Rosuvastatin

Small increases in HbA1c (mean: ~0.1%) and fasting blood glucose have been reported with rosuvastatin; however, the benefits of statin therapy far outweigh the risk of dysglycemia.

Hematuria (microscopic) and proteinuria have been observed; more commonly reported in adults receiving rosuvastatin 40 mg daily. Typically, transient and not associated with a decrease in renal function. Consider dosage reduction if unexplained hematuria and proteinuria persists.

Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart rosuvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary.

Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, have been reported.

IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be useful for treatment.

Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of other lipid-lowering medications (fibric acid derivatives or niacin doses ≥1 g/day), other interacting drugs, other drugs associated with myopathy (eg, colchicine), age ≥65 years, female gender, uncontrolled hypothyroidism, and renal dysfunction. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or dark urine. Disease-related concerns:

Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated with active liver disease or unexplained transaminase elevations.

Dosage adjustment required in patients with a CrCl 2 and not receiving hemodialysis. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Increased risk of rosuvastatin-associated myopathy in certain subgroups; dosage adjustment should be considered for patients of Asian descent.

Use with caution in patients with advanced age; these patients are more predisposed to myopathy.

The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality. Other warnings/precautions:

Secondary causes of hyperlipidemia should be ruled out prior to therapy. Rosuvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).