Clofibrate adverse effects

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. 

A comparative study in men, women, and women taking combined oral contraceptives found that the clearance of clofibrate was increased by 48% in those taking combined oral contraceptives, apparently due to an increase in clofibrate glucuronidation. Another study found that combined oral contraceptives increased the excretion of clofibric acid glucuro-nide (the pharmacologically active form of clofibrate) by 25%. None of these studies addressed the question of whether concurrent use significantly reduces clofibrate efficacy, but it would seem prudent to monitor for increases in blood lipid levels. It should be noted that combined oral contraceptives themselves can have various adverse effects on lipid levels, and these may impair the effects of treatment. 

Increasingly, attempts have been made to minimize the adverse effects of drugs by combining 2 agents with differing mechanisms of action and administering each in a lower dose than usual. Etofibrate, mentioned above, is in effect a (chemically bound) combination of clofibric acid and nicotinic acid. 

Treatment with clofibrate in patients with nephrotic syndrome receiving furosemide has sometimes led to marked diuresis and severe and disabling adverse muscular effects. An isolated report describes rhabdomyolysis in a patient taking bezafibrate and furosemide. 

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