 per cent of breast, 49 per cent of endometrial, 28 per cent of kidney and 35 per cent of oesophageal cancers are attributable to obesity.6 This association carries relative risk (RR) estimates of 1·1 to 1·6 per 5kg/ m2 incremental increase in BMI.5 Obesity also increases cancer-related mortality with studies reporting that obesity could account for 14 per cent of all deaths from cancer in men and 20 per cent in women.7 The causative link between obesity and cancer is further strengthened by research in animal models which demonstrates that restricted caloric intake decreases spontaneous tumour occurrence.7,8 Furthermore, emerging clinical research suggests that weight loss following bariatric surgery leads to a reduction in cancer incidence.9 Thus, the potential mechanisms by which obesity increases the incidences of certain malignancies and cancer deaths have become the focus of considerable research. In the study of obesity and its pathogenic effects on health, it has become evident that fat is more than an inert energy store, and its location in the body is of great significance. It has been observed that individuals

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Treating Obesity The Cancer Diet

with excessive amounts of fat around their abdomen (visceral fat) are at a higher health risk than individuals who carry fat around their hips and buttocks (subcutaneous fat). Visceral fat is more metabolically active than subcutaneous fat. It is infiltrated with immune cells and secretes hormones, growth factors and other chemical substances known as adipokines. This creates a stressed environment of chronic, systemic, lowgrade inflammation with a disordered metabolism. The clinical manifestation of this environment is atherogenic dyslipidaemia (raised TAG and reduced HDL cholesterol), elevated fasting plasma glucose/type 2 diabetes, and hypertension; collectively referred to as metabolic syndrome. The importance of adipose tissue location in terms of dysmetabolism risk is evident, as an increased ratio of visceral fat area to subcutaneous fat area has been shown to be strongly related to disorders of glucose and lipid metabolism in obese subjects.10 Furthermore, visceral obesity is more strongly associated with metabolic syndrome and cardiovascular disease than is BMI alone.11

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In the study of the associations between obesity and malignancy, oesophageal cancer represents an exemplar model. In Ireland, the incidence of oesophageal adenocarcinoma increased 150 per cent between 1994 and 200912 in tandem with the rising prevalence of obesity. A study carried out by an Irish cohort reported that the risk of adenocarcinoma of the lower oesophagus was 11.3 times higher (95 per cent, CI: 3.5 to 36.4) in individuals with a BMI greater than 30kg/m2 than it was in individuals with a BMI lower than 22kg/m2.13 Several other studies have also reported a strong association between obesity and oesophageal adenocarcinoma.14,15 The link between oesophageal cancer and obesity was initially believed to relate solely to the physical and mechanical implications of excess abdominal fat leading to increased acid reflux in the oesophagus, giving rise to the pre-cancerous lesion known as Barrett’s oesophagus. However, the observation that obesity is a risk factor for oesophageal adenocarcinoma independent of acid reflux suggests that

055

other mechanisms are at play. A study by Ryan et al., (2008) reported that the prevalence of metabolic syndrome in Barrett’s oesophagus patients far exceeded population norms, with metabolic syndrome present in 46 per cent of patients and excess visceral fat present in 78 per cent. The syndrome was also significantly associated with the degree of Barrett’s oesophagus present. Furthermore, long-segment Barrett’s oesophagus was also associated with systemic inflammation, with significantly higher circulating levels of inflammatory interleukin-6 observed in patients.16 Similarly, in studies of pancreatic and colorectal cancer, a high prevalence of metabolic syndrome, visceral obesity and systemic inflammation has been identified.17-19 The exact mechanism by which this triad of inflammation, dysmetabolism and altered hormone profile increases cancer risk is still being elucidated. The hypothesis is that as visceral adipose tissue expands it becomes infiltrated with immune cells such as macrophages and T-cells. Adipocytes and these immune cells produce adipokines, including leptin, interleukins and TNF-α. These adipokines recruit more immune cells into the adipose tissue, resulting in the establishment of a vicious cycle of inflammation. The secretion of these pro-inflammatory adipokines into the circulatory system, in conjunction with increased non-esterified fatty acids being released from adipose tissue, leads to peripheral insulin resistance. This results in hyperinsulinaemia and increased circulating levels of the growth factor IGF-1. The net result of this medley of dysmetabolism, excessive growth factors and disordered immune system function is an environment that is permissive for tumour growth.10

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Treating Obesity The Cancer Diet

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In addition to obesity arising from excessive energy intake and inadequate physical activity, the quality of our diet is also deteriorating and may be influencing cancer risk. The World Cancer Research Fund, in its report on diet and cancer, described a number of dietary compounds that have demonstrated anti-cancer properties. They recommend an energy-balanced diet which includes fresh foods, fruits rich in polyphenol and anti-oxidant compounds, cruciferous vegetables, and oily fish.6 Foods such as these are typically found in a Mediterranean-style diet, the health benefits of which have been proclaimed for many years. Unfortunately, the Irish diet has fallen foul to the global changes in the food system, which is producing more processed, affordable, and effectively-marketed food than ever before. Over the last 50 years, our diet has changed remarkably, with increasing consumption of highly refined sugar (corn syrup, fructose), bleached flour and hydrogenated vegetable oils, and an increased reliance on convenience foods. Currently, the population is falling below the recommended 400g per day of fruit and vegetable intake, one in two adults do not consume any fish at all and 63 per cent of the population exceed the generally recommended upper limit of 35 per cent food energy from fat.1

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The rising prevalence of obesity in Ireland is multifactorial and it is now necessary that it be tackled by a number of public health and social interventions. What is unequivocal is the detrimental effect obesity has on the body, manifesting in cardiovascular disease, diabetes and cancer. If the obesity epidemic continues on its current path, we are facing an exponential increase in obesity related cancer in Ireland in the coming decades. Professor John Reynolds is the academic head of the Trinity Centre’s department of clinical surgery at St. James’s Hospital. He is the regional director for cancer services in south-west Dublin and is scientific director of the Cancer Clinical Trials Consortium. 1. Irish Universities Nutrition Alliance, National Adult Nutrition Survery. 2011. 2. National Longitudinal Study of Children, Growing up in Ireland, overweight and obesity amongst 9-year-olds, Report 2. 2011. 3. Serdula, M.K., et al, Do Obese Children Become Obese Adults? A Review of the Literature. Preventive Medicine, 1993. 22(2): pp 167-177. 4. Klein, S., T. Wadden, and H.J. Sugerman, AGA technical review on obesity. Gastroenterology, 2002. 123(3): pp 882-932. 5. Renehan, A.G., et al, Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 371(9612): pp 569-578.

6. World Cancer Research Fund, American Institute for Cancer Research, Food, Nutrition, Physical Activity and the Prevention of Cancer: Global Perspective. 2007. 7. Calle, E.E., et al, Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults. New England Journal of Medicine, 2003. 348(17): pp 1625-1638. 8. Dirx, M.J.M., et al, Energy restriction and the risk of spontaneous mammary tumors in mice: A meta-analysis. International Journal of Cancer, 2003. 106(5): pp 766770. 9. Sjostrom, L., et al, Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. The Lancet Oncology, 2009. 10(7): pp 653-662. 10. Doyle, S.L., et al, Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proceedings of the Nutrition Society. 71(01): pp 181-189. 11. Nedungadi, T.P. and D.J. Clegg, Sexual dimorphism in body fat distribution and risk for cardiovascular diseases. J Cardiovasc Transl Res, 2009. 2(3): pp 321-327. 12. National Cancer Registry of Ireland. 13. R yan, A.M., et al, Adenocarcinoma of the oesophagus and gastric cardia: male preponderance in association with obesity. Eur J Cancer, 2006. 42(8): pp 1151-1158. 14. Renehan, A.G., et al, Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet, 2008. 371(9612): pp 569-578. 15. K ubo, A. and D.A. Corley, Body Mass Index and Adenocarcinomas of the Esophagus or Gastric Cardia: A Systematic Review and Meta-analysis. Cancer Epidemiology Biomarkers & Prevention, 2006. 15(5): p. 872-878. 16. Ryan, A.M., et al, Barrett Esophagus: Prevalence of Central Adiposity, Metabolic Syndrome, and a Proinflammatory State. Annals of Surgery, 2008. 247(6): pp 909-915. 17. Russo, A., M. Autelitano, and L. Bisanti, Metabolic syndrome and cancer risk. European Journal of Cancer, 2008. 44(2): pp 293-297. 18. K ang, H.W., et al, Visceral Obesity and Insulin Resistance as Risk Factors for Colorectal Adenoma: A Cross-Sectional, Case-Control Study. Am J Gastroenterol, 2009. 105(1): pp 178-187. 19. Siegel, E.M., et al, The effects of obesity and obesity-related conditions on colorectal cancer prognosis. Cancer Control. 17(1): pp 52-57.

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The Plant Stanol Ester in Benecol® foods has been proven to lower cholesterol by 7-10%. Over 40 independent clinical trials have been conducted. The European Commission has also authorised the cholesterol lowering benefits of Plant Stanol Ester following a review by the EFSA.

SPECIALIST IN CHOLESTEROL LOWERING FOODS

High cholesterol is a risk factor in the development of coronary heart disease. As heart disease has multiple risk factors your patients may need to change more than one to lower overall risk. The plant stanols in Benecol® 1.5 to 2.4g daily - lower cholesterol as part of a healthy balanced diet and lifestyle within 2 to 3 weeks. May not be nutritionally suitable for pregnant or breastfeeding women and children under 5 years old. Do not consume more than 3g of plant stanols per day. People taking cholesterol lowering medication should consult their GP.

Information for Health Care Professionals

TreatingObesityCover.indd 1 3 Benecol_A4_APR12.indd

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NEW

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BYDUREON the first and only therapy to provide continuous glycaemic control with a once weekly injection1

• Mean HbA1C reduction between 1.3% and 1.9% • Sustained HbA1C reduction of 1.5% at 2 years • Sustained weight loss of 2.4kg at 2 years

1,2

BYDUREON is indicated for treatment of type 2 diabetes mellitus in combination with metformin, sulphonylurea, thiazolidinedione, or combinations of metformin and sulphonylurea or metformin and thiazolidinedione, in adults who have not achieved adequate glycaemic control on maximally tolerated doses of these oral therapies BYDUREON® (EXENATIDE) REPUBLIC OF IRELAND ABBREVIATED PRESCRIBING INFORMATION Presentation: Exenatide 2mg powder and solvent for prolonged-release suspension for injection. Each single-dose kit contains one vial of 2mg exenatide and one pre-filled syringe of 0.65ml solvent. Uses: Bydureon is indicated for treatment of Type 2 diabetes mellitus in combination with metformin, sulphonylureas, thiazolidinediones, or combinations of metformin and a sulphonylurea or metformin and a thiazolidinedione, in adults who have not achieved adequate glycaemic control on maximally tolerated doses of these oral therapies. Dosage and Administration: The recommended dose is 2mg once weekly, on the same day each week. Each dose should be administered in the abdomen, thigh, or the back of the upper arm as a subcutaneous injection immediately after suspension of the powder in the solvent. Instructions on the suspension and administration of Bydureon can be found in the ‘Instructions for the User’ provided in the carton and must be followed carefully by the patient. Appropriate training is recommended for non-healthcare professionals administering the product. Patients switching from exenatide twice daily (Byetta) to Bydureon may experience transient elevations in blood glucose concentrations, which generally improve within the first two weeks after initiation of therapy. When Bydureon is added to existing metformin and/or thiazolidinedione therapy, the current dose of metformin and/or thiazolidinedione can be continued. When Bydureon is added to sulphonylurea therapy, a reduction in the dose of sulphonylurea should be considered to reduce the risk of hypoglycaemia. Blood glucose selfmonitoring may be necessary to adjust the dose of sulphonylurea. If a different antidiabetic treatment is started after the discontinuation of Bydureon, consideration should be given to the prolonged release of Bydureon. Elderly: No dose adjustment is required based on age. Consideration should be given to the patient’s renal function. Renal or hepatic impairment: No dosage adjustment is necessary in patients with mild renal impairment (creatinine clearance 50-80ml/min) or hepatic impairment. Not recommended in patients with moderate renal impairment (creatinine clearance 30-50ml/min), severe renal impairment (creatinine clearance <30ml/min), or end-stage renal disease. Paediatric population: The safety and efficacy in children and adolescents aged under 18 years have not yet been established. No data are available. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Special Precautions: Should not be used in

patients with Type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Must not be administered by intravenous or intramuscular injection. Not recommended for use in patients with moderate or severe renal impairment or end-stage renal disease. There have been rare, spontaneously reported events of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring haemodialysis. Some of these occurred in patients experiencing events that may affect hydration and/or receiving medicinal products known to affect renal function/hydration status, including angiotensin converting enzymes inhibitors, angiotensin-II antagonists, non-steroidal anti-inflammatory medicinal products, and diuretics. Not recommended in patients with severe gastro-intestinal disease. There have been rare, spontaneously reported events of acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed with supportive treatment, but very rare cases of necrotizing or haemorrhagic pancreatitis and/or death have been reported. If pancreatitis is suspected, Bydureon and other potentially suspect medicinal products should be discontinued. Treatment with Bydureon should not be resumed after pancreatitis has been diagnosed. The concurrent use of Bydureon with insulin, D-phenylalanine derivatives (meglitinides), alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors, or other GLP-1 receptor agonists has not been studied. The concurrent use of Bydureon and exenatide twice daily (Byetta) has not been studied and is not recommended. The risk of hypoglycaemia was increased when Bydureon was used in combination with a sulphonylurea in clinical trials. Furthermore, patients on a sulphonylurea combination, with mild renal impairment, had an increased incidence of hypoglycaemia compared to patients with normal renal function. To reduce the risk of hypoglycaemia associated with the use of a sulphonylurea, reduction in the dose of sulphonylurea should be considered. Rapid weight loss (>1.5 kg per week) has been reported in patients treated with exenatide. Weight loss of this rate may have harmful consequences. There have been some reported cases of increased INR, sometimes associated with bleeding, with concomitant use of warfarin and exenatide. After discontinuation, the effect of Bydureon may continue as plasma levels of exenatide decline over 10 weeks. Choice of other medicinal products and dose selection should be considered accordingly until exenatide levels decline. Interactions: The following interaction studies

were conducted using 10 micrograms exenatide twice daily, but not exenatide once weekly: HMG CoA reductase inhibitors: Lovastatin AUC and Cmax were decreased and Tmax was delayed when exenatide (10μg BD) was administered concomitantly with a single dose of lovastatin (40mg). Concomitant use of exenatide twice daily and HMG CoA reductase inhibitors was not associated with consistent changes in lipid profiles. Lipid profiles should be monitored as appropriate. Warfarin: Tmax was delayed when warfarin was administered 35 min after exenatide twice daily. No clinically relevant effects on Cmax or AUC were observed. Increased INR has been reported during concomitant use of warfarin and exenatide twice daily. INR should be monitored during initiation of Bydureon therapy in patients on warfarin and/or cumarol derivatives. Digoxin and lisinopril: A delay in Tmax was observed in interaction studies between digoxin or lisinopril and exenatide twice daily. No clinically relevant effects on Cmax or AUC were observed. Fertility, Pregnancy, and Lactation: Women of childbearing potential should use contraception during treatment with Bydureon. Bydureon should be discontinued at least 3 months before a planned pregnancy. Bydureon should not be used during pregnancy and the use of insulin is recommended. Bydureon should not be used during breast-feeding. Driving, etc: No studies on the effects on the ability to drive and use machines have been performed. When Bydureon is used in combination with a sulphonylurea, avoid hypoglycaemia while driving and using machines. Undesirable Effects: Adverse Reactions Reported From Clinical Studies.Very common: Hypoglycaemia (with a sulphonylurea), constipation, diarrhoea, nausea, vomiting, injection site pruritus, injection site nodules. Common: Decreased appetite, dizziness, headache, abdominal distention, abdominal pain, dyspepsia, eructation, flatulence, gastrooesophageal reflux, fatigue, injection site erythema, injection site rash, somnolence. Rapid weight loss has been reported with Bydureon. Patients may develop anti-exenatide antibodies following treatment with Bydureon. These patients tend to have more injection site reactions (eg, skin redness, itching). Acute pancreatitis and acute renal failure have been reported rarely and anaphylactic reaction has been reported very rarely in spontaneous post-marketing reports with exenatide twice daily. For full details of these and other side-effects, please see the Summary of Product Characteristics, which is available at http://www.medicines.ie/. Legal Category: POM. Marketing Authorisation Number and Holder: EU/1/11/696/001. Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands. Date of Preparation or Last Review June 2011. Full Prescribing Information is Available From: Eli Lilly and Company Limited, Lilly House, Priestley Road, Basingstoke, Hampshire, RG24 9NL. Telephone: Basingstoke (01256) 315 000. E-mail: ukmedinfo@lilly.com or Eli Lilly and Company (Ireland) Limited, Hyde House, 65 Adelaide Road, Dublin 2, Republic of Ireland, Telephone: Dublin (01) 661 4377. E-mail: ukmedinfo@ lilly.com. BYDUREON® (exenatide) is a registered trademark of Amylin Pharmaceuticals, Inc. References: 1. BYDUREON summary of product characteristics. 2. Duration 6 press release. Available at: https://investor.lilly.com/releasedetail2. cfm?ReleaseID=554248 3. Taylor et al. BMC Endocrine Disorders 2011, 11:9, http://www.biomedcentral. com/1472-6823/11/9

*Rapid weight loss at a rate of > 1.5kg per week has been reported in patients treated with exenatide. Weight loss of this rate may have harmful consequences. *BYDUREON is not indicated for the management of obesity, and weight change was a secondary endpoint in clinical trials.

IEBDR00036 ©2011 AMYLIN PHARMACEUTICALS, INC. AND LILLY, LLC. September 2011 ALL RIGHTS RESERVED. BYDUREON is a registered trade mark and BYDUREON By Your Side is a trade mark of Amylin Pharmaceuticals, Inc. Further information is available in the SPC

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