Lovastatin
FDA Drug Information • Also known as: Lovastatin
- Brand Names
- Lovastatin
- Drug Class
- HMG-CoA Reductase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
DESCRIPTION Lovastatin is a cholesterol lowering agent isolated from a strain of Aspergillus terreus. After oral ingestion, lovastatin, 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. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol. Lovastatin is [1 S -[1α( R * ),3α,7β,8β(2 S * ,4 S * ),8aβ]]-1,2,3,7, 8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2 H -pyran-2-yl)ethyl]-1-naphthalenyl 2-methylbutanoate. The empirical formula of lovastatin is C 24 H 36 O 5 and its molecular weight is 404.55. Its structural formula is: Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile. Lovastatin tablets USP are supplied as 10 mg, 20 mg and 40 mg tablets for oral administration. In addition to the active ingredient lovastatin, each tablet contains the following inactive ingredients: D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, lactose anhydrous, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized corn starch. Butylated hydroxyanisole (BHA) is added as a preservative. lovastatin
What Is Lovastatin Used For?
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. Primary Prevention of Coronary Heart Disease In individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C and below average HDL-C, lovastatin tablets USP are indicated to reduce the risk of: -Myocardial infarction -Unstable angina -Coronary revascularization procedures (See Error! Hyperlink reference not valid. ). Coronary Heart Disease Lovastatin tablets USP are indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels. Hypercholesterolemia Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Lovastatin tablets USP are indicated as an adjunct to diet for the reduction of elevated total-C and LDL-C levels in patients with primary hypercholesterolemia (Types IIa and IIb 2 ), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate. 2 Classification of Hyperlipoproteinemias IDL = intermediate-density lipoprotein. Type Lipoproteins elevated Lipid Elevations major minor I chylomicrons TG ↑→C IIa LDL C — IIb LDL,VLDL C TG III (rare) IDL C/TG — IV VLDL TG ↑→C V (rare) chylomicrons,VLDL TG ↑→C Adolescent Patients with Heterozygous Familial Hypercholesterolemia Lovastatin tablets USP are indicated as an adjunct to diet to reduce total-C, LDL-C and apolipoprotein B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with heFH if after an adequate trial of diet therapy the following findings are present: 1. LDL-C remains >189 mg/dL or 2. LDL-C remains >160 mg/dL and:
Dosage and Administration
DOSAGE AND ADMINISTRATION The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin tablets USP and should continue on this diet during treatment with lovastatin tablets USP (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin tablets USP 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. Doses should be individualized according to the recommended goal of therapy (see Error! Hyperlink reference not valid. 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 tablets. A starting dose of 10 mg of lovastatin 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 tablets if cholesterol levels fall significantly below the targeted range. Dosage in Patients taking Danazol, Diltiazem, Dronedarone or Verapamil In patients taking danazol, diltiazem, dronedarone or verapamil concomitantly with lovastatin, therapy should begin with 10 mg of lovastatin and should not exceed 20 mg / day (see , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). Dosage in Patients taking Amiodarone In patients taking amiodarone concomitantly with lovastatin, the dose should not exceed 40 mg/day (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). Adolescent Patients (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia The recommended dosing range of lovastatin is 10 to 40 mg / day; the maximum recommended dose is 40 mg / day. Doses should be individualized according to the recommended goal of therapy (see Error! Hyperlink reference not valid. 4 , CLINICAL PHARMACOLOGY , and INDICATIONS AND USAGE ). Patients requiring reductions in LDL-C of 20% or more to achieve their goal should be started on 20 mg/day of lovastatin. A starting dose of 10 mg of lovastatin may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more. Concomitant Lipid-Lowering Therapy Lovastatin tablets USP are effective alone or when used concomitantly with bile-acid sequestrants (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid. ). Dosage in Patients with Renal Insufficiency In patients with severe renal insufficiency (creatinine clearance <30 mL / min), dosage increases above 20 mg / day should be carefully considered and, if deemed necessary, implemented cautiously (see...
Side Effects (Adverse Reactions)
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 Error! Hyperlink reference not valid. ). Persistent increases of serum transaminases have been noted (see Error! Hyperlink reference not valid. ). 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 was 9 percent. This was attributable to the noncardiac fraction of CK. Large increases in CK have sometimes been reported (see Error! Hyperlink reference not valid. ). Expanded Clinical Evaluation of Lovastatin (EXCEL) Study Lovastatin was compared to placebo in 8,245 patients with hypercholesterolemia (total-C 240 to 300 mg / dL [6.2 to 7.8 mmol / L]) in the randomized, double-blind, parallel, 48-week EXCEL study. Clinical adverse experiences reported as possibly, probably or definitely drug-related in ≥1% in any treatment group are shown in the table below. For no event was the incidence on drug and placebo statistically different. Placebo (N =1663) % Lovastatin 20 mg q.p.m. (N = 1642) % Lovastatin 40 mg q.p.m. (N = 1645) % Lovastatin 20 mg b.i.d. (N = 1646) % Lovastatin 40 mg b.i.d. (N = 1649) % Body As a Whole Asthenia 1.4 1.7 1.4 1.5 1.2 Gastrointestinal Abdominal pain 1.6 2.0 2.0 2.2 2.5 Constipation 1.9 2.0 3.2 3.2 3.5 Diarrhea 2.3 2.6 2.4 2.2 2.6 Dyspepsia 1.9 1.3 1.3 1.0 1.6 Flatulence 4.2 3.7 4.3 3.9 4.5 Nausea 2.5 1.9 2.5 2.2 2.2 Musculoskeletal Muscle cramps 0.5 0.6 0.8 1.1 1.0 Myalgia 1.7 2.6 1.8 2.2 3.0 Nervous System/ Psychiatric Dizziness 0.7 0.7 1.2 0.5 0.5 Headache 2.7 2.6 2.8 2.1 3.2 Skin Rash 0.7 0.8 1.0 1.2 1.3 Special Senses Blurred vision 0.8 1.1 0.9 0.9 1.2 Other clinical adverse experiences reported as possibly, probably or definitely drug-related in 0.5 to 1.0 percent of patients in any drug-treated group are listed below. In all these cases the incidence on drug and placebo was not statistically different. Body as a Whole: chest pain; Gastrointestinal: acid regurgitation, dry mouth, vomiting; Musculoskeletal: leg pain, shoulder pain, arthralgia; Nervous System/Psychiatric: insomnia, paresthesia; Skin: alopecia, pruritus; Special Senses: eye irritation. In the EXCEL study (see Error! Hyperlink reference not valid. ) , 4.6% of the patients treated up to 48 weeks were discontinued due to clinical or laboratory adverse experiences which were rated by the investigator as possibly, probably or definitely related to therapy with lovastatin. The value for the placebo group was 2.5%. Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) In AFCAPS/TexCAPS (see Error! Hyperlink reference not valid. ) involving 6,605 participants treated with 20 to 40 mg/day of lovastatin (n=3,304) or placebo (n=3,301), the safety and tolerability profile of the group treated with lovastatin was comparable to that of the group treated with placebo during a median of 5.1 years of follow-up. The adverse experiences reported in AFCAPS/TexCAPS were similar to those reported in EXCEL (see Error! Hyperlink reference not valid. ). Concomitant Therapy In controlled clinical studies in which lovastatin was administered concomitantly with cholestyramine, no adverse reactions peculiar to this concomitant treatment were observed. The adverse reactions that occurred were limited to those reported previously with lovastatin or cholestyramine. Other lipid-lowering agents were not administered concomitantly with lovastatin during controlled clinical studies. Preliminary data suggests that the addition of gemfibrozil to therapy with lovastatin is not associated with greater reduction in LDL-C than that achieved with lovastatin alone. In uncontrolled clinical studies, most of the patients who have developed myopathy were receiving concomitant therapy with cyclosporine,...
Warnings and Precautions
WARNINGS Myopathy/Rhabdomyolysis Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. The risk of myopathy/rhabdomyolysis is dose related. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily. All patients starting therapy with lovastatin, or whose dose of lovastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persists after discontinuing lovastatin. Lovastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with lovastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy. Many of the patients who have developed rhabdomyolysis on therapy with lovastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. Lovastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Lovastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy. The risk of myopathy/rhabdomyolysis is increased by concomitant use of lovastatin with the following: Strong inhibitors of CYP3A4 Lovastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of cytochrome P450 3A4 (CYP3A4). Certain drugs which inhibit this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or cobicistat-containing products. Combination of these drugs with lovastatin is contraindicated. If short-term treatment with strong...
Contraindications
CONTRAINDICATIONS Hypersensitivity to any component of this medication. Active liver disease or unexplained persistent elevations of serum transaminases (see ). 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 Error! Hyperlink reference not valid. ). Pregnancy and lactation (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid. ). 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 Error! Hyperlink reference not valid. ).
Overdosage
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.
How Supplied
HOW SUPPLIED Lovastatin Tablets USP, 10 mg are light green colored, oval shaped, uncoated tablets, debossed with 'LU' on one side and 'G01' on the other side. They are supplied as follows: NDC 68788-8287-3 Bottles of 30 NDC 68788-8287-6 Bottles of 60 NDC 68788-8287-9 Bottles of 90 NDC 68788-8287-1 Bottles of 100 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Lovastatin tablets must be protected from light and stored in a well-closed, light-resistant container. 1 Kantola, T, et al., Clin Pharmacol Ther 1998; 63(4): 397-402 3 Manson, J.M., Freyssinges,C.Ducrocq, M.B., Stephenson, W.P., Postmarketing Surveillance of Lovastatin and Simvastatin Exposure During Pregnancy. Reproductive Toxicology. 10(6):439-446, 1996. 4 National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics . 89(3):495-501. 1992. Manufactured for Lupin Pharmaceuticals, Inc. Baltimore, Maryland 21202 United States Manufactured by Lupin Limited Goa 403 722 INDIA Revised: January 2021 ID#: 266228’ Repackaged By: Preferred Pharmaceuticals, Inc.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.