Introduction
Lovastatin is a lipid-lowering agent belonging to the statin class (HMG-CoA reductase inhibitors). Originally derived from the fungus Aspergillus terreus, it was the first statin approved by the FDA in 1987. Lovastatin remains an important therapeutic option for managing dyslipidemia and reducing cardiovascular risk.
Mechanism of Action
Lovastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This inhibition decreases hepatic cholesterol production, leading to upregulation of LDL receptors on hepatocytes. The increased receptor activity enhances clearance of circulating LDL particles, resulting in reduced serum LDL cholesterol, total cholesterol, and triglycerides, with modest increases in HDL cholesterol.
Indications
- Primary hypercholesterolemia (Types IIa and IIb)
- Secondary prevention of cardiovascular events in patients with coronary heart disease
- Slowing progression of coronary atherosclerosis
- Primary prevention of coronary heart disease in patients without clinical evidence of CHD but with multiple risk factors
Dosage and Administration
Initial dose: 20 mg orally once daily with evening meal Maintenance dose: 10-80 mg daily in single or divided doses Maximum dose: 80 mg daily Special populations:- Renal impairment: Use caution with severe impairment (CrCl <30 mL/min)
- Hepatic impairment: Contraindicated in active liver disease
- Geriatric patients: No dosage adjustment necessary
- Pediatric patients: 10-40 mg daily for adolescents (10-17 years)
Pharmacokinetics
Absorption: Incomplete (30%) with extensive first-pass metabolism; food increases bioavailability by approximately 50% Distribution: Protein binding >95%; crosses blood-brain barrier poorly Metabolism: Extensive hepatic metabolism via CYP3A4 to active metabolites Elimination: Half-life 1-2 hours; primarily excreted in feces (83%), urine (10%) Onset of effect: LDL reduction noticeable within 2 weeks, maximal effect at 4-6 weeksContraindications
- Active liver disease or unexplained persistent elevations in hepatic transaminases
- Pregnancy and breastfeeding
- Hypersensitivity to lovastatin or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, HIV protease inhibitors)
Warnings and Precautions
Hepatotoxicity: Monitor liver enzymes before initiation and periodically thereafter Myopathy/Rhabdomyolysis: Risk increases with higher doses, advanced age, renal impairment, and concomitant interacting medications Renal effects: May cause proteinuria in some patients Cognitive effects: Reports of memory impairment and confusion (usually reversible) Diabetes: May increase HbA1c and fasting glucose Avoid in pregnancy: Category X - may cause fetal harmDrug Interactions
Strong CYP3A4 inhibitors: Contraindicated (e.g., clarithromycin, itraconazole, HIV protease inhibitors) Moderate CYP3A4 inhibitors: Use with caution and consider lower lovastatin dose (e.g., diltiazem, verapamil, amiodarone) Gemfibrozil: Avoid combination due to increased rhabdomyolysis risk Other lipid-lowering agents: Use with caution Warfarin: May potentiate anticoagulant effect; monitor INR closely Cyclosporine: ContraindicatedAdverse Effects
Common (>10%): Headache, gastrointestinal disturbances, muscle pain Less common (1-10%): Constipation, diarrhea, dyspepsia, rash, insomnia Serious (<1%): Rhabdomyolysis, hepatotoxicity, myopathy, peripheral neuropathy Rare: Lupus-like syndrome, memory impairment, gynecomastiaMonitoring Parameters
- Lipid profile at baseline, 4-8 weeks after initiation, and periodically thereafter
- Liver function tests at baseline, 12 weeks after initiation, then annually
- CPK levels if muscle symptoms develop
- Renal function in patients with pre-existing renal impairment
- Blood glucose/HbA1c in patients with diabetes risk factors
- Signs/symptoms of myopathy
Patient Education
- Take with evening meal for optimal absorption
- Report unexplained muscle pain, tenderness, weakness, or brown urine immediately
- Avoid grapefruit and grapefruit juice during therapy
- Maintain regular follow-up appointments for monitoring
- Continue dietary modifications and exercise program
- Use effective contraception; notify provider if pregnancy is planned or suspected
- Be aware of potential cognitive side effects (memory issues, confusion)
References
1. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. 2. Thompson PD, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410. 3. FDA Prescribing Information for Lovastatin. Revised 2022. 4. Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. 5. Stone NJ, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Circulation. 2014;129(25 Suppl 2):S1-S45.