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. |
| Molecular Weight | 480.6 |
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 | Avoid. EYDENZELT is a selective estrogen receptor degrader (SERD) used in breast cancer. Estrogen receptor antagonism can interfere with fetal development and pregnancy maintenance. Animal studies show embryotoxicity and fetal harm. Contraception is mandatory. |
| 2nd trimester | Avoid. Potential for fetal harm due to ER modulation. No adequate human data; animal studies indicate risk. Not recommended during pregnancy. |
| 3rd trimester | Avoid. Risks similar to other trimesters. May affect fetal development or cause premature labor. Discontinue if pregnancy occurs. |
Clinical note
Comprehensive clinical and safety monograph for EYDENZELT (EYDENZELT).
| Placental transfer | EYDENZELT has a molecular weight of 480.6 Da and is highly protein bound (99%). Based on its physicochemical properties and animal studies, placental transfer is expected. In animal studies, fetal exposure was observed. |
| Breastfeeding |
■ 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 |
PregnancyHypersensitivity to elacestrant or any excipients
| 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. |
| Food/Dietary | Avoid alcohol as it can worsen orthostatic hypotension and nausea. Take with a low-fat meal to reduce gastrointestinal side effects. Grapefruit juice may increase drug concentration via CYP3A4 inhibition; avoid. High-protein meals may reduce absorption; separate by 2 hours if possible. |
Loading safety data…
| Not recommended. EYDENZELT is a small molecule likely excreted in human milk. Potential for serious adverse effects in the nursing infant, including tumor response or ER-related effects. Advise to discontinue breastfeeding during treatment and for at least 1 week after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | EYDENZELT (bromocriptine mesylate) is a dopamine receptor agonist used for type 2 diabetes. Start with 0.8 mg daily, titrate weekly by 0.8 mg to maximum 4.8 mg daily. Administer within 2 hours of waking to exploit circadian dopamine rhythms. Avoid in patients with syncopal migraines or severe psychotic disorders. May cause orthostatic hypotension; monitor blood pressure. Contraindicated with ergot alkaloids and CYP3A4 inhibitors. |
| Patient Advice | Take EYDENZELT within 2 hours of waking with food to reduce nausea. · Avoid alcoholic beverages; they may increase dizziness and low blood pressure. · Stand up slowly from sitting or lying to prevent fainting. · Report unusual urges (gambling, hypersexuality) to your doctor. · Do not drive if you feel dizzy or drowsy. |