Gemfibrozil Disease Interactions

The use of fibric acid derivatives is contraindicated in patients with primary biliary cirrhosis. These agents may further raise the already elevated cholesterol in these patients.

The use of fibric acid derivatives is contraindicated in patients with gallbladder disease. A significantly increased incidence of cholelithiasis has been observed in patients treated with the fibric acid derivative, clofibrate, presumably because of increased cholesterol excretion into the bile. Based on two separate studies (the WHO study and the Coronary Drug Project study), clofibrate use was associated with twice the risk of developing cholelithiasis and cholecystitis requiring surgery. Due to their structural and pharmacologic similarities, use of other fibric acid derivatives may be expected to carry the same risk.

Severe myopathy, including rhabdomyolysis with acute renal failure secondary to myoglobinuria, has been reported rarely with the use of fibric acid derivatives. The myopathy may be dose-related and is characterized by muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with fibric acid derivatives should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. Therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

The use of gemfibrozil is considered by the manufacturer to be contraindicated in patients with hepatic impairment. Gemfibrozil is primarily metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and musculoskeletal adverse effects. Therapy with gemfibrozil should be administered cautiously in patients with active liver disease. Liver function tests, including serum transaminase levels, should be performed periodically. Therapy should be withdrawn if persistent abnormalities occur and are thought to be related to the drug.

The use of gemfibrozil is considered by the manufacturer to be contraindicated in patients with severely impaired renal function. The rate of clearance of gemfibrozil may be decreased in such patients, with possible accumulation during chronic dosing. Increased adverse effects, including rhabdomyolysis (with or without secondary renal failure) and severe hyperkalemia, have been associated with the use of fibric acid derivatives in patients with renal insufficiency. Some patients, usually those with baseline plasma creatinine above 2.0 mg/dL, have also experienced a deterioration of renal function when treated with gemfibrozil. Therapy with gemfibrozil should be administered cautiously in patients with significant renal impairment. Reduced dosages and close clinical monitoring are recommended.

Mild to moderate hemoglobin, hematocrit and white blood cell decreases have been observed in patients following initiation of fibric acid derivatives therapy. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with these agents. Caution is recommended when treating patients predisposed to hematologic changes. Periodic monitoring of red and white blood cell counts is recommended during the first 12 months of therapy.