Vytorin - Warnings & Precautions

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In an analysis of clinical trials involving 25,248 patientstreated with simvastatin 20 to 80 mg, the incidence of myopathy was higher in patients receiving verapamil and simvastatin (4/635; 0.63%) than in patients taking simvastatin without a calcium channel blocker (13/21,224; 0.061%).• The risk of myopathy/rhabdomyolysis is dose related for simvastatin. The incidence in clinical trials, in which patients were carefully monitored and some interacting drugs were excluded, has been approximately 0.02% at 20 mg, 0.07% at 40 mg and 0.3% at 80 mg.Consequently:

1. Use of VYTORIN concomitantly with itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice (>1 quart daily) shouldbe avoided. If treatment with itraconazole, ketoconazole, erythromycin, or clarithromycin is unavoidable, therapy with VYTORIN should be suspended during the course of treatment. Concomitant use with othermedicines labeled as having a potent inhibitory effect on CYP3A4 at therapeutic doses should be avoidedunless the benefits of combined therapy outweigh the increased risk.

2. There is an increased risk of myopathy when simvastatin is used concomitantly with gemfibrozil orother fibrates; the safety and effectiveness of ezetimibe administered with fibrates have not been established. Therefore, the concomitant use of VYTORIN and fibrates should be avoided. (SeePRECAUTIONS, Drug Interactions, Other Drug Interactions, Fibrates.)

3. Caution should be used when prescribing lipid-lowering doses (=1 g/day) of niacin with VYTORIN, asniacin can cause myopathy when given alone. The benefit of further alterations in lipid levels by thecombined use of VYTORIN with niacin should be carefully weighed against the potential risks ofthis drug combination.

4. The dose of VYTORIN should not exceed 10/10 mg daily in patients receiving concomitantmedication with cyclosporine. The benefits of the use of VYTORIN in patients receiving cyclosporineshould be carefully weighed against the risks of this combination. (See PRECAUTIONS, Drug Interactions, Other Drug Interactions, Cyclosporine.)