Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a precursor of sterols, including cholesterol.The primary site of action of rosuvastatin is the liver, the target organ for lowering cholesterol. Rosuvastatin increases the number of hepatic LDL receptors on the cell surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualized according to the goal of therapy and patient response, using current consensus guidelines.
Treatment of hypercholesterolemia: Patient of Asian origin or with risk factors for myopathy or rhabdomyolysis: initially 5 mg once daily increased if necessary to max. 20 mg daily.
Prevention of cardiovascular events: Patient of Asian origin or with risk factors for myopathy or rhabdomyolysis: initially 5 mg once daily increased if necessary to max. 20 mg daily.
Pediatric Use (Hyperlipidemia including familial hypercholesterolemia):
Child younger than 6 years: not recommended.
Child 6–9 years: initially 5 mg daily, increased if necessary at intervals of at least 4 weeks to usual max. 10 mg once daily.
Child 10–18 years: initially 5 mg daily, increased if necessary at intervals of at least 4 weeks to usual max. 20 mg once daily.
[Reduced dose required with concomitant atazanavir, darunavir, ezetimibe, fibrate, itraconazole, lopinavir, or tipranavir]
Use in the elderly (>70 years): A start dose of 5 mg is recommended. No dose adjustment necessary.
Renal insufficiency: Initially 5mg once daily (do not exceed 20 mg daily) if eGFR is 30-60 mL/minute/1.73 m2. Avoid if eGFR is less than 30 mL/minute/1.73 m2
Child-Pugh scores of <7: no increase in systemic exposure to rosuvastatin. Child-Pugh scores of 8 and 9: increased systemic exposure has been observed. In these patients an assessment of renal function should be considered. Child-Pugh scores >9: no study.
Rosuvastatin is contraindicated in patients with active liver disease.
Race: Increased systemic exposure has been seen in Asian subjects. The recommended starting dose is 5 mg for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients.
Genetic polymorphisms: Specific types of genetic polymorphisms are known that can lead to increased rosuvastatin exposure. For patients who are known to have such specific types of polymorphisms, a lower daily dose of Rosuvastatin is recommended.
Dosage in patients with pre-disposing factors to myopathy: The recommended starting dose is 5 mg in patients with predisposing factors to myopathy. The 40 mg dose is contraindicated in some of these patients.