atorvastatin calcium
Lipitor

Available forms
Available by prescription only
Tablets: 10 mg, 20 mg, 40 mg, 80 mg

Indications and dosages
 Adjunct to diet to reduce elevated low-density lipoprotein (LDL), total cholesterol, apo B, triglyceride levels and to increase HDL in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb); adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV); primary dysbetalipoproteinemia (Fredrickson Type III) that does not respond adequately to diet. Adults: Initially, 10 or 20 mg P.O. once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. Increase dose, p.r.n., to maximum of 80 mg daily as single dose. Dosage based on blood lipid levels drawn within 2 to 4 weeks after starting therapy.
 Alone or as an adjunct to lipid-lowering treatments such as LDL apheresis to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia. Adults and children older than age 9: 10 to 80 mg P.O. once daily.

Pharmacodynamics
Antilipemic action: Inhibits HMG-CoA reductase, an early (and rate-limiting) step in cholesterol biosynthesis.

Pharmacokinetics
Absorption: Rapidly absorbed.
Distribution: Mean volume of distribution is about 565 L. Drug is 98% or more bound to plasma proteins with poor drug penetration into RBCs. It’s likely to appear in breast milk.
Metabolism: Extensively metabolized to orthohydroxylated and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by orthohydroxylated and parahydroxylated metabolites is equivalent to that of atorvastatin. About 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. In vitro studies suggest the importance of atorvastatin metabolism by cytochrome P-450 CYP3A4.
Excretion: Eliminated primarily in bile following hepatic or extrahepatic metabolism; however, drug doesn’t appear to undergo enterohepatic recirculation. Mean plasma elimination half-life of atorvastatin is about 14 hours, but the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30 hours because of the contribution of active metabolites. Less than 2% of a dose of atorvastatin is recovered in urine following oral administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients with active hepatic disease or conditions linked to unexplained persistent elevations of serum transaminase levels. Also contraindicated in pregnant or breast-feeding women and in women of childbearing age (except those with no risk of becoming pregnant).
  Use cautiously in patients with history of hepatic disease or heavy alcohol use.

Interactions
Drug-drug. Antacids: May decrease atorvastatin levels. LDL-cholesterol reduction not affected. Monitor patient.
Azole antifungals, cyclosporine, erythromycin, fibric acid derivatives, niacin: May increase risk of rhabdomyolysis. Avoid use together.
Digoxin: May increase plasma digoxin levels. Monitor serum digoxin level.
Erythromycin: Increases plasma atorvastatin level. Monitor patient for adverse effects.
Hormonal contraceptives: May increase hormone levels. Consider this effect when selecting hormonal contraceptive.
Drug-food. Grapefruit juice: Elevates drug levels and increases risk of adverse effects. Tell patient to take drug with liquid other than grapefruit juice.
Drug-lifestyle. Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: asthenia, headache.
EENT: pharyngitis, sinusitis.
GI: abdominal pain, constipation, diarrhea, dyspepsia, flatulence.
Hematologic: thrombocytopenia.
Hepatic: hepatic dysfunction.
Musculoskeletal: arthralgia, back pain, myalgia.
Skin: rash.
Other: accidental injury, allergic reaction, flulike syndrome, infection.

Effects on lab test results
• May increase ALT, AST, and CK levels.
• May decrease platelet count.

Overdose and treatment
Atorvastatin overdose may cause adverse GI effects and increase liver function test levels.
 There’s no specific treatment for overdose. Treat patient symptomatically, and provide supportive measures as required. Because of extensive drug binding to plasma proteins, hemodialysis isn’t expected to significantly enhance drug clearance.

Special considerations
• Before starting drug, exclude secondary causes of hypercholesterolemia and perform a baseline lipid profile. Obtain periodic liver function tests and lipid levels before starting treatment, at 6 and 12 weeks after treatment starts, or after an increase in dosage and periodically thereafter.
• Withhold or discontinue drug in patients with serious, acute conditions that suggest myopathy or those at risk for renal failure secondary to rhabdomyolysis as a result of trauma; major surgery; severe metabolic, endocrine, and electrolyte disorders; severe acute infection; hypotension; or uncontrolled seizures.
 ALERT The risk of rhabdomyolysis is increased when used in combination with other cholesterol-lowering agents.
• Use drug only after diet and other nonpharmacologic treatments prove ineffective. Patient should follow a standard low-cholesterol diet before and during therapy.
• Drug may be given as a single dose at any time of day with or without food.
• Watch for signs of myositis.
Breast-feeding patients
• Because of the potential for adverse reactions in breast-fed infants, women taking atorvastatin shouldn’t breast-feed.
Pediatric patients
• Experience in children is limited to drug doses up to 80 mg daily for 1 year in eight patients with homozygous familial hypercholesteremia. No clinical or biochemical abnormalities were reported in these patients. Safety and efficacy haven’t been established in children younger than age 9.
Geriatric patients
• Safety and efficacy in patients age 70 and older with drug doses up to 80 mg daily were similar to those of patients younger than age 70.

Patient education
• Teach patient proper dietary management, weight control, and exercise. Explain the importance of controlling elevated serum lipid levels.
• Warn patient to avoid alcohol.
• Tell patient to report adverse reactions, such as muscle pain, malaise, and fever.
• Warn women that drug is contraindicated during pregnancy because of potential danger to the fetus. Advise her to call immediately if pregnancy occurs.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use