XTANDI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XTANDI (XTANDI).
Androgen receptor inhibitor; binds to the androgen receptor, inhibits nuclear translocation, DNA binding, and transcription of androgen-responsive genes.
| Metabolism | Hepatic via CYP2C8 and CYP3A4; active metabolite (M2) formed by CYP2C8; co-administration with strong CYP2C8 inhibitors increases exposure. |
| Excretion | Primarily hepatic metabolism; 77% of dose recovered in feces (as metabolites), 15% in urine (as metabolites); less than 1% excreted unchanged. |
| Half-life | Enzalutamide: 5.8 days; active metabolite N-desmethyl enzalutamide: 7.8-8.6 days. Steady state achieved after ~28 days. |
| Protein binding | Enzalutamide: 97-98% bound to plasma proteins (primarily albumin); N-desmethyl enzalutamide: 95% bound. |
| Volume of Distribution | Enzalutamide: ~110 L (approximately 1.4 L/kg for a 70 kg adult); extensive tissue distribution. |
| Bioavailability | Oral bioavailability not directly reported; absorption is rapid with Tmax 1-2 hours post-dose; no significant food effect. |
| Onset of Action | Clinical effects (e.g., PSA decline) observed within 4-12 weeks of continuous oral dosing. |
| Duration of Action | Duration of effect persistent throughout continuous therapy; maximal PSA response by 12-24 weeks; duration dependent on disease progression. |
160 mg orally once daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl 30-89 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 80 mg once daily. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no dosing guidelines available. |
| Geriatric use | No specific dose adjustment required; clinical studies included patients ≥65 years with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XTANDI (XTANDI).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Due to potential for serious adverse reactions in breastfed infants (e.g., antiandrogenic effects), advise discontinuing breastfeeding during treatment and for 2 weeks after last dose. |
| Teratogenic Risk | Risk category D (positive evidence of human fetal risk). Based on mechanism (androgen receptor inhibitor), can cause fetal harm. First trimester: high risk of external genitalia abnormalities in male fetuses (hypospadias, genital ambiguity). Second and third trimesters: potential for antiandrogenic effects leading to feminization of male fetuses. Avoid in pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pregnancy (can cause fetal harm)","Severe hepatic impairment (Child-Pugh C)"]
| Precautions | ["Seizure risk (higher incidence with dose >160 mg/day)","Posterior reversible encephalopathy syndrome (PRES)","Hypertension","Falls and fractures","Cardiovascular events","Hyperglycemia in diabetic patients","Fetal harm if used during pregnancy (for patients with partners of childbearing potential)"] |
Loading safety data…
| Fetal Monitoring | Pregnancy test before initiation. Monitor for fetal development via ultrasound if exposure occurs. Assess for signs of androgen deprivation in male infants postnatally (e.g., hypospadias, cryptorchidism). |
| Fertility Effects | Reversible impairment of spermatogenesis in males (oligospermia or azoospermia) due to androgen receptor blockade. Effects on female fertility unknown, but ovarian suppression possible. May impair fertility in both sexes; counsel on fertility preservation. |