NPC Archive Item: July Drug Safety Update from MHRA/CHM

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7th July 2009

The MHRA and CHM have published the July edition of Drug Safety Update. This issue gives drug safety advice on the interaction between clopidogrel and proton pump inhibitors, and on the possible increased risk of MI with abacavir. The hot topic discusses the use of long-acting beta-agonists in COPD.

Drug Safety Update (DSU) is an essential read for everyone whose professional practice involves medicines. It is published every month in electronic format only.

Clopidogrel and proton pump inhibitors (PPIs): interaction
As we previously blogged, the EU Committee for Medicinal products for Human Use has reviewed the available evidence for an interaction between clopidogrel and PPIs. They concluded that the data support a clinically significant interaction that makes clopidogrel less effective when given with these medicines.

In the June edition of DSU, the MHRA recommended that the need for PPI therapy in patients who are also taking clopidogrel should be reviewed at their next appointment and these medicines should only be used concomitantly when essential. PPIs should be prescribed strictly in line with their licensed indications and healthcare professionals should check that patients who are taking clopidogrel are not buying over-the counter omeprazole. This advice remains unchanged in the July edition of DSU, which provides a link to further information, including a series of questions and answers for patients.

The article discusses the interaction between clopidogrel and PPIs. As a class, PPIs share many pharmacokinetic features and in-vitro studies have found that all five PPI products licensed in the UK exhibit competitive inhibition of CYP2C19, albeit to different degrees. Observational studies have shown that concomitant use of PPIs in patients with previous coronary artery restenosis or acute myocardial infarction (MI) reduces the clinical benefits of clopidogrel. However, the outcome studies do not fully reflect the pharmacokinetics of PPIs so there may be more than one explanation for their effect on clopidogrel. More evidence is required from clinical outcome studies before any specific recommendations can be made about the risks associated with individual PPIs. Although, on the basis of pharmacokinetic data, H2 receptor antagonists (except cimetidine) and antacids would not be expected to interact with clopidogrel, there are currently no substantial data from outcome studies to support this.

Concomitant use of other medicines that inhibit CYP2C19 (e.g. fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, and chloramphenicol) would be expected to reduce the efficacy of clopidogrel and should be avoided.

Abacavir: risk of MI
Abacavir is used in combined antiretroviral therapy for the treatment of HIV infection. In 2008, preliminary results from a large, prospective observational study (n>33,000) suggested a possible increased risk of MI in patients receiving abacavir. This article reviews the latest data and concludes that the preferential use of abacavir in patients with high cardiovascular (CV) risk, and lack of an established biological mechanism that could explain a potential increase in risk of MI, means that no firm conclusions can be drawn on the association between abacavir and MI. The safety of abacavir-containing medicines remains under close review.

Healthcare professionals are advised to use abacavir-containing medicines in line with current treatment guidelines and with caution in patients at high risk of CV disease. Patients taking these medicines should be advised to minimise their CV risk factors (e.g. smoking, high blood pressure, high blood-lipid levels and diabetes).

Use of long-acting beta-agonists (LABAs) in COPD
This month’s hot topic article advises that the overall benefits of LABAs, both alone and in combination with inhaled corticosteroids (ICS), continue to outweigh any risks in patients with chronic obstructive pulmonary disease (COPD), when used in line with current GOLD and NICE guidelines. In all trials, combination therapy was better than monotherapy. However, the benefit is limited and ICS should be introduced only when COPD progresses to severe disease.

Healthcare professionals are reminded that ICS should not be used alone in COPD. There is an increased risk of pneumonia when patients with COPD are treated with ICS, which isn’t apparent when LABAs are used alone.

Stop press

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