CLOFIBRATE
(kloe-fy'brate)
Atromid-S, Claripex , Novofibrate 
Classifications: cardiovascular drug; antilipemic; fibrate
Prototype: Fenofibrate
Pregnancy Category: C

Availability

500 mg capsules

Actions

Structurally related to gemfibrozil. Reduces very low density lipoproteins (VLDL) to a greater extent than it reduces low density lipoproteins (LDL). Mechanism of action is unclear; it appears to inhibit cholesterol biosynthesis prior to transfer of triglycerides from liver to serum. Interferes with binding of free fatty acids to albumin and increases fecal excretion of neutral sterols. It affects the mobilization of cholesterol from tissue. Reduces platelet adhesiveness and increases release of ADH from posterior pituitary.

Therapeutic Effects

Reduces very low density lipoproteins (VLDL) to a greater extent than it reduces low density lipoproteins (LDL).

Uses

Adjunct for treatment of severe primary (type III) hyperlipidemia.

Unlabeled Uses

Management of diabetes insipidus.

Contraindications

Impaired renal or hepatic function, primary biliary cirrhosis; pregnancy (category C), lactation. Safe use in children <14 y not established.

Cautious Use

History of jaundice or hepatic disease; gallstones; peptic ulcer; hypothyroidism; cardiovascular disease.

Route & Dosage

Hyperlipidemia
Adult: PO 2 g/d in 2–4 divided doses

Diabetes Insipidus
Adult: PO 1.5–2 g/d in 2–4 divided doses

Administration

Oral

Adverse Effects (1%)

CV: Increase or decrease in angina, CHF, arrhythmias. GI: Nausea, vomiting, loose stools, diarrhea, flatulence, abdominal distress, gastritis, stomatitis, cholelithiasis. Hematologic: Neutropenia, leukopenia, anemia, eosinophilia, agranulocytosis, potentiation of anticoagulant effect. Metabolic: Elevated AST and ALT. Musculoskeletal: Flu-like symptoms. CNS: Drowsiness, dizziness, headache. Skin: Swelling and phlebitis at xanthoma sites, skin rash, allergy, urticaria, pruritus. Urogenital: Renal insufficiency, impotence, decreased libido.

Diagnostic Test Interference

Clofibrate therapy may lead to increased BSP retention, thymol turbidity; increased serum creatine phosphokinase (CPK); proteinuria, parodoxical increase in LDL or cholesterol levels (if there is a large decrease in VLDL level). Lower fasting blood glucose and serum insulin levels in patients with diabetes mellitus.

Interactions

Drug: oral anticoagulants increase hypoprothrombinemia and increase risk of bleeding; probenecid increases effects of clofibrate; sulfonylureas increase hypoglycemic effects.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 4–6 h. Distribution: Distributed to extracellular space; crosses placenta; distribution into breast milk unknown. Metabolism: Hydrolyzed in plasma to clofibric acid, which is further metabolized in liver. Elimination: Excreted in urine. Half-Life: 12–35 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education


Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug