Rosuvastatin

Mechanism :

Rosuvastatin is a competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver. Decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low-density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low-density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL. In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties. Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration (PMID: 11375257). The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts (PMID: 15914111). Rosuvastatin increases the bioavailability of nitric oxide (PMID: 11375257, 12031849, 15914111) by upregulating NOS (PMID: 12354446) and by increasing the stability of NOS through post-transcriptional polyadenylation (PMID: 17916773). It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.

Indication :

• Used as an adjunct to dietary therapy to treat primary hyperlipidemia (heterozygous familial and non-familial), mixed dyslipidemia and hypertriglyceridemia.
• Homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies or when other such therapies are not available.
• Slow the progression of atherosclerosis and for primary prevention of cardiovascular disease.

Contraindications :

Hypersensitivity, Pregnancy, breastfeeding, CK >10x ULN, Myopathy, persistent AST or ALT >3x ULN, unexplained Elevated LFTs, active Hepatic disease.

Caution in pts >65 yo, Asian pts, female pts.

Caution if renal impairment, alcohol abuse, hepatic disease hx, diabetes mellitus, hypothyroidism.

Dosing :

Adverse Effect :

Serious Reactions: Myopathy, rhabdomyolysis, acute renal failure, hepatotoxicity, pancreatitis, hypersensitivity reactions, angioedema, thrombocytopenia, diabetes mellitus.

Common Reactions: Myalgia, arthralgia, headache, dizziness, nausea, constipation, diabetes mellitus, asthenia, elevated CK/AST/ALT, abdominal pain, proteinuria, cognitive impairment, photosensitivity.

Interaction :

Colchicine: Increased risk of rhabdomyolysis with this combination.
Cyclosporine: May increase the serum concentration of rosuvastatin. Limit rosuvastatin dosing to 5 mg/day and monitor for changes in the therapeutic and adverse effects of rosuvastatin if cyclosporine is initiated, discontinued or dose changed.
Fenofibrate: May cause additive myotoxicity. Monitor for symptoms of muscle toxicity during concomitant therapy.
Gemfibrozil: May increase the therapeutic and toxic effects of rosuvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of rosuvastatin if gemfibrozil is initiated, discontinued or dose changed.
Magnesium: Magnesium-containing antacids may decrease the absorption of rosuvastatin.
Tipranavir: Concomitant therapy of Rosuvastatin and Tipranavir/Ritonavir may increase Rosuvastatin and Tipranavir concentrations. Consider alternate therapy.

Renal Dose :

Hepatic Dose :