Atorvastatin

Atorvastatin is a statin that lowers LDL cholesterol by inhibiting HMG-CoA reductase in the liver. It reduces total cholesterol (30-46%), LDL-cholesterol (41-61%), and triglycerides (14-33%) while increasing HDL cholesterol.

Atorvastatin reduces the risk of myocardial infarction, stroke, and revascularization procedures in adults with multiple risk factors for coronary heart disease, type 2 diabetes, or established CHD.

Common side effects include nasopharyngitis, diarrhea, arthralgia, and headache.

• Primary hyperlipidemia, heterozygous familial hypercholesterolemia, dysbetalipoproteinemia, hypertriglyceridemia
• Homozygous familial hypercholesterolemia (HoFH) in patients aged 10 years and older
• Reduction of MI, stroke, and revascularization in adults with multiple CHD risk factors or type 2 diabetes

Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate in cholesterol synthesis. It increases hepatic LDL receptors, enhancing LDL catabolism.

In dose-response studies, atorvastatin reduces total cholesterol by 30-46%, LDL-C by 41-61%, apolipoprotein B by 34-50%, and triglycerides by 14-33%. Approximately 70% of circulating HMG-CoA reductase inhibitory activity is attributed to active metabolites.

Atorvastatin inhibits hepatic HMG-CoA reductase, reducing cholesterol synthesis. This increases LDL receptors on liver cells, enhancing clearance of LDL from the blood. It lowers total cholesterol, LDL cholesterol, and triglycerides while increasing HDL cholesterol.

Adults:

• Primary hyperlipidemia, dysbetalipoproteinemia, hypertriglyceridemia: 10-20 mg once daily; may increase to 40 mg.
• Heterozygous familial hypercholesterolemia: 10 mg initial; may increase to 20-40 mg.
• Cardiovascular event prevention: 10-20 mg daily (40 mg in older adults).

Pediatric (10-17 years - HeFH):

• Initial dose: 10 mg daily.
• Maximum dose: 20 mg daily (increase at ≥4-week intervals).

Dose Modifications for Drug Interactions:

• Clarithromycin, itraconazole, saquinavir+ritonavir, darunavir+ritonavir: Do not exceed 20 mg daily.
• Nelfinavir: Do not exceed 40 mg daily.

Take once daily at any time, with or without food. LDL reduction is the same regardless of the time of day.

If you miss a dose, skip the missed dose and take the next scheduled dose. Do not double the dose.

• Common (≥5%): Nasopharyngitis, diarrhea, arthralgia, pain in extremity, urinary tract infection
• Other: Headache, constipation, muscle pain, nausea, indigestion
• Serious (rare): Myopathy/rhabdomyolysis, hepatic injury, diabetes, increased blood glucose

Serious Precautions:

• Report any muscle pain, tenderness, or weakness during treatment.
• Do not use during pregnancy or breastfeeding.
• Do not use if you have active liver disease or unexplained liver enzyme elevations.
• Monitor blood sugar in diabetic patients (atorvastatin may slightly increase blood glucose).
• If signs of serious liver injury (abdominal pain, dark urine, yellow skin/eyes) occur, discontinue and consult your doctor.
• Use caution in patients with substantial alcohol consumption, history of liver disease, or hypothyroidism.

• Allergy to atorvastatin or any component
• Active liver disease or unexplained liver enzyme elevations
• Pregnancy and lactation
• Porphyria

• CYP3A4 Inhibitors (itraconazole, ketoconazole, clarithromycin): Increase risk of myopathy. Do not exceed 20 mg/day.
• Antivirals (saquinavir+ritonavir, darunavir+ritonavir): Do not exceed 20 mg/day.
• Rifampin: May reduce atorvastatin plasma levels; administer simultaneously.
• Gemfibrozil, fibrates, niacin: Increase risk of myopathy.
• Digoxin: May increase digoxin levels.
• Oral contraceptives: May increase norethindrone and ethinyl estradiol levels.
• Grapefruit juice: May increase atorvastatin blood levels; avoid excessive consumption (>1 L/day).

[CAUTION] Caution with alcohol consumption. Excessive alcohol may increase risk of liver problems.

[UNSAFE] Do not use during pregnancy. Cholesterol is essential for fetal development; cholesterol-lowering drugs may cause fetal harm.

[UNSAFE] Atorvastatin may be excreted in human milk. Do not use during breastfeeding.

Pediatric patients 10-17 years with HeFH: 10 mg daily initial, maximum 20 mg. Safety in patients <10 years not established.

Elderly patients (≥70 years): Effective for primary prevention of cardiovascular events. Plasma concentrations are ~40% higher than in younger adults; lower starting doses may be considered.

Renal Impairment: No dose adjustment needed, but inform your doctor.

Hepatic Impairment: Use with caution. Not recommended in severe liver disease or active liver disease.

No specific antidote for overdose. Symptomatic and supportive treatment is recommended.

Store below 30°C, away from light and moisture. Keep out of reach of children.

Atorvastatin calcium (C₃₃H₃₅FN₂O₅·Ca)