Atromid-S Disease Interactions

The use of clofibrate has been associated with an increased incidence of adverse cardiovascular effects, including cardiac arrhythmias, intermittent claudication, thromboembolic events, and angina. Because of these risks, as well as the lack of substantial evidence demonstrating a beneficial effect on cardiovascular mortality, therapy with clofibrate should be considered and administered cautiously in patients with a history of cardiovascular or cerebrovascular disease.

The use of clofibrate is considered by the manufacturer to be contraindicated in patients with clinically significant hepatic and/or renal impairment. The protein-binding of clofibrate may be reduced under these circumstances, resulting in higher concentrations of free (active) drug. Increased adverse effects, including rhabdomyolysis (with or without secondary renal failure) and severe hyperkalemia, have been associated with preexisting renal insufficiency, presumably due to both decreased drug clearance and protein-binding. If clofibrate is used in patients with impaired renal and/or hepatic function, reduced dosages should be considered. Close clinical monitoring is recommended during therapy.

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.

Reactivation of peptic ulcer has been reported during treatment with clofibrate. Although a causal relationship has not been established, therapy with clofibrate should be administered cautiously in patients with a history of peptic ulcers.