A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin calciumand with other drugs in this class. 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, like other statins, occasionally causes myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 times ULN. The concomitant use of higher doses of atorvastatin with certain drugs such as cyclosporine and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., clarithromycin, itraconazole, and HIV and HCV protease inhibitors) increases the risk of myopathy/rhabdomyolysis. Atorvastatin, like other statins, occasionally causes myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 times ULN. The concomitant use of higher doses of atorvastatin with certain drugs such as cyclosporine and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., clarithromycin, itraconazole, and HIV and HCV protease inhibitors) increases the risk of myopathy/rhabdomyolysis. 

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: 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.There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: 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.

Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing atorvastatin. Atorvastatin calcium therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing atorvastatin. Atorvastatin calcium 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 the drugs listed in Table 2. Physicians considering combined therapy of atorvastatin with any of these drugs should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs or 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. Lower starting and maintenance doses of atorvastatin should be considered when taken concomitantly with the aforementioned drugs [see ]. 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. The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of the drugs listed in Table 2. Physicians considering combined therapy of atorvastatin with any of these drugs should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs or 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. Lower starting and maintenance doses of atorvastatin should be considered when taken concomitantly with the aforementioned drugs [see Drug Interactions (7)]. 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. 

Prescribing recommendations for interacting agents are summarized in Table 2 [see ]. Prescribing recommendations for interacting agents are summarized in Table 2 [see  Dosage and Administration (2.6), Drug Interactions (7) and, Clinical Pharmacology (12.3)]. 

Table 2. Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis

*Use the lowest dose necessary (12.3) ]*Use the lowest dose necessary (12.3) ]

Atorvastatin calcium 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).