Sign Out
Musculoskeletal Effects: Myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported in patients receiving rosuvastatin. These adverse effects can occur at any dosage, but the risk is increased with the highest dosage of rosuvastatin (40 mg daily).
Creatine Kinase Measurement: Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline (>5 x ULN) a confirmatory test should be carried out within 5-7 days. If the repeat test confirms a baseline CK >5 x ULN, treatment should not be started.
Before Treatment: Rosuvastatin, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include: renal impairment, hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, age >70 years, situations where an increase in plasma levels may occur, concomitant use of fibrates.
In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If Creatine Kinase (CK) levels are significantly elevated at baseline (>5 x ULN) treatment should not be started.
Whilst on Treatment: Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5 x ULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are less than or equal to 5 x ULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing rosuvastatin or an alternative HMG-CoA reductase inhibitor at the lowest dose with close monitoring. Routine monitoring of CK levels in asymptomatic patients is not warranted. There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or after treatment with statins, including rosuvastatin, IMNM is clinically characterized by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.
In clinical trials there was no evidence of increased skeletal muscle effects in the small number of patients dosed with rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors. Therefore, the combination of rosuvastatin and gemfibrozil is not recommended. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of such combinations.
Rosuvastatin should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
Hepatic Effects: In patients with secondary hypercholesterolemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with rosuvastatin. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternative etiology is not identified, do not restart rosuvastatin.
Used with caution in patients who consume large amounts of alcohol or have a history of liver disease.
Increases in serum aminotransferase (i.e., AST [SGOT], ALT [SGPT]) concentrations have been reported in patients receiving rosuvastatin. These increases usually were transient and resolved or improved with continued therapy or after temporary interruption of therapy.
It is recommended that liver function tests should be carried out prior to initiation and 12 weeks following initiation of therapy or any increase in dosage and as clinically indicated.
Renal Effects: Transient dipstick-positive proteinuria and microscopic hematuria have been reported in patients receiving rosuvastatin, more frequently in patients receiving doses of 40 mg daily compared with lower doses of rosuvastatin or comparator statins, but typically transient and not associated with a decrease in renal function. Consider dosage reduction if unexplained proteinuria and/or hematuria persists.
Race: Pharmacokinetic studies shows an approximate 2-fold elevation in median exposure to rosuvastatin (AUC and Cmax) in Asian patients compared with Caucasian patients. Dosage of rosuvastatin should be adjusted in Asian patients.
Endocrine effect: Increases in glycosylated hemoglobin (HbA1C) and fasting serum glucose concentrations have been reported in patients receiving rosuvastatin. Treatment with statins including rosuvastatin may increase the risk of developing diabetes mellitus.
