DANZITEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DANZITEN (DANZITEN).
Selective inhibitor of nuclear export (SINE) that binds to and inhibits exportin 1 (XPO1), preventing export of tumor suppressor proteins and growth regulators from the nucleus, leading to cell cycle arrest and apoptosis.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19, CYP2D6, and CYP1A1. |
| Excretion | Primarily hepatic metabolism followed by renal excretion of metabolites; <5% excreted unchanged in urine. |
| Half-life | Approximately 10-12 hours in adults; may be prolonged in hepatic impairment (up to 20 hours). |
| Protein binding | 98% bound to albumin. |
| Volume of Distribution | 0.15 L/kg (low, indicating limited extravascular distribution). |
| Bioavailability | Oral: 75-85% (first-pass effect reduces bioavailability from near-complete absorption). |
| Onset of Action | Oral: 30-60 minutes; IV: Immediate (within minutes). |
| Duration of Action | Oral: 8-12 hours; IV: 6-8 hours based on clinical response. |
| Molecular Weight | 408.45 |
1.5 mg orally once daily, increased at 2-week intervals to 3 mg once daily, then 5 mg once daily based on tolerability and efficacy.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-89 mL/min: No adjustment. eGFR 15-29 mL/min: Not recommended. eGFR <15 mL/min: Contraindicated. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use 1.5 mg once daily, titrate with caution. Child-Pugh Class C: Not recommended. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | Initiate at 1.5 mg once daily; titrate slowly; monitor for orthostatic hypotension and falls. |
| 1st trimester | Limited data; avoid unless benefit outweighs risk. Animal studies show embryotoxicity at high doses. |
| 2nd trimester | No adequate human studies; use only if clearly needed. |
| 3rd trimester | May cause neonatal hypotension, bradycardia, or hypoglycemia; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for DANZITEN (DANZITEN).
| Placental transfer | Crosses placenta; documented in human studies. |
| Breastfeeding | Excreted in breast milk in low amounts; monitor infant for hypotension, bradycardia, and sedation. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to danzitenSevere hepatic impairmentConcomitant use with strong CYP3A4 inhibitors
| Precautions | Bone marrow suppression (neutropenia, thrombocytopenia), Infection risk (including opportunistic infections), Gastrointestinal toxicity (nausea, vomiting, diarrhea), Tumor lysis syndrome, Neurological toxicity (confusion, dizziness), Cataracts, Embryo-fetal toxicity |
| Food/Dietary | Grapefruit and grapefruit juice may increase danazol levels and risk of toxicity; avoid concurrent use. High-fat meals can enhance absorption; take with food to improve tolerability. Alcohol should be limited as it may exacerbate hepatotoxicity. No other significant food interactions. |
Loading safety data…
| Teratogenic Risk | First trimester: Increased risk of neural tube defects and cardiac malformations based on animal studies; limited human data. Second/third trimester: Risk of fetal growth restriction and oligohydramnios; may cause fetal renal impairment. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and liver enzymes. Serial ultrasound for fetal growth and amniotic fluid index. Fetal heart rate monitoring during labor. Assess for preeclampsia symptoms. |
| Fertility Effects | Animal studies show impaired fertility in females (prolonged estrous cycle, reduced implantation). Human data insufficient to assess effect on fertility. |
| Clinical Pearls | DANZITEN (danazol) is an attenuated androgen used for endometriosis and fibrocystic breast disease. Monitor liver function tests and lipid profiles due to hepatotoxicity and dyslipidemia. Avoid in pregnancy (androgenic effects on female fetus). May cause pseudomenopause; breakthrough bleeding possible. Use non-hormonal contraception. Watch for voice deepening, hirsutism, and weight gain. Dose adjustment needed in hepatic impairment. Check for history of porphyria (can precipitate attacks). |
| Patient Advice | Take exactly as prescribed; do not skip doses or discontinue without consulting your doctor. · This drug may cause masculinizing effects such as deepening of voice, increased body hair, and acne; report these to your healthcare provider. · Do not take if you are pregnant or planning to become pregnant; use effective non-hormonal birth control during treatment and for at least 3 months after stopping. · Avoid alcohol and grapefruit juice while taking this medication. · You will need regular blood tests to monitor liver function and cholesterol levels. · If you experience jaundice, dark urine, or abdominal pain, seek medical attention immediately. · This drug may cause weight gain, fluid retention, and mood changes; discuss any concerns with your doctor. |