Simvastatin

Action

Inhibits hepatic enzyme HMG-CoA reductase, interrupting cholesterol synthesis and low-density lipoprotein (LDL) consumption. Net effect is total cholesterol and serum triglyceride reductions.

Availability

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.

Dosage adjustment

• Severe renal impairment

• Concurrent use of amiodarone, amlodipine, diltiazem, fibrates, niacin, ranolazine, verapamil, or voriconazole

• Elderly patients

Contraindications

• 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

Precautions

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).

Administration

• Check liver function tests before starting therapy.

• Give with evening meal. Don't give with large amounts of grapefruit juice.

Adverse reactions

CNS: headache, asthenia

GI: nausea, vomiting, diarrhea, constipation, abdominal pain or cramps, flatulence, dyspepsia

Musculoskeletal: myalgia, rhabdomyolysis

Respiratory: upper respiratory infection

Interactions

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

Patient monitoring

☞ 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.

Patient teaching

• 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.