DANOCRINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DANOCRINE (DANOCRINE).
Danazol is a synthetic androgen derived from ethisterone. It suppresses the pituitary-ovarian axis by inhibiting gonadotropin (LH and FSH) release, leading to anovulation and amenorrhea. It also binds to androgen, progesterone, and glucocorticoid receptors, exerting weak androgenic, antiestrogenic, and antigonadotropic effects. Additionally, it may directly inhibit ovarian steroidogenesis and increase clearance of endogenous sex hormones.
| Metabolism | Danazol is extensively metabolized in the liver via hydroxylation and conjugation. It is a substrate of CYP3A4 and may inhibit CYP3A4, CYP2C9, and CYP2C19. The major metabolites include 2-hydroxymethylethisterone and ethisterone, which exhibit some androgenic activity. |
| Excretion | Renal (metabolites, ~50%), biliary/fecal (~30%), unchanged drug minimal. |
| Half-life | Terminal elimination half-life: 10–30 hours (mean 15 hours); clinically, steady-state reached after 2–4 days. |
| Protein binding | ~80–90%, primarily to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Vd ~0.5–1.0 L/kg; moderate tissue distribution. |
| Bioavailability | Oral: ~80–100% (well absorbed). |
| Onset of Action | Oral: 2–4 hours for androgenic effects; 1–2 weeks for clinical response in endometriosis. |
| Duration of Action | Oral: 8–24 hours; daily dosing required; effects on endometriosis persist days to weeks after discontinuation. |
| Molecular Weight | Danazol has a molecular weight of 337.46 Da. |
100-200 mg orally twice daily for endometriosis; 200-400 mg twice daily for fibrocystic breast disease; 200 mg twice daily for hereditary angioedema. Maximum dose: 800 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in renal impairment. Monitor fluid balance and renal function. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment, use reduced dose and monitor liver function; avoid in active liver disease. |
| Pediatric use | Not recommended for use in pediatric patients due to potential for premature epiphyseal closure and other adverse effects. |
| Geriatric use | No specific dosing adjustments; use lowest effective dose due to potential for increased sensitivity to androgenic effects and hepatic metabolism changes. |
| 1st trimester | Danocrine is contraindicated in pregnancy. It can cause virilization of the female fetus, including clitoral hypertrophy, labial fusion, and urogenital sinus abnormalities. Androgenic effects are dose-dependent and more likely with higher doses. |
| 2nd trimester | Contraindicated. Continued risk of fetal virilization and potential for other adverse effects such as masculinization of external genitalia in female fetuses. Avoid use during pregnancy. |
| 3rd trimester | Contraindicated. Similar risks as in first and second trimesters. Additionally, danocrine may affect placental function and fetal development. Use is not recommended. |
Clinical note
Comprehensive clinical and safety monograph for DANOCRINE (DANOCRINE).
| Placental transfer | Danocrine crosses the placenta. Fetal serum concentrations are approximately 3-10% of maternal serum concentrations. The extent of transfer is sufficient to cause fetal androgenic effects. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyBreastfeeding (relative contraindication, but often considered absolute due to risk)Undiagnosed abnormal genital bleedingSeverely impaired hepatic, renal, or cardiac functionPorphyriaThromboembolic disease or history thereofAndrogen-dependent tumors (e.g., prostate cancer)Hypersensitivity to danocrine or any component
| Precautions | Risk of thromboembolic events (DVT, pulmonary embolism), Hepatotoxicity (elevated liver enzymes, jaundice, peliosis hepatis, benign hepatic adenoma), Intracranial hypertension (pseudotumor cerebri), Androgenic effects (acne, hirsutism, voice deepening, weight gain, clitoral hypertrophy), Carcinogenicity (increased risk of hepatocellular carcinoma), Use in pregnancy causes pseudothermalphroditism in female fetuses, May suppress the immune system; increased risk of infections, Can cause pancreatitis, hyperglycemia, and insulin resistance, May increase LDL and decrease HDL cholesterol, Monitor liver function, lipid profile, and signs of thrombosis |
| Food/Dietary | No significant food interactions. Grapefruit juice may affect metabolism; advise caution. |
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| Danocrine is excreted into breast milk. Concentrations in milk are low, but due to potential androgenic effects in the nursing infant, breastfeeding is generally not recommended. If used, the infant should be monitored for signs of virilization. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Danocrine (danazol) is contraindicated in pregnancy. It is an androgen derivative and can cause virilization of the female fetus, including clitoromegaly, labial fusion, and urogenital sinus abnormalities. Risk is highest during the first trimester when genital differentiation occurs; exposure at any gestational age may result in androgenic effects. |
| Fetal Monitoring | Monitor pregnancy status before and during treatment via pregnancy testing. If pregnancy occurs, discontinue danocrine immediately and refer for obstetrical evaluation. Monitor fetal development with ultrasound if inadvertent exposure occurs. |
| Fertility Effects | Danocrine suppresses ovulation and may inhibit fertility during treatment. This effect is reversible upon discontinuation. It has been used off-label for endometriosis-associated infertility. |
| Clinical Pearls | Danocrine suppresses pituitary-ovarian axis by inhibiting gonadotropin release; monitor liver function, lipid profile, and for signs of virilization. Avoid in pregnancy and porphyria. |
| Patient Advice | Take with food to reduce GI upset. · Report symptoms of thromboembolism (chest pain, leg swelling) immediately. · Use non-hormonal contraception due to teratogenicity and pregnancy disruption. · May cause weight gain, edema, acne, or voice deepening; notify doctor if severe. · Avoid alcohol due to potential hepatotoxicity. |