CLOFIBRATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLOFIBRATE (CLOFIBRATE).
Clofibrate is a fibric acid derivative that activates peroxisome proliferator-activated receptor alpha (PPARα), leading to increased lipolysis and clearance of triglycerides-rich lipoproteins from plasma, and reduced hepatic secretion of VLDL.
| Metabolism | Hepatic metabolism via glucuronidation (major) and hydrolysis to clofibric acid; clofibric acid is the active form. Clofibrate is a prodrug. |
| Excretion | Approximately 60% renal as glucuronide conjugate; 40% biliary/fecal as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life 6-25 hours (mean 15 hours); may increase in renal impairment. |
| Protein binding | 96-99% bound to albumin. |
| Volume of Distribution | 0.12-0.15 L/kg; reflects distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Oral: 90-100% (almost complete absorption; undergoes extensive first-pass metabolism to active form clofibric acid). |
| Onset of Action | Oral: 2-5 days for serum lipid changes; maximal effect 3-4 weeks. |
| Duration of Action | Lipid-lowering persists for several weeks after discontinuation due to enterohepatic recirculation. |
500-1000 mg orally twice daily, not to exceed 2 g daily.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-59 mL/min: reduce dose by 50%; eGFR <30 mL/min: avoid use (contraindicated). |
| Liver impairment | Contraindicated in Child-Pugh class B and C cirrhosis; use with caution in class A with dose reduction (consider 50% of normal dose). |
| Pediatric use | Not established; not recommended for use in children. |
| Geriatric use | Initiate at 500 mg once daily; monitor renal function and titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CLOFIBRATE (CLOFIBRATE).
| Breastfeeding | Clofibrate is excreted in human milk; the milk-to-plasma ratio is approximately 0.5. Potential for serious adverse reactions in nursing infants; decision should be made to discontinue nursing or discontinue the drug, taking into account importance to the mother. |
| Teratogenic Risk | Clofibrate is contraindicated in pregnancy. Animal studies have shown teratogenic effects, and there are no adequate human studies. Risk cannot be ruled out; use is not recommended in any trimester. |
| Fetal Monitoring |
■ FDA Black Box Warning
Clofibrate is indicated only for patients with very high serum triglyceride levels who are at risk of pancreatitis and who do not respond to diet. It is not indicated for the treatment of hypercholesterolemia. The drug is associated with an increased risk of cholelithiasis and may have carcinogenic potential in humans based on animal studies.
| Serious Effects |
Severe hepatic or renal dysfunction, primary biliary cirrhosis, gallbladder disease, known hypersensitivity to clofibrate, pregnancy and lactation.
| Precautions | Hepatotoxicity (elevated liver enzymes, cholestatic hepatitis), increased risk of gallstones, myopathy (especially in renal impairment), malignancy risk (liver tumors in rodents), and increased risk of non-cardiovascular mortality. |
Loading safety data…
| Monitor maternal liver function (AST, ALT, alkaline phosphatase), renal function (serum creatinine, BUN), complete blood count, and serum lipids. Fetal monitoring includes ultrasound for growth and development if exposure occurs. Monitor for cholelithiasis and myopathy in mother. |
| Fertility Effects | No specific human data on fertility impairment. In animal studies, clofibrate has shown effects on spermatogenesis and fertility at high doses. Clinical relevance unknown. |