Prescribing Advice for GPs

Drug Safety Update – March 2010

March 9, 2010 at 11:14 am | In Prescribing Extra - Drugs |  Print | No Comments

The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for March 2010 (PDF).

This issue contains drug safety advice regarding a possible small increase in the risk of congenital cardiac defects when fluoxetine is taken early in pregnancy. This information comes from an analysis of epidemiological data from seven cohort studies. The background rate of congenital cardiac defects is approximately 1/100 and these results indicate that fluoxetine increased absolute risk to less than 2/100 pregnancies. This is similar to the risk increase seen with paroxetine. Clinicians are advised that this potential for increased risk should be considered in the context of the benefits of treating depression in pregnancy.

Attention is also drawn to inter-test differences when monitoring therapeutic levels of sirolimus. These differences may inadvertently lead to inappropriate dose adjustments. Care should be taken to ensure that the test used is unchanged before making dose adjustments.

Finally, Drug Safety Update has been accredited by NHS Evidence in recognition of the high quality guidance that is issued. Future Drug Safety Updates will be available at http://www.evidence.nhs.uk and will display the accreditation mark.

Action: Clinicians will find this publication to be a useful review of current issues in drug safety.

Aspirin ineffective in those with low ABI

March 4, 2010 at 3:38 pm | In Prescribing Extra - Drugs |  Print | No Comments

The Journal of the American Medical Association (JAMA) has published the results of a study that aimed to assess the efficacy of aspirin in preventing primary cardiovascular events in patients with a low ankle brachial index (ABI).

ABI is the ratio of systolic blood pressure at the ankle and arm. ABI is used to diagnose peripheral vascular disease and is associated with an elevated risk of coronary events.

3,350 men and women aged 50 to 75 were recruited to the study. None had clinical cardiovascular disease but all had ABI less than or equal to 0.95. Follow up was for a mean of 8.2 years for a primary composite outcome of fatal or nonfatal coronary event, stroke or revascularisation. Participants were randomly assigned to treatment with 100mg aspirin daily or matching placebo.

The study found no significant difference in the rate of the primary outcome between the two study groups (Hazard Ratio 1.03, 95% confidence interval 0.84 – 1.27). Additionally, there were no differences in the two secondary outcomes (a composite of the primary outcome and angina, intermittent claudication or transient ischaemic attack or all-cause mortality). The study also assessed the rate of major haemorrhage requiring a hospital admission. This was higher in the patients treated with aspirin but the difference was not significant (HR 1.71, 95% CI 0.99 – 2.97).

The authors conclude that among this population “the administration of aspirin compared to placebo did not result in a significant reduction in vascular events“. The authors also suggest that ABI assessment is unlikely to be a useful screening tool in primary care settings.

The results of the study may be limited by low levels of medication compliance with the treatments taken for 60% of the trial person-years. Also, the study was designed and powered to detect a 25% relative reduction in events. Recent analyses have indicated that aspirin may only produce a 12% reduction and perhaps this study was underpowered.

Action: This study adds some more weight to the conclusions reached by the Drug and Therapeutics Bulletin that the use of aspirin in the primary prevention of cardiovascular events is unjustified.

Rosiglitazone heart risks were hidden

March 1, 2010 at 1:24 pm | In Prescribing Extra - Drugs |  Print | No Comments

According to the findings of a report prepared by the United States Senate Committee on Finance the manufacturer of rosiglitazone failed to warn patients or regulatory authorities of cardiovascular concerns. This publication has been reported in the British Medical Journal.

A two year investigation has reviewed over 250,000 documents submitted by GlaxoSmithKline, the Food and Drugs Administration (FDA) and other organisations after the publication of a study in the New England Journal of Medicine that raised concerns that rosiglitazone increased the risk of myocardial infarction.

This investigation found that the manufacturer of rosiglitazone knew for several years prior to this study that there were possible cardiac risks associated with [rosiglitazone] Avandia^®. Additionally, independent physicians were intimidated, the risks were misrepresented and positive results for competing drugs were downplayed.

Finally, this investigation is critical of the role played by the FDA. The FDA requested a cardiovascular safety trial be conducted however internal FDA documents note that two safety officials conducted an analysis of the available data at that time and concluded that any proposed head-to-head trial of rosiglitazone vs. pioglitazone would be unethical and exploitative.

Action: As previously advised, clinicians should continue to implement the existing guidelines. Glitazones (and gliptins) are considered as alternatives to metformin or sulphonylureas when these agents are contraindicated or poorly tolerated. Pioglitazone currently has fewer prescribing restrictions and may be a better choice where a glitazone is indicated.

Statins and diabetes risk

February 17, 2010 at 11:33 am | In Prescribing Extra - Drugs |  Print | No Comments

The Lancet has published the results of a meta-analysis of randomised statin trials with the aim of establishing whether any association exists between statin use and development of diabetes. This analysis has been reported in the general media (BBC).

This analysis included data from 13 trials involving 91,140 participants. 4,278 participants developed diabetes during the trial periods (mean duration 4 years) with 2,226 assigned statins and 2,052 assigned control treatment.

Statin therapy was found to be associated with a statistically significant 9% increase in the risk of developing diabetes (odds ratio [OR] 1·09; 95% CI 1·02–1·17). The risk was found to be highest in older participants while baseline BMI and change in low-density lipoprotein-cholesterol (LDL-C) concentrations appear to be unimportant predictive factors.

Despite this finding the authors conclude that, “in view of the overwhelming benefit of statins for the reduction of cardiovascular events, the small absolute risk for development of diabetes is outweighed by cardiovascular benefit in the short and medium term“. They recommend that current practice for statin therapy remains unchanged.

The authors also note that this analysis does not prove a causal relationship and that the observed difference may be due to residual confounding factors. They therefore also suggest that development of diabetes is included in future statin studies as a secondary outcome.

Action: Clinicians should be aware of these results and the associated media reports. Patients taking statins should be reassured that the benefits of therapy outweigh the risks. Screening for diabetes in patients taking statins, especially in older patients, may be a sensible strategy.

Drug Safety Update – February 2010

February 9, 2010 at 9:53 am | In Prescribing Extra - Drugs |  Print | No Comments

The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for February 2010 (PDF).

This issue contains drug safety advice informing clinicians about a new oral liquid formulation of tacrolimus (Modigraf^®) with particular attention drawn to the requirement of careful monitoring if switching formulation.

The Yellow Card update section notifies readers of a recent issue identified within the Royal Mail where some cards have been returned to the sender. If you have had a card returned, or if you have submitted a card and not received an acknowledgement letter, you should resubmit the report.

This section also contains a review of the reporting information for swine flu vaccines and antiviral medication. The safety profile is reassuring since the “number and the nature of suspected adverse effects reported are very much as we expected at this stage in the immunisation campaign“.

The Hot Topic section provides an update on safety information for orlistat (Xenical^® and Alli^®) including to some potential drug interactions with levothyroxine and antiepileptic agents. This section also informs readers of the license extension for nicotine replacement therapy (NRT) products to include harm reduction as it is now widely accepted that there are no circumstances in which it is safer to smoke than to use NRT.

Finally, the Stop Press section reminds readers of the recent withdrawal of sibutramine (Reductil^®) after a review identified that the cardiovascular risks of treatment outweigh its benefits.

Action: Clinicians will find this publication to be a useful review of current issues in drug safety.