Danazol Capsule

Danazol is indicated for the following treatment-

• Endometriosis
• Benign breast disease
• Menorrhagia
• Gynecomastia
• Preoperative thinning of the endometrium before hysteroscopic endometrial ablation.

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.

Usually given in up to 4 divided doses; in women of child-bearing potential, treatment should start during menstruation, preferably on first day.

Endometriosis: 200-800 mg daily in up to 4 divided doses, adjusted to achieve amenorrhoea, usually for 6 months (up to 9 months in some cases).

Menorrhagia: In menorrhagia daily doses of 100-200 mg have been found effective but 200 mg daily for 3 months is usually sufficient to reduce menstrual blood flow to acceptable levels.

Severe cyclical mastalgia: 100-400 mg daily usually for 3-6 months.

Benign breast cysts: 300 mg daily usually for 3-6 months.

Gynaecomastia: 400 mg daily in up to 4 divided doses for 6 months (adolescents 200 mg daily, increased to 400 mg daily if no response after 2 months).

For pre-operative thinning of endometrium: 400 mg-800 mg daily in up to 4 divided doses for 3-6 weeks.

Children: Danazol is not used in children.

Insulin: Patients taking Danazol may show increased insulin resistance. The significance of this is not known but such patients should be carefully monitored.

Estrogens and progestogens: Theoretically Danazol may interact with exogenous estrogens and/or progestogens. It has been suggested that Danazol acts by binding to estrogen, progesterone or androgen receptors at various levels in the hypothalamic pituitary-ovarian axis. Therefore, women of child bearing age should use effective, non hormonal methods of contraception.

Anticonvulsant therapy: Danazol may affect the plasma concentration of carbamazepin and possibly the patient's response to this agent and to phenytoin. A similar interaction is possible for phenobarbital.

Antihypertensive therapy: Danazol can oppose the action of antihypertensive agents, possibly through effects on fluid retention.

Cyclosporine: Danazol can increase the plasma concentration of cyclosporine.

Migraine therapy: Danazol itself may provoke migraine and it may possibly reduce the effectiveness of medication to prevent the condition.

• Pregnancy and breast-feeding
• Impaired hepatic, renal, or cardiac function
• Porphyria
• Thromboembolic disease
• Androgen-dependent tumor
• Abnormal vaginal bleeding that has not been fully investigated.
• Hypersensitivity to danazol.

Nausea, dizziness, skin reactions including rashes, photosensitivity and exfoliative dermatitis, fever, backache, nervousness, mood changes, anxiety, changes in libido, vertigo, fatigue, epigastric and pleuritic pain, headache, weight gain; menstrual disturbances, vaginal dryness and irritation, flushing and reduction in breast size; musculo-skeletal spasm, joint pain and swelling, hair loss; androgenic effects including acne, oily skin, oedema, hirsutism, voice changes and rarely clitoral hypertrophy; temporary alteration in lipoproteins and other metabolic changes, insulin resistance; thrombotic events; leucopenia, thrombocytopenia, eosinophilia, reversible erythrocytosis or polycythaemia reported; headache and visual disturbances may indicate benign intracranial hypertension.

The drug should not be given to pregnant women, because of risk of virilization of a female fetus, particularly when high doses are given for several weeks. Patients taking the drug should not breast-feed.

Cardiac, hepatic or renal impairment, elderly, polycythaemia, epilepsy, diabetes mellitus, hypertension, migraine, lipoprotein disorder, history of thrombosis or thromboembolic disease. If signs of virilization occur, e.g. voice changes or hirsutism, therapy should be stopped immediately.

Drugs affecting (inhibiting) gonadotrophin

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.