Brands, Medical Use, Clinical Data
- Anticholesteremic Agents
- HMG-CoA Reductase Inhibitors
Brands / Synonyms
For the treatment of pure hypercholesterolaemia and mxed hyperlipidaemia
Rosuvastatin is an antilipemic agent and a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides. It is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).
Mechanism of Action
Rosuvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, this results in a decrease in mevalonate, a precursor of cholesterol, and a subsequent decrease in hepatic cholesterol levels and increase in uptake of LDL cholesterol.
Biotrnasformation / Drug Metabolism
CRESTOR is contraindicated in patients with a known hypersensitivity to any component of this product.
Rosuvastatin is contraindicated in patients with active liver disease or with unexplained persistent elevations of
Pregnancy and Lactation
Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have
little impact on the outcome of long-term therapy of primary hypercholesterolemia. Cholesterol and other products of
cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell
membranes). Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other
biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant
women. Therefore, HMG-CoA reductase inhibitors are contraindicated during pregnancy and in nursing mothers.
ROSUVASTATIN SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO
CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this drug,
therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus.
Cyclosporine: When rosuvastatin 10 mg was co-administered with cyclosporine in cardiac transplant patients,
rosuvastatin mean cmax and mean AUC were increased 11-fold and 7-fold, respectively, compared with healthy
volunteers. These increases are considered to be clinically significant and require special consideration in the
dosing of rosuvastatin to patients taking concomitant cyclosporine .
Warfarin: Coadministration of rosuvastatin to patients on stable warfarin therapy resulted in clinically
significant rises in INR (>4, baseline 2-3). In patients taking coumarin anticoagulants and rosuvastatin
concomitantly, INR should be determined before starting rosuvastatin and frequently enough during early therapy to
ensure that no significant alteration of INR occurs. Once a stable INR time has been documented, INR can be monitored
at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of rosuvastatin is changed,
the same procedure should be repeated. Rosuvastatin therapy has not been associated with bleeding or with changes in
INR in patients not taking anticoagulants.
Gemfibrozil: Coadministration of a single rosuvastatin dose to healthy volunteers on gemfibrozil (600 mg
twice daily) resulted in 2.2- and 1.9-fold, respectively, increase in mean cmax and mean AUC of
Although clinical studies have shown that rosuvastatin alone does not reduce basal plasma cortisol concentration
or impair adrenal reserve, caution should be exercised if any HMG-CoA reductase inhibitor or other agent used to
lower cholesterol levels is administered concomitantly with drugs that may decrease the levels or activity of
endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.
CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of
perivascular spaces, have been observed in dogs treated with several other members of this drug class. A chemically
similar drug in this class produced dose-dependent optic nerve degeneration (Wallerian degeneration of
retinogeniculate fibers) in dogs, at a dose that produced plasma drug levels about 30 times higher than the mean drug
level in humans taking the highest recommended dose. Edema, hemorrhage, and partial necrosis in the interstitium of
the choroid plexus was observed in a female dog sacrificed moribund at day 24 at 90 mg/kg/day by oral gavage
(systemic exposures 100 times the human exposure at 40 mg/day based on AUC comparisons). Corneal opacity was seen in
dogs treated for 52 weeks at 6 mg/kg/day by oral gavage (systemic exposures 20 times the human exposure at 40 mg/day
based on AUC comparisons). Cataracts were seen in dogs treated for 12 weeks by oral gavage at 30 mg/kg/day (systemic
exposures 60 times the human exposure at 40 mg/day based on AUC comparisons). Retinal dysplasia and retinal loss were
seen in dogs treated for 4 weeks by oral gavage at 90 mg/kg/day (systemic exposures 100 times the human exposure at
40 mg/day based on AUC). Doses ≤30 mg/kg/day (systemic exposures ≤60 times the human exposure at 40 mg/day
based on AUC comparisons) following treatment up to one year, did not reveal retinal findings.