EYDENZELT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EYDENZELT (EYDENZELT).
EYDENZELT (bexarotene) is a retinoid that selectively binds to and activates retinoid X receptors (RXRs), which regulate gene expression involved in cell differentiation, proliferation, and apoptosis. It induces apoptosis and inhibits cell growth in malignant T-cells.
| Metabolism | Hepatic metabolism primarily via CYP3A4 isoform; also metabolized by CYP1A2 and CYP2C8. |
| Excretion | Primarily renal excretion as unchanged drug (approximately 70-80%) and minor fecal elimination (≤10%). Biliary excretion is negligible. |
| Half-life | Terminal elimination half-life is approximately 12-14 hours, allowing once-daily dosing with steady-state reached within 3-5 days. |
| Protein binding | ≥99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is about 0.3-0.5 L/kg, indicating moderate distribution into total body water with limited extravascular penetration. |
| Bioavailability | Absolute oral bioavailability is approximately 90%, with minimal first-pass metabolism. Subcutaneous bioavailability is 100%. |
| Onset of Action | Oral: Onset of clinical effect is 1-2 hours post-dose, with peak plasma concentrations achieved in 3-4 hours. |
| Duration of Action | Duration of action is approximately 24 hours due to sustained plasma levels, supporting once-daily dosing for continuous clinical effect. |
1 mg subcutaneously once weekly.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required in renal impairment. For GFR <15 mL/min/1.73 m2, use with caution due to limited data. |
| Liver impairment | Child-Pugh A or B: No dose adjustment. Child-Pugh C: Not recommended due to lack of data. |
| Pediatric use | Not approved in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function as elderly may have reduced renal clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EYDENZELT (EYDENZELT).
| Breastfeeding | It is unknown whether selinexor is excreted in human milk. Based on its physicochemical properties (molecular weight ~555 Da, high protein binding ~95%), minimal excretion is expected, but due to the potential for serious adverse reactions in breastfed infants (e.g., gastrointestinal toxicity, myelosuppression), breastfeeding is not recommended during treatment and for 1 week after the last dose. No M/P ratio is available. |
| Teratogenic Risk | EYDENZELT (selinexor) is contraindicated in pregnancy based on its mechanism of action (inhibition of nuclear export) and animal studies showing embryofetal toxicity. In rats, maternal exposure at doses ≥0.25 mg/kg (approximately 0.04 times the recommended human dose) resulted in increased post-implantation loss, reduced fetal body weight, and skeletal variations. There are no adequate human data; however, due to the high risk of teratogenicity, pregnancy should be excluded before initiation, and women of childbearing potential must use effective contraception during treatment and for 1 week after the last dose. If used in the first trimester, there is a high risk of structural anomalies; in second and third trimesters, risks include fetal growth restriction and potential developmental delays. |
■ FDA Black Box Warning
EYDENZELT may cause severe pancreatitis, which can be fatal. Discontinue if pancreatitis is suspected. Concomitant use with gemfibrozil is contraindicated due to risk of increased bexarotene levels and toxicity.
| Serious Effects |
Hypersensitivity to bexarotene or any component; women who are or may become pregnant (teratogenic); nursing mothers; concurrent use with gemfibrozil.
| Precautions | Monitor for pancreatitis (amylase/lipase), hyperlipidemia, hypothyroidism, neutropenia, and hepatic transaminase elevations. Women of childbearing potential must use two forms of contraception. Avoid concomitant gemfibrozil. |
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| Fetal Monitoring | Before starting EYDENZELT, confirm pregnancy status in women of childbearing potential. Monitor for fetal effects with serial ultrasound (e.g., fetal growth, anatomy) if inadvertent exposure occurs. For pregnant patients (if therapy cannot be avoided), monitor maternal complete blood counts, liver function tests, and electrolytes weekly due to increased risk of cytopenias, hepatotoxicity, and metabolic disturbances, which may indirectly affect fetal well-being. Report any fetal abnormalities to the pregnancy registry. |
| Fertility Effects | Based on animal studies, selinexor may impair female fertility. In rats, ovarian atrophy and reduced corpora lutea were observed at doses comparable to human exposure. There are no human data on male fertility; however, testicular degeneration was noted in male rats at ≥0.5 mg/kg. Advise patients that fertility may be compromised during treatment, but effects may be reversible after discontinuation. |