Danamet

Approved Indications:

• Endometriosis:
• Treatment of endometriosis-associated pain and symptoms to induce remission.
• Hereditary Angioedema (HAE):
• Prophylaxis to reduce frequency and severity of angioedema attacks.
• Fibrocystic Breast Disease:
• Management of moderate to severe symptoms including pain and nodularity.
• Idiopathic Thrombocytopenic Purpura (ITP):
• Adjunctive therapy in adult patients to increase platelet counts.

Clinically Accepted Off-label Uses:

• Treatment of menorrhagia and dysfunctional uterine bleeding.
• Management of certain hormone-responsive breast disorders.

Adults:

• Endometriosis:
• 200 to 400 mg orally per day, divided into two doses, for 3 to 6 months.
• Hereditary Angioedema:
• Initial dose 200 mg twice daily; maintenance dose individualized (usually 100–400 mg/day).
• Fibrocystic Breast Disease:
• 100 to 400 mg daily in divided doses for 3 to 6 months.
• Idiopathic Thrombocytopenic Purpura:
• 200 to 400 mg daily in divided doses.

Pediatrics:

• Safety and efficacy not established.

Elderly:

• No specific dosage adjustments; monitor for adverse effects.

Renal and Hepatic Impairment:

• Use with caution in hepatic impairment; no specific dose adjustment guidelines.
• Renal impairment: No adjustment generally required.

Administration Route:

• Oral tablets, taken with food to reduce gastrointestinal discomfort.

Danazol is a synthetic androgen derivative that suppresses the mid-cycle surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) through negative feedback on the hypothalamic-pituitary-ovarian axis. It creates a hypoestrogenic and hyperandrogenic environment by inhibiting ovarian steroidogenesis and gonadotropin secretion, leading to atrophy of ectopic endometrial tissue and reduction in estrogen-dependent symptoms. Additionally, danazol has weak progestogenic, androgenic, and glucocorticoid receptor agonist activities contributing to its therapeutic effects, including modulation of immune function relevant in hereditary angioedema.

Absorption:

• Well absorbed orally; peak plasma concentrations reached within 2 to 8 hours.

Distribution:

• Highly protein-bound (>90%), mainly to sex hormone-binding globulin and albumin.

Metabolism:

• Extensively metabolized in the liver via CYP3A4 to active and inactive metabolites.

Elimination:

• Primarily excreted in urine and feces as metabolites.
• Elimination half-life approximately 3 to 9 hours, with some active metabolites having longer half-lives.

• Pregnancy:
• Category X (FDA): Contraindicated due to risk of virilization and fetal harm.
• Lactation:
• Excreted in breast milk; potential androgenic effects on infant.
• Breastfeeding is contraindicated during therapy.

• Primary Class: Hormonal agent
• Subclass: Synthetic androgen/anabolic steroid derivative

• Known hypersensitivity to danazol or any component.
• Pregnancy and lactation.
• Severe hepatic impairment.
• Androgen-dependent tumors (e.g., prostate or breast cancer).
• Active thromboembolic disease or history of thrombophlebitis.

• Hepatotoxicity: Monitor liver function tests periodically; discontinue if severe abnormalities develop.
• Thromboembolism: Increased risk; avoid in patients with thrombophilic disorders.
• Androgenic Effects: Possible virilization, acne, hirsutism, voice changes, and lipid alterations.
• Lipid Profile: Monitor for hypercholesterolemia or changes in lipid metabolism.
• Psychiatric Effects: Mood changes, depression, and irritability reported.
• Fluid Retention and Hypertension: Monitor blood pressure.
• Use with caution in patients with cardiac or renal disease.

Common:

• Weight gain
• Acne and oily skin
• Hirsutism
• Menstrual irregularities (amenorrhea or spotting)
• Hot flashes
• Headache

Serious/Rare:

• Hepatotoxicity including hepatic adenomas and peliosis hepatis
• Thromboembolic events
• Voice deepening (may be irreversible)
• Mood disturbances
• Edema and hypertension

• CYP3A4 Substrate:
• Levels may be affected by CYP3A4 inhibitors (e.g., ketoconazole increases danazol levels) or inducers (e.g., rifampin decreases levels).
• Anticoagulants: May alter effects of warfarin; monitor INR.
• Other Androgens or Estrogens: Concomitant use may alter hormonal effects.
• Cyclosporine: Potential increase in cyclosporine levels; monitor.
• Alcohol may exacerbate hepatotoxicity.

• Use of danazol for endometriosis is now less common due to availability of safer alternatives; still recommended where other therapies fail or are contraindicated.
• Guidelines emphasize risk monitoring for thromboembolism and hepatotoxicity during prolonged use.
• Newer therapies have largely supplanted danazol in hereditary angioedema, but it remains an option in resource-limited settings.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container.
• Do not freeze.
• Keep out of reach of children.