simvastatin

simvastatin

(sim va stah' tin)

Zocor

Pregnancy Category X

Drug classes

Antihyperlipidemic

HMG-CoA reductase inhibitor

Therapeutic actions

Inhibits HMG-CoA reductase, 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

·        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

·        Treatment of adolescents 10-17 yr with heterozygous familial hypercholesterolemia

Contraindications and cautions

·        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 acidsequestrants. Combined with cyclosporine, start with 5 mg/day; do not exceed 20 mg/day. Combination with amiodarone or verapamil, dose should not exceed 20 mg/day.

PEDIATRIC PATIENTS (10-17 YR)

10 mg/day PO in the evening. Range, 10-40 mg/day based on response.

GERIATRIC PATIENTS AND PATIENTS WITH RENAL IMPAIRMENT

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

Pharmacokinetics

Route	Onset	Peak
Oral	Slow	1.3–2.4 hr

Metabolism: Hepatic; T_1/2: 3 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Feces, urine

Adverse effects

·        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

·        WARNING: 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 amiodarone, verapamil; do not exceed 20 mg simvastatin daily

·        Increased risk of myopathy and rhabdomyolysis with cyclosporine, fibrates, niacin; monitor patient closely if use together cannot be avoided. Do not 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

·        History: Allergy to simvastatin, fungal byproducts; impaired hepatic function; pregnancy; lactation

·        Physical: Orientation, affect; liver evaluation, abdominal examination; lipid studies, LFTs

Interventions

·        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

·        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.

·        You may experience these side effects: Nausea (eat frequent small meals); headache, muscle and joint aches and pains (may lessen); sensitivity to light (use asuncreen 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.