OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Clofibrate	637-07-0	C12-H15-Cl-O3

ANNOTATED BIBLIOGRAPHY

References updated: 24 January 2017

• Zimmerman HJ. Drugs used in the treatment of hypercholesterolemia and hyperlipidemia. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 660-2.

  (Expert review of hepatotoxicity of lipid lowering agents including clofibrate, fenofibrate and gemfibrozil, all three of which can lead to mild-to-moderate serum aminotransferase elevations, and which have been associated with hepatic injury).
• De Marzio DH, Navarro VJ. Fibrates. Hepatotoxicity of cardiovascular and antidiabetic drugs: fibrates. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 527. (Review of hepatotoxicity of fibrates; fenofibrate is the most commonly implicated fibrate in causing liver injury, which can be severe and prolonged with autoimmune features and the potential for chronicity.

  ).
• Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 877-908. (Textbook.

  of pharmacology and therapeutics).
• Smith AL, Macfie WG, Oliver MF. Clofibrate, serum enzymes and muscle pain. Br Med J 1970; 2: 86-8. [PMC free article: PMC1699923] [PubMed: 5420239]

  (Cross sectional study of 101 patients on clofibrate, 110 untreated and 85 controls, found no difference in mean AST levels, 2 patients had raised AST during follow up [117 and 140 U/L] not further characterized, but without accompanying CPK elevations).
• Vester JW, Sunder JH, Aarons JH, Danowski TS. Long-term monitoring during clofibrate therapy. Clin Pharmacol Ther 1970; 11: 689-97. [PubMed: 5460240]

  (Analysis of 22 patients given clofibrate for 2-5 years, no changes in serum enzymes; one patient had rise in BSP clearance without other abnormalities).
• Summerfield JA, Elias E, Sherlock S. Effects of clofibrate in primary biliary cirrhosis: hypercholesterolemia and gallstones. Gastroenterology 1975; 69: 998-1000. [PubMed: 1175893]

  (52 year old woman with primary biliary cirrhosis developed worsening cholestasis and multiple intra- and extra-hepatic gallstones 2 months after starting clofibrate, with resolution of stones with stopping therapy).
• Jacobs WH. Intrahepatic cholestasis following the use of Atromid-S. Am J Gastroenterol 1976; 66: 69-71. [PubMed: 970388]

  (70 year old woman developed jaundice 2 years after starting clofibrate [bilirubin 10.5 mg/dL, ALT 45 U/L, Alk P 125 U/L], biopsy showing intrahepatic cholestasis, degree of recovery not given).
• Bateson MC, Maclean D, Ross PE, Bouchier IAD. Clofibrate therapy and gallstone induction. Am J Dig Dis 1978; 23: 623-8. [PubMed: 685927]

  (Among patients with hyperlipidemia, 9 of 19 on clofibrate compared to 15 of 112 untreated patients had gallstones by oral cholecystograms; biliary cholesterol was higher in clofibrate treated group, saturation index 1.46 vs 1.03 ).
• Schwandt P, Klinge O, Immich H. Clofibrate and the liver. Lancet 1978; 2: 325. [PubMed: 79123]

  (40 patients had liver biopsy before and 3 month after starting clofibrate; slight decrease in hepatic fat, but no evidence of liver injury found).
• Pierce EH, Chesler DL. Possible association of granulomatous hepatitis with clofibrate therapy. N Engl J Med 1978; 299: 314. [PubMed: 661938]

  (69 year old woman developed jaundice 3 months after starting clofibrate [bilirubin 7.3 mg/dL, ALT 149 U/L, Alk P 454 U/L], biopsy showing intrahepatic cholestasis and granulomas, resolution 1 month after stopping).
• Migneco G, Mascarella A, La Ferla A, Attianese R. [Clofibrate hepatitis. A case report] Minerva Med 1986; 77: 799-800. [PubMed: 3714094]

  (51 year old developed abdominal pain and fatigue 3 months after starting clofibrate [bilirubin normal, ALT 210 U/L] and rapid resolution on stopping; 4 months later she presented again having taken fenofibrate for 1 month [ALT 76 U/L, Alk P normal], and rapid resolution again on stopping).
• Athyros VG, Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP, Carina MV, Kranitsas DF, et al. Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia. Am J Cardiol 1997; 80: 608-13. [PubMed: 9294990]

  (389 patients treated with statin and fibrate combination for average of 2.5 years; 1.3% stopped because of ALT >3 times normal, all resolving within 4 weeks; no hepatitis or jaundice reported).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 4 cases [0.5%] were attributed to fibrates, but all to fenofibrate and none to clofibrate).