Atostin Special Precautions

Skeletal muscle effects: Myalgia has been reported in atorvastatin-treated patients. Myopathy, defined as muscle aching or muscle weakness in conjunction with increase in creatine phosphokinase (CPK) values > 10 x ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients must 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 (> 10 x ULN) occur or if myopathy diagnosed or suspected. The risk of myopathy during treatment is with drugs in this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, azole antifungals, colchicine, telaprevir, boceprevir, 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. Periodic 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 CPK.
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).
Physicians considering combined therapy with atorvastatin and fibrates, erythromycin, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin (≥1g/day) 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.
Hemorrhagic stroke: The potential risk of hemorrhagic stroke should be carefully considered before initiating treatment with atorvastatin in patients with recent (1 to 6 months) stroke or TIA.
Endocrine Function: Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin. The risk of hyperglycemia, however, is outweighed by the reduction in vascular risk with statins.
Immune-Mediated Necrotizing Myopathy (IMNM): There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or after treatment with some statins. IMNM is clinically characterized by: persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
Hepatic effects: As with any other lipid-lowering agents of the same class, moderate [>3 x upper limit of normal (ULN)] elevations of serum transaminases have been reported following therapy with atorvastatin. Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggestive of liver injury should have liver function tests performed. Patients who develop increased transaminase levels should be monitored until the abnormality(ies) resolve. Should an increase in ALT or AST of greater than 3 times the ULN persist, reduction of dose or withdrawal of atorvastatin is recommended.
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.