Generic

Danazol

Indications

Danazol is indicated for the following treatment-

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

Pharmacology

Danazol, as a gonadotropin inhibitor, inhibits the pituitary-ovarian axis, perhaps by reducing pituitary gonadotropin production. Danazol also reduces ovarian estrogen synthesis by suppressing the preovulatory spike in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) output. Danazol may also decrease ovarian steroidogenesis, bind to androgen, progesterone, and glucocorticoid receptors, bind to sex-hormone-binding globulin and corticosteroid-binding globulin, and raise progesterone metabolic clearance rate. Danazol may also operate by reducing IgG, IgM, and IgA concentrations, as well as phospholipid and IgG isotope autoantibodies, to aid in the regression of endometriosis. Danazol, when used to treat endometriosis, causes both normal and ectopic endometrial tissues to become inactive and atrophic as a result of ovarian function suppression. This results in anovulation and amenorrhea. Danazol's specific mechanism of action in fibrocystic breast disease is uncertain, although it may be connected to reduced estrogenic stimulation as a result of decreased ovarian estrogen production. It is also likely that the drug will have a direct effect on steroid receptor sites in breast tissue. This results in nodularity disappearing, pain and discomfort alleviation, and perhaps alterations in the menstrual cycle. Danazol corrects the underlying biochemical deficiency in hereditary angioedema by raising blood concentrations of the defective C1 esterase inhibitor, leading in higher serum concentrations of the C4 component of the complement system.

Dosage & Administration

Preoperative thinning of the endometrium:

• Adult: 400-800 mg daily, in up to 4 divided doses for 3-6 week.

Benign breast disorders:

• Adult: Initially, 100-400 mg daily in 2 divided doses adjusted according to response and continued for 3-6 month.

Hereditary angioedema:

• Adult: Initially, 200 mg bid-tid reduced thereafter according to patient's response.

Endometriosis:

• Adult: 200-800 mg daily in 2 divided doses adjusted according to response, for 3-6 month or if necessary, up to 9 month.

Menorrhagia:

• Adult: 200 mg once daily. Review treatment 3 month later.

Gynaecomastia:

• Adult: Male adolescents: Initially, 200 mg daily, may increase to 400 mg daily after 2 month if no response occurs; adult men: Initial: 400 mg daily in up to 4 divided doses. Usual treatment duration: 6 month.
• Child: Male adolescents: Initially, 200 mg daily increased to 400 mg after 2 month if no response occurs. Treatment usually up to 6 months.

Interaction

Insulin: Danazol users may experience increased insulin resistance. Although the relevance of this is unknown, such patients should be closely followed.

Estrogens and progestogens: Danazol has the potential to interact with exogenous estrogens and/or progestogens. Danazol may function via binding to estrogen, progesterone, or androgen receptors at various levels of the hypothalamus pituitary-ovarian axis. As a result, women of childbearing age should utilize effective nonhormonal contraceptive techniques.

Danazol may alter the plasma levels of carbamazepin and perhaps the patient's reaction to this and phenytoin anticonvulsant treatment. Phenobarbital may have a similar interaction.

Hypertension therapy: Danazol may interfere with the action of antihypertensive medications, perhaps through affecting fluid retention.

Cyclosporine: Danazol can raise cyclosporine plasma concentrations.

Migraine treatment: Danazol may cause migraines and may decrease the efficacy of migraine prevention medicines.

Contraindications

• 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.

Side Effects

Oedema, weight gain, sweating, acne, hirsutism, flushing, oily skin or hair, voice deepening, clitoral hypertrophy, amenorrhoea, hepatic dysfunction, CNS or GI disturbances, benign intracranial hypertension, breast reduction, visual disturbances, high LFT values.

Pregnancy & Lactation

Category X: Fetal abnormalities have been established in animal or human studies, or there is evidence of fetal danger based on human experience, or both, and the risk of using the medication in pregnant women obviously outweighs any potential benefit. The medication is not recommended for women who are pregnant or may become pregnant.

Precautions & Warnings

Epilepsy, migraine, as well as cardiac, hepatic, and renal problems. Children with severe hypertension, diabetes, polycythaemia, and a history of thrombosis.

Therapeutic Class

Drugs that influence (inhibit) gonadotrophin

Storage Conditions

Store between 15 and 30°C.

Pharmaceutical Name

Incepta Pharmaceuticals Ltd.