The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for April 2012 (PDF).
This update contains drug safety information regarding proton pump inhibitors (PPIs) and an association with hypomagnesia and also epidemiological evidence of increased risk of fracture.
Hypomagnesia has been reported following prolonged use of PPIs which is clarified as more than 1 year. In serious cases this can present with fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia however the development of symptoms may be slow and thus overlooked. It is recommended that consideration is given to checking magnesium level before starting treatment that is expected to be long terms and then periodically, especially in patients on digoxin and drugs than can cause hypo magnesia, e.g. diuretics.
Recent epidemiological evidence has associated PPIs with an increased risk of fracture at 10–40% above baseline. Again, this is associated with prolonged use of PPIs. It is recommended that patients who are at risk of osteoporosis are treated according to current clinical guidelines to ensure an adequate intake of vitamin D and calcium.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The manufacturer of Xamiol® has written to healthcare professionals advising that this product is being discontinued. The same letter advised that the 120g tube size of Dovonex® ointment is being replaced by a 30g tube size.
Xamiol contains calcipotriol and betamethasone in a gel formulation. It was licensed for use in scalp psoriasis. The manufacturer points out that Dovobet Gel is an identical product with a wider license; it can be used on the body as well as the scalp.
Dovonex ointment (calcipotriol) is also being replaced by a 30g tube size which the manufacturer says will allow greater flexibility to prescribe clinically appropriate quantities for smaller areas of psoriasis.
Action: Clinicians should be aware of these changes. Current prescriptions for Xamiol can be changed to generic to allow continued supply and quantities of Dovonex prescribed can be amended if necessary at routine reviews.
PLoS Medicine has published the results of a meta-analysis that aimed to assess the efficacy of metformin in reducing all-cause and cardiovascular mortality in patients with type 2 diabetes.
The authors note that UKPDS 34 identified a significant risk reduction in all-cause mortality in overweight patients with type 2 diabetes when compared to dietary control alone. This same study reported an increased risk of mortality in non-overweight individuals who were treated with metformin and a sulphonylurea. This contrary finding, whilst still significant, has been largely ignored.
This analysis identified 13 randomised controlled trials involving 13,000 individuals. Around three quarters of these participants received metformin while the remainder received other treatments or a placebo. It was found that metformin had no effect on all-cause mortality (RR = 0.99; 95% CI 0.75 to 1.31) or cardiovascular mortality (RR = 1.05; 95% CI 0.67 to 1.64).
The authors note that the number and quality of studies available are insufficient to draw hard conclusions and that this study "cannot exclude a 25% reduction or a 31% increase in all-cause mortality". They conclude that "although metformin is considered the gold standard, its benefit/risk ratio remains uncertain". They also recognise that while further research is needed to help clarify the situation, metformin may not be the best comparator for newer hypoglycaemic drugs but remains unclear which comparator should be used.
Action: Clinicians should be aware of this analysis. While this study found metformin to have a neutral effect on mortality a significant benefit or harm could not be excluded. Pending further research, clinicians should continue to implement the current NICE Guideline for type 2 diabetes.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Fampridine (Fampyra®) has been rejected for use to improve walking in adult patients with multiple sclerosis with walking disability. The manufacturer failed to make a submission. The manufacturer already recommends that use is restricted to prescription and supervision by physicians experienced in the management of multiple sclerosis.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The 63rd Edition of the British National Formulary has been published and it is currently being distributed in the NHS.
New or revised content in this version includes updated advice in the following areas:
- Using bowel cleansing preparations with other oral drugs
- Advice regarding antiepileptic hypersensitivity syndrome
- Application of the ‘less suitable for prescribing’ symbol to stavudine
- Use of antithyroid drugs in pregnancy
- Prescribing notes for hypertension, oral anticoagulants and stable angina
- Several updates based on NICE Guidance
The web version has already been updated but requires registration or an Athens account for continued access. The printed version is available for purchase.
Action: All clinicians should start using BNF 63 as soon as the print version arrives. The web version can be used to access the latest information if necessary.