Overview
DESCRIPTION Danazol is a synthetic steroid derived from ethisterone. It is a white to pale yellow crystalline powder, practically insoluble or insoluble in water, and sparingly soluble in alcohol. Chemically, danazol is 17α-Pregna-2,4-dien-20-yno [2,3- d ]- isoxazol-17-ol. The molecular formula is C 22 H 27 NO 2 . It has a molecular weight of 337.
Mechanism of Action
CLINICAL PHARMACOLOGY Danazol suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and interaction of danazol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of danazol to receptors of gonadal steroids at target organs.
Indications
- INDICATIONS AND USAGE Endometriosis. Danazol capsules are indicated for the treatment of endometriosis amenable to hormonal management. Hereditary Angioedema. Danazol capsules are indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.
Common Doses
- 800 mg
- 200 mg
- 400 mg
Dosage
DOSAGE AND ADMINISTRATION Endometriosis. In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation.
Black Box Warning
WARNINGS Use of danazol in pregnancy is contraindicated. A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally a non-hormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking danazol, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus.
Contraindications
- CONTRAINDICATIONS Danazol capsules should not be administered to patients with: Undiagnosed abnormal genital bleeding. Markedly impaired hepatic, renal, or cardiac function. Pregnancy (see WARNINGS ). Breast feeding. Porphyria-Danazol capsules can induce ALA synthetase activity and hence porphyrin metabolism. Androgen-dependent tumor. Active thrombosis or thromboembolic disease and history of such events. Hypersensitivity to danazol.
Side Effects
- ADVERSE REACTIONS The following events have been reported in association with the use of danazol capsules: Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare. Other possible endocrine effects are menstrual disturbances including spotting, alteration of the timing of the cycle and amenorrhea.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.