Initial Therapy: Before instituting bezafibrate therapy, attempts should be made to control serum lipids with appropriate diet, exercise and weight loss in obese patients, as well as other medical problems, such as diabetes mellitus and hypothyroidism. In patients at high risk, consideration should be given to the control of other risk factors such as smoking, excessive alcohol intake, hormonal contraceptive use, and inadequately controlled hypertension. Long-term Therapy: Since long-term administration of bezafibrate is recommended, the potential risks and benefits should be carefully weighed. Adequate pretreatment laboratory studies should be performed to ensure patients have elevated serum cholesterol and/or triglycerides with or without low HDL levels. Periodic determinations of serum lipids, fasting glucose, creatinine, ALT, CGT and CPK should be considered during bezafibrate treatment, particularly during the first months of therapy. Reproduction Studies: Standard tests for teratology, fertility and peri- and post-natal effects in animals have shown a relative absence of risk, however, embryotoxicity has occurred in animals at toxic doses. Hematologic Changes: Mild hemoglobin, leukocyte and platelet decreases have occurred occasionally following initiation of bezafibrate therapy. However, these levels stabilize during long-term administration. Periodic blood counts are recommended during the first 12 months of administration. Liver Function: Abnormal liver function tests have been observed occasionally during bezafibrate administration, including elevated transaminases, and decreased or, rarely, increased alkaline phosphatase. However, these abnormalities are reversible upon discontinuation of the drug. Therefore, periodic liver function tests (AST, ALT and GGT [if originally elevated]) in addition to other baseline tests are recommended after 3 to 6 months and at least yearly thereafter. Bezafibrate therapy should be terminated if drug-related abnormalities persist. Hepatobiliary Disease: In patients with a past history of jaundice or hepatic disorder, bezafibrate should be used with caution. Skeletal Muscle: Treatment with drugs of the fibrate class including bezafibrate has been associated on rare occasions with myositis or rhabdomyolysis, usually in patients with impaired renal function. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness/weakness, or marked elevations in creatinine phosphokinase levels. Patients should be advised to report unexplained muscle pain, tenderness or weakness promptly, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and bezafibrate therapy should be discontinued if markedly elevated CPK levels (10 times the upper limit of normal) occur or myopathy is diagnosed. Drug Interactions (see also Warnings): Resins: When bezafibrate is used concurrently with cholestyramine or any other resin, an interval of at least 2 hours should be maintained between the 2 drugs, since the absorption of bezafibrate is impaired by cholestyramine. Estrogens: Since estrogens may lead to a rise in lipid levels, the prescribing of bezafibrate in patients taking estrogens or estrogen-containing contraceptives must be critically considered on an individual basis. Renal Function: In patients with hypoalbuminemia, e.g., nephrotic syndrome, and in patients with renal insufficiency, the dosage of bezafibrate must be reduced and renal function should be monitored regularly (see Precautions, Skeletal Muscle). In dialysis patients, the dosage must be reduced to one 200 mg tablet every third day (see Dosage). Adverse Reactions: In two separate double-blind placebo-controlled trials, a total of 88 patients on 200 mg bezafibrate t.i.d. and 87 patients on placebo were evaluated for adverse events. Listed in Table I are those adverse events with a positive induced risk occurring during the first 2 months of bezafibrate treatment. The most common adverse reactions observed in clinical trial patients treated for up to 2 years with bezafibrate and from surveillance studies in countries where bezafibrate has been marketed for up to 14 years include: gastrointestinal: epigastric distress, flatulence, nausea, diarrhea, constipation; dermatologic: pruritus, urticaria or erythema. Less common adverse reactions observed include: musculoskeletal: muscular weakness, pain and muscle cramps; CNS: headache, dizziness, alopecia. In isolated cases, the occurrence of gallstones and potency disorders have been reported. Abnormal liver function tests have been observed occasionally during bezafibrate therapy including elevated transaminases and decreased or rarely increased alkaline phosphatase. Mild decreases in hemoglobin, leukocytes and platelets have been observed occasionally in patients receiving bezafibrate therapy. Slight increase in serum creatinine may occur. In patients with existing renal failure, if dosage recommendations are not followed, myositis and rhabdomyolysis may develop (see Precautions). Bezafibrate also has the potential to provoke CPK elevations which generally subsides when the drug is discontinued (see Precautions). Symptoms And Treatment Of Overdose: Symptoms and Treatment: While there has been no reported case of overdosage, symptomatic and supportive measures should be taken. Because bezafibrate is highly bound to plasma proteins, hemodialysis should not be considered. In patients with existing impaired renal function, if dosage recommendations are not followed, overdosage may occur and severe rhabdomyolysis may develop. Administration of bezafibrate must be stopped immediately and renal function must be carefully monitored (see Precautions). Dosage And Administration: Recommended Dosage: 200 mg: The standard dosage is one 200 mg immediate-release tablet 3 times daily. In cases of good therapeutic response, especially in hypertriglyceridemia, the dosage can be reduced to one 200 mg tablet twice daily. For patients with a history of gastric sensitivity, the dosage may be gradually increased to the maintenance level.