Gallstones with fibrates

EZETIMIBE LIPID-LOWERING DRUGS Risk of gallstones with fibrates Uncertain Stop co-administration if symptoms develop... 

Despite these seemingly favourable results, the UK manufacturers of ezetimibe state that the safety of eombined use with fibrates is not yet established. This is because both fibrates and ezetimibe increase cholesterol excretion into the bile, which could promote the production of gallstones. They say that if gallstones or gall bladder disease is suspected then the combination should be discontinued. 

Fibrates Yes Reduces VLDL Reduces IDL Raises HDL III, IV lib with niacin severe IV with niacin GI distress, myositis, gallstone risk, erectile dysfunction... 

The fibrates are generally well tolerated, with GI distress being the most likely complaint. Other adverse effects include myositis and erectile dysfunction, particularly with clofibrate. There is ongoing concern about the fibrates increasing the risk of gallstones, although the extent of risk is unclear. Because clofibrate was associated with increased mortality in early clinical trials, it should be considered as a second-line drug. 

Rare adverse effects of fibrates include rashes, gastrointestinal symptoms, myopathy, arrhythmias, hypokalemia, and high blood levels of aminotransferases or alkaline phosphatase. A few patients show decreases in white blood count or hematocrit. Both agents potentiate the action of coumarin and indanedione anticoagulants, and doses of these agents should be adjusted. Rhabdomyolysis has occurred rarely. Risk of myopathy increases when fibrates are given with reductase inhibitors. The use of fenofibrate with rosuvastatin appears to minimize this risk. Fibrates should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones. 

Fibrates produce bile that is supersaturated with cholesterol. Although gallstones are common with clofi-brate, no excess frequency has been observed with fenofibrate (23). In the WHO study, 59 patients taking clofibrate had to be operated on for gallstones, compared with 24 and 25 respectively in the two placebo groups (29). 

Fibrates produce bile that is supersaturated with cholesterol. Although gallstones are common with clofibrate, no excess frequency has been observed with fenofibrate (22). 

All of the fibrates increase the lithogenicity of bile. Clo-fibrate use has been associated with increased risk of gallstone formation gemfibrozil and fenofibrate reportedly do not increase biliary tract disease. 

All fibrates increase the lithogenicity of bile. Clofibrate has been associated with increased risk of gallstone formation gemfibrozil and fenofibrate reportedly do not increase biliary tract disease. Renal failure and hepatic dysfunction are relative contraindications to fibrate therapy. Combined statin-fibrate therapy should be avoided in patients with impaired renal function. Gemfibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women. 

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