Drug interactions between Calan and simvastatin
| Results for the following 2 drugs: |
|---|
| Calan (verapamil) |
| simvastatin |
Interactions between your selected drugs
verapamil ↔ simvastatin
Applies to:Calan (verapamil) and simvastatin
ADJUST DOSE: Coadministration with verapamil may significantly increase the plasma concentrations of simvastatin and lovastatin and potentiate the risk of statin-induced myopathy. In 12 healthy volunteers, verapamil (240 mg/day for 2 days) increased the mean peak serum concentration (Cmax) and area under the concentration-time curve (AUC) of unchanged simvastatin (40 mg single dose) by 2.6-fold and 4.6-fold, respectively, compared to placebo. The proposed mechanism is verapamil inhibition of simvastatin metabolism via intestinal and hepatic CYP450 3A4. Although not studied, the interaction is also expected to occur with lovastatin due to its similar metabolic profile to simvastatin. Clinically, high levels of statin or HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. 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%). There is also a reported case of rhabdomyolysis and acute renal failure in a patient receiving multiple drugs that inhibit CYP450 3A4, including verapamil.
MANAGEMENT: Simvastatin dosage should not exceed 10 mg daily and lovastatin dosage not exceed 20 mg daily when used in combination with verapamil. The benefits of this combination should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. Fluvastatin, pravastatin, and rosuvastatin are probably safer alternatives in patients receiving verapamil, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark-colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.
See also...
Drug Interaction Classification
The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to determine using this tool alone given the large number of variables that may apply.
| Major | Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. |
| Moderate | Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. |
| Minor | Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. |
Do not stop taking any medications without consulting your healthcare provider.
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