Atorvastatin

LIPITOR is indicated: • To reduce the risk of: o Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD o MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD o Non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident CHD • As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: o Adults with primary hyperlipidemia. o Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).

LIPITOR is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In animal models, LIPITOR lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL, LIPITOR also reduces LDL production and the number of LDL particles.

• Take orally once daily with or without food. • Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating LIPITOR, and adjust dosage if necessary. • Adults: o Recommended starting dosage is 10 or 20 mg once daily, dosage range is 10 mg to 80 mg once daily. o Patients requiring LDL-C reduction >45% may start at 40 mg once daily. • Pediatric Patients Aged 10 Years of Age and Older with HeFH: Recommended starting dosage is 10 mg once daily, dosage range is 10 to 20 mg once daily. • Pediatric Patients Aged 10 Years of Age and Older with HoFH: Recommended starting dosage is 10 to 20 mg once daily, dosage range is 10 to 80 mg once daily. • See full prescribing information for LIPITOR dosage modifications due to drug interactions.

• Acute liver failure or decompensated cirrhosis • Hypersensitivity to atorvastatin or any excipients in LIPITOR. Hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported. • Acute liver failure or decompensated cirrhosis. • Hypersensitivity to atorvastatin or any excipient in LIPITOR.

• Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher LIPITOR dosage. Discontinue LIPITOR if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue LIPITOR in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing LIPITOR dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. • Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported with statin use. Discontinue LIPITOR if IMNM is suspected.

The following important adverse reactions are described below and elsewhere in the labeling: • Myopathy and Rhabdomyolysis • Immune-Mediated Necrotizing Myopathy • Hepatic Dysfunction • Increases in HbA1c and Fasting Serum Glucose Levels Most common adverse reactions (incidence ≥5%) are nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection.

• See full prescribing information for details regarding concomitant use of LIPITOR with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis. • Rifampin: May reduce atorvastatin plasma concentrations. Administer simultaneously with LIPITOR. • Oral Contraceptives: May increase plasma levels of norethindrone and ethinyl estradiol, consider this effect when selecting an oral contraceptive. • Digoxin: May increase digoxin plasma levels, monitor patients appropriately.

Storage Store at controlled room temperature 20-25°C (68-77°F).