Rosuvastatin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher rosuvastatin calcium dosage.

Asian patients may be at higher risk for myopathy.

Discontinue rosuvastatin calcium if markedly elevated CK levels occur or myopathy is diagnosed or suspected.

Temporarily discontinue rosuvastatin calcium in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis.

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing rosuvastatin calcium dosage.

Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. • Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported with statin use.

Discontinue rosuvastatin calcium if IMNM is suspected. • Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent.

Rare reports of fatal and non-fatal hepatic failure have occurred.

Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter.

If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue rosuvastatin calcium.

5.1 Myopathy and Rhabdomyolysis Rosuvastatin calcium may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis.

Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin calcium.

Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher rosuvastatin calcium dosage.

Asian patients on rosuvastatin calcium may be at higher risk for myopathy [ see Drug Interactions and Use in Specific Populations ].

The myopathy risk is greater in patients taking rosuvastatin calcium 40 mg daily compared with lower rosuvastatin calcium dosages.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis The concomitant use of rosuvastatin calcium with cyclosporine or gemfibrozil is not recommended.

Rosuvastatin calcium dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [ see Dosage and Administration ].

Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [ see Drug Interactions ].

Discontinue rosuvastatin calcium if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected.

Muscle symptoms and CK elevations may resolve if rosuvastatin calcium is discontinued.

Temporarily discontinue rosuvastatin calcium in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the rosuvastatin calcium dosage.

Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

5.2 Immune-Mediated Necrotizing Myopathy There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered.

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents.