indication

Used as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate.

pharmacology

Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).

mechanism of action

Cerivastatin competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for converting HMG-CoA to mevalonate. As mevalonate is a precursor of sterols such as cholesterol, this results in a decrease in cholesterol in hepatic cells, upregulation of LDL-receptors, and an increase in hepatic uptake of LDL-cholesterol from the circulation.

toxicity

Rhabdomyolysis, liver concerns

biotransformation

Hepatic. Biotransformation pathways for cerivastatin in humans include the following: demethylation of the benzylic methyl ether to form Ml and hydroxylation of the methyl group in the 6'-isopropyl moiety to form M23.

absorption

The mean absolute oral bioavailability 60% (range 39 - 101%).

half life

2-3 hours

drug interactions

Bezafibrate: Increased risk of myopathy/rhabdomyolysis

Bosentan: Bosentan may decrease the serum concentration of cerivastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if bosentan is initiated, discontinued or dose changed.

Clarithromycin: The macrolide, clarithromycin, may increase the toxicity of the statin, cerivastatin.

Colchicine: Increased risk of rhabdomyolysis with this combination

Cyclosporine: Possible myopathy and rhabdomyolysis

Diltiazem: Diltiazem may increase the serum concentration of cerivastatin. Cerivastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.

Erythromycin: The macrolide, erythromycin, may increase the toxicity of the statin, cerivastatin.

Fenofibrate: Increased risk of myopathy/rhabdomyolysis

Gemfibrozil: Increased risk of myopathy/rhabdomyolysis

Imatinib: Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if imatinib is initiated, discontinued or dose changed.

Itraconazole: Increased risk of myopathy/rhabdomyolysis

Josamycin: The macrolide, josamycin, may increase the toxicity of the statin, cerivastatin.

Ketoconazole: Increased risk of myopathy/rhabdomyolysis

Nefazodone: Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if nefazodone is initiated, discontinued or dose changed.

Quinupristin: This combination presents an increased risk of toxicity

Rifabutin: Rifabutin may decrease the effect of cerivastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cerivastatin if rifabutin is initiated, discontinued or dose changed.

Rifampin: Rifampin may decrease the effect of cerivastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cerivastatin if rifampin is initiated, discontinued or dose changed.