Generic Name

Zocor

Brand Names

is a triumph of early statin marketing; it is now extensively generic and cost‑effective, often the first line in lipid protocols.

Mechanism

• Competitive inhibition of hepatic HMG‑CoA reductase, the rate‑limiting enzyme in cholesterol biosynthesis.
• ↓ intracellular cholesterol → ↑ LDL‑receptor expression on hepatocytes → enhanced clearance of plasma LDL‑cholesterol.
• Modest reductions in VLDL, triglycerides, and raise HDL‑cholesterol.

Pharmacokinetics

• Absorption: Oral, peak plasma concentration (Tmax) ~4–6 h; absorption reduced by a high‑fat meal.
• Bioavailability: 35 % (highly variable; first‑pass metabolism by CYP3A4).
• Protein binding: ~85 % (primarily to albumin).
• Metabolism: Extensive hepatic oxidation via CYP3A4 → inactive metabolites.
• Half‑life: Terminal plasma t½ ≈ 2 h; the active metabolite has a t½ 4–12 h.
• Excretion: <5 % unchanged in urine; biliary excretion dominates.
• Drug interactions: Strongly inhibited by CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) → ↑ simvastatin levels → ↑ myopathy risk.
• Food interactions: Take with a low‑fat meal; avoid grapefruit juice.

Indications

• Primary hypercholesterolemia (familial or non‑familial).
• Mixed dyslipidemia with elevated LDL.
• Secondary prevention of cardiovascular events in patients with a history of MI, stroke, peripheral arterial disease, or diabetes.
• Esthetic and risk‑reduction therapy in patients with high LDL (>190 mg/dL).

Contraindications

• Contraindications:
• Concomitant use with potent CYP3A4 inhibitors.
• Active liver disease (elevated ALT/AST >3× ULN).
• Pregnancy or lactation.
• Known hypersensitivity to simvastatin.
• Warnings:
• Myopathy – especially rhabdomyolysis with concomitant myotoxic agents (e.g., fibrates).
• Hepatotoxicity – monitor LFTs; discontinue if ALT/AST >3× ULN.
• Drug‑drug interactions – avoid co‑administering with azoles, macrolides, protease inhibitors.
• Renal impairment: Usually safe, but monitor.

Dosing

• Initial adult dose:
• 10 mg once daily (morning) → 20 mg if tolerated.
• Titrate to ≤80 mg daily based on lipid goal achievement.
• Elderly: Start at 10 mg, titrate slowly.
• Children 12–17 y: 10 mg daily 3–4 y; 20 mg daily 4–7 y; 10 mg twice daily 7–12 y.
• Surgical patients: Hold 24 h pre‑operative; resume 24 h post‑op if no bleeding.
• Administration: Oral, with or without food; avoid high‑fat meals.

Adverse Effects

• Common:
• Muscle aches, cramps, fatigue.
• GI upset (nausea, diarrhea, abdominal pain).
• Headache, mild rash.
• Serious:
• Rhabdomyolysis (CK > 10× ULN).
• Hepatotoxicity (ALT/AST > 3× ULN).
• Stroke (rare, not statistically significant).
• Birth defects if used in pregnancy (fetal demyelination).

Monitoring

Clinical Pearls

• Take it at night? The hepatic cholesterol synthesis peaks overnight; dosing in the evening may improve LDL reduction, but recent trials show little difference—time of day can be patient‑preferrable.
• High‑fat meal caution: A single high‑fat meal can halve bioavailability – educate patients to keep meals low‑fat.
• Drug‑drug labyrinth: Avoid ritonavir/clarithromycin/ketoconazole; if avoidance impossible, lower the simvastatin dose to 10 mg.
• Elderly & CKD: Start low/toxic dosing. Cross‑check renal function, consider rosuvastatin or atorvastatin for higher potency.
• Pregnancy test: Since simvastatin is category X, confirm pregnancy status before initiation in women of childbearing potential.
• Muscle pain red‑flag: Any unexplained myalgia with elevated CK warrants stopping the drug; monitor for rhabdo.
• Liver‑K correlation: An LFT rise 2–4 weeks post‑initiate often resolves; persistent >3× ULN needs drug discontinuation.
• Patent portfolio: Zocor’s brand name is a triumph of early statin marketing; it is now extensively generic and cost‑effective, often the first line in lipid protocols.

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• *This drug card is intended for educational purposes and does not replace clinical judgement. Always consult up‑to‑date prescribing information and institutional guidelines.*