SIM-va-sta-tin

Therapeutic Classification: lipid-lowering agents

Pharmacologic Classification: hmg coa reductase inhibitors (statin)

• Adjunctive management of primary hypercholesterolemia and mixed dyslipidemias.
• Secondary prevention of myocardial infarction, coronary revascularization, stroke, and cardiovascular mortality in patients with clinically evident coronary heart disease.

• Inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that is responsible for catalyzing an early step in the synthesis of cholesterol.

• Lowering of total and LDL cholesterol (LDL-C) and triglycerides. Slightly increases HDL cholesterol (HDL-C).
• Slows the progression of coronary atherosclerosis with resultant decrease in coronary heart disease-related events.

Absorption: 85% absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 95%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; excreted in bile and feces; 13% excreted unchanged by the kidneys.

Half-life: Unknown.

(cholesterol-lowering effect)

†After discontinuation.

Contraindicated in:

• Hypersensitivity
• Concurrent use of strong CYP3A4 inhibitors (protease inhibitors, itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, nefazodone, cobicistat-containing products), gemfibrozil, cyclosporine, or danazol (↑ risk of myopathy/rhabdomyolysis)
• Active liver failure or decompensated cirrhosis
• Chinese patients receiving 1 g/day of niacin (↑ risk of myopathy/rhabdomyolysis)
• Lactation: Lactation.

Use Cautiously in:

• History of liver disease
• Alcoholism
• Uncontrolled hypothyroidism and renal impairment (↑ risk of myopathy/rhabdomyolysis)
• OB: Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta)
• Women of reproductive potential
• Pedi: Children <10 yr (safety and effectiveness not established)
• Geri: ↑risk of myopathy/rhabdomyolysis in older adults.

Derm: rash, pruritus.

Endo: hyperglycemia.

GI: abdominal cramps, constipation, diarrhea, flatus, heartburn, altered taste, drug-induced hepatitis, dyspepsia, ↑ liver enzymes, nausea, pancreatitis.

GU: erectile dysfunction.

MS: arthralgia, immune-mediated necrotizing myopathy, myopathy (↑ risk with 80 mg dose), RHABDOMYOLYSIS.

Neuro: amnesia, confusion, dizziness, headache, insomnia, memory loss, weakness.
Misc: (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Risk of myopathy and rhabdomyolysis are significantly ↑ with concurrent use of cyclosporine, gemfibrozil, danazol, erythromycin, clarithromycin, protease inhibitors, nefazodone, ketoconazole, itraconazole, voriconazole, posaconazole, or cobicistat-containing products; concurrent use contraindicated.
• Bioavailability may be ↓ by bile acid sequestrants.
• Risk of myopathy is ↑ by concurrent use of amiodarone, amlodipine, daptomycin, diltiazem, dronedarone, verapamil, ranolazine, lomitapide, or niacin; avoid concurrent use with niacin at doses of 1 g/day in Chinese patients; temporarily suspend simvastatin therapy during treatment with daptomycin; use ↓ doses with amiodarone, amlodipine, diltiazem, dronedarone, lomitapide, ranolazine, or verapamil.
• May slightly ↑ serum digoxin levels.
• May ↑ risk of bleeding with warfarin.

Drug-Food:

• Risk of myopathy and rhabdomyolysis are significantly ↑ with concurrent use of grapefruit juice;.

The 80 mg dose should be restricted to patients who have been taking this dose for 12 mo without evidence of muscle toxicity.

• PO (Adults): 20–40 mg once daily in the evening; if LDL-C goal cannot be achieved with 40 mg/day dose, add another lipid-lowering therapy (do not ↑ simvastatin dose to 80 mg/day). Concurrent use of verapamil, diltiazem, or dronedarone: Not to exceed 10 mg/day. Concurrent use of amiodarone, amlodipine, or ranolazine: Not to exceed 20 mg/day; Concurrent use of lomitapide: ↓dose by 50% (not to exceed 20 mg/day or 40 mg/day for patients who previously received 80 mg/day chronically [for 12 mo] without evidence of myopathy).
• PO (Children 10–17 yr): 10 mg once daily in the evening initially; may be ↑ at 4-wk intervals up to 40 mg once daily. Concurrent use of amiodarone, amlodipine, or ranolazine: Not to exceed 20 mg/day Concurrent use of verapamil or diltiazem: Not to exceed 10 mg/day.

(Generic available)

• Oral suspension: 20 mg/5 mL; 40 mg/5 mL;
• Tablets: 5 mg; 10 mg; 20 mg; 40 mg; 80 mg;
• In combination with: ezetimibe (Vytorin). See Appendix [not included in this PDA edition].

• Obtain a diet history, especially with regard to fat consumption.

• Evaluate serum cholesterol, LDL-C, HDL-C, and triglyceride levels before initiating, after 4 wk of therapy, and periodically thereafter.
  • Monitor liver function tests prior to initiation of therapy and as clinically indicated. If symptoms of serious liver injury, hyperbilirubinemia, or jaundice occur, discontinue simvastatin and do not restart. May also cause ↑ alkaline phosphatase and bilirubin levels.
  • If patient develops muscle tenderness during therapy, CK levels should be monitored. If CK levels are markedly ↑ or myopathy occurs, therapy should be discontinued. Predisposing factors for myopathy include 65 yr, female, uncontrolled hypothyroidism, and renal impairment. Chinese patients may be at increased risk for myopathy.

• Do not confuse Zocor with Cozaar or Zyrtec.
• PO: Administer once daily in the evening. May be administered without regard to food.
  • Avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.

• Instruct patient to take medication as directed, not to skip doses or double up on missed doses. Advise patient to avoid drinking more than 1 quart of grapefruit juice/day during therapy. Medication helps control but does not cure elevated serum cholesterol levels.
• Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
• Instruct patient to notify health care professional if unexplained muscle pain, tenderness, or weakness occurs, especially if accompanied by fever or malaise.
• Advise patient to wear sunscreen and protective clothing to prevent photosensitivity reactions (rare).
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional of medication regimen before treatment or surgery.
• Instruct females of reproductive potential to use effective contraception during therapy, to notify health care professional promptly if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta).
• Emphasize the importance of follow-up exams to determine effectiveness and to monitor for side effects.

• Decrease in LDL-C and total cholesterol levels.
  • Increase in HDL-C cholesterol levels.
  • Decrease in triglyceride levels.
• Slowing of the progression of coronary artery disease.

FloLipid, Zocor