Lovastatin

Usage

• Lovastatin is prescribed for the management of hyperlipidemia, including primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson Types IIa and IIb). It is also used to slow the progression of coronary atherosclerosis in patients with coronary heart disease and reduce the risk of myocardial infarction, unstable angina, and coronary revascularization procedures in adults at high risk for coronary heart disease.
• Pharmacological Classification: HMG-CoA reductase inhibitor (statin), antihyperlipidemic agent.
• Mechanism of Action: Lovastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. This inhibition leads to a decrease in intracellular cholesterol synthesis, resulting in increased hepatic LDL receptor expression and reduced plasma LDL cholesterol levels.

Alternate Names

• Mevinolin
• Brand Names: Mevacor, Altoprev (extended-release)

How It Works

• Pharmacodynamics: Lovastatin lowers total cholesterol, LDL cholesterol, apolipoprotein B (Apo B), and triglycerides, and increases HDL cholesterol. Its primary effect is on LDL cholesterol reduction.

• Pharmacokinetics:

  • Absorption: Lovastatin is readily absorbed orally, with peak plasma concentrations achieved within 2-4 hours after administration. The extended-release formulation (Altoprev) reaches peak concentrations later. Absorption is enhanced when taken with food.
  • Metabolism: Lovastatin is extensively metabolized in the liver, primarily by CYP3A4, to active metabolites, including the beta-hydroxyacid form.
  • Elimination: Primarily eliminated via the biliary route with minimal renal excretion.

• Mode of Action: Lovastatin’s beta-hydroxyacid form competitively inhibits HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate, a crucial precursor for cholesterol synthesis.

• Receptor Binding/Enzyme Inhibition: Competitive inhibition of HMG-CoA reductase.

• Elimination Pathways: Hepatic metabolism (CYP3A4) and biliary excretion.

Dosage

Standard Dosage

Adults:

• Immediate-release tablets (Mevacor): Initial dose: 20 mg once daily with the evening meal. Dosage range: 10-80 mg daily, given as a single dose or in two divided doses. Maximum dose: 80 mg/day.
• Extended-release tablets (Altoprev): Initial dose: 20-60 mg once daily in the evening at bedtime. Starting dose for elderly (≥65 years): 20 mg once daily at bedtime. Maximum dose: 60 mg/day.

Children:

• Immediate-release tablets (Mevacor): For heterozygous familial hypercholesterolemia in children 10-17 years: 10-40 mg daily, with the evening meal. Initial dose: 10 mg (for smaller LDL-C reductions) or 20 mg (for reductions ≥20%). Maximum dose: 40 mg/day.
• Extended-release tablets (Altoprev): Not approved for use in children.
• Children <10 years: Use and dose must be determined by a doctor.
• Pediatric Safety Considerations: Close monitoring of liver function and muscle enzymes is recommended.

Special Cases:

• Elderly Patients (≥65 years): Start with a lower dose (20 mg/day for Altoprev) and titrate cautiously, considering potential risks and benefits.
• Patients with Renal Impairment: For severe renal impairment (creatinine clearance <30 mL/min), doses >20 mg/day should be carefully considered and implemented cautiously.
• Patients with Hepatic Dysfunction: Lovastatin is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases. Use with caution in patients with a history of liver disease or substantial alcohol consumption.
• Patients with Comorbid Conditions: Dose adjustments may be needed based on concomitant medications and other medical conditions.

Clinical Use Cases Lovastatin’s clinical use focuses primarily on chronic cholesterol management and cardiovascular risk reduction, not acute settings like intubation, surgery, mechanical ventilation, or ICU/emergency situations. These scenarios might require different therapeutic approaches.

Dosage Adjustments

• Dose adjustments are based on patient response, renal function, and concomitant medications (see Drug Interactions section). Genetic polymorphisms affecting drug metabolism may also necessitate dose modifications, though specific guidelines are not routinely available.

Side Effects

Common Side Effects:

• Headache, dizziness, fatigue
• Gastrointestinal disturbances (constipation, diarrhea, abdominal pain, nausea)
• Muscle aches or weakness
• Elevated liver enzymes

Rare but Serious Side Effects:

• Myopathy, rhabdomyolysis (muscle breakdown) with potential for acute renal failure
• Hepatotoxicity (liver damage)
• Allergic reactions (rash, hives, itching, difficulty breathing or swallowing, swelling)

Long-Term Effects:

• The long-term effects of lovastatin are primarily related to its benefits in reducing cardiovascular risk. Continued monitoring for muscle and liver toxicity is advised with prolonged use.

Adverse Drug Reactions (ADR):

• Myopathy/rhabdomyolysis, hepatotoxicity, and serious allergic reactions require immediate intervention.

Contraindications

• Hypersensitivity to lovastatin
• Active liver disease or unexplained persistent elevations in serum transaminases
• Pregnancy
• Breastfeeding
• Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin, erythromycin, HIV protease inhibitors)

Drug Interactions

• CYP3A4 Inhibitors: Strong CYP3A4 inhibitors (see Contraindications) significantly increase lovastatin levels and the risk of myopathy. These combinations are contraindicated or require significant dose reductions.
• Other Drug Interactions:
  • Gemfibrozil (and other fibrates): Increased risk of myopathy. Avoid combined use of gemfibrozil and lovastatin.
  • Niacin (high doses >1g/day): Increased risk of myopathy. Use with caution.
  • Amiodarone, verapamil, diltiazem, dronedarone: Increased risk of myopathy. Limit lovastatin dose.
  • Cyclosporine, danazol: Increased risk of myopathy.
  • Grapefruit juice: Increased lovastatin levels. Avoid excessive consumption.
  • Colchicine: Increased risk of myopathy.
• CYP450 Interactions: Lovastatin is primarily metabolized by CYP3A4. Inhibitors of CYP3A4 increase lovastatin exposure.
• Other Medications: Consult drug interaction resources for a complete list.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: X (Contraindicated). Lovastatin can cause fetal harm. Women of childbearing potential should use effective contraception.
• Fetal Risks: Skeletal malformations and other birth defects.
• Breastfeeding: Lovastatin is contraindicated during breastfeeding due to the potential for serious adverse reactions in nursing infants. Women who require lovastatin therapy should not breastfeed.

Drug Profile Summary

• Mechanism of Action: HMG-CoA reductase inhibitor, reducing cholesterol biosynthesis.
• Side Effects: Muscle pain, liver enzyme elevations, gastrointestinal issues. Rarely, rhabdomyolysis and hepatotoxicity.
• Contraindications: Active liver disease, pregnancy, breastfeeding, strong CYP3A4 inhibitors.
• Drug Interactions: CYP3A4 inhibitors, gemfibrozil, niacin, amiodarone, verapamil, diltiazem, cyclosporine, danazol, grapefruit juice.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 10-80 mg/day (immediate-release), 20-60 mg/day (extended-release). Children (10-17 years): 10-40 mg/day (immediate-release).
• Monitoring Parameters: Liver function tests (LFTs), creatine kinase (CK) levels, lipid profile.

Popular Combinations

• Lovastatin is sometimes combined with other cholesterol-lowering agents like ezetimibe or bile acid sequestrants for enhanced LDL-C reduction when monotherapy is insufficient. However, combining with fibrates (especially gemfibrozil) should be avoided due to increased myopathy risk.

Precautions

• General Precautions: Monitor LFTs and CK levels. Assess renal function, especially in elderly patients.
• Specific Populations:
  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Contraindicated.
  • Children & Elderly: Start with lower doses and titrate cautiously. Monitor liver function and muscle enzymes.
• Lifestyle Considerations: Encourage lifestyle modifications (diet, exercise) to complement drug therapy. Avoid excessive alcohol consumption.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lovastatin?

A: Adults: 10-80 mg/day (immediate-release), 20-60 mg/day (extended-release). Children (10-17 years): 10-40 mg/day (immediate-release).

Q2: What are the most common side effects of Lovastatin?

A: Common side effects include headache, gastrointestinal disturbances (constipation, diarrhea, abdominal pain), muscle aches, and fatigue.

Q3: What are the serious side effects of Lovastatin that require immediate attention?

A: Myopathy/rhabdomyolysis (muscle breakdown) and hepatotoxicity (liver damage) are rare but serious side effects. Signs of muscle pain, weakness, or dark urine should prompt immediate evaluation.

Q4: Can Lovastatin be used during pregnancy or breastfeeding?

A: No, Lovastatin is contraindicated in both pregnancy and breastfeeding due to potential risks to the fetus or nursing infant.

Q5: What are the major drug interactions with Lovastatin?

A: Strong CYP3A4 inhibitors (e.g., certain antifungals and antibiotics), gemfibrozil, and high-dose niacin are among the most significant drug interactions.

Q6: How does Lovastatin work to lower cholesterol?

A: It inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, leading to decreased cholesterol production and increased LDL receptor expression in the liver.

Q7: Are there any dietary restrictions while taking Lovastatin?

A: Patients should limit grapefruit juice consumption, as it can increase lovastatin levels. Moderate alcohol intake is advised.

Q8: How often should monitoring tests be done for patients on Lovastatin?

A: Liver function tests and creatine kinase levels should be monitored periodically, especially at the start of therapy and with dose adjustments. Lipid profile monitoring is also important to assess treatment effectiveness.

Q9: What should a patient do if they miss a dose of Lovastatin?

A: They should take the missed dose as soon as they remember, unless it is close to the time for their next dose. They should not double the dose to catch up.

Q10: What is the difference between Lovastatin and Altoprev?

A: Altoprev is the brand name for the extended-release formulation of lovastatin. It is taken once daily at bedtime, whereas immediate-release lovastatin is usually taken once or twice daily with meals.