NPC Archive Item: April 2010 Drug Safety Update from MHRA/CHM

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09 April 2010

The MHRA and CHM have published the April edition of Drug Safety Update

Highlights include:

  • Updated advice regarding the interaction between clopidogrel and proton pump inhibitors (PPIs).
  • Advice regarding the risk of venous thromboembolism (VTE) with the combined oral contraceptive (COC) Yasmin.
  • A reminder to healthcare professionals that intravenous (IV) zoledronic acid is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction

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

Updated advice on clopidogrel and PPI interaction
In light of recent evidence, the previous MHRA advice (to avoid all PPIs unless absolutely necessary for patients taking clopidogrel) is no longer considered necessary. Nevertheless, as a precaution, concomitant use of clopidogrel with omeprazole or esomeprazole should be discouraged unless considered essential. The current evidence does not support extending this advice to other PPIs.

Prescribers should consider using PPIs other than omeprazole or esomeprazole in patients who are taking clopidogrel. However, because it is not possible to completely exclude a possible interaction with these PPIs on the basis of available data, the potential risk of a slight reduction in efficacy of clopidogrel should be weighed against the potential gastrointestinal benefit of the PPI. Other gastrointestinal therapy such as H2 receptor antagonists (except cimetidine) or antacids may be more suitable in some patients. Doctors should check whether patients who are taking clopidogrel are also buying over-the counter omeprazole and consider whether other gastrointestinal therapies would be more suitable. Pharmacists should check whether patients buying omeprazole are also taking clopidogrel. As we blogged previously, this represents a good opportunity to review the need for either the clopidogrel, the PPI or indeed both agents to make sure their use is in line with NICE guidance.

Concomitant use of other known CYP2C19-inhibiting medicines with clopidogrel should be discouraged as these are expected to have a similar effect to omeprazole and esomeprazole (CYP2C19 inhibitors include fluvoxamine, fluoxetine, moclobemide, fluconazole, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, and chloramphenicol).

The antiplatelets section of NPC is currently being updated – materials are due to be published in the next month or so.

Update on risk of venous thromboembolism with Yasmin
Recently published studies suggest that the risk of VTE in association with use of the COC Yasmin may be slightly higher than previously estimated, and somewhere between the risk associated with combined pills containing levonorgestrel (otherwise known as ‘second generation’) and those containing desogestrel or gestodene (known as ‘third generation’). The risk of VTE with Yasmin remains very small and, like other oral contraceptives, is less than that associated with pregnancy.

As there were some limitations in the methodology of these recent studies, further analyses are needed before any firm conclusions can be drawn. In the meantime, when jointly discussing the choice of contraceptive with an individual woman, prescribers should be aware of the new evidence when discussing the most suitable type of contraceptive for any woman who wants to start or switch contraception. Any prescribing decision should take into account each woman’s personal risk factors and any contraindications. When used appropriately, the benefits of all combined oral contraceptives far outweigh the risk of VTE, which is rare.

The contraception section of NPC reviews the evidence for all COCs including Yasmin.

Adverse effects on renal function of IV zoledronic acid
Zoledronic acid is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction or other risk factors. Renal function should be measured before each dose, and patients should be adequately hydrated before treatment. Renal function monitoring is recommended after use of zoledronic acid in at-risk patients — especially those with pre-existing renal impairment; those on concomitant nephrotoxic drugs or diuretic therapy; the elderly; or those who are dehydrated. Use in patients with severe renal impairment is generally not recommended, but may be considered for tumour-induced hypercalcaemia, if the benefits outweigh the risks.

Additional news from the April 2010 Drug Safety Update includes:

  • A warning of the fatal overdose risk due to confusion between lipid-based and non-lipid based formulations of parental amphotericin B.
  • Notification that the solvent used in the preparation of Rifadin (rifampicin) infusion has been reformulated. As a result, it can only be diluted with either dextrose 5% solution or sodium chloride 0.9% solution
  • A precautionary warning has been issued contraindicating the use of becaplermin (Regranex) in patients with any known malignancy.

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