In

simvastatin (sim va stah' tin) Zocor Pregnancy Category X Drug classes

Antihyperlipidemic HMG-CoA inhibitor Therapeutic actions

Inhibits HMG-CoA, the enzyme that catalyzes the first step in the cholesterol synthesis pathway, resulting in a decrease in serum cholesterol, serum LDLs, and either an increase or no change in serum HDLs. Indications

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Adjunct to diet in the treatment of elevated total cholestrol and LDL cholesterol with primary hypercholesterolemia (types IIa and IIb) in those unresponsive to dietary restriction of saturated fat and cholesterol and other nonpharmacologic measures To reduce the risk of coronary disease, mortality, and CV events, including stroke, TIA, MI and reduction in need for bypass surgery and angionplasty in patients with coronary heart disease and hypercholesterolemia Treatment of patients with isolated hypertriglyceridemia Treatment of type III hyperlipoproteinemia

Contraindications and cautions

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Contraindicated with allergy to simvastatin, fungal byproducts, pregnancy, lactation. Use cautiously with impaired hepatic and renal function, cataracts.

Available forms

Tablets—5, 10, 20, 40, 80 mg Dosages ADULTS

Initially, 20 mg PO up to 80 mg PO daily in the evening. Usual range, 5–80 mg/day. Maximum dose, 80 mg/day. Adjust at 4-wk intervals. • Familial hypercholesterolemia: 40 mg/day PO in the evening, or 80 mg/day divided into doses of 20 mg, 20 mg, and 40 mg in the evening. • Combination therapy: Do not combine with other statins; if used with fibrates or niacin, do not exceed 10 mg/day; regular dose if combined with bile acid sequestrants. Combined with cyclosporine, start with 5 mg/day; do not exceed 10 mg/day. PEDIATRIC PATIENTS

Safety and efficacy not established.

GERIATRIC PATIENTS AND PATIENTS WITH RENAL IMPAIRMENT

Starting dose, 5 mg/day PO; increase dose slowly, monitoring response. Pharmacokinetics Route Oral

Onset Slow

Peak 1.3–2.4 hr

Metabolism: Hepatic; T1/2: 3 hr Distribution: Crosses placenta; enters breast milk Excretion: Urine and feces Adverse effects

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CNS: Headache, asthenia, sleep disturbances GI: Flatulence, diarrhea, abdominal pain, cramps, constipation, nausea, dyspepsia, heartburn, liver failure Respiratory: Sinusitis, pharyngitis Other: Rhabdomyolysis, acute renal failure, arthralgia, myalgia

Interactions

Drug-drug • Increased risk of myopathy and rhabdomyolysis with amiodarone, verapamil; do not exceed 20 mg simvastatin daily • Increased risk of myopathy and rhabdomyolysis with clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone; avoid concomitant use, or suspend therapy during treatment with clarithromycin, erythromycin, itraconazole, and ketoconazole • Increased risk of myopathy and rhabdomyolysis with cyclosporine, fibrates, niacin; monitor patient closely if use together can’t be avoided. Don’t exceed 10 mg simvastatin daily • Digoxin levels may increase slightly; closely monitor plasma digoxin levels at the start of simvastatin therapy • Increased risk for hepatotoxicity with hepatotoxic drugs; avoid concurrent use • Simvastatin may slightly enhance the anticoagulant effect of warfarin; monitor PT and INR at the start of therapy and during dose adjustment Drug-food • Decreased metabolism and risk of toxic effects if combined with grapefruit juice; avoid this combination Nursing considerations Assessment

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History: Allergy to simvastatin, fungal byproducts; impaired hepatic function; pregnancy; lactation Physical: Orientation, affect; liver evaluation, abdominal exam; lipid studies, liver function tests

Interventions

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Ensure that patient has tried a cholesterol-lowering diet regimen for 3–6 mo before beginning therapy. Give in the evening; highest rates of cholesterol synthesis are between midnight and 5 AM. Advise patient that this drug cannot be taken during pregnancy; advise patient to use barrier contraceptives. Arrange for regular follow-up during long-term therapy. Consider reducing dose if cholesterol falls below target.

Teaching points

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Take drug in the evening. Do not drink grapefruit juice while using this drug. Have periodic blood tests. This drug cannot be taken during pregnancy; using barrier contraceptives is recommended. These side effects may occur: Nausea (eat frequent small meals); headache, muscle and joint aches and pains (may lessen); sensitivity to light (use a suncreen and wear protective clothing). Report severe GI upset, changes in vision, unusual bleeding or bruising, dark urine or light-colored stools, fever, muscle pain, or soreness.

Adverse effects in Italic are most common; those in Bold are life-threatening.