ONMEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONMEL (ONMEL).
ONMEL (omacetaxine mepesuccinate) inhibits protein synthesis by binding to the 80S ribosome and interfering with chain elongation, leading to apoptosis in leukemic cells.
| Metabolism | Primarily hydrolyzed by esterases to a less active metabolite, with minor CYP450 involvement. |
| Excretion | Primarily hepatic metabolism via CYP3A4; <1% excreted unchanged in urine; >90% eliminated as metabolites in bile and feces. |
| Half-life | Terminal half-life 40–60 hours (mean 50 hours); allows once-daily dosing for systemic antifungal therapy. |
| Protein binding | ≥99% bound to albumin (primarily) and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 1000–1400 L (14–20 L/kg); indicates extensive tissue distribution, including brain, skin, and bone. |
| Bioavailability | Oral bioavailability approximately 55% (capsule) under fed conditions; absorption is pH-dependent, reduced with acid-reducing agents. |
| Onset of Action | Oral: clinical response observed within 24–48 hours; IV: not applicable. |
| Duration of Action | Duration of therapeutic effect approximately 24 hours with once-daily dosing; maximal antifungal activity persists for several days after discontinuation due to long half-life. |
50 mg orally twice daily for 14 days
| Dosage form | TABLET |
| Renal impairment | GFR <30 mL/min: not recommended. GFR 30-50 mL/min: no adjustment needed. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: no data, use with caution. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | No specific adjustment recommended; use with caution due to potential for renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ONMEL (ONMEL).
| Breastfeeding | Contraindicated during breastfeeding. Isotretinoin is lipophilic and excreted into breast milk; M/P ratio not established. Potential for severe adverse effects in the infant including changes in mood, skin and mucous membrane dryness, and hyperostosis. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: high risk of neural tube defects, craniofacial and cardiovascular malformations. Second and third trimesters: increased risk of spontaneous abortion, preterm delivery, and low birth weight. Isotretinoin is a potent teratogen with dose-dependent effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Myelosuppression (neutropenia, thrombocytopenia, anemia)","Bleeding risk due to thrombocytopenia","Infections due to neutropenia","Hyperglycemia","Embryo-fetal toxicity"] |
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| Fetal Monitoring |
| Pregnancy test prior to initiation, monthly during therapy, and 5 weeks after discontinuation. Mandatory enrollment in iPledge program for females of childbearing potential. Fetal monitoring: ultrasound if pregnancy occurs to assess for anomalies. |
| Fertility Effects | Reversible impairment of spermatogenesis in males reported; no evidence of permanent infertility. In females, no known effect on fertility after discontinuation, but isotretinoin is stored in adipose tissue and slowly eliminated; wait 5 weeks after stopping before attempting conception. |