DANAZOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DANAZOL (DANAZOL).
Danazol is a synthetic androgen derived from ethisterone that suppresses pituitary-ovarian axis by inhibiting gonadotropin release, leading to decreased estrogen and progesterone levels. It also has weak androgenic and progestational activity.
| Metabolism | Primarily hepatic: undergoes oxidation and conjugation via CYP3A4, with metabolites excreted in urine and feces. |
| Excretion | Primarily hepatic metabolism; approximately 60% excreted in feces, 30% in urine as metabolites. |
| Half-life | Terminal elimination half-life is 4-4.5 hours; clinical context: requires multiple daily dosing to maintain therapeutic levels. |
| Protein binding | Highly protein bound: 97-99%, primarily to albumin. |
| Volume of Distribution | Approximately 1.5 L/kg; indicates extensive distribution into tissues, exceeding total body water. |
| Bioavailability | Oral bioavailability is approximately 100% due to extensive absorption, but first-pass metabolism reduces systemic availability to about 70-80%. |
| Onset of Action | Oral: 2-8 weeks for therapeutic effect in endometriosis; up to 3 months for fibrocystic breast disease. |
| Duration of Action | Duration varies with condition; relief persists for several months after discontinuation in endometriosis; symptoms may recur after stopping. |
300-600 mg orally twice daily; maximum 800 mg/day
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required for GFR ≥10 mL/min; avoid use in GFR <10 mL/min due to fluid retention risk |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated |
| Pediatric use | 2-5 mg/kg/dose orally twice daily; maximum 400 mg/day |
| Geriatric use | Start at low end of adult dose, titrate cautiously due to increased risk of fluid retention and thromboembolism |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DANAZOL (DANAZOL).
| Breastfeeding | Danazol is excreted in human milk; M/P ratio not determined. Potential for adverse effects in breastfed infant (e.g., androgenization). Use is contraindicated during breastfeeding due to risk of virilization and other hormonal effects. |
| Teratogenic Risk | Danazol is contraindicated in pregnancy. First trimester exposure is associated with virilization of female fetus including clitoromegaly, labioscrotal fusion, and urogenital sinus abnormalities. Risk in second and third trimesters is also significant due to androgenic effects; fetal growth restriction and preterm birth may occur. No safe gestational period exists. |
■ FDA Black Box Warning
Danazol may cause thrombotic events, including pulmonary embolism and thrombophlebitis. It is contraindicated in patients with a history of thrombosis.
| Serious Effects |
Pregnancy, lactation, porphyria, severe hepatic/renal/cardiac disease, undiagnosed abnormal genital bleeding, history of thromboembolic disorders, androgen-dependent tumors.
| Precautions | Hepatotoxicity (monitor LFTs), pseudotumor cerebri (benign intracranial hypertension), androgenic effects (hirsutism, acne, voice deepening), lipid changes (decreased HDL, increased LDL), thromboembolic events, and premature closure of epiphyses in children. |
Loading safety data…
| Fetal Monitoring | Monitor maternal liver function, lipid profile, and signs of androgenic effects. In pregnancy, if inadvertent exposure occurs, perform ultrasound for fetal anatomy and growth; assess for signs of virilization in female fetus. Evaluate infant for adrenal suppression if used near term. |
| Fertility Effects | Danazol suppresses ovulation via antigonadotropic effects and is used to treat endometriosis-associated infertility. Reversible suppression; ovulation typically returns within 8 weeks after discontinuation. May impair spermatogenesis in males. |