The US Food and Drug Administration has warned of continued reports of a rare muscle injury when patients are concurrently treated with cholesterol drug simvastatin and antiarrhythmic drug amiodarone.

The agency released an alert on Friday stating patients were at risk of developing the rare condition rhabdomyolysis, which can lead to kidney failure and death, when they took a dose of simvastatin greater than 20mg per day in combination with amiodarone.

The announcement harks back to 2001 when Bayer’s Baycol/Lipobay (cerivastatin) was withdrawn from the market because it had been linked to rhabdomyolysis. The German company was forced to pay out more than $1 billion to settle injury claims.

Following the withdrawal and intense scrutiny of the simvastatin market, a revision of the labelling of the drug was brought in in 2002. This described an increased risk of rhabdomyolysis when amiodarone was taken with simvastatin doses greater than 20mg per day.

However, in the FDA alert, the agency acknowledged that despite the labelling changes in 2002, it was still receiving reports of the muscles condition as an adverse event.

The risk of the rhabdomyolysis was dose-related and increased when simvastatin doses increased, the FDA said.

FDA revising Cordarone labelling
The muscle injury disease has been reported with the use of all statins regardless of whether they are administered with amiodarone, though simvastatin has the most pronounced effects when given with the antiarrhythmic drug.

The exact mechanism on how the risk is increased is unknown but it is related to amiodarone’s ability to inhibit the cytochrome enzyme P450 3A4, which is the enzyme that metabolises simvastatin.

The FDA is now in the process of revising Cordarone (amiodarone) prescribing information to warn of this increased risk.

Bayer has not been the only drug company to be hit by the statin relationship with rhabdomyolysis. In 2005, AstraZeneca’s Crestor (rosuvastatin) was linked to a fatality from the muscle injury. In 2006, Pfizer was forced to defend Lipitor (atorvastatin) after a lawsuit was filed claiming the drug had caused muscle damage.