Interactions between amlodipine and atorvastatin
Any time when the patient with stroke in on 80 mg of simvastatin if you add norvasc a window will pop-up saying that the interactions between these two drugs could be harmful. If you overwrite the order the pharmacist will call you and tell you to reduce the dose of simvastatin to 20 mg daily if there is no other choice to avoid the combo. Here it is some more info.
ADJUST DOSE: Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and potentiate the risk of statin-induced myopathy. The proposed mechanism is amlodipine inhibition of simvastatin metabolism via intestinal and hepatic CYP450 3A4. When a single 80 mg dose of simvastatin was administered on day 10 of amlodipine given at a dosage of 10 mg once daily, simvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by an average of 1.5- and 1.8-fold, respectively, while simvastatin acid Cmax and AUC increased by an average of 1.6-fold each. 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.
MANAGEMENT: Simvastatin dosage should not exceed 20 mg daily when used in combination with amlodipine. 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 amlodipine, 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.
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