Astin

• Primary Hypercholesterolemia (Heterozygous Familial and Non‑Familial):
  Lowering elevated LDL‑cholesterol, total cholesterol, apolipoprotein B, and triglycerides; increasing HDL‑cholesterol.
• Homozygous Familial Hypercholesterolemia (HoFH):
  Adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or when such options are unavailable.
• Mixed Dyslipidemia:
  Combined elevations of LDL and triglycerides with low HDL.
• Cardiovascular Risk Reduction:
• Prevention of cardiovascular events (myocardial infarction, stroke, revascularization) in individuals with or at high risk for atherosclerotic cardiovascular disease.
• Secondary prevention in patients with established coronary artery disease.
• Hypertriglyceridemia:
  Adjunct therapy to reduce elevated triglycerides.
• Other Approved Uses:
  Adjunct to diet in patients with elevated LDL-C as part of management guidelines.

Route: Oral; with or without food.

Adults (≥18 years):

• Starting dose: 10–20 mg once daily.
• Usual maintenance range: 10–80 mg daily, adjusted every 4 weeks as needed.

Pediatrics (10–17 years with familial hypercholesterolemia):

• Starting: 10 mg once daily; maximum 20 mg/day after appropriate evaluation.

Elderly (>65 years):

• No specific adjustment; start low and monitor for tolerability.

Hepatic Impairment:

• Contraindicated in active liver disease or persistent transaminase elevations.

Renal Impairment:

• No dosage adjustment needed for mild-to-moderate impairment; caution in severe impairment.

Administration Notes:

• Prefer evening dosing for maximal LDL reduction, though effect is consistent throughout day.

Atorvastatin competitively inhibits HMG‑CoA reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis. This inhibition lowers intracellular cholesterol, prompting upregulation of LDL receptors and enhanced clearance of LDL particles from circulation. Additional beneficial effects include improved endothelial function, reduced inflammation, and stabilization of atherosclerotic plaques.

• Absorption: Rapid with peak plasma levels in ~1–2 hours; bioavailability ~14% due to first-pass metabolism.
• Distribution: ~98% bound to plasma proteins.
• Metabolism: Hepatically metabolized via CYP3A4 to active ortho‑ and para‑hydroxyatorvastatin metabolites.
• Half-life: Parent drug ~14 hours; active metabolites ~20–30 hours.
• Elimination: Primarily via bile; negligible renal excretion (<2% unchanged).

• Pregnancy: Contraindicated. Lipid-lowering benefit does not outweigh potential fetal risk. Avoid use pre‑pregnancy, during pregnancy, and while breastfeeding.
• Lactation: Excreted in animal milk; human data lacking. Avoid breastfeeding during therapy and for several days after last dose.

• Primary Class: Lipid-lowering agent (Statin)
• Subclass: HMG‑CoA reductase inhibitor (synthetic statin)

• Hypersensitivity to atorvastatin or components
• Active liver disease or unexplained persistent transaminase elevation
• Pregnancy and lactation
• Concurrent use of strong CYP3A4 inhibitors (e.g. ciclosporin, clarithromycin) at high statin doses without adjustment
• History of severe statin-related muscle toxicity

• Hepatotoxicity: Monitor LFTs before initiation; periodic monitoring thereafter. Interrupt therapy if persistent elevations >3 × ULN.
• Myopathy/Rhabdomyolysis: Elevated risk with high doses, renal impairment, or drug interactions (e.g. fibrates, CYP3A4 inhibitors). Monitor CK levels if muscle symptoms occur.
• Diabetes Risk: Slight increased incidence of new-onset type 2 diabetes; monitor glucose.
• Cognitive Effects: Rare reversible memory impairment or confusion reported.
• Renal Impairment: Dose-related risk of myopathy increased; monitor.
• Elderly: May be more vulnerable to adverse events; monitor dosage and tolerability.

Common (≥1%):

• Upper respiratory infections, nasopharyngitis
• Myalgia, arthralgia, back pain
• Gastrointestinal: dyspepsia, diarrhea, flatulence
• Headache

Less Common but Clinically Important:

• Elevated liver enzymes
• Myopathy, cramps

Rare/Serious:

• Rhabdomyolysis leading to acute renal failure
• Hepatitis, jaundice
• Immune-mediated necrotizing myopathy
• Hypersensitivity (rash, angioedema)

Timing:

• Liver enzyme elevations typically emerge within first 3 months; muscle symptoms may occur any time but more common early or with dose escalation.

• CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, HIV protease inhibitors): Increase atorvastatin levels → elevated rhabdomyolysis risk.
• Grapefruit juice: Inhibits CYP3A4; increases atorvastatin plasma levels.
• Fibrates (e.g., gemfibrozil): Additive myotoxicity; use caution.
• Niacin: Increased risk of myopathy and hepatotoxicity.
• Caution with ciclosporin: Elevates statin levels; dose adjustment recommended.
• Warfarin: May potentiate anticoagulant effect; monitor INR.
• Oral contraceptives: May increase estrogen/progestin levels.
• Alcohol: Excessive use can worsen hepatotoxicity risk.

• ACC/AHA 2018/2022 Guidelines: Recommend high-intensity atorvastatin therapy for secondary prevention and in high-risk primary prevention; LDL-C goals tailored by risk profile.
• FDA Update: Reinforces warnings about potential myopathy and liver enzyme elevation; emphasizes benefit-risk assessment.
• ESC/EAS 2019: Support adding non-statin agents like ezetimibe if LDL-C goals unmet on atorvastatin alone.

• Store at 20 °C to 25 °C (68 °F to 77 °F).
• Protect from light and moisture; keep in original container.
• Do not freeze.
• Keep out of reach of children.
• No special reconstitution required.