By Ed Silverman
November 8th, 2010
Since its approval last year, the Sanofi-Aventis Multaq heart drug has been controversial. For instance, a study published last spring found the pill is only modestly effective and has no clear safety benefits (see this) and more recently, questions were raised about the study that led to FDA approval (look here).
Now, a new analysis of FDA adverse event reports indicate Multaq may cause or worsen heart failure, trigger potentially lethal irregular heartbeats and impair kidney function. There is also a glaring discrepancy between the language in the Med Guide given docs and patients, and the warning label about pregnant patients. And the findings led The Institute for Safe Medicine Practices, which conducted the analysis, to conclude that “we have seldom seen a drug with so many issues in so many areas of its safety profile.”
Why? The non-profit points out that development stopped several years ago after a study of patients with severe heart failure found the drug doubled the risk of death; other data found signals of cancer and birth defects in animals; there are potentially serious interactions with other drugs used to treat atrial fibrillation, and Multaq causes new heart rhythm disturbances in some patients.
In its analysis, ISMP found 387 domestic serious adverse events cited Multaq as he primary suspect in reports involving 24 deaths, two cases of disability, and 361 other serious reactions. Overall, 25.8 percent indicated new or worsened heart failure. “This was of concern given that worsened heart failure was identified as the reason for increased mortality in the company’s trial in heart failure patients; the current prescribing information cautions doctors to consider discontinuing or suspending the drug if heart failure develops,” ISMP writes.
Heart rhythm disturbances were also reported, including 18 potential cases of abnormally slow heartbeats, 47 cases of rapid heartbeats and 13 cases of ventricular tachycardia. ISMP says this was determined after noticing earlier this year that Multaq accounted for more reported cases of these kinds of rhythm disturbances than any other drug it monitors. There were also 15 cases of kidney failure or impairment, including four cases of acute kidney failure, but computer excerpts did not provide sufficient info to evaluate them, ISMP reports.
And so ISMP asked Sanofi-Aventis for a reply and this came back: “The company said it believed that some studies showed that the reporting rate for adverse drug events may be higher during the first two years after introduction.” In other words, wait a few years and adverse events may drop? The drugmaker acknowledged, though, that the FDA is evaluating “at least two signals” in the adverse event data - heart failure and Torsades de Points, a lethal form of ventricular tachycardia.
One final note: ISMP found the Medication Guide has a “serious lapse.” The non-profit notes the FDA classified Multaq is teratogenic, or a risk for pregnant women. The label says: Multaq may cause fetal harm when administered to a pregnant woman…(and) is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.”
Yet, the Med Guide says: “It is not known if Multaq will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.” ISMP writes that “we raised this issue with Sanofi-Aventis, which told us the company believed the current wording was appropriate.”