Drug Interactions between amlodipine / atorvastatin and fenofibrate

GENERALLY AVOID: Severe myopathy and rhabdomyolysis have been reported during concomitant use of HMG-CoA reductase inhibitors and fibric acid derivatives, especially gemfibrozil. Gemfibrozil has been reported to significantly increase the plasma concentrations of some HMG-CoA reductase inhibitors and/or their active metabolites, including lovastatin, simvastatin, pravastatin, cerivastatin, and rosuvastatin (but not fluvastatin). High levels of 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. Other fibrates have not been shown to significantly affect the pharmacokinetics of HMG-CoA reductase inhibitors. However, the use of fibrates alone has also been associated with development of myopathy, thus a pharmacodynamic interaction could conceivably occur.

MANAGEMENT: Concurrent use of fibric acid derivatives and HMG-CoA reductase inhibitors should generally be avoided unless the benefit of further alterations in lipid levels is anticipated to outweigh the potential risks. Addition of fibrates to HMG-CoA reductase inhibitor therapy typically provides little additional reduction in LDL cholesterol, but further reductions of triglycerides and increases in HDL cholesterol may be attained. If the combination is prescribed, a fibrate other than gemfibrozil may be preferable, along with lower initial dosages of the HMG-CoA reductase inhibitor. If gemfibrozil is used, rosuvastatin daily dosage should not exceed 10 mg. Lovastatin labeling recommends that the dosage not exceed 20 mg daily when prescribed with gemfibrozil or other fibrates. All patients treated with HMG-CoA reductase inhibitors and/or fibrates 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. In addition, patients should be closely monitored for hepatotoxicity.

Switch to consumer interaction data

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of HMG-CoA reductase inhibitors (i.e., statins) that are metabolized by the isoenzyme. Lovastatin and simvastatin are particularly susceptible because of their low oral bioavailability, but others such as atorvastatin and cerivastatin may also be affected. High levels of 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. Clinically significant interactions have been reported with potent CYP450 3A4 inhibitors such as macrolide antibiotics, azole antifungals, protease inhibitors and nefazodone, and moderate inhibitors such as amiodarone, cyclosporine, danazol, diltiazem and verapamil.

MANAGEMENT: Caution is recommended if atorvastatin, cerivastatin, lovastatin, simvastatin, or red yeast rice (which contains lovastatin) is prescribed with a CYP450 3A4 inhibitor. It is advisable to monitor lipid levels and use the lowest effective statin dose. 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. Fluvastatin, pravastatin, and rosuvastatin are not expected to interact with CYP450 3A4 inhibitors.

Switch to consumer interaction data