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Immune-mediated myopathy related to anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies as an emerging cause of necrotizing myopathy induced by statins. Lahaye C1, Beaufrére AM2, Boyer O3, Drouot L4, Soubrier M1, Tournadre A5.
Dosage adjustment for simvastatin with concomitant medications: Cyclosporine or danazol: Patient must first demonstrate tolerance to simvastatin >/= 5 mg once daily: Initial: 5 mg, should not exceed 10 mg/day. Fibrates or niacin: Dose should not exceed 10 mg/day. Amiodarone or verapamil: Dose should not exceed 20 mg/day. Mechanism Of Action Simvastatin is a prodrug and is hydrolyzed to its active -hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme.
Cerivastatin sodium is an entirely synthetic, enantiomerically pure inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
HMG-CoA (or 3-hydroxy-3-methylglutaryl-coenzyme A) is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase.
43. Parker, R. A. , et al. , Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem, 1993. 268(15): p. 11230-8. 44. Pearce, B.