Drug Interactions between ezetimibe / rosuvastatin and sirolimus

MONITOR: Higher dosages of lipid-lowering agents may be required during concomitant administration of sirolimus or temsirolimus. Dose-related serum lipid abnormalities, including but not limited to increased serum cholesterol and triglycerides, have been frequently reported in patients treated with sirolimus or temsirolimus.

MANAGEMENT: Close clinical monitoring of serum cholesterol and triglycerides is recommended if sirolimus or temsirolimus is prescribed to patients receiving lipid-lowering agents. Modification of the antihyperlipidemic regimen or dosages may be necessary.

MONITOR: Higher dosages of lipid-lowering agents may be required during concomitant administration of sirolimus or temsirolimus. Dose-related serum lipid abnormalities, including but not limited to increased serum cholesterol and triglycerides, have been frequently reported in patients treated with sirolimus or temsirolimus.

MANAGEMENT: Close clinical monitoring of serum cholesterol and triglycerides is recommended if sirolimus or temsirolimus is prescribed to patients receiving lipid-lowering agents. Modification of the antihyperlipidemic regimen or dosages may be necessary.

MONITOR: Coadministration with ezetimibe may rarely increase the risk of myopathy and serum transaminase elevations associated with HMG-CoA reductase inhibitors (i.e., statins). The mechanism of interaction is unknown. A case report describes two patients whose serum creatine kinase increased after ezetimibe was added to their statin therapy (atorvastatin and fluvastatin, respectively). One of the patients also developed myalgia and tendinopathy, which resolved promptly after withdrawal of both drugs. Statin therapy was subsequently reintroduced at the previous dosage without incident. In the other patient, serum creatine kinase returned to normal within 4 weeks after discontinuation of ezetimibe while the statin was continued. On the contrary, no cases of myopathy or tendinopathy occurred in a study of 33 hypercholesterolemic patients treated with ezetimibe and atorvastatin or simvastatin. There were also no reports of myopathy or significant increases in serum creatine kinase in a study of 32 subjects treated with ezetimibe and fluvastatin. In controlled clinical studies, the incidence of consecutive elevations (greater than 3 times the upper limit of normal) in serum transaminases was 1.3% for patients treated with ezetimibe in combination with a statin versus 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

MANAGEMENT: Until further information is available, use of a statin in combination with ezetimibe should be approached with caution. Some authorities consider concomitant use to be contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases. Patients should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. The drugs 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, liver function tests should be performed at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor.