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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DANOCRINE (DANOCRINE).
| Breastfeeding | Danazol is excreted into breast milk. The M/P ratio is unknown. Due to potential androgenic effects in the nursing infant (e.g., virilization), breastfeeding is not recommended during danocrine therapy. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Undiagnosed abnormal genital bleeding","Severely impaired hepatic, renal, or cardiac function","Pregnancy or breastfeeding","Porphyria","Androgen-dependent tumors (e.g., prostate carcinoma)","Breast cancer in males","History of thromboembolic disease","Hypersensitivity to danazol or components"]
| 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"] |
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| 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. |