Apo-Atorvastatin Special Precautions





Full Prescribing Info
Special Precautions
Hepatic Effects: As with other lipid-lowering agents of the same class, moderate (>3x upper limit of normal [ULN]) elevations of serum transaminases have been reported following therapy with Atorvastatin. Liver function was monitored during pre-marketing as well as post-marketing clinical studies of Atorvastatin given at doses of 10, 20, 40 and 80 mg.
Persistent increases in serum transaminases (>3x ULN on two or more occasions) occurred in 0.7% of patients who received Atorvastatin in these clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40 and 80 mg respectively. Increases were generally not associated with jaundice or other clinical signs or symptoms. When the dosage of Atorvastatin was reduced, or drug treatment interrupted or discontinued, transaminase levels returned to pre-treatment levels. Most patients continued treatment on a reduced dose of Atorvastatin without sequelae.
Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggesting liver injury should have liver function tests performed. Patients who develop increased transaminase levels should be monitored until the abnormality(ies) resolve(s). Should an increase in ALT or AST of greater than three times the upper limit of normal persist, reduction of dose or withdrawal of Atorvastatin is recommended. Atorvastatin can cause an elevation in transaminases (see Adverse Reactions).
Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of Atorvastatin (see Contraindications).
Skeletal Muscle Effects: Myalgia has been reported in Atorvastatin-treated patients (see Adverse Reactions). Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10x ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, azole antifungals, colchicines, telaprevir, or the combination of tipranavir/ritonavir. Many of these drugs inhibit cytochrome P450 3A4 metabolism and/or drug-transport. CYP 3A4 is the primary hepatic isoenzymes known to be involved in the biotransformation of Atorvastatin. Physicians considering combined therapy with Atorvastatin and fibric acid derivatives, erythromycin, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Therefore, lower starting and maintenance doses of Atorvastatin should also be considered when taken concomitantly with the aforementioned drugs. Temporary suspension of Atorvastatin may be appropriate during fusidic acid therapy (See Interactions). Periodic creatine phosphokinase (CPK) determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy. Atorvastatin may cause an elevation of creatine phosphokinase (see Adverse Reactions).
As with other drugs in this class, rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria, have been reported. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects. Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis, (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Endocrine Functions: Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Atorvastatin.
Hemorrhagic Stroke: A post-hoc analysis of a clinical study in 4,731 patients without CHD who had a stroke or TIA within the preceding 6 months and were on Atorvastatin 80 mg, revealed a higher incidence of hemorrhagic stroke in the Atorvastatin 80 mg group compared to placebo (55 Atorvastatin vs 33 placebo).
Information for the Patient: Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Adolescent females and women of childbearing potential should be counseled on appropriate contraceptive methods while on Atorvastatin therapy (see Use in Pregnancy & Lactation).
Effects on Ability to Drive and Use Machines: None known.
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