DANOCIL

Indications

• Endometriosis
• Fibrocystic breast disease
• Hereditary angioedema

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing information as it may vary based on the condition being treated.

Mechanism of action

Danazol acts as a gonadotropin inhibitor, suppressing the pituitary-ovarian axis by reducing the output of pituitary gonadotropins, specifically follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in decreased ovarian estrogen production. Additionally, danazol may inhibit ovarian steroidogenesis, bind to various hormone receptors, and alter immunoglobulin concentrations to facilitate the regression of endometriosis. In fibrocystic breast disease, it is believed to suppress estrogenic stimulation, potentially through direct effects on steroid receptors in breast tissue.

Pharmacodynamics

Danazol exhibits antigonadotropic and anti-estrogenic activities, functioning as a suppressant of anterior pituitary hormone release. It has some androgenic properties due to its structural similarity to testosterone. The drug was the first approved treatment for endometriosis but has been largely supplanted by gonadotropin-releasing hormone (GnRH) agonists.

Pharmacokinetics

Danazol is well absorbed when administered orally and has a half-life of approximately 14 to 24 hours. It undergoes extensive hepatic metabolism and is primarily eliminated via the urine. The pharmacokinetic profile may be influenced by individual patient factors, including hepatic function.

Contra-indications

• Pregnancy
• Breastfeeding
• History of thromboembolic disorders
• Active liver disease
• Hormone-sensitive tumors

Adverse effects

• Weight gain
• Acne
• Oily skin
• Hot flashes
• Menstrual irregularities
• Hair loss
• Changes in libido
• Headache
• Nausea
• Fatigue
• Potential for hepatotoxicity

Interactions

• Oral anticoagulants (may enhance effects)
• Corticosteroids (may increase effects)
• Cyclosporine (increased blood levels of cyclosporine)
• Hormonal contraceptives (may alter effectiveness)

Precautions

• Monitor liver function during treatment
• Use caution in patients with cardiovascular disease
• Assess for potential androgenic side effects
• Long-term use should be regularly evaluated

Pregnancy

Danazol is contraindicated during pregnancy due to potential harm to the fetus.

Breast-feeding

Due to potential effects on the infant, danazol is contraindicated during breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Capsules

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)

Pharmacodynamics

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.