APHS Pharmacy Circuit Newsletter June 2014

APHS PHARMACY

June 2014

RESEARCHAT

circuit

In 2013, APHS Pharmacies across Australia conducted a number of research projects to advance Pharmacy Practice in hospital and oncology settings. Of these, eight projects were submitted and accepted for presentation at the annual Society of Hospital Pharmacists (SHPA) conference, an outstanding result in recognition of the quality of each submission. Two of these won conference awards, recognising their value as innovative, high-standard pharmacy practices. These projects aren’t often shared with our hospital partners, last month we included four of the eight abstracts; here are the remaining four. We hope this gives you some understanding of APHS’ behindthe-scenes innovations. To view all posters presented at SHPA go to: http://www.aphs.com.au/index.php/news/2014/02/aphs-research-in-2013/

clinical initiatives, research and current updates in treatment A close look at Dry Eye Syndrome

AN AUDIT OF VITAMIN D DEFICIENCY IN HOSPITALISED ELDERLY PATIENTS AIM: To determine the number of patients admitted to an elderly care medical/rehabilitation ward with blood serum levels indicating a deficiency in Vitamin D (<74 nanograms/L). BACKGROUND: Private regional hospital pharmacies face the challenges of no direct government funding and limited human resources in providing clinical ward pharmacist services, while adhering to SHPA guidelines. METHOD: All patients admitted to the ward from 1 September to 31 December 2012 were included in the audit. Patients had blood levels of vitamin D, calcium and U&Es taken on admission. Results were reviewed and patients categorised as having adequate levels (>74 nanograms/L), mild deficiency (50-73 nanograms/L), moderate deficiency (25-49 nanograms/L) or severe deficiency (<24 nanograms/L) and a recommendation for dosing of supplementation was made by the pharmacist where required. Patients with high calcium levels did not have vitamin D supplementation suggested and those with severe renal impairment were considered for calcitriol treatment if warranted. RESULT: A total of 122 patients were reviewed for the audit. Adequate levels were found in 59 patients (48%), mild deficiency was found in 29 patients (24%) and moderate deficiency found in 33 patients (27%). One patient (<1%) was found to be severely deficient. Of the patients reviewed, 55 (45%) were already prescribed some form of vitamin D supplementation. Of patients already on vitamin D supplements, 13 (23%) were found to have inadequate blood levels. Of patients not prescribed supplementation before admission 15 (22%) had adequate blood levels and 52 (78%) had levels indicating a deficiency, one patient (1.5%) with a severe deficiency and 33 (50%) moderate deficiency. CONCLUSION: Vitamin D deficiency correlates with falls risk in the elderly, as low levels of vitamin D are associated with impaired muscle function and weakness. This audit reveals inadequate levels in 52% of patients admitted to this ward, and subtherapeutic doses prescribed for 23% of patients on existing supplementation therapy. Suggestions include routine screening of vitamin D levels in elderly patients admitted to hospital, and certainly in those assessed to have an increased falls risk. Tanya Hutchinson APHS Pharmacy Hollywood

GET SMART WITH IMPREST SCANNING AIM: To evaluate time critical elements in scanning ward imprests and determine which elements influence efficiencies. METHOD: Imprest cupboards are scanned twice weekly and an order generated. Imprest sizes range from 11 to 557 items. Pharmacy technicians recorded the time taken to scan and prepare the order. Technicians timed wards they were familiar and unfamiliar with. To establish a “degree of difficulty” for each imprest, an “imprest naïve” pharmacist was given a list of six drugs to locate and the time taken to find these items was recorded. The effect of operator experience was analysed with different technicians having used the system for between 4 and 18 months. RESULTS: The average time to scan each imprest was 19.4 minutes (range 1-70). The average speed was 17 items per minute (range 1.57 – 78). The degree of difficulty in the imprest took an average of 85 seconds (range 18-300) and this was a significant factor in scanning time. There was no difference in time taken between staff who had been scanning for 18 months versus four months. There was limited time difference between technicians scanning an imprest that they were familiar with versus a new one. The number of items didn’t make a significant difference to the time taken. The layout of an imprest cupboard, use of sloping shelving and tall man labeling can save at least half an hour of technician time per ward. CONCLUSION: Sites reviewed are undergoing redevelopment in the next two years, and this data indicates that attention to detail in the physical layout of imprests can save technician time. In addition, the time taken for an imprest naïve person to find six items in each imprest could be extrapolated to nursing time spent finding medication. “Getting smart” with our imprest cupboards will be time saving for hospitals. Rachel Taylor, Sarah Holster, Judy Dodds, Sandra Studman, Amber Dixon, Melissa Brennan APHS Pharmacy Port Macquarie APHS Pharmacy Kempsey

IMPLEMENTATION OF THE MEDSCHECK PROGRAM IN A HOSPITAL AIM: To evaluate the application of the MedsCheck program in a private hospital setting. BACKGROUND: There is widespread recognition of the benefit of clinical pharmacy services in hospitals, however traditional funding models have limited implementation of these services in private hospitals. The 5th Community Pharmacy Agreement funds Section 90 approved pharmacies to deliver MedsCheck programs aiming to identify medication problems and improve the effective use of medicines by consumers. In this study, the implementation of the MedsCheck program as a component of a clinical pharmacy service within a private hospital pharmacy was evaluated. METHODS: Patients identified as suitable for a Medscheck consultation included those on multiple medications, with multiple co-morbidities, or numerous changes to their current medication regime. At the end of each consultation, an individualised report, medication list and recommendations was distributed to the patient and their physician. Structured and semi-structured interviews with pharmacists, a survey of patients receiving services and a review of the results were performed to obtain data for the analysis. RESULTS: During the program (conducted 7–31 March 2013), 121 MedsChecks were completed by eight registered pharmacists. The median age of MedsCheck patients was 70 to 74 years. Comparative data from the equivalent period in 2012 indicated an increase in the number of patients discharged with a full medication profile during the study. Of the 121 services, 116 (95.86%) were claimed through Medicare. An average time of 72 minutes was spent per consultation due to considerable time finalising the service. The accessibility of consultant physicians allowed medication issues to be usually addressed and corrected prior to the patient’s discharge. CONCLUSION: Integration of the MedsCheck service within current pharmacy workflow was a viable option to improve clinical pharmacy services and increase productivity within the private hospital setting, therefore enhancing continuity of care into the community. Sarah Coleman, Alainah Oats, Noreen Ebrahim APHS Pharmacy Northside, Holy Spirit Northside Private Hospital

THE TRANSCRIBING ADMISSION PHARMACIST A MUCH NEEDED SERVICE IN ELECTIVE SURGERY PATIENTS BACKGROUND: An audit of inpatient medication charts identified that the most common error on medication charts was omission of patient’s current medications. The cause of these errors is multifactorial and in an effort to reduce errors, an admissions pharmacist service was implemented. This involves the pharmacist conducting a pre-operative medication assessment in addition to transcribing patients’ regular medication on the medication chart. AIM: To describe and evaluate the role of an admission pharmacist service on elective surgical patients. METHOD: Approval from the hospital Drugs and Therapeutics Committee was granted for implementation of an admissions pharmacy service. Review of the literature and research into how the service operated in other facilities was conducted. A retrospective audit assessing the accuracy of medication charts was conducted and a staff survey was undertaken. RESULTS: The service entails the pharmacist completing a medication history and transcribing medication charts as the patient is admitted to hospital for elective surgery. The chart audit showed the charts completed by the pharmacist were 85% accurate compared to 16% for doctors. A positive impact of the role is the presence and availability of the pharmacist in the admission unit. This enables the pharmacist to liaise directly with nursing and medical staff, provide drug information and to resolve additional medication issues promptly. Pharmacists completed NPS National Inpatient Medication Chart (NIMC) training modules. The challenges of the role include financial, staffing, physical space, acceptance by medical and allied health staff and training.

Eve Finn, APHS Pharmacy Lismore Dry Eye Syndrome (DES), also known as keratoconjunctivitis sicca, keratitis sicca or xerophthalmia is a common chronic condition affecting approximately one million Australians ≥ 50 years.1 DES is a disease of the tears and ocular surface that results in discomfort, visual disturbance, tear film instability and potential damage to the ocular surface.2 Pathophysiology Tear film dysfunction resulting in tear deficiency or excessive tear evaporation causes dry eye. DES can be classified according to the severity (refer to Table 1), cause and pathophysiology. Failure of lacrimal tear secretion may be due to Sjögren’s syndrome (a chronic auto-immune inflammatory condition affecting exocrine glands) or a number of other conditions (non- Sjögren’s), the most common being age-related aqueous deficient dry eye.2 Other secondary causes include rheumatoid arthritis, contact lenses, surgery, Meibomian gland dysfunction or adverse drug effects. Evaporative dry eye is excessive evaporation of water in the presence of normal lacrimal function, caused by intrinsic disease affecting the lid or extrinsic ocular surface disease.2 The causative mechanisms of DES are tear film instability and tear hyperosmolarity.

To view all posters presented at SHPA, go to: http://www.aphs.com.au/index.php/ews/2014/02/aphs-research-in-2013/

The presence of preservative is an important consideration: Preservatives can damage and irritate the ocular surface, benzalkonium chloride is the most commonly used preservative and is also the most irritant.3 Patients with reduced tear film are less able to dilute and remove the preservative, and therefore more susceptible to a preservative’s adverse effects.3 Preservative-free ocular lubricants, although often harder to administer, are preferred in DES, particularly for patients with severe DES or punctal occlusions.3 Another option for symptom management is is lecithin spray (Tears Again®), which is applied to closed eyes and may control excess tear evaporation by stabilising the lipid layer of the tear film5. cont >

The anatomy of dry eye Lacrimal Sac

Lacrimal Gland

Meibomian Glands

The tear film has three main components: lipid, aqueous and mucin. Outer (Lipid) Layer The lipid layer’s most important function is to prevent the evaporation of tears. The Meibomian Glands manufacture the lipid layer.

Goblet Cells

CONCLUSION: The role of the transcribing pharmacist on admission for elective surgery patients has been successfully implemented. The service has been shown to be effective and that medication errors such as omissions are greatly reduced. Rebecca Sbeghen, Quyen Pham, John Jackson APHS Pharmacy, Brisbane Private Hospital

Treatment options Ocular lubricants are recommended for symptom relief and are available in drops, gels and ointments differing in viscosity, osmolarity, electrolytes and presence of preservative. There is no evidence that any lubricant is superior to another.3,4 Hypo-osmotic carmellose-based tear preparations such as TheraTears and Optive™ have been developed to protect against potential cellular damage caused by hyperosmolar tears which occur in DES.5 Ocular lubricants with electrolyte composition similar to human tears, including TheraTears and BION Tears, may be beneficial in maintaining the mucin layer of tear film and treating ocular surface damage.5

Punctum Nasolacrimal Duct Inner Mucin

Middle Aqueous

Occular Surface

Figure 1 – Physiology of the Tear Film3

Outer Lipid

Mucin concentrations Goblet Cells

Middle (Aqueous) Layer The largest portion of the tear film is made of aqueous with different types and concentrations of mucins (sticky proteins) throughout. Most tear film components are dissolved in this layer, including the oxygen supply to the cornea. The Lacrimal Gland creates most of the aqueous layer. Inner (Mucin) Layer The thickest concentrations of mucins is at the eye’s surface. This layer helps to spread tears and stabilise the tear film, which works to prolong the tear break-up time. Goblet cells produce the mucin.

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June 2014

Severity level

1

2

3

4

Discomfort, Severity and Frequency

Mild and/or episodic: occurs under environmental stress

Moderate episodic or chronic, stress or no stress

Severe frequent or constant without stress

Severe and/or disabling and constant

Visual Symptoms

None or episodic mild fatigue

Annoying and/or activitylimiting episodic

Annoying, chronic and/or constant, limiting activity

Constant and/or possibly disabling

Corneal Staining Severity, Location

None to mild

Variable

Marked central

Severe punctate erosions

Table 1 – Classification of DES based on severity (adapted from reference 2)

Evidence suggests ocular surface inflammation is present in all dry eye. Although some ocular lubricants have demonstrated both protection of the ocular surface epithelium and improvement in patient symptoms, they have not resolved the ocular surface inflammation.5 Anti-inflammatory agents such as topical corticosteroids (fluorometholone, dexamethasone, prednisolone or hydrocortisone) may be considered for patients with ocular surface inflammatory signs and irritation inadequately controlled by lubricants.5,7 However, ocular toxicity (e.g. ocular hypertension, glaucoma, retarded corneal healing) and risk of systemic adverse effects will limit the long term use of corticosteroids for DES.3,7,7 Cyclosporin is a treatment option in patients experiencing DES with an immunebased inflammatory component. An immunosuppressive agent with antiinflammatory activity, cyclosporin is thought to act by reducing inflammation of the ocular surface.1 Indications for ophthalmic cyclosporin include chronic dry eye, keratoconjunctivitis sicca, acute corneal graft rejection, conjunctival graft-versushost disease.3 Access to ophthalmic cyclosporin 0.05% (Restasis®) in Australia is via the Special Access Scheme (SAS), requiring annual approval by the Therapeutic Goods Administration (TGA) for each patient. Tetracycline antimicrobials (doxycycline and minocycline) also possess antiinflammatory and anti-angiogenic activity5 and have been used for other chronic inflammatory conditions such as rosacea, a skin condition commonly associated with blepharoconjunctivitis.5,8 Their proposed mechanism of action in DES is the reduction of lipolytic enzyme-producing bacterial flora and lipase production, thereby reducing Meibomian lipid breakdown products.5 Non-pharmacological approaches to DES Environmental management of DES includes cessation of causative medications (e.g. drugs with anticholinergic properties including sedating antihistamines and tricyclic antidepressants), use of a humidifier in dry climates, reduction of air conditioning exposure and periodic eye closure breaks when working at a computer or reading.5 Taking oral omega-6 essential fatty acid may improve ocular dryness and comfort in contact lens wearers with DES. Tear retention can be achieved by moisture chamber spectacles or contact lenses. Punctal occlusion to reduce tear drainage may be considered in symptomatic patients with a Schirmer’s test result <5mm at 5 minutes (a test to measure tear production rate).5 Conclusion DES is a common condition, with numerous treatment options depending on the cause and severity. Management includes reducing environmental causes and contributing factors. Ocular lubricants provide symptom relief but have not been proven to resolve ocular surface damage and inflammation. Anti-inflammatory agents may be required for moderate to severe DES.

References available on request.

Inhibiting PD-1 – Unleashing the Immune System’s Potential Ben Stevenson, ICON Pharmacy Services One of the greatest challenges in the treatment of cancer has been the struggle to focus the power of the immune system on the tumour. Whether it is with vaccines or other forms of immunotherapy, tumour cells have demonstrated an excellent ability to evade the immune response. Recently, approaches aimed at restoring and boosting the ability of killer T-cells to detect and attack cancer cells have been developed. The focus has been on targeting receptors that would normally dampen the immune response, otherwise known as immunecheckpoint targeting. Without getting too bogged down in the gritty details, PD-1, or Programmed Cell Death-1, is an immunoreceptor located on T-cells (and other cells) which, upon interacting with either of the main ligands located on the tumour cells, appropriately named PD-L1 and PD-L2, causes inhibition of T-cells and a dampened immune response.1 When T-cells interact with tumour cells in peripheral tissues, tumour cells can present an antigen to the T-cell receptor, resulting in a stimulatory signal to the T-cell (+) or tumour cells may also express PD-L1, which interacts with PD-1 on activated T-cells, and results in inhibition (–) of the anti-tumour T-cell response (see Figure 1). Targeting either PD-1 (with agents such as nivolumab) or PD-L1 (with agents such as BMS-936559) aims to increase the anti-tumour T-cell response at a tumour-specific level.2

T-cell

versus dacarbazine.2 In NSCLC, an early phase I study demonstrated a response rate of 17% in previously treated patients with advanced disease. Although the median progression free survival was only 2.3 months and the median overall survival was 9.9 months, the duration of response was 17 months showing that the benefit was clear for those who did respond to treatment.1 Importantly, across tumour groups, nivolumab has been well tolerated. There was no association between drug dose and toxicity and the most common toxicities were fatigue, rash, diarrhoea and pruritis. Pneumonitis is a significant, but rare toxicity, causing the death of 3 patients in a trial involving a range of solid tumours.2 Lambrolizumab is a humanised monoclonal antibody and has a similar function to nivolumab. Early studies have demonstrated a response rate of 52% in melanoma patients(4) and in NSCLC a response rate of 24% has been shown. As with nivolumab, lambrolizumab is also well tolerated with only 53% of patients experiencing drug-related adverse events in the phase I NSCLC trial, with fatigue, rash and pruritis being the most common (16% each).1 There are also anti PD-L1 agents in development, including MPDL3280A from Genentech/Roche but they are at earlier stages of development so will not be covered in this article.

infusions may have been under-used due to concerns about the risk of serious allergic reactions.6

Development efforts appear to be focused on PD-1 at this stage, but it is unknown whether it is better to target PD-1 or PD-L1. Head-to-head, randomised trials are needed to appropriately compare these two approaches but at this time, it appears targeting PD-L1 may be less toxic but also less effective than when targeting PD-1 (which effectively blocks signalling to both PD-L1 and PD-L2).3

Ferinject® is for IV administration only and can be given by infusion, injection, or during dialysis. Ferinject® dosing must be individualised and is based on the calculated iron deficit derived from the Ganzoni formula or the ‘Simplified Method’ (for patients over 35kg body weight). The maximum dose of Ferinject® that can be infused or injected as a single dose is 1000mg. However, this dose must not exceed 20mg/kg of body weight and must not be given more than once a week. To administer Ferinject® by IV infusion the dose should be diluted in normal saline. The dilution and administration times recommended by the manufacturer are as follows:7

Given the impressive single agent efficacy of these agents this far, the next logical question is whether combination therapy will demonstrate even further improvements. In the past, the EGFR inhibitor trials in combination with chemotherapy taught us valuable lessons regarding the notion that the combination of targeted therapy and chemotherapy will improve outcomes.5 The opportunities for combination therapy include dual checkpoint blockade with another immune checkpoint inhibitor such as ipilimumab (a CTLA-4 inhibitor)6, vaccine combinations, VEGF inhibitor combinations and potentially traditional chemotherapy combinations.3 Perhaps the most exciting of these approaches may well be the vaccine combinations. Despite a long run of underwhelming results, vaccines have shown excellent activity at promoting and increasing T cells but these efforts were constantly negated by a remarkably immunosuppressive tumour microenvironment.1 Some have said that if they awarded a ‘drug of the year’, PD-1/PD-L1 monoclonal antibodies would have taken the title in 2013. With the excitement surrounding these molecules, they may well be worthy of taking out the title again in 2014 and for many years to follow. They have brought immunotherapy to the forefront of therapeutic strategies as we continue to strive for long term tumour control. Harnessing the immensely powerful human immune system against cancer has taken an important step forward.

+

Tumour

References available on request.

Many hospital protocols state that iron infusions must be carefully monitored due to the possible incidence of allergic reactions. While reactions rarely occur, it is this monitoring and rate-control which results in iron polymaltose infusions taking on average five hours.6 Ferric carboxymaltose could be the answer to this problem. The TGA approved ferric carboxymaltose (Ferinject®) in early 2011 for the treatment of iron deficiency in patients when oral iron preparations are ineffective or cannot be used.2 An immediate allergic reaction with the use of Ferinject® is very rare,2 but as allergic reactions have occurred after intravenous injections of other iron preparations, the manufacturer (Vifor Pharma) advises that resuscitation facilities should be available during the administration of ferric carboxymaltose.7

Ferinject

Iron

Amount of sterile 0.9% NaCl solution

Minimum administration time

2 to 4 mL

100 to 200 mg

50 mL

3 minutes

>4 to 10 mL

>200 to 500 mg

100 mL

6 minutes

>10 to 20 mL

>500 to 1,000 mg

250 mL

15 minutes

To administer Ferinject® by IV injection it is given undiluted. Doses between 200mg and 500mg must be given at 100mg iron per minute, and doses greater than 500mg must be given over 15 minutes. In haemodialysis-dependant chronic kidney disease patients a single daily injection of Ferinject® should not exceed 200mg.7 No test dose is required for either route of administration. Ferinject® is not recommended for use in pregnancy as there are no adequate and well-controlled studies. A careful risk/benefit evaluation is required before deeming its use necessary.2 Ferinject® has been used amongst breastfeeding women, as clinical studies showed that transfer of iron from Ferinject® to human milk was extremely low (<1%).2 Use in children (<14 years old) has not been evaluated or recommended. The efficacy of Ferinject in replenishing iron has been demonstrated in several trials. In a study evaluating 255 non-dialysis chronic kidney disease patients, Ferinject® was shown to improve haemoglobin levels and change mean serum ferritin much faster and greater than oral iron. This study also showed that adverse events occurred in 2.7% of patients treated with Ferinject® compared with 26.2% treated with oral iron.8

In a recent press release, the Australian Minister for Health stated that Ferinject® would be approved for listing on the PBS from the 1st of June, 2014.10 The reduced infusion time and few side effects observed with Ferinject® appear to have influenced the decision. These benefits, in combination with the reduced cost to the consumer, could mean that some IDA patients are treated in an outpatient setting, hence minimising hospital costs and increasing the availability of critical care beds. The impact of Ferinject® after June in Australia is therefore likely to be significant.

BMS-936559

PD-L1

PD-1

Figure 1 – PD-1/PD-L1 Inhibition

2

Contemporary therapeutics: ferric carboxymaltose (Ferinject®) Bella Diprose, APHS Pharmacy Geelong Private Hospital

Tumours can escape the immune response by expressing the PD-1 ligands, PD-L1 and PD-L2. Many tumour types have been shown to express the ligand PD-L1 and this would likely contribute to immune suppression and poor prognosis. These tumour types include renal cell, melanoma, stomach, pancreatic and lung cancer.3 Several companies have PD-1 targeted agents under development with BMS (nivolumab) and Merck (lambrolizumab) the furthest along. Nivolumab is a fully human monoclonal antibody and was the first PD-1 inhibitor to be tested in clinical trials. A search of www.clinicaltrials.gov, using the search terms ‘nivolumab’ and ‘phase III’ shows there are at least six phase III trials currently underway in melanoma, renal cell and non-small cell lung cancer (NSCLC). In melanoma, early studies demonstrated a response rate of 41% using 3mg/kg and this is the dose that has been taken forward to be used in the phase III melanoma study

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Iron deficiency anaemia (IDA) is a common condition among Australian patients that often requires hospitalisation. Iron deficiency anaemia can arise from blood loss (e.g. menstrual bleed) or internal bleeding, a malabsorption problem (e.g. Crohn’s disease), a reduced dietary intake of iron or an increased need for iron in certain population groups (e.g. athletes, pregnant women, teenagers).1 Treatment options for IDA include oral iron supplements, and less-often IV iron infusions.1 Oral iron is first-line therapy, however poor absorption, drug interactions and the long length of treatment can often mean that some patients do require the use of IV iron.5 The three types of IV iron available in Australia are iron polymaltose (Ferrum H® and Ferrosig®), iron sucrose (Venofer®) and ferric carboxymaltose (Ferinject®). In the Australian healthcare system IV iron

Another trial conducted in America in 2013 compared Ferinject® with other standard IV iron therapy (predominantly iron sucrose). This randomised multicentre study examined 507 patients with IDA who had an intolerance or inadequate response to oral iron. Ferinject® had the highest observed haemoglobin at any time between day 1 and day 35 after treatment, with levels of 2.9g/dL compared with a haemoglobin level of 2.1g/dL with other preparations.9 The Pharmaceutical Benefits Advisory Committee (PBAC) recommended Ferinject for PBS subsidy in November 2013. The approval for PBS listing has till now been delayed due to the lack of evidence of benefit of Ferinject® over other iron preparations. Currently there is no other evidence available demonstrating this increased benefit. The PBAC have however recognised the potential of Ferinject® to minimise hospital costs.

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®

Apical membrane

SGLT2 sodium

glucose

Na /K

GLUT2

+

potassium

References available on request.

Renal vessel B SGLT2 inhibited Lumen of proximal tubule inhibitors glucose Apical SGLT2 membrane

New Drug Brief: Canagliflozin (Invokana®) and dapagliflozin (Forxiga®) Heather Sullivan, St Andrews Pharmacy, Toowoomba Canagliflozin and dapagliflozin are the first of a new class of oral antidiabetics for Type 2 Diabetes Mellitus (T2DM), the sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibition in the proximal renal tubule has been shown to cause 50–80 grams of blood glucose a day to be excreted in the urine.2,3 The resultant energy deficit is compensated for by utilising body fat stores resulting in improved weight loss. Patients taking these agents experienced a modest reduction in both blood volume and pressure.4,5 However, caution should be used in patients >65 years or with reduced renal function due to increased risk of hypovolaemic events and hyperkalaemia, which may also be exacerbated by concurrent use of ACE inhibitors, Angiotensin 2 antagonists and diuretics (although potassium effect varies with diuretics).6,7,8 Patients should be monitored closely for urogenital infections which increase due to high urinary glucose concentrations.4,5,6,7 Animal studies indicate it is possible that use of these agents in pregnant and breastfeeding women may interrupt their child’s normal renal development, which continues until 2 years of age.6,7

Na+/K+

GLUT2

potassium

glucose

Renal vessel Figure 2 – Action of SGLT2 in the proximal tubule (adapted from reference 9) postprandial glucose control.8 Used in this setting they provide decreases in HbA1c levels similar to that of other combination therapies. While they also modestly reduce weight and blood pressure and confer a lower risk of severe hypoglycaemic events, long term efficacy data (for vascular complications of diabetes) and safety data are not yet available.8 These drugs represent another beneficial new direction for glycaemic control in refractory T2DM.3,4,5

References available on request.

glomerulus 90% of S1 glucose reabsorbed by SGLT2

distal tubule

®

nivolumab lambrolizumab

A Normal function Lumen of proximal tubule sodium glucose

collecting duct

proximal tubule S2 remaining 10% of glucose S3 reabsorbed by SGLT1 loop of Henle

Did you know? APHS Pharmacy Practice unit also publishes Short Circuit; brief articles with important clinical content and Medication Safety Updates which highlight practical medication-related safety issues. Earlier this year we took the opportunity to survey some of our readers about what they thought of Circuit. We were pleased to see that 84% of those surveyed thought that this publication had benefits for thier staff. Over 50% also requested Circuit electronically. If you would like to receive either of these publications or wish to receive Circuit electronically, please contact us at circuit.editor@aphs.com.au

Figure 1 – Location of SGLT1 and SGLT2 in the proximal tubules of the kidney9 Canagliflozin and dapagliflozin are subsidised on the Pharmaceutical Benefits Scheme in combination with metformin or a sulfonylurea where a metforminsulfonylurea combination is inadequate or contraindicated. Both may be dosed either with or without food, however dosing prior to breakfast allows for better

circuit If you have any queries regarding Circuit content and authors please contact the APHS Pharmacy Practice Unit by email: circuit.editor@aphs.com.au Every effort has been made to ensure this newsletter is free from error or omission.