Lipitor (Atorvastatin) Contraindications and Precautions
- breast-feeding
- cholestasis
- hepatic disease
- hepatic encephalopathy
- hepatitis
- jaundice
- pregnancy
- rhabdomyolysis
- alcoholism
- children
- elderly
- electrolyte imbalance
- endocrine disease
- females
- hypotension
- infection
- myopathy
- organ transplant
- renal disease
- renal failure
- renal impairment
- seizure disorder
- surgery
- trauma
Lipitor (Atorvastatin) Contraindications and Precautions
Atorvastatin is contraindicated in patients with active hepatic disease (including cholestasis, hepatic encephalopathy, hepatitis, and jaundice) or unexplained persistent elevations in serum aminotransferase concentrations. In addition, patients should minimize alcohol intake while receiving atorvastatin therapy, and atorvastatin should be avoided in patients with alcoholism. In patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin are markedly increased. In patients with Childs-Pugh A disease, atorvastatin Cmax and AUC are each 4-fold greater. Cmax and AUC are approximately increased 16-fold and 11-fold, respectively, in patients with Childs-Pugh B disease. Liver function tests should be performed prior to and at 12 weeks following both the initiation of therapy and any elevation in dose, and periodically (e.g., semiannually) thereafter. Patients who develop elevated hepatic enzymes should be monitored until the abnormalities resolve. Atorvastatin should be discontinued if significant enzyme elevations persist.
Atorvastatin has been classified as a pregnancy category X drug by the FDA and is contraindicated for use during pregnancy, because of the potential effects of HMG-CoA reductase inhibitors on cholesterol pathways and the potential for fetal harm. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Treatment should be immediately discontinued as soon as pregnancy is recognized. Other HMG-CoA reductase inhibitors have been shown to cause malformations of vertebrae and ribs in fetal rats when given in high doses. In a prospective review of about 100 pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidence of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. However, atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. If the patient becomes pregnant while taking this drug, atorvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Atorvastatin should only be administered to females of child-bearing potential, including adolescents at least 1 year post-menarche, when such patients are highly unlikely to conceive and have been informed of the potential hazards. Females should be counseled regarding appropriate methods of contraception while on therapy.
Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. Because of the ability of HMG-CoA reductase inhibitors to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, atorvastatin is contraindicated for use during breast-feeding.
Safe use of atorvastatin in children under 10 years of age or in pre-pubertal females has not been established. Safety and effectiveness in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in controlled clinical trials of 6 months duration in adolescent boys and postmenarchal females. Adolescent females should be counseled on appropriate contraceptive methods while receiving HMG-CoA reductase inhibitor therapy. Atorvastatin should be administered to females of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.
Other HMG-CoA reductase inhibitors have been associated with toxicity to the skeletal muscle system. Myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values > 10 times upper limit of normal (ULN), should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Any evidence of myalgia, muscle weakness, or elevated CPK values may indicate myopathy, particularly if symptoms include fever or malaise. Clinicians should note that rhabdomyolysis and renal failure have been associated with HMG-CoA reductase inhibitor therapy. The risk of developing myopathy appears to be increased when HMG-CoA reductase inhibitors are used in combination with other drugs (see Drug Interactions). Atorvastatin should be discontinued immediately in any patient who develops myopathy or elevations in CPK. In addition, atorvastatin may be contraindicated in conditions that can cause decreased renal perfusion because renal failure is possible if atorvastatin-induced rhabdomyolysis occurs. Predisposing conditions include renal disease or renal impairment, hypotension, acute infection, endocrine disease, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Atorvastatin should be used with caution in organ transplant patients receiving immunosuppressant therapy such as cyclosporine because of an increased risk of rhabdomyolysis and renal failure (see Drug Interactions). Renal disease has no influence on atorvastatin plasma concentrations or LDL cholesterol reductions; dosage adjustments are not needed in patients with renal impairment.
In general, elderly patients may have an increased cholesterol-lowering response to HMG-CoA reductase inhibitors. Plasma concentrations of atorvastatin are higher (about 40% for Cmax and 30% for AUC) in healthy elderly subjects than in young adults. In addition, the LDL-cholesterol reduction at a given atorvastatin dosage is greater than that seen in younger patient populations.
[ Last revised: 2/19/2004 2:38:00 PM ]
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