www.kirklees-pct.nhs.uk
June 07 issue 16
Prescribing & Medicines Management Newsletter News and Updates
Growing pressure to prevent diabetes by medication
SPC (indication) changes: Desmopressin nasal sprays NO LONGER recommended for primary nocturnal enuresis: • Higher incidence of Serious ADRs for the nasal vs oral formulations • Patients may complete their current supply of treatment • Patients should be switched to an oral formulation when they next attend for their next prescription / review. • Use lowest recommended dose. • No generic available currently (desmopressin is offpatent). • Desmotabs (standard) or DesmoMelt (sublingual) tablets. • No extra charge for sublingual formulation (at chemically equivalent doses: 200mcg Desmotabs ≡ 120mcg DesmoMelt). • DesmoMelt may be useful for young children who dislike swallowing (although NB Desmotabs are very small). • Possible risk of severe hyponatraemia when nasal desmopressin is used for cranial diabetes insipidus also.
A BMJ analysis ((2007, 334:882-884 - also reported by BBC), particularly of the DREAM study (Rosiglitazone for the prevention of diabetes in patients with impaired glucose control/fasting glucose), argues that drugs to prevent diabetes will bring:
Cabergoline (Cabaser): • SECOND-LINE only for Parkinson’s disease • Evidence of similar risk of heart valve damage as pergolide (Celance): see SPC for further details. AstraZeneca has followed Pfizer into direct-topharmacy distribution of its medicines – again please report any major problems through the PCT incident reporting process. Discontinued: • Stelazine Spansules (trifluoperazine) 2mg, 10mg and 15mg (Stelazine tablets 1mg and 5mg remain available). • Benzamycin (benzoyl peroxide 5% + erythromycin 3%) gel • HeliClear (amoxicillin 500mg, clarithromycin 500mg,lansoprazole 30mg) • HumaJect Pens, Prefilled Insulin Pens, Soluble, Mixture 3 • Dermovate-NN (clobetasol 0.05%, neomycin 0.5% & nystatin 100,000 units/g) cream – the advantages of including antibacterials etc with corticosteroids are uncertain (may have a place for infected eczema) Supply problems: zaleplon (Sonata) 10mg capsules Advice on NEW/NOVEL diabetes treatments: sitagliptin (Januvia) [& vildagliptin] and exenatide (Byetta). The Diabetes Network locally is considering their place in diabetes therapy and will issue guidance presently. In the meantime, clinicians are respectfully requested NOT to prescribe these agents. Reminder: prescribing of Gardasil (HPV vaccine) is NOT currently PCT-supported (awaiting national guidance from JCVI).
• harms (e.g. increased rate of heart failure with glitazones) • additional costs (see chart below) • benefits for patients which remain questionable: - reduced progression to type 2 diabetes or death BUT - lack of information on the long-term safety of rosiglitazone (e.g. recent finding of detrimental effect on bone formation/BMD with increased fracture risk) - patients with cardiovascular disease were excluded from DREAM. - lifestyle changes including weight loss/eating a healthy diet/taking regular exercise greatly reduce the risk of developing diabetes and are much safer Suggested action: lifestyle changes 1st line to prevent diabetes. Clinical use of hypoglycaemic agents to prevent diabetes is not justified based on the current efficacy and safety data. Oral Antidiabetic Drugs rosiglitazone (8mg) pioglitazone (30mg) 'Competact' 30mg/1.7g 'Avandamet' (4mg/2g) rosiglitazone (4mg) pioglitazone (15mg) nateglinide (180mg) 'Glucophage' SR 1.5g tolbutamide (1.5g) repaglinide (4mg) 'Diamicron' MR 60mg acarbose (150mg) glipizide (10mg) glimepiride (2mg) glibenclamide (10mg) chlorpropamide (250mg) metformin (1.5g) gliclazide (160mg) 0
10
Doses given do not imply therapeutic equivalence
20 30 40 £/28 days supply (June 07 Drug Tariff)
An assessment of the JBS2 guidelines for prevention and treatment of cardiovascular disease (Int J Clin Pract published early online, 26/3/07) -"contain serious deficiencies, are of low quality and should not be recommended for clinical practice". - highlights the risks involved in drawing up consensus-based, as opposed to evidence-based advice. - Interestingly the guidelines were rated at the lowest possible score in all aspects of the ‘editorial independence’ domain. National targets for Cholesterol remain at 5 / 3 mmol/l (ref Prof. Boyle). Grazax s/l tablets: Meds. Management team position vindicated by: • Recent MeReC (National Prescribing Centre) review • Rejection by the SMC for NHS use in Scotland. MeReC indicated that the clinical benefits of Grazax:
50
60
Treatment Advice Notes (TAN) have been firmly rejected by Calderdale and Huddersfield Foundation Trust Medicines Management Committee. It was felt there was no place for such "notes" in the supply chain and if a consultant or hospital doctor felt a patient should be on a particular item then they should prescribe it themselves. TAN could be seen to be used as a way of by-passing other "restrictions" on secondary/tertiary care prescribers (i.e. if hospital pharmacy do not keep a drug because they don't feel it has any advantage over other available items, a TAN is sometimes used to get round this by asking if the GP will prescribe). In summary, TAN are not a recognized/approved way of requesting GPs to take on prescribing. "appear very modest in comparison with symptomatic treatment alone." MHRA have asked the manufacturers of Grazax to withdraw promotional material ("It’s never too early to think about grass allergy") as it could promote the use of Grazax only 2-3 months before the expected start of the grass pollen season as opposed to the recommended ≥ 4 months.
Etoricoxib & American regulatory authority (FDA): • Etoricoxib (Arcoxia) is a COX II-selective NSAID. • UK license for osteoarthritis (OA), rheumatoid arthritis & gout. • FDA has rejected etoricoxib license application for OA and requested additional data in support of the benefit-to-risk profile of etoricoxib. Suggested actio: Based on this cautious American approach, it may be prudent to restrict use of this drug in OA.
Savings! Savings! Epanutin 100mg capsules are significantly more cost-effective than generic phenytoin 100mg tablets. May also be of advantage for the minority of patients whose seizure control is acutely sensitive to very subtle changes in the pharmacokinetic profile of different phenytoin preparations. Cost/84 (Drug Tariff May 07) Phenytoin 100mg tablets £186.87 Epanutin 100mg capsules £2.83 NB Switching of well-controlled drivers is not recommended.
Can a standard FP10 prescription be issued to treat impotence due to "severe distress"? • A GP* cannot issue a NHS script for erectile dysfunction (ED) due to "severe distress" even when asked to do so by a consultant. • The Medicines Management Team are aware that some local hospital departments are "requesting"/"implying" that a GP practice can take over prescribing at NHS expense for "severe distress" once the diagnosis has been made in secondary care BUT this is NOT the case. • Such patients should be referred to a local "specialist centre" to confirm diagnosis and, if appropriate, prescribe treatment at NHS expense. • FP10 (HP) are used [endorsed "SLS" if to be dispensed in the community]. • Patients qualifying due to stress can only continue to obtain their prescriptions at NHS expense via the "specialist centre". • A GP practice can only prescribe for a diagnosis of "severe distress" on PRIVATE prescriptions under the terms and conditions of supply. • If NO "specialist service" is available then the
Bisphosphonates & Osteonecrosis of the jaw This has been discussed in both the BMJ (Nov 06) & by the MHRA in Current Problems in Pharmacovigilance (May 06). Main points would appear to be: • A rare adverse effect (although there is some debate about whether, by its very nature, it has been under-reported). • Non-healing ulcerated oral lesions and visible necrotic bone, which are sometimes associated with a diffuse jaw or facial pain. • Mean onset time after treatment start is 1-3 years. • Ocurs more frequently with intravenous (e.g. for metastatic cancer) rather than oral (mainly osteoporosis) bisphosphonate therapy (UK - 77 spontaneous osteonecrosis reports for intravenous versus 9 for oral bisphosphonates - MHRA). • Incidence (est.) of 1 in 100,000 patient-years (oral therapy). • Worldwide many of the patients who developed osteonecrosis while on bisphosphonates were also receiving chemotherapy and/or corticosteroids.
• The majority of reported cases have been associated with dental procedures such as tooth extraction, and many had signs of local infection including osteomyelitis. • For patients requiring dental procedures, no data is available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis. Further dental surgery may exacerbate osteonecrosis once present. Importance of good dental hygiene should be emphasised to patients on bisphosphonate treatment. Lack of evidence to guide best practice, but MHRA advises: • A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids and poor oral hygiene). • While on treatment, patients with concomitant risk factors should avoid invasive dental procedures if possible.
Further evidence of the risk of unrestrained antibiotic prescribing A recent randomized, double-blind placebocontrolled trial in Belgium (Lancet 2007; 369:482-90) - demonstrated that two macrolide antibiotics, azithromycin and clarithromycin (measured against placebo) generated a clearly defined effect on commensal pharyngeal streptococci, with both drugs selecting for macrolide resistance. A previous paper (Lancet 2005; 365:579-87) from the group showed a clear correlation on a national level between antibiotic use and the prevalence of resistant organisms but the current study goes further providing evidence on an individual level. Those patients who demand and receive multiple scripts for antibiotics may be at risk of becoming
colonised with resistant organisms. The question is: Is this the end of the beginning, or the beginning of the end, of the antibiotic era? If you are concerned it is the latter, advice would be to use the following tactics to reduce non-essential antibiotic prescribing: 1) Ask directly whether the patient is expecting an antibiotic - they may well not be 2) Avoid telephone prescribing 3) Use delayed prescriptions (as appropriate) – patient information leaflets available via practice pharmacists/Meds Management team.
regulations would ONLY permit a GP to prescribe on a Private prescription (NOT FP10). The other patient groups for whom GPs (& other primary care prescribers*) can prescribe Erectile Dysfunction (ED) treatments, are men who: (a) have diabetes; multiple sclerosis; Parkinson's disease; poliomyelitis; prostate cancer; severe pelvic injury; single gene neurological disease; spina bifida; spinal cord injury OR (b) are receiving treatment for renal failure by dialysis; OR (c) who have had the following surgery prostatectomy; radical pelvic surgery; renal failure treated by transplant. (d) were receiving CaverjectR, ErecnosR , MUSER , ViagraR or ViridalR for erectile dysfunction at NHS expense, on 14th September 1998. (Prescriptions must be endorsed ‘SLS’).
Dovonex (calcipotriol) ointment discontinuation: • Locally stocks are now reported to be exhausted. • A generic version is available from Sandoz (same price & composition – prescribe as ‘calcipotriol 50mcg/g ointment x 120g’) • Other options include: 1) Calcitriol (Silkis) ointment – similar action, somewhat less potent but also less irritant, may be more cost-effective than Dovonex for mild to moderate psoriasis (lower £/g) 2) If cream acceptable – calcipotriol (Dovonex) cream 3) Dovobet (calcipotriol + betametasone) ointment: - Manufacturer applying pressure to prescribe based on recently updated indication allowing repeated 28 day courses + potency of combination being greater than the individual components alone, BUT - Long-term data regarding relapse rates is not yet established - Long-term topical steroid risk, even if not continuous (near doubling (5 v 3%) of risk of steroid "ADRs of concern" in one 52wk trial comparing prn Dovobet to alternating Dovobet/calipotriol or calcipotriol alone). - Risk of vigorous or pustular rebound following steroid withdrawal post-course which may increase with duration of continuous Dovobet treatment. - If Dovobet is prescribed as a repeat, may lead to inappropriate continuous - rather than pulsed - patient use. - Dovobet is significantly more expensive than above alternatives, but manufacturers suggest more cost-effective (query whether this is case even for the mild/moderate psoriasis = appropriate to treat in 1ry care). The information contained in this newsletter is issued on the understanding it is the best available from the resources at our disposal at the time of going to print.For further information or to share any suggestions of your own please contact the Prescribing Team on 01484 344352.
This newsletter is available to download from the intranet: nww.kirklees-pct.nhs.uk
Produced by Kirklees PCT Prescribing Team: Shohaib Ali, Michael Duckworth, Linda Fox, Patrick Heaton, Tasawer Hussain, Helen Knapp, Nikki Lawton, Lisa Meeks, Majid Mehboob, Neill McDonald, Helen Pickering, Anna Place, Judith Stones, Maghira Younis.