Generic Name and Formulations:
Ezetimibe, simvastatin; 10mg/10mg, 10mg/20mg, 10mg/40mg, 10mg/80mg; tabs.
Merck & Co., Inc.
Indications for VYTORIN:
Adjunct to diet in primary hyperlipidemia (heterozygous familial and non-familial) or mixed hyperlipidemia: to reduce elevated total-C, LDL-C, apo B, TG and non-HDL-C, and to increase HDL-C. Adjunct to or when other lipid-lowering treatments for homozygous familial hypercholesterolemia (HoFH) are not available: to reduce elevated total-C and LDL-C.
Limitations Of use:
No incremental benefit on cardiovascular morbidity/mortality over and above that demonstrated for simvastatin has been established. Not studied in Fredrickson type I, III, IV, and V dyslipidemias.
Take once daily in the PM. ≥17yrs: Initially 10mg/10mg or 10mg/20mg; for LDL-C reduction >55%: may start at 10mg/40mg; monitor lipids after 2 wks then periodically. HoFH: 10mg/40mg. Concomitant verapamil, diltiazem, dronedarone: max 10mg/10mg. Concomitant amiodarone, amlodipine, ranolazine: max 10mg/20mg. Concomitant bile acid sequestrants: give Vytorin dose either ≥2hrs before or ≥4hrs after bile acid sequestrant administration. Concomitant lomitapide: reduce Vytorin dose by 50%; max 10mg/20mg daily (or 10mg/40mg daily for those previously taken simvastatin 80mg/day chronically). Renal insufficiency (CrCl<60mL/min): 10mg/20mg/day. Chinese patients taking niacin ≥1g/day or niacin-containing products: use caution with Vytorin doses >10mg/20mg/day; do not use 10mg/80mg dose. Restrict 10mg/80mg dose to chronic users (≥12mos) without evidence of muscle toxicity; if currently tolerating Vytorin 10mg/80mg dose and need to start a contraindicated drug or one associated with a simvastatin dose cap: switch to an alternative statin with less potential drug interaction. If patients unable to achieve their LDL-C goal using Vytorin 10/40mg: do not titrate to 10mg/80mg dose, switch to alternative regimen that provides greater LDL-C lowering.
Concomitant strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, cobicistat-containing agents), gemfibrozil, cyclosporine, danazol. Active liver disease. Unexplained persistent elevated serum transaminases. Pregnancy (Cat.X). Nursing mothers.
Increased risk of myopathy/rhabdomyolysis with simvastatin 80mg doses including predisposing factors (eg, age ≥65yrs, female gender, uncontrolled hypothyroidism, renal impairment). Discontinue if markedly elevated CPK (>10xULN) levels occur or myopathy diagnosed or suspected. Temporarily withhold if acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis occurs. Monitor liver function prior to initation and repeat as clinically indicated. Interrupt therapy if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs; do not restart if alternate etiology not found. History of liver disease. Substantial alcohol consumption. Moderate-to-severe renal impairment. Elderly. Women of childbearing potential who needs treatment: use effective contraception; discontinue if pregnancy occurs.
Cholesterol absorption inhibitor + HMG-CoA reductase inhibitor.
See Contraindications. Avoid concomitant grapefruit juice >1 quart daily. Caution with fenofibrates, niacin ≥1g/day or niacin-containing products (esp. Chinese patients), or lomitapide (in HoFH patients). Antagonized by cholestyramine. Reduce max simvastatin dose if amiodarone, verapamil, diltiazem, amlodipine, ranolazine, voriconazole must be used. Caution with colchicine. Monitor digoxin, oral anticoagulants.
Headache, myalgia, pain in extremity, myopathy, rhabdomyolysis, upper respiratory tract infection, diarrhea, elevated serum transaminases, increased HbA1c and fasting serum glucose; rare: immune-mediated necrotizing myopathy.
Tabs 10mg/10mg, 10mg/20mg—30, 90, 1000, 10000; 10mg/40mg—30, 90, 500, 5000; 10mg/80mg—30, 90, 500, 2500