Co-administration with verapamil may significantly increase the plasma concentrations of Zocor® and Mevacor® and potentiate the risk of statin-induced myopathy according to the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH). This is not well known among physicians and is seldom considered, even when a patient on the combination presents with muscle complaints.
Verapamil is one of the group of drugs called calcium channel blockers, used frequently over two decades for hypertension, angina, arrythmias and even cluster headaches.
A recent study involving high dose Zocor (80mg/day) brought out this verapamil issue along with other major concerns. This negative appraisal of high-dose Zocor was prompted by new results from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), presented at the Scientific Sessions of the American Heart Association held in November of 2008.
In this randomized, double-blind, multicenter United Kingdom trial of 12,064 patients with a prior myocardial infarction, some participants were given 80 mg of Zocor daily while others were given 20 mg of Zocor daily.
The researchers found that those taking 80 mg of Zocor daily compared with those receiving a daily 20-mg dose showed no difference in the primary end point of major coronary events, stroke, and revascularization, with 1477 events (24.5%) reported in the 80-mg group and 1553 (25.7%) in the 20-mg group. However, the 2 dosage groups differed significantly in terms of adverse effects, with 53 patients taking the 80-mg dose developing myopathy compared with only 3 in the 20-mg group.
In 12 healthy volunteers, verapamil (240 mg/day for 2 days) increased the serum concentration of simvastatin (40 mg single dose) by 2.6-fold and 4.6-fold, over the two day period, respectively, compared with placebo.
In an analysis of clinical trials involving over 25,000 patients treated with simvastatin 20 mg to 80 mg, the incidence of myopathy was higher in patients receiving concomitant verapamil than in those not receiving a calcium channel blocker (0.63% vs 0.061%). Please note that this is a major difference!
The proposed mechanism is verapamil inhibition of Zocor metabolism via intestinal and hepatic CYP450 3A4. Although not studied, the interaction is also expected to occur with Mevacor due to its similar metabolic profile to Zocor.
In addition, all statins are well known to be associated with greater incidence of myopathy and rhabdomyolysis at higher doses by their inevitable consequence of CoQ10 suppression.
Zocor and Mevacor have this verapamil linked mechanism in addition to account for their muscle damage. A recent review of raw Medwatch reports for Lipitor® from the beginning of marketing through 2006 found 1,591 reports of rhabdomyolysis hospitalizations, reflecting this general tendency of all stronger statins to have the potential to cause serious muscle damage.
Lower dosing of statins is now a general trend. My own experience with 2 episodes of Lipitor associated transient global amnesia warns me that even a 5 mg/day dose may be hazardous. But with my past experience as a medical researcher and doctor, I recognize that some may be particularly sensitive and a truly safe dose for general use is yet to be defined.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor