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. |
| Molecular Weight | Ombitasvir: 804.92 Da; Paritaprevir: 765.89 Da; Ritonavir: 720.95 Da (combination product). |
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 | Avoid. ONMEL (ombitasvir/paritaprevir/ritonavir) is not recommended during the first trimester due to potential teratogenic effects based on animal studies and lack of human data. |
| 2nd trimester | Use only if clearly needed. No adequate human studies; ribavirin component in some regimens is contraindicated in pregnancy. |
| 3rd trimester | Use only if clearly needed. Limited human data; risk of adverse effects on fetus unknown. |
Clinical note
Comprehensive clinical and safety monograph for ONMEL (ONMEL).
| Placental transfer | Animal studies indicate ombitasvir and paritaprevir cross the placenta. Human data are limited, but based on molecular weight and protein binding, placental transfer is expected. |
| Breastfeeding | No human data on excretion in breast milk. Ritonavir is present in breast milk at low levels; ombitasvir and paritaprevir are highly protein-bound, limiting milk transfer. Caution advised; avoid breastfeeding during therapy due to potential for adverse effects in the infant. |
■ FDA Black Box Warning
None.
| Serious Effects |
Moderate to severe hepatic impairment (Child-Pugh B or C)Concurrent use with drugs highly dependent on CYP3A for clearance (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, oral midazolam, pimozide, sildenafil for PAH, triazolam)Coadministration with ethinyl estradiol-containing contraceptives due to risk of ALT elevationsHypersensitivity to any component
| Precautions | Myelosuppression (neutropenia, thrombocytopenia, anemia), Bleeding risk due to thrombocytopenia, Infections due to neutropenia, Hyperglycemia, Embryo-fetal toxicity |
| Food/Dietary | Administer with food to enhance absorption. Avoid grapefruit products as they may alter drug levels. |
Loading safety data…
| Lactation Rating | L3 - Limited data; probably compatible but caution advised. |
| 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. |
| 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. |
| Clinical Pearls | ONMEL (ombitasvir, paritaprevir, ritonavir, and dasabuvir) is used for chronic hepatitis C (genotype 1). Concomitant use with ethinyl estradiol-containing contraceptives is contraindicated due to risk of ALT elevations. Monitor hepatic function closely in patients with cirrhosis. |
| Patient Advice | Take with food to improve absorption. · Do not take any estrogen-containing medications (birth control pills, hormone replacement therapy) during treatment. · Report any signs of liver injury (yellowing of skin/eyes, dark urine, abdominal pain) immediately. · Complete full course of therapy as prescribed; do not skip doses. · Avoid alcohol during treatment. |