Dosing and uses of Danazol
Adult dosage forms and strengths
capsule
- 50mg
- 100mg
- 200mg
Endometriosis
Mild: 200-400 mg/day PO divided BId
Moderate-to-severe: 800 mg/day PO divided BId
Titrate downward to dose sufficient to maintain amenorrhea
Therapy typically continued for 6 months; may continue up to 9 months
Fibrocystic Breast Disease
100-400 mg/day PO divided BId
Maintenance therapy continued for 3-6 months
Hereditary Angioedema
200 mg PO BID/TID initially, THEn
Decrease dose by 50% at intervals of at least 1-3 months
If attack occurs, increase dose by increments up to 200 mg/day
Pediatric dosage forms and strengths
Safety & efficacy not established
Danazol adverse (side) effects
Frequency not defined
Intracranial hypertension
Increased blood pressure
Thromboembolism
Anxiety
Depression
Dizziness
Urticaria
Androgenic Effects (common)
- Mild hirsutism
- Decreased breast size
- Voice changes
- Sore throat, acne
- Increased oiliness of skin or hair
- Hair loss
Menstrual irregularities (common)
Gastroenteritis
Nausea
Vomiting
Elevated LFTs
Joint pain
Muscle spasm
Warnings
Black box warnings
Contraindicated in pregnancy
Thromboembolism, thrombophlebitic, and thrombotic events, including life-threatening or fatal strokes, have been reported
Peliosis hepatitis and benign hepatic adenoma have been observed with long-term use
Benign intracranial hypertension (pseudotumor cerebri) has been reported
Contraindications
Pregnancy, breastfeeding
Porphyria
Undiagnosed abnormal genital bleeding
Severe liver/renal/cardiac disease,
Hypersensitivity
Cautions
Breast cancer
Epilepsy
Migraine
Cardiac dysfunction
Renal impairment
Preliminary epidemiological evidence suggests that the use of danazol might increase the baseline risk of ovarian cancer in patients being treated for endometriosis
Pregnancy and lactation
Pregnancy category: X
Lactation: enters breast milk/contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Danazol
Half-Life: 4.5 hr
Peak Plasma Time: 2 hr
Bioavailability: well absorbed
Metabolism: extensively in the liver to 2-hydroxymethyl ethisterone
Metabolites: 2-hydroxymethyl ethisterone (activity unknown)
Excretion: mainly in urine, small amount in feces
Mechanism of action
Suppresses pituitary-ovarian axis by inhibition of pituitary gonadotropin output
