Fibrates drug interactions

Myopathy caused by drug interactions The incidence and severity of myopathy are increased by concomitant administration of HMG-CoA reductase inhibitors with drugs that can cause myopathy when given alone, such as gemfibrozil and other fibrates, and lipid-lowering doses (greater than or equal to 1 g/day) of niacin (nicotonic acid). 

Drug Interactions Gemfibrozil Niacin Erythromycin Cholestyramine Digoxin Cimetidine/ranitidine/ omeprazole Rifampicin Warfarin Itraconazole Gemfibrozil Niacin Erythromycin Propranolol Digoxin Warfarin Antacids Colestipol Digoxin Erythromycin Oral contraceptives Fibrates Niacin Azole antifungals... 

Susceptibility factors Drug-drug interactions (for example, with fibrates)... 

TOLBUTAMIDE FIBRATES Fibrates may t efficacy of sulphonylureas Uncertain postulated that fibrates displace sulphonylureas from plasma proteins and l their hepatic metabolism. In addition, fenofibrate may inhibit CYP2C9-mediated metabolism of tolbutamide Monitor blood glucose levels closely. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

It has been an attractive option to use combination therapy of statin and fibrate when HDL remains low but there is no data from RCTs to support this approach. It is ironic that gemfibrozil with the best outcome data should not be used in this context given drug interactions. The results of the FIELD trial with fenofibrate as sole therapy were disappointing [59] however, a combination trial with fenofibrate and statin in type 2 diabetes, the ACCORD study, is in progress. 

All other statins, which entered the market, are produced by total synthesis (Fig. 5.153). Fluvastatin is marketed as the racemate. After the Lipobay scandal, cerivastatin was withdrawn from the market worldwide in 2001, due to reports of fatal rhabdomyolysis associated with renal failure. The reasons behind these toxicities were a too narrow therapeutic window (effective dose compared to toxic dose) and the drug interaction with fibrates, especially with gemfibrozil. 

The fibrates potentiate the actions of the coumarin anticoagulants, such as warfarin, so care should be taken to reduce the dose of simultaneously administered anticoagulants, and plasma prothrombin should be frequently measured until the level stabilizes. As mentioned earlier, great care should be given to combining a statin with a fibrate, since this combination may increase the risk of myositis and perhaps rhabdomyolysis. Table 23.4 summarizes major interactions of drugs that lower cholesterol. 

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