Generic Name

Lipitor

Mechanism

Atorvastatin competitively inhibits HMG‑CoA reductase, the rate‑limiting enzyme in hepatic cholesterol biosynthesis. This reduces endogenous cholesterol production, upregulates LDL‑receptor expression on hepatocyte membranes, and increases clearance of plasma LDL‑cholesterol. Additionally, statins modestly raise HDL‑cholesterol and lower triglycerides.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration 2–4 h post‑dose.
• Bioavailability: ~12‑15 % (affected by food).
• Metabolism: Primarily hepatic via CYP3A4 to active metabolites; limited enterohepatic recirculation.
• Elimination: 90 % fecal, 10 % urinary.
• Half‑life: 14‑27 h (active metabolites).
• Drug interactions: Strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) of CYP3A4 alter atorvastatin exposure.

Indications

• Primary prevention of atherosclerotic cardiovascular disease in adults ≥40 yr with ≥1 risk factor.
• Secondary prevention after myocardial infarction, stroke, or peripheral arterial disease.
• Treatment of heterozygous familial hypercholesterolemia.
• Hyperlipidemia with LDL-C > 100 mg/dL when lifestyle modification alone is insufficient.

Contraindications

• Contraindicated in pregnancy, lactation, and known hypersensitivity to atorvastatin.
• Avoid in acute liver disease or uncontrolled hepatitis; monitor liver enzymes.
• Use cautiously in patients with renal insufficiency; dose adjustment may be required.
• Drug‑drug interactions: Avoid concurrent use with strong CYP3A4 inhibitors (e.g., clarithromycin).
• Statin‑associated myopathy: higher doses increase risk; monitor symptoms.

Dosing

• Take in the evening or at bedtime to coincide with the diurnal peak of HMG‑CoA reductase activity.
• Long‑acting formulations allow once‑daily dosing.

Adverse Effects

• Common: muscle aches, headache, gastrointestinal upset (nausea, diarrhea), cold‑like symptoms.
• Serious:
• Myopathy/Muscle pain (rarely rhabdomyolysis).
• Elevated liver enzymes > 3× ULN; serious liver injury (very rare).
• Lipid‐related paradoxical effects (e.g., increase in serum creatinine).

Monitoring

• Baseline: CBC, CMP (ALT/AST), lipid panel, fasting glucose.
• Follow‑up:
• Liver enzymes at 4–12 wk after initiation or dose change.
• Renal function every 6–12 mo if CK≥150 U/L or creatinine rising.
• LDL‑cholesterol every 4–12 wk to assess therapeutic response.
• Pregnancy: Counsel to discontinue if conception is possible.

Clinical Pearls

• Time of Day Matters: Take Lipitor in the evening to match higher nocturnal HMG‑CoA reductase activity, optimizing LDL‑lowering.
• Food Effect: A high‑fat meal can increase plasma concentration. For patients on high‑intensity doses, take with a light meal or use the standard dosing schedule to avoid erratic peaks.
• Dose‑Response Relationship: Incremental titrations improve LDL goals in > 70 % of patients; however, beyond 40 mg may not yield proportional benefit but increases myopathy risk.
• Renal Considerations: While dosage isn’t adjusted for mild renal impairment, in patients with CrCl  70 mg/dL after maximally tolerated atorvastatin.
• Clinical Trial Insight: The JUPITER trial underscored that statins can reduce cardiovascular events even when LDL‑C is normal but hs‑CRP is elevated; thus inflammatory markers can guide therapy intensification.

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• Key Terms Highlighted:
• LDL‑cholesterol
• HMG‑CoA reductase
• CYP3A4
• Atorvastatin
• Statin‑associated myopathy

These elements provide a concise, reference‑friendly drug card that serves both medical students and clinical professionals.