Lovastatin

Brand names: Advicor, Altoprev, MEVACOR, Lovastatin

Warnings

Contraindicated in "active liver disease or unexplained persistent elevations of serum transaminases," in pregnancy and lactation (fetal risk), and with known hypersensitivity to any component. Key warnings: risk of "myopathy manifested as muscle pain, tenderness or weakness" with marked creatine kinase elevation, which can progress to "rhabdomyolysis with or without acute renal failure," especially with certain interacting drugs; risk of liver dysfunction evidenced by "persistent increases of serum transaminases."

Contraindications

CONTRAINDICATIONS Hypersensitivity to any component of this medication. Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS ). Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin ,nefazodone, and cobicistat-containing products) (see WARNINGS , Myopathy/Rhabdomyolysis ) . Pregnancy and lactation. ( see PRECAUTIONS, Pregnancy and Nursing Mothers ). Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as lovastatin to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, lovastatin is contraindicated during pregnancy and in nursing mothers. Lovastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, lovastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see PRECAUTIONS , Pregnancy ).

Overdose

OVERDOSAGE After oral administration of lovastatin to mice, the median lethal dose observed was >15 g/m 2 . Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences. A few cases of accidental overdosage have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5 to 6 g. Until further experience is obtained, no specific treatment of overdosage with lovastatin can be recommended. The dialyzability of lovastatin and its metabolites in man is not known at present.

Drug interactions

Drug Interactions CYP3A4 Interactions Lovastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin. (See CONTRAINDICATIONS , WARNINGS, Myopathy/Rhabdomyolysis , and CLINICAL PHARMACOLOGY, Pharmacokinetics .)

Uses

Lovastatin is indicated: - As "an adjunct to diet for the reduction of elevated total-C and LDL-C levels" in primary hypercholesterolemia - For "primary prevention of coronary heart disease" to reduce the risk of myocardial infarction and unstable angina - To slow "the progression of coronary atherosclerosis in patients with coronary heart disease" - In adolescents (10-17 years) with heterozygous familial hypercholesterolemia.

Dosage forms & strengths

Tablet Tablet, Extended Release TABLET POWDER

LOVASTATIN 10 mg LOVASTATIN 20 mg LOVASTATIN 40 mg LOVASTATIN 60 mg Lovastatin 10 mg Lovastatin 20 mg Lovastatin 40 mg NIACIN 1000 mg NIACIN 500 mg NIACIN 750 mg lovastatin 10 mg lovastatin 20 mg lovastatin 40 mg LOVASTATIN 20 mg/1 LOVASTATIN 40 mg/1 LOVASTATIN 10 mg/1 LOVASTATIN 1 kg/kg LOVASTATIN 100 kg/100kg LOVASTATIN 1 g/g LOVASTATIN 100 g/100g

DOSAGE AND ADMINISTRATION The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin and should continue on this diet during treatment with lovastatin (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin should be given with meals. Adult Patients The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Guidelines and CLINICAL PHARMACOLOGY ). Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE ) should be started on 20 mg/day of lovastatin. A starting dose of 10 mg may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more. Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin if cholesterol levels fall significantly below the targeted range.