indication

For the treatment of endometriosis and fibrocystic breast disease (in patients unresponsive to simple measures). Also used for the prophylactic treatment of all types of hereditary angioedema in males and females.

pharmacology

Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis, but its role as a treatment for endometriosis has been largely replaced by the gonadotropin-releasing hormone (GnRH) agonists. Danazol has antigonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties.

mechanism of action

As a gonadotropin inhibitor, danazol suppresses the pituitary-ovarian axis possibly by inhibiting the output of pituitary gonadotropins. Danazol also depresses the preovulatory surge in output of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby reducing ovarian estrogen production. Danazol may also directly inhibits ovarian steroidogenesis; bind to androgen, progesterone, and glucocorticoid receptors; bind to sex-hormone-binding globulin and corticosteroid-binding globulin; and increases the metabolic clearance rate of progesterone. Another mechanism of action by which danazol may use to facilitate regression of endometriosis is by decreasing IgG, IgM, and IgA concentrations, as well as phospholipid and IgG isotope autoantibodies. In the treatment of endometriosis, as a consequence of suppression of ovarian function, danazol causes both normal and ectopic endometrial tissues to become inactive and atrophic. This leads to anovulation and associated amenorrhea. In fibrocystic breast disease, the exact mechanism of action of danazol is unknown, but may be related to suppressed estrogenic stimulation as a result of decreased ovarian production of estrogen. A direct effect on steroid receptor sites in breast tissue is also possible. This leads to a disappearance of nodularity, relief of pain and tenderness, and possibly changes in the menstrual pattern. In terms of hereditary angioedema, danazol corrects the underlying biochemical deficiency by increasing serum concentrations of the deficient C1 esterase inhibitor, resulting in increased serum concentrations of the C4 component of the complement system. (Source: PharmGKB)

biotransformation

Hepatic, to principal metabolites, ethisterone and 17-hydroxymethylethisterone.

half life

Approximately 24 hours.

drug interactions

Acenocoumarol: The androgen, danazol, may increase the anticoagulant effect of acenocoumarol.

Anisindione: The androgen, danazol, may increase the anticoagulant effect of anisindione.

Carbamazepine: Danazol may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of carbamazepine if danazol is initiated, discontinued or dose changed.

Cyclosporine: The androgen, danazol, may increase the effect and toxicity of cyclosporine.

Dicumarol: The androgen, danazol, may increase the anticoagulant effect of dicumarol.

Lovastatin: Risk of severe myopathy/rhabdomyolysis with this combination

Tacrolimus: Danazol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Danazol therapy is initiated, discontinued or altered.

Warfarin: Danazol may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if danazol is initiated, discontinued or dose changed.