Overview
DESCRIPTION Lovastatin, USP is a cholesterol lowering agent isolated from a strain of Aspergillus terreus . After oral ingestion, lovastatin, USP, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.
Mechanism of Action
CLINICAL PHARMACOLOGY The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL-C and low high-density lipoprotein cholesterol (HDL-C) are both associated with coronary heart disease. However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (total-C) and LDL-C in the lower end of this range. Lovastatin has been shown to reduce elevated LDL-C concentrations.
Indications
- INDICATIONS AND USAGE Therapy with Lovastatin Tablets USP should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease. Lovastatin Tablets USP should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total-C and LDL-C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk.
Common Doses
- 20 mg
- 80 mg
- 10 mg
- 40 mg
Dosage
DOSAGE AND ADMINISTRATION The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin tablets and should continue on this diet during treatment with lovastatin tablets (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin tablets 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 of lovastatin is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day.
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 .
Side Effects
- ADVERSE REACTIONS Phase III Clinical Studies In Phase III controlled clinical studies involving 613 patients treated with lovastatin, the adverse experience profile was similar to that shown below for the 8,245 patient EXCEL study (see Expanded Clinical Evaluation of Lovastatin [EXCEL] Study ). Persistent increases of serum transaminases have been noted (see WARNINGS, Liver Dysfunction ). About 11% of patients had elevations of CK levels of at least twice the normal value on one or more occasions. The corresponding values for the control agent cholestyramine were 9 percent.
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 ,...