The effect of long-term danazol prophylaxis on liver function in hereditary angioedema-a longitudinal study

Eur J Clin Pharmacol. 2010 Apr;66(4):419-26. doi: 10.1007/s00228-009-0771-z. Epub 2009 Dec 19.

Abstract

Background: Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients.

Methods: Characteristic parameters of liver function (including bilirubin, GOT, GPT, gammaGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively.

Results: From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study.

Conclusions: Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

MeSH terms

  • Angioedemas, Hereditary / drug therapy*
  • Angioedemas, Hereditary / genetics
  • Autoimmune Lymphoproliferative Syndrome / drug therapy*
  • Autoimmune Lymphoproliferative Syndrome / genetics
  • Complement C1 Inactivator Proteins / genetics
  • Complement C1 Inhibitor Protein / genetics
  • Danazol / adverse effects
  • Danazol / therapeutic use*
  • Humans
  • Liver Diseases / physiopathology
  • Liver Diseases / prevention & control*
  • Liver Function Tests
  • Longitudinal Studies

Substances

  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • SERPING1 protein, human
  • Danazol