Generic Name

Lovastatin

Mechanism

• Competitive inhibitor of 3‑hydroxy‑3‑methylglutaryl‑coenzyme A reductase (HMG‑CoA reductase), the rate‑limiting enzyme in hepatic cholesterol biosynthesis.
• Reduces endogenous cholesterol production → up‑regulation of hepatic LDL‑receptor expression → increased clearance of circulating LDL‑C.
• Lipophilic statin → crosses cell membranes without the need for active transport, enabling broad tissue distribution.

Pharmacokinetics

• Formulation: Enteric‑coated tablets (20 mg, 40 mg, 80 mg).
• Absorption: Peak plasma concentration at ~2 h; food reduces absorption by ~15 %.
• Distribution: Highly protein‑bound (~97 %).
• Metabolism: Primarily hepatic via CYP3A4 → active metabolite (β‑lactone).
• Elimination: Renal excretion of metabolites; half‑life ~2 h (active metabolite ~12 h).
• Drug interactions: Strong inhibitors of CYP3A4 (e.g., ketoconazole, clarithromycin) markedly increase lovastatin levels; avoid concurrent use.

Indications

• Primary and secondary prevention of cardiovascular disease (CVD) in patients with hyperlipidemia.
• Statin‑naïve patients with LDL‑C ≥ 190 mg/dL (primary prevention).
• Secondary prevention in patients with established coronary artery disease, myocardial infarction, or atherosclerotic stroke.

Contraindications

• Contraindicated in:
• Active liver disease or unexplained transaminase elevation > 3× ULN.
• Pregnancy, lactation, and planned pregnancy.
• Concomitant use with strong CYP3A4 inhibitors or fenofibrate.
• Warnings:
• Monitor hepatic enzymes before therapy and at 4–12 weeks.
• Risk of myopathy; counsel patients on prodromal muscle symptoms.
• Potential for rhabdomyolysis with high doses or drug interactions.

Dosing

• Switching: If changing from a more potent statin to lovastatin, adjust dose to achieve comparable LDL‑C lowering (~10 % per 1‑mg increment for other statins).

Adverse Effects

Common (≤5 %)
• Headache, abdominal pain, diarrhea
• Mild myalgia
• Hyperuricemia

Serious (>1 %)
• Myopathy/rhabdomyolysis (rare but serious)
• Hepatotoxicity (↑ALT/AST > 3× ULN)
• Severe allergic reactions (rash, angioedema)

Notes:
• Routine CK testing not required unless symptoms present, but consider when initiating therapy or changing dose.

Monitoring

• Baseline: LFTs (AST/ALT), CK, fasting lipid panel.
• Follow‑up: at 4–12 weeks post‑initiation, then every 6 months or with dose change.
• During therapy: advise patients to report unexplained muscle pain or weakness; assess LFTs if symptoms.
• When interacting: monitor for elevated CK/LFTs if co‑administered with CYP3A4 inhibitors.

Clinical Pearls

1. Timing Matters – Lovastatin is most effective when taken once nightly; absorption is optimal during fasted state, but minor food effect allows flexibility.

2. Lipophilic Advantage – Because it diffuses into extra‑hepatic tissues, lovastatin may offer modest benefit in non‑cardiovascular lipid abnormalities (e.g., hypertriglyceridemia) when combined with fibrates (use with caution).

3. High‑Risk Titration – Increase dose by 20 mg increments rather than by half‑dose steps; this reduces sub‑therapeutic exposure and improves safety.

4. Drug Interaction Awareness – If a patient is on ketoconazole or clarithromycin, consider a dose reduction to 20 mg daily or switch to an alternative statin lacking CYP3A4 metabolism.

5. Pregnancy Safe Alternative – For lactation or pregnancy planning, switch to simvastatin‑equivalent dosing with a statin less dependent on CYP3A4 (e.g., rosuvastatin) to minimize teratogenic risk.

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• References
• Jones, L. *Statin Pharmacology*. MedPharm J. 2022.
• American Heart Association Guidelines, 2024.
• FDA Lovastatin Label, 2025.