Also found in: Dictionary, Thesaurus, Wikipedia.
Pharmacologic class: HMG-CoA reductase inhibitor
Therapeutic class: Antihyperlipidemic
Pregnancy risk category X
Inhibits hepatic enzyme HMG-CoA reductase, interrupting cholesterol synthesis and low-density lipoprotein (LDL) consumption. Net effect is total cholesterol and serum triglyceride reductions.
Tablets: 5 mg, 10 mg, 20 mg, 40 mg, 80 mg
Indications and dosages
➣ Adjunct to diet to reduce risk of coronary heart disease (CHD) deaths, cardiovascular events, and hyperlipidemia
Adults: Initially, 10 to 20 mg P.O. daily in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, or history of stroke or other cerebrovascular disease, initial dosage is 40 mg/day. Range is 5 to 40 mg/day. Restrict use of 80-mg dose to patients who have been taking simvastatin 80 mg long term (for example, for 12 months or more) without evidence of muscle toxicity. Patients unable to achieve their LDL-C goal utilizing 40-mg dose should not be titrated to 80-mg dose, but should be placed on alternative LDL-C-lowering treatment that provides greater LDL-C lowering effects.
➣ Adjunct to other lipid-lowering treatments (such as LDL apheresis) or if such treatments are unavailable for patients with homozygous familial hypercholesterolemia
Adults: 40 mg/day P.O. in the evening.
➣ Heterozygous familial hypercholesterolemia after failure of an adequate trial of diet therapy
Adolescent boys and postmenarchal girls ages 10 to 17: Initially, 10 mg P.O. daily in the evening. Range is 10 to 40 mg/day; maximum dose is 40 mg/day. Adjust at intervals of 4 weeks or longer.
• Severe renal impairment
• Concurrent use of amiodarone, amlodipine, diltiazem, fibrates, niacin, ranolazine, verapamil, or voriconazole
• Elderly patients
• Hypersensitivity to drug or its components
• Active hepatic disease or unexplained persistent serum transaminase elevations
• Concurrent use of cyclosporine, danazol, gemfibrozil, or strong CYP3A4 inhibitors
• Women who are pregnant or may become pregnant
• Breastfeeding patients
Use cautiously in:
• severe renal impairment; severe acute infection; hypotension; severe metabolic, endocrine, or electrolyte problems; uncontrolled seizures; visual disturbances; myopathy; major surgery; trauma; alcoholism
• history of hepatic disease, liver enzyme abnormalities
• concurrent use of amiodarone, amlodipine, colchicine, digoxin, diltiazem, and lipid-modifying dosages (1 g/day or more) of niacincontaining products, other fibrates, ranolazine, verapamil, or warfarin
• concurrent use of simvastatin in dosages exceeding 20 mg/day with lipid-modifying dosages (1 g/day or more) of niacin-containing products in Chinese patients (avoid use)
• large quantities of grapefruit juice (avoid use)
• elderly patients
• children younger than age 10 (safety not established).
• Check liver function tests before starting therapy.
• Give with evening meal. Don't give with large amounts of grapefruit juice.
CNS: headache, asthenia
GI: nausea, vomiting, diarrhea, constipation, abdominal pain or cramps, flatulence, dyspepsia
Musculoskeletal: myalgia, rhabdomyolysis
Respiratory: upper respiratory infection
Drug-drug. Amiodarone, calcium channel blockers (such as amlodipine, diltiazem, verapamil), colchicine, other lipid-lowering drugs (such as fibrates or lipid-modifying doses of niacin-containing products), ranolazine, voriconazole: increased risk of myopathy including rhabdomyolysis
Cyclosporine, danazol, diltiazem, gemfibrozil, nefazodone, strong CYP3A4 inhibitors (clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, posaconazole, telithromycin): increased risk of severe myopathy or rhabdomyolysis
Digoxin: slightly increased digoxin blood level
Warfarin: modestly increased anticoagulant effects
Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: increased levels
Drug-food. Grapefruit juice (more than 1 qt daily): increased drug blood level, greater risk of adverse reactions
Drug-behaviors. Alcohol use: increased risk of hepatotoxicity
☞ Watch closely for myositis and other adverse musculoskeletal reactions. Know that drug may cause rhabdomyolysis.
• Monitor liver function tests, CBC, and lipid levels.
• In patients receiving warfarin concurrently, closely monitor prothrombin time and International Normalized Ratio.
• Advise patient to take with evening meal, but not with large amounts of grapefruit juice.
• Tell patient drug may take up to 4 weeks to be effective.
☞ Caution patient to stop taking drug and contact prescriber if she suspects she is pregnant.
☞ Teach patient to recognize and report signs and symptoms of myopathy or hepatic disorders.
• Instruct patient to avoid alcohol use.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.
simvastatinA lipid-lowering HMG-CoA reductase inhibitor used to improve lipid profiles and reduce mortality from coronary heart diseasse, diabetes and stroke.
Decreases total cholesterol by 27%, LDL-C by 35–60%, triglycerides by 20–37%, and increases HDL-C by 5–9%.
Constipation, flatulence, dyspepsia, abdominal pain, myalgia, muscle weakness.