Introduction
Atorvastatin is a synthetic lipid-lowering agent belonging to the HMG-CoA reductase inhibitor class, commonly known as statins. First approved by the FDA in 1996, it has become one of the most widely prescribed medications worldwide for managing dyslipidemia and reducing cardiovascular risk.
Mechanism of Action
Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. This inhibition decreases hepatic cholesterol synthesis, resulting in upregulation of LDL receptors on hepatocytes and increased clearance of circulating LDL cholesterol. Atorvastatin also reduces LDL production by inhibiting hepatic VLDL synthesis.
Indications
- Primary hypercholesterolemia (including heterozygous and homozygous familial hypercholesterolemia)
- Mixed dyslipidemia
- Primary prevention of cardiovascular disease in patients with multiple risk factors
- Secondary prevention of cardiovascular events in patients with established coronary heart disease
- Pediatric patients (10-17 years) with heterozygous familial hypercholesterolemia
Dosage and Administration
Initial dosing: 10-20 mg orally once daily Maintenance range: 10-80 mg daily Maximum dose: 80 mg daily Special populations:- Hepatic impairment: Use with caution; contraindicated in active liver disease
- Renal impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment necessary
- Asian patients: Consider lower starting doses due to increased systemic exposure
Pharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations within 1-2 hours; absolute bioavailability approximately 14% Distribution: Highly protein-bound (>98%); volume of distribution ~381 L Metabolism: Extensive hepatic metabolism via CYP3A4 to active ortho- and parahydroxylated metabolites Elimination: Primarily biliary excretion; elimination half-life 14 hours; prolonged inhibitory effect on HMG-CoA reductase due to active metabolitesContraindications
- Active liver disease or unexplained persistent elevations of serum transaminases
- Pregnancy and breastfeeding
- Hypersensitivity to atorvastatin or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors in patients taking high-dose atorvastatin
Warnings and Precautions
Hepatotoxicity: Monitor liver enzymes before initiation and periodically thereafter Myopathy/Rhabdomyolysis: Risk increases with higher doses, advanced age, renal impairment, and concomitant use with certain medications Diabetes: May increase HbA1c and fasting serum glucose levels Cognitive effects: Rare reports of cognitive impairment Avoid in pregnancy: May cause fetal harmDrug Interactions
Strong CYP3A4 inhibitors: Clarithromycin, itraconazole, HIV protease inhibitors - increase atorvastatin exposure Gemfibrozil: Increases risk of myopathy Cyclosporine: Significantly increases atorvastatin concentrations Oral contraceptives: Increases ethinyl estradiol and norethindrone concentrations Warfarin: May potentiate anticoagulant effect; monitor INR closely Colchicine: Increased risk of myopathyAdverse Effects
Common (≥2%): Headache, myalgia, arthralgia, diarrhea, nausea, elevated liver enzymes Serious but rare:- Rhabdomyolysis with renal failure
- Severe hepatotoxicity
- Immune-mediated necrotizing myopathy
- Hemorrhagic stroke (in patients with recent stroke)
- Stevens-Johnson syndrome
Monitoring Parameters
- Lipid panel at baseline, 4-12 weeks after initiation or dose change, and periodically thereafter
- Liver enzymes at baseline and as clinically indicated
- CPK levels in patients with muscle symptoms
- Renal function in patients at risk for rhabdomyolysis
- HbA1c and fasting glucose in patients with diabetes risk factors
- Signs and symptoms of myopathy
Patient Education
- Take atorvastatin at the same time each day, with or without food
- Report unexplained muscle pain, tenderness, weakness, or brown urine immediately
- Avoid excessive alcohol consumption
- Inform all healthcare providers about atorvastatin use
- Maintain regular follow-up appointments for monitoring
- Continue lifestyle modifications (diet, exercise)
- Use effective contraception if of childbearing potential
- Be aware of potential interactions with other medications
References
1. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. 2. Atorvastatin prescribing information. FDA-approved labeling. 3. Thompson PD, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410. 4. Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. 5. Newman CB, et al. Statin Safety and Associated Adverse Events. Arterioscler Thromb Vasc Biol. 2019;39(5):e38-e81.