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

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, γGT, 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.

Angioedema Recidivante Idiopático: Uma Possível Apresentação de Angioedema Hereditário Tipo III

“…Se esses medicamentos não forem disponíveis, deverá ser feito plasma fresco congelado é de 10 mL/kg, mas o seu uso é ainda controverso. [17][18][19] Medicamentos como C1-INH, progesterona, andrógenos atenuados particularmente o danazol, e os antifibrinolíticos como o ácido tranexâmico e ácido épsilon-aminocapróico têm sido utilizados de forma eficaz na prevenção de crises. [20][21][22][23] Um novo fármaco, um inibidor da calicreína oral (avoralstat), está em estudo para o tratamento profilático do AEH.…”

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

“…59 -62,70,72-76 We found that many patients experience adverse effects while taking attenuated androgens. 59,62,72,77,78 These adverse effects can be controlled or minimized by using the lowest effective dose, and some patients are capable of tolerating the adverse effects associated with attenuated androgen therapy. It should be noted, however, that many of the patients in these reports were treated with attenuated androgens at a time when there were very limited options for prophylactic therapy for HAE.…”

“…58 This underscores the importance of titrating to the lowest dose that confers adequate prophylaxis to avoid or at least mitigate adverse effects. 2,78 …”

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

“…To review the published safety data on these agents, we performed a literature search and identified articles that included an evaluation of the safety of long-term attenuated androgen therapy in HAE (Table 2)[59-62,70,72-76]. We found that many patients experience adverse effects while taking attenuated androgens[59,62,72,77,78]. These adverse effects can be controlled or minimized by using the lowest effective dose, and some patients are capable of tolerating the adverse effects associated with attenuated androgen therapy.…”

“…The side effects associated with attenuated androgens seem to be dose dependent and increase with duration of therapy[58]. This underscores the importance of titrating to the lowest dose that confers adequate prophylaxis to avoid or at least mitigate adverse effects[2,78]. …”