VESANOID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VESANOID (VESANOID).
Retinoic acid receptor (RAR) agonist, inducing differentiation and apoptosis of acute promyelocytic leukemia (APL) cells.
| Metabolism | Primarily hepatic via CYP450 enzymes (CYP2C8, CYP2C9, CYP3A4); undergoes glucuronidation. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for <15% of dose; biliary/fecal excretion accounts for >85% of dose as metabolites. |
| Half-life | Terminal elimination half-life approximately 40-50 hours in adults; clinical context: steady state achieved after 7-10 days of continuous dosing. |
| Protein binding | >95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.6-0.8 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral: Approximately 50% (range 30-70%) due to first-pass metabolism; taken with food increases bioavailability. |
| Onset of Action | Oral: Clinical remission of acute promyelocytic leukemia (APL) typically observed within 30-90 days of continuous therapy. |
| Duration of Action | Duration of action is sustained for the treatment period; complete remission is achieved in 72-90% of patients; maintenance therapy may be required. |
| Action Class | Retinoids- First generation |
| Brand Substitutes | Isac 10 Capsule, Cutitret 10mg Capsule, Systroin 10 Capsule, Resoten 10 Capsule, Isoace 10mg Capsule |
45 mg/m2/day orally divided into two equal doses. Administer with food.
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based adjustments are recommended; use caution in severe renal impairment due to potential accumulation. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. For mild impairment (Child-Pugh A), no dose adjustment required; monitor liver function closely. |
| Pediatric use | Not established for children; safety and efficacy have not been determined for pediatric populations. |
| Geriatric use | No specific dose adjustment required; monitor for adverse effects as elderly patients may have decreased tolerance, especially for pseudotumor cerebri and hepatotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VESANOID (VESANOID).
| Breastfeeding | Contraindicated. Excreted in breast milk; M/P ratio unknown. Potential for serious adverse effects in nursing infant. |
| Teratogenic Risk | Category D. All trimesters: Very high risk of major congenital malformations (CNS, cardiovascular, craniofacial), spontaneous abortion, and fetal death. Contraindicated in pregnancy. |
| Fetal Monitoring | Pregnancy test before initiation, monthly during therapy, and 5 weeks after discontinuation. Monitor LFTs, serum lipids, CBC, and renal function periodically. |
■ FDA Black Box Warning
WARNING: Retinoic Acid Syndrome (RAS) - characterized by fever, dyspnea, pulmonary infiltrates, pleural/pericardial effusions, weight gain, peripheral edema, hepatic/renal dysfunction; can be fatal. Discontinue if severe and treat with high-dose corticosteroids.
| Serious Effects |
Absolute: Pregnancy (Category X), hypersensitivity to retinoids. Relative: Severe hepatic or renal impairment, uncontrolled hyperlipidemia.
| Precautions | Pseudotumor cerebri (especially in children), leukocytosis, elevated liver enzymes, lipid abnormalities, teratogenicity (must avoid pregnancy for at least 1 month after discontinuation). Monitor CBC, coagulation, liver and renal function, lipids, and pregnancy status. |
Loading safety data…
| Fertility Effects | May impair fertility in males and females; reversible after discontinuation in most cases. Consult specialist. |