Causation Theory: Zocor Is Metabolized By Same Enzyme Which Is Being Inhibited By Amiodarone
On March 14, 2006 The Annals of Pharmacotherapy published online an article about what the authors described as "the fifth reported instance, as of February 15, 2006, of a severe interaction between simvastatin and amiodarone." Simvastatin in sold by Merck under the trade name Zocor. Amiodarone is sold by Wyeth as Cordarone, and by Upsher-Smith as Pacerone; several companies sell a generic version of amiodarone, also.
This latest case report involves a 72-year-old white man who started taking amiodarone (200 mg/day) on July 10, 2004, and on August 13 started taking Zocor (80 mg/day) while continuing the amiodarone. The patient was hospitalized on September 21, 2004 after complaining of thigh weakness and achiness; he also reported having dark urine for 7 days.
At the time of his hospital admission, the patient's relevant lab results were as follows:
- creatine kinase (CK) 19,620 U/L (reference range 60-224);
- blood urea nitrogen 50 mg/dL;
- creatinine 2.6 mg/dL;
- aspartate aminotransferase (AST) 912 U/L (30-60);
- alanine aminotransferase (ALT) 748 U/L (30-60);
- urine myoglobin 71,100 µg/L (<50); and,
- serum myoglobin 13,877 µg/L (<110).
Upon admission, the Zocor and amiodarone were discontinued. The patient was ultimately diagnosed with rhabdomyolysis, renal failure, and possibly hepatotoxicity. After appropriate treatment, the patient recovered over the course of the next couple of weeks.
The authors of this drug-drug interaction case report in The Annals of Pharmacotherapy arrived at these conclusions:
- "An objective causal assessment suggests that rhabdomyolysis, renal failure, and possibly hepatotoxicity were probably related to an amiodarone-simvastatin [i.e., Zocor] interaction."
- "[Zocor] is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This may, therefore, account for the presumed drug interaction."
The authors pointed out that this patient had pre-existing diabetes mellitus, hyperlipidemia, and hypertension, as well as mild azotemia. They did not, however, believe that these pre-existing medical conditions were substantial contributing causes as concerned the drug-induced rhabdomyolysis.
(Posted by: Tom Lamb)