Atorvastatin Calcium

Trade Names:Lipitor- Tablets 10 mg- Tablets 20 mg- Tablets 40 mg- Tablets 80 mg

Pharmacology

Increases rate at which body removes cholesterol from blood and reduces production of cholesterol by inhibiting enzyme that catalyzes early rate-limiting step in cholesterol synthesis; increases HDL; reduces LDL, VLDL, and triglycerides (TGs).

Pharmacokinetics

Absorption

Rapidly absorbed; T _max is 1 to 2 h. Bioavailability is approximately 14%; low bioavailability is because of presystemic Cl in GI mucosa and/or hepatic first-pass metabolism. Food decreases rate and extent of absorption approximately 25% and 9%, respectively, but does not alter efficacy.

Distribution

Vd is approximately 381 L. At least 98% is protein bound.

Metabolism

Undergoes hepatic and extrahepatic metabolism, including first-pass metabolism and CYP3A4. Extensively metabolized to active metabolites, which produce approximately 70% of circulating inhibitory activity of HMG-CoA reductase.

Elimination

Atorvastatin and metabolites eliminated primarily in bile. Less than 2% of dose is recovered in the urine. Plasma t _½ is approximately 14 h.

Duration

The t _½ of HMG-CoA reductase inhibition is 20 to 30 h.

Special Populations

Plasma levels are markedly increased in patients with chronic alcoholic liver disease.

Indications and Usage

Reduce risk of MI or stroke and reduce risk for revascularization procedures and angina in patients with multiple risk factors for coronary heart disease (CHD), such as age, smoking, hypertension, low HDL cholesterol (C), or family history of early CHD. Reduce risk of non-fatal MI and fatal and non-fatal stroke in patients with type 2 diabetes, and without clinically evident CHD, but with multiple risk factors for CHD, such as albuminuria, hypertension, retinopathy, or smoking. Reduce risk of angina, non-fatal MI, and fatal and non-fatal stroke, or hospitalization for CHD, and reduce risk for revascularization procedures in patients with clinically evident CHD.

Adjunct to diet to reduce elevated total-C, LDL-C, apolipoprotein B (apo B), and TG levels, and increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb). Adjunct to diet for treatment of patients with elevated serum TG levels (Fredrickson type IV). Treatment of primary dysbetalipoprotein (Fredrickson type III) in patients who do not respond adequately to diet. Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatment (LDL aphaeresis), or if such treatments are unavailable. Adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls 10 to 17 yr of age with heterozygous familial hypercholesterolemia if, after an adequate trial of diet therapy, the following are present: LDL-C remains at a level of at least 190 mg/dL; LDC-C remains at a level of least 160 mg/dL and there is a positive family history of premature CV disease; 2 or more other CV disease risk factors are present in children.

Contraindications

Active liver disease or unexplained persistent elevation of serum transaminases; pregnancy; lactation; hypersensitivity to any component of the product.

Dosage and Administration

PO 10 to 80 mg/day.

PO Start with 10 mg/day (max, 20 mg/day).

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F).

Drug Interactions

Coadministration may decrease atorvastatin levels.

Severe myopathy or rhabdomyolysis may occur.

May increase AUC for norethindrone and ethinyl estradiol.

Elevated digoxin levels may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (17%); asthenia (4%); dizziness, insomnia (at least 2%).

Dermatologic

Rash (4%); bullous rashes including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).

EENT

Sinusitis (6%); pharyngitis (3%); rhinitis (at least 2%).

GI

Diarrhea (5%); abdominal pain (4%); constipation, dyspepsia, flatulence (3%); nausea (at least 2%).

Genitourinary

Albuminuria, hematuria, UTI (at least 2%).

Metabolic

Peripheral edema (at least 2%).

Musculoskeletal

Myalgia (6%); arthralgia (5%); back pain (4%); arthritis (at least 2%); rhabdomyolysis (postmarketing).

Respiratory

Bronchitis (at least 2%).

Miscellaneous

Accidental injury (4%); flu-like symptoms (3%); chest pain (at least 2%); anaphylaxis, angioneurotic edema (postmarketing).

Precautions

Pregnancy

Category X .

Lactation

Contraindicated in breast-feeding women.

Children

Safety and efficacy not established, except in children 10 to 17 yr of age with heterozygous familial hypercholesterolemia.

Hypercholesterolemia

Ensure secondary causes of hypercholesterolemia (eg, poorly controlled diabetes, hypothyroidism, drugs that increase LDL-C and decrease HDL-C) are excluded, or, if appropriate, treated, before starting therapy.

LFTs

Ensure that LFTs (transaminases) are determined before and 12 wk following initiation of therapy, after increase in dose, and periodically thereafter (eg, every 6 mo).

Liver disease

Use with caution in patients who consume substantial quantities of alcohol or have a history of liver disease.

Myopathy

Ensure therapy is temporarily withheld in patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (eg, hypotension, major surgery, sepsis, trauma).

Skeletal muscle effects

Rhabdomyolysis with renal function impairment secondary to myoglobinuria has occurred in this class of drugs. Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, or marked elevation of CPK.

Patient Information

• Explain name, dose, action, potential side effects of medication, and cholesterol goals.
• Advise patient that dose of medication may change, based on results of cholesterol blood tests, in an effort to reach cholesterol goals.
• Advise patient to take prescribed dose once daily without regard to meals, but to take with food if stomach upset occurs.
• Advise patient to try to take each dose at about the same time each day.
• Caution patient not to take atorvastatin with grapefruit juice.
• Advise patient that if a dose is missed to take as soon as remembered but to never take more than 1 dose of atorvastatin a day.
• Advise patient that atorvastatin helps control, but does not cure, cholesterol abnormality and to continue taking as prescribed when cholesterol goals has been reached.
• Emphasize to patient the importance of other modalities for cholesterol control: dietary changes (eg, reduced saturated fat intake, increased soluble fiber intake), weight control, regular exercise, and smoking cessation.
• Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
• Instruct patient to immediately notify health care provider if experiencing dark urine; fatigue; flu-like symptoms; pain under the right rib cage; persistent nausea; unexplained muscle pain, tenderness, and/or weakness; yellowing of skin or eyes; or any other unusual feelings.
• Advise women of childbearing potential to use effective contraception during treatment with atorvastatin.

Copyright © 2009 Wolters Kluwer Health.