Stronger heart attack warning for Avandia

-NZ.doctor.co.nz

12/5/2007 - Prescribing information about the diabetes drug rosi-glitazone (Avandia) is being updated to include a stronger warning about the risk of heart attack.

Medsafe told Avandia’s manufacturer GlaxoSmithKline last month it expected it to strengthen the warning following a change in the drug’s labelling in the US to include a warning about the potential increased risk for heart attacks.

GSK is currently in discussions with Medsafe over precisely how the warning will be strengthened, and the process should only take a matter of weeks, says GSK Australia’s brand communications manager Jo Doyle.

The company is proposing the same changes already made in the US and Australia, according to the Ministry of Health.

A “black box” warning was added to Avandia in Australia last month stating its use is “not recommended in patients with known ischaemic heart disease...[and that] Avandia has been shown to be associated with an increased risk of myocardial ischaemia (angina, infarction) in pooled short term clinical studies, particularly in those who needed several antidiabetic drugs or nitrates.”
New Zealand prescribing information already contains information about a risk of heart attack and heart failure with Avandia, especially when used with insulin, so the drug should not be started as add-on therapy to patients already taking insulin, Medsafe interim manager Steward Jessamine says.

Otago University professor of medicine Jim Mann says he will be taking a slightly more cautious approach to the use of glitazones but will not be abandoning their use altogether.

“Certainly if there’s any suspicion of heart failure or myocardial ischaemia one would be very cautious about using them,” Professor Mann says. But there is no need to withdraw them when patients are responding well and have no obvious side effects, he adds.

Only about 400 patients in New Zealand are taking Avandia, according to Medsafe. Pio-glitazone (Actos) is the only funded glitazone in this country and it may not carry the same heart attack risk as rosiglitazone, says New Zealand Pharmacovigilance Centre medical assessor Ruth Savage.

Meanwhile, Dr Savage has written a prescriber update article reminding prescribers glitazones can cause dose-related fluid retention, particularly when used in combination with insulin or sulphonylureas, leading to new worsening heart failure and macular oedema.

The Medicines Adverse Reactions Committee (MARC), which has been monitoring glitazones since March last year, concluded in September this year, while glitazones still have a role in managing diabetes, their safety needs ongoing review.

Earlier this year, a meta-analysis linked rosiglitazone with a substantially higher risk of myocardial infarction than placebo or active comparator (New Zealand Doctor, 6 June), but the interim results of a large ongoing study found no excess risk of myocardial infarction or death (New Zealand Doctor, 4 July).

Last month, a report by the US Senate Committee of Finance found GSK used “intimidation” to silence early concerns about Avandia’s increased cardiovascular risk.