General Before instituting therapy with clofibrate, attempts should be made to control serum lipids with appropriate dietary regimens, weight loss in obese patients, control of diabetes mellitus, etc. Because of the long-term administration of a drug of this nature, adequate baseline studies should be performed to determine that the patient has significantly elevated serum lipid levels. Frequent determinations of serum lipids should be obtained during the first few months of Atromid-S (clofibrate) administration, and periodic determinations made thereafter. The drug should be withdrawn after three months if response is inadequate. However, in the case of xanthoma tuberosum, the drug should be employed for longer periods (even up to one year) provided that there is a reduction in the size and/or number of the xanthomata. Since cholelithiasis is a possible side effect of clofibrate therapy, appropriate diagnostic procedures should be performed if signs and symptoms related to disease of the biliary system should occur. Clofibrate may produce "flu-like" symptoms (muscular aching, soreness, cramping) associated with increased creatine kinase levels indicative of drug-induced myopathy. The physician should differentiate this from actual viral and/or bacterial disease. Use with caution in patients with peptic ulcer, since reactivation has been reported. Whether this is drug related is unknown. Various cardiac arrhythmias have been reported with the use of clofibrate. Laboratory Tests Subsequent serum lipid determinations should be done to detect a paradoxical rise in serum cholesterol or triglyceride levels. Clofibrate will not alter the seasonal variations of serum cholesterol: peak elevations in midwinter and late summer and decreases in fall and spring. If the drug is discontinued, the patient should be continued on an appropriate hypolipidemic diet, and serum lipids should be monitored until stabilized, as a rise in these values to or above the original baseline may occur. During clofibrate therapy, frequent serum-transaminase determinations and other liver-function tests should be performed, since the drug may produce abnormalities in these parameters. These effects are usually reversible when the drug is discontinued. Hepatic biopsies are usually within normal limits. If the hepatic-function tests steadily rise or show excessive abnormalities, the drug should be withdrawn. Therefore, use with caution in those patients with a past history of jaundice or hepatic disease. Complete blood counts should be done periodically since anemia, and more frequently, leukopenia have been reported in patients who have been taking clofibrate. Drug Interactions Caution should be exercised when anticoagulants are given in conjunction with Atromid-S (clofibrate) . Usually, the dosage of the anticoagulant should be reduced by one-half (depending on the individual case) to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been determined definitely that the prothrombin level has been stabilized. Atromid-S (clofibrate) may displace acidic drugs such as phenytoin or tolbutamide from their binding sites. Caution should be exercised when treating patients with either of these drugs or other highly protein-bound drugs and Atromid-S (clofibrate) . The hypoglycemic effect of tolbutamide has been reported to increase when Atromid-S (clofibrate) is given concurrently. Fulminant rhabdomyolysis has been seen as early as three weeks after initiation of combined therapy with another fibrate and lovastatin but may be seen after several months. For these reasons, it is felt that, in most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefits of combined therapy with lovastatin and a fibrate do not outweigh the risks of severe myopathy, rhabdomyolysis, and acute renal failure. While it is not known whether this interaction occurs with fibrates other than gemfibrozil, myopathy and rhabdomyolysis have occasionally been associated with the use of fibrates alone, including clofibrate. Therefore, the combined use of lovastatin with fibrates should generally be avoided. Carcinogenesis, Mutagenesis, Impairment of Fertility See WARNINGS section for information on carcinogenesis and mutagenesis. Arrest of spermatogenesis has been seen in both dogs and monkeys at doses approximately 2 times the maximum recommended human dose (based on surface area). Electron microscopy studies have demonstrated peroxisomal proliferation following clofibrate administration to the rat. Changes in peroxisome morphology and numbers have been observed in humans after treatment with several members of the fibrate class, including clofibrate, when liver biopsies were compared before and after treatment in the same individual. Pregnancy Teratogenic effects Pregnancy Category C. Animal reproduction studies have not been conducted with Atromid-S (clofibrate) . It is also not known whether Atromid-S (clofibrate) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. However, animal reproduction studies with clofibrate plus androsterone showed increases in neonatal deaths and pup mortality during lactation. Nursing Mothers Atromid-S (clofibrate) is contraindicated in lactating women, since an active metabolite (CPIB) has been measured in breast milk. Pediatric Use Safety and efficacy in pediatric patients have not been established. Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.