The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update Issue 9 (PDF).
This issue includes the following drug safety advice articles:
- Hormonal contraceptives: cervical cancer - latest evidence
- Combined hormonal contraceptives: venous thromboembolism - update
- Cyproterone acetate with ethinylestradiol (co-cyprindiol): recommended duration of use
- Carbamazepine: genetic testing in some Asian populations
In addition, this issue contains a hot topic containing information about the newly introduced Traditional Herbal Registration (THR) scheme. This scheme provides certain herbal medicines with a registration number that demonstrates the product has been assessed and met meet systematic standards of safety, quality, and patient information. Recommend indications are based on traditional usage rather than proven efficacy. A list of registered products is available on the MHRA website. Finally, there is a stop press section highlighting important safety issues that have arisen in the last month.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The New England Journal of Medicine has published the results of the ONTARGET Study. The study compared ramipril, telmisartan or the combination of both drugs in patients at high risk of vascular events.
The study recruited 25,620 patients who were then randomised to treatment with ramipril 10mg, an angiotensin converting enzyme inhibitor (ACEI), telmisartan 80mg, an angiotensin receptor blocker (ARB), or both drugs. Baseline characteristics were similar for age, gender, ethnicity, blood pressure, smoking history and drug treatment. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure and follow up was for a median of 56 months.
The primary outcome occurred in 16.5% of patients taking ramipril, 16.7% of patients taking telmisartan and 16.3% of patients taking both drugs. Statistically, there were no differences between the groups. In terms of adverse reactions and discontinuations, there was more cough in the ramipril group compared to telmisartan but fewer cases of hypotensive symptoms. The group taking the combination were more likely to discontinue treatment with higher rates of hypotensive symptoms and cough.
The authors conclude that, "telmisartan was equivalent to ramipril in patients with vascular disease or high risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit".
To date, this is the largest comparative study of an ACEI and an ARB. It confirms that ARBs are no better than ACEIs in prevention of cardiovascular events. The higher acquisition cost of ARBs must be weighed very carefully against the small advantage of lower incidence of cough. This study also indicates that using a combination of ACEI and ARB is not justified in routine practice and is only likely to be appropriate in patients with heart failure as indicated by the CHARM-Added study.
Action: Clinicians should ensure that ACEIs are used in preference to ARBs and that ARBs are only used in cases of genuine intolerance to ACEIs. The combined use of ACEI and ARB is not justified in routine practice.
The Journal of the American Medical Association has published the results of a study that aimed to determine whether weight loss and metabolic effects of the rimonabant reduced progression of coronary heart disease (CHD) in patients with abdominal obesity and metabolic syndrome.
The study recruited 839 patients who received dietary counselling and rimonabant 20mg daily or matching placebo for a period of 18 months. 676 patients underwent baseline and completion intravascular ultrasonography to assess changes in atheroma volume.
The primary outcome was not significant (p=0.22); rimonabant produced a +0.25% change in atheroma volume while placebo produced a +0.51% change. A secondary outcome of normalised atheroma volume was significantly different but this difference should be viewed with caution because the primary outcome was not statistically different.
The authors of the paper conclude that, "determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials".
Action: Clinicians should not use rimonabant in preference to other anti-obesity drugs on the presumption that reductions on some cardiometabolic risk factors will translate to reductions in cardiovascular morbidity and mortality.
Coversyl® and Coversyl Plus® are being discontinued and replaced by Coversyl Arginine® and Coversyl Arginine Plus® according to the manufacturer.
This decision has been taken to allow for "the global simplification and harmonisation of the manufacturing process for perindopril". The new products also benefit from a longer shelf life. This discontinuation only applies to the branded products and should not impact upon generic perindopril. Patients prescribed branded perindopril or the combination product will need to have their treatment reviewed and amended.
A phased change over period is expected due to the overlap of both products in the supply chain; the new product will be distributed from 1st April 2008 with supplies of the existing product expected to last for about 8 weeks. The licensed indications for the new products are identical to those being discontinued.
Coversyl Arginine is not dose equivalent to the existing perindopril products; conversion details are as follows:
- Perindopril 2mg is equivalent to perindopril arginine 2.5mg
- Perindopril 4mg is equivalent to perindopril arginine 5mg
- Perindopril 8mg is equivalent to perindopril arginine 10mg
Action: Clinicians should be aware of this discontinuation. Patients who are currently prescribed branded Coversyl or Coversyl Plus will need to be reviewed and have their prescriptions altered.
By far the busiest article on this site, in terms of follow up comments, is about the discontinuation of Gynol II.
It would seem that the discontinuation of this product 2 years ago is still causing problems for patients. Ortho-Creme® was initially recommended as a suitable alternative however some people found that the different presentation caused irritation and it too has now been discontinued.
According to the Clinical Knowledge Summary for barrier contraception Gygel 2% contraceptive jelly® is the only licensed spermicide marketed in the UK. It is available in 30g tubes costing the NHS £4.75 per tube. This product is listed in the Drug Tariff in the Nurse Prescribers' Formulary (Part XVIIB(i)) as Medicinal Preparation, it is therefore allowed on NHS prescription and should be free of charge when dispensed.
Action: Clinicians should be aware of the availability of this product and of the limited pack size in comparison to previous products.