Vytorin - Warnings & Precautions

WARNINGS

Myopathy/Rhabdomyolysis

In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the relevant control arm (placebo or HMG-CoA reductase inhibitor alone). However, myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs. In clinical trials, the incidence of CK >10 X the upper limit of normal [ULN] was 0.2%for VYTORIN. Simvastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested asmuscle pain, tenderness or weakness with creatine kinase above 10 X ULN. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.•

Because VYTORIN contains simvastatin, the risk of myopathy/rhabdomyolysis is increased by concomitant use of VYTORIN with the following:

Potent inhibitors of CYP3A4:

Cyclosporine, itraconazole, ketoconazole, erythromycin,clarithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice(>1 quart daily), particularly with higher doses of VYTORIN (see CLINICAL PHARMACOLOGY,Pharmacokinetics; PRECAUTIONS, Drug Interactions, CYP3A4 Interactions).

Other drugs:

Gemfibrozil, particularly with higher doses of VYTORIN (see CLINICAL PHARMACOLOGY,Pharmacokinetics; PRECAUTIONS, Drug Interactions, Interactions with lipid-lowering drugs that cancause myopathy when given alone).

Other lipid-lowering drugs (other fibrates or =1 g/day of niacin) that can cause myopathy when given alone (see PRECAUTIONS, Drug Interactions, Interactions with lipid-lowering drugs that can cause myopathy when given alone). Amiodarone or verapamil with higher doses of VYTORIN (see PRECAUTIONS, Drug Interactions, Other drug interactions). In an ongoing clinical trial, myopathy has been reported in 6% of patients receiving simvastatin 80 mg and amiodarone.