Rhabdomyolysis Warning Issued by FDA

The FDA issued an alert on Friday to remind doctors and the public about the risk of rhabdomyolysis, a rare and potentially fatal muscle condition, which could arise from the combined use of cholesterol drugs containing simvastatin, such as Zocor, Vytorin and Simcor, and heart drugs containing amiodarone, such as Cordarone and Pacerone.

The FDA has warned healthcare professionals to not administer more than 20 mg/day of simvastatin to patients receiving amiodarone, as the combined usage increases the risk of rhabdomyolysis. Patients using amiodarone, who also receive an initial dose or increased dose of simvastatin, have been urged to report any muscle pain, stiffness, weakness or spasms to their doctor. The use of other statins, other than Zocor, Vytorin and Simcor, in patients using amiodarone has also been recommended.

All cholesterol drugs in the class of medications known as statins, which include medications containing simvastatin, are associated with a risk of rhabdomyolysis when used on their own. However, the risk increases when simvastating is combined with a heart drug like amiodarone, which is used to treat abnormal heartbeat. The risk increases further when a patient using amiodarone are given doses of over 20 mg/day of simvastatin.

Rhabdomyolysis is a rare condition of muscle injury in which the skeletal muscle is damaged and releases myoglobin into the bloodstream. This may cause severe kidney failure and death. Symptoms include muscle cramps, tenderness, stiffness, pain or spasms. The illness is usually reported in patients over 65 years of age or those who have renal impairment or uncontrolled hypothyroidism.

While the precise mechanism that causes rhabdomyolysis as a side effect of these drugs remains unknown, it is associated with the fact that amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme, which metabolizes simvastatin.

Simvastatin is the generic name of an anti-cholesterol drug. It is an ingredient in Merck’s Zocor and Abbott’s Simcor, as well as generic versions of those drugs. It is one of two components contained in the popular cholesterol drug Vytorin.

Amiodarone is the generic name of an anti-arrhythmia drug. It is an ingredient in Wyeth’s Cordarone and Upsher-Smith’s Pacerone. The FDA indicates that they are working with the manufacturer of Cordarone to include a warning about the increased risk of rhabdomyolysis when Cordarone is combined with simvastatin or any anti-cholesterol medication containing simvastatin, such as Zocor, Simcor or Vytorin.

The FDA previously issued a warning in May 2002 about the increased risk of rhabdomyolysis caused when simvastatin is combined with amiodarone. However, the FDA has received 52 reports of rhabdomyolysis since then.