Altoprev (Lovastatin) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

Drug interaction studies have not been performed with ALTOPREV^®. The types, frequencies and magnitude of drug interactions that may be encountered when ALTOPREV^® is administered with other drugs may differ from the drug interactions encountered with the lovastatin immediate-release formulation. In addition, as the drug exposure with ALTOPREV^® 60 mg is greater than that with lovastatin immediate-release 80 mg (maximum recommended dose), the severity and magnitude of drug interactions that may be encountered with ALTOPREV^® 60 mg are not known. It is therefore recommended that the following precautions and recommendations for the concomitant administration of lovastatin immediate-release with other drugs be interpreted with caution, and that the monitoring of the pharmacologic effects of ALTOPREV^® and/or other concomitantly administered drugs be undertaken where appropriate.

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. Potent inhibitors of CYP3A4 (below) increase the risk of myopathy by reducing the elimination of lovastatin.

See WARNINGS, Myopathy/Rhabdomyolysis, and CLINICAL PHARMACOLOGY, Pharmacokinetics.

•   Itraconazole
•   Ketoconazole
•   Erythromycin
•   Clarithromycin
•   HIV protease inhibitors
•   Nefazodone
•   Cyclosporine
•   Large quantities of grapefruit juice (>1 quart daily)

OVERDOSAGE

After oral administration of lovastatin immediate-release to mice the median lethal dose observed was >15 g/m².

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 with lovastatin immediate-release have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5 g - 6 g.

Until further experience is obtained, no specific treatment of overdosage with ALTOPREV^® can be recommended.

The dialyzability of lovastatin and its metabolites in man is not known at present.

CONTRAINDICATIONS

Hypersensitivity to any component of this medication. Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS).

Pregnancy and Lactation

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 ALTOPREV^® to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, ALTOPREV^® is contraindicated during pregnancy and in nursing mothers. ALTOPREV^® 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, ALTOPREV^® should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see PRECAUTIONS, Pregnancy).