clofibrate
Atromid-S

Available forms
Available by prescription only
Capsules: 500 mg

Indications and dosages
 Hyperlipidemia and xanthoma tuberosum; type III hyperlipidemia that doesn’t respond adequately to diet. Adults: 2 g P.O. daily in two to four divided doses. Some patients may respond to lower doses as assessed by serum lipid monitoring.
 Diabetes insipidus ◇. Adults: 1.5 to 2 g P.O. daily in divided doses.

Pharmacodynamics
Antilipemic action: Clofibrate may lower serum triglyceride levels by accelerating catabolism of very low-density lipoproteins; drug lowers serum cholesterol levels (to a lesser degree) by inhibiting cholesterol biosynthesis. Both mechanisms are unknown. Drug is closely related to gemfibrozil.

Pharmacokinetics
Absorption: Absorbed slowly but completely from GI tract. Serum triglyceride levels decrease in 2 to 5 days, with peak clinical effect at 21 days.
Distribution: Distributed into extracellular space as its active form, clofibric acid, which is up to 98% protein-bound. Animal studies suggest that fetal concentration levels may exceed maternal concentration levels.
Metabolism: Hydrolyzed by serum enzymes to clofibric acid, which is metabolized by the liver.
Excretion: About 20% is excreted unchanged in urine; 70% is eliminated in urine as conjugated metabolite. Plasma half-life after a single dose ranges from 6 to 25 hours; in patients with renal impairment and cirrhosis, half-life can be as long as 113 hours.

Contraindications and precautions
Contraindicated in pregnant women, in breast-feeding women, in patients hypersensitive to drug, and in patients with primary biliary cirrhosis or significant hepatic or renal dysfunction. Use cautiously in patients with peptic ulcer or history of gallbladder disease.

Interactions
Drug-drug. Cholestyramine: Reduces rate of clofibrate absorption. Avoid use together.
Furosemide: Increases diuresis. Use together cautiously.
Oral anticoagulants: Potentiates anticoagulant effects. If combination is needed, reduce oral anticoagulant dosage by 50% and evaluate PT and INR frequently.
Sulfonylureas: Enhances sulfonylurea effects, causing hypoglycemia. Dosage adjustment may be needed.

Adverse reactions
CNS: fatigue, weakness, drowsiness, dizziness, headache.
CV: arrhythmias, angina, thromboembolic events, intermittent claudication.
GI: nausea, diarrhea, vomiting, stomatitis, dyspepsia, flatulence, cholelithiasis, cholecystitis.
GU: impotence, renal dysfunction (dysuria, hematuria, proteinuria, decreased urine output).
Hematologic: leukopenia, anemia, eosinophilia, agranulocytosis.
Hepatic: gallstones, hepatomegaly.
Metabolic: weight gain, polyphagia.
Musculoskeletal: myalgia, arthralgia, myositis, myopathy.
Skin: rash, urticaria, pruritus, dry skin and hair, alopecia, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.
Other: decreased libido, flulike symptoms.

Effects on lab test results
• May cause increased AST and ALT levels and creatinine phosphokinase levels.
• May cause decreased hemoglobin, hematocrit, eosinophils, and WBC and granulocyte counts.

Overdose and treatment
No information available.

Special considerations
• Clofibrate shouldn’t be used indiscriminately; it may pose an increased risk of gallstones, heart disease, and cancer.
• Clofibrate may increase risk of death from cancer, postcholecystectomy complications, and pancreatitis.
• Monitor serum cholesterol and triglyceride levels regularly during clofibrate therapy.
• Observe patient thrombophlebitis, pulmonary embolism, angina, and dysrhythmias; monitor renal and hepatic function, blood counts, and serum electrolyte and blood glucose levels.
Breast-feeding patients
• Clofibrate is contraindicated in breast-feeding women.
Pediatric patients
• Safety and efficacy haven’t been established in children.

Patient education
• Warn patient to report flulike symptoms immediately.
• Stress importance of close medical supervision and of reporting adverse reactions; encourage compliance with prescribed regimen and diet.
• Warn patient not to exceed prescribed dose.
• Advise patient to take drug with food to minimize GI discomfort.
• Emphasize that drug therapy won’t replace diet, exercise, and weight reduction for the control of hyperlipidemia.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use