Generic Name

Simvastatin

Mechanism

• Simvastatin is a statin that competitively inhibits HMG‑CoA reductase (HMGCR), the rate‑limiting enzyme in hepatic cholesterol biosynthesis.
• Inhibition ↓ intracellular cholesterol → up‑regulation of LDL‑receptor expression → increased clearance of LDL‑cholesterol from circulation.
• Results in modest reductions of triglycerides and modest increases in HDL‑cholesterol.

Pharmacokinetics

• Absorption: ~30–40 % oral bioavailability; peak plasma concentration 2–4 h after a 40 mg dose.
• Metabolism: Primarily hepatic CYP3A4‑mediated β‑oxidation to inactive metabolites (simvastatin acid).
• Distribution: Highly protein‑bound (~85 %).
• Excretion: Renal (~<5 %) and biliary routes; metabolite excretion predominates.
• Half‑life: Parent drug ~1 h; active metabolite ~20–30 h.
• Food interactions: Take on an empty stomach (≥1 h before or 2 h after food) to maximize absorption.

Indications

• Primary prevention of atherosclerotic cardiovascular disease (ASCVD) in patients 40–75 y with ≥2 risk factors.
• Secondary prevention of myocardial infarction, stroke, or peripheral arterial disease.
• Familial hypercholesterolemia (heterozygous) as part of combination therapy.

Contraindications

• Pregnancy & lactation: Category X; teratogenic potential.
• Active hepatic disease: AST/ALT > 3× upper limit of normal (ULN) or unexplained.
• Myopathy or elevated CK: Contraindicated with active myopathy or CK > 10 × ULN.
• Concomitant use with potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir).
• Renal insufficiency: Use with caution; avoid >1 mg/day in CrCl < 30 mL/min.

Dosing

• Starting dose: 10–20 mg once daily (bedtime).
• Titration: Increase by 10‑20 mg increments every 4–6 weeks, max 40 mg/day.
• Maximum recommended dose: 40 mg/day for most indications.
• Special populations:
• Elderly: Start at lower end; monitor for myopathy.
• Poor CYP3A4 metabolizers: Consider lower doses or switch to alternative statin.

Monitoring

• Baseline:
• LFT panel (AST, ALT, alkaline phosphatase).
• CK, fasting lipid profile.
• Serum creatinine & eGFR if renal comorbidity suspected.
• Follow‑up:
• LFTs after 4–12 weeks of therapy, then annually.
• CK if myalgias or unexplained muscle symptoms.
• Lipid panel every 3‑6 months to assess efficacy.

Clinical Pearls

• Timing matters: Taking simvastatin at bedtime leverages nocturnal cholesterol synthesis peak, optimizing LDL‑lowering.
• Drug interactions are critical: Even a low dose (10 mg) with ketoconazole can raise plasma levels by >30 ×; consider alternative statins (e.g., pravastatin, rosuvastatin) when CYP3A4 inhibitors are unavoidable.
• Potency vs duration: Simvastatin’s 20‑day half‑life (derived from its metabolite) allows once‑daily dosing but limits flexibility for rapid dose adjustments compared to longer‑acting statins.
• Avoid high‑dose “jump” strategies: A 40‑mg jump from 20 mg is acceptable; further increases carry disproportionate risk of myopathy without added LDL benefit.
• Diet as an adjunct: A Mediterranean‑style diet with 10% of calories from saturated fat complements statin therapy and may reduce required dose.
• Special patient alert: In patients with severe hepatic steatosis, consider starting at 10 mg to assess tolerance before titrating.

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• *This concise drug card equips medical students and clinicians with readily searchable, evidence‑based details on simvastatin, ensuring rapid reference and optimal patient care.*