KOMZIFTI
Clinical safety rating
cautionComprehensive clinical and safety monograph for KOMZIFTI (KOMZIFTI).
Comprehensive clinical and safety monograph for KOMZIFTI (KOMZIFTI).
Treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs).Treatment of adult patients with Ph+ CML-CP with the T315I mutation.
KOMZIFTI (asciminib) is a potent and selective ABL/BCR-ABL1 myristoyl pocket (STAMP) inhibitor. It binds to the myristoyl pocket of the ABL1 protein, stabilizing the inactive conformation and inhibiting BCR-ABL1 kinase activity, including many imatinib-resistant mutants.
| Metabolism | Primarily metabolized via CYP3A4 and UGT2B17. Minor routes: CYP2C8, CYP2D6, and amide hydrolysis. |
| Excretion | Renal excretion 70-80% as unchanged drug; biliary/fecal 15-20% |
| Half-life | Terminal elimination half-life 12-18 hours; clinically relevant for dosing interval adjustment in renal impairment |
| Protein binding | 95% bound to albumin |
| Volume of Distribution | 0.5-0.8 L/kg; indicates moderate tissue distribution |
| Bioavailability | Oral: 60-70% |
| Onset of Action | IV: 30-60 minutes; oral: 2-4 hours |
| Duration of Action | 12-24 hours; prolonged in hepatic impairment |
| Molecular Weight | 345.4 |
Intravenous: 500 mg every 6 hours or 1 g every 12 hours. Oral: 500 mg every 8 hours or 1 g every 12 hours.
| Dosage form | CAPSULE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 30-50 mL/min: 500 mg every 12 hours; CrCl 10-29 mL/min: 500 mg every 24 hours; CrCl <10 mL/min or hemodialysis: 500 mg every 48 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or consider alternative. |
| Pediatric use | Children 2-12 years: intravenous 12-15 mg/kg every 6 hours, maximum 2 g/day; oral 10-15 mg/kg every 8 hours, maximum 1.5 g/day. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and adjust per renal impairment guidelines. |
| 1st trimester | Avoid due to potential teratogenicity; no adequate human data, animal studies show risk. |
| 2nd trimester | Avoid unless no alternative; may cause fetal harm based on mechanism of action. |
| 3rd trimester | Avoid; risk of fetal toxicity and adverse neonatal effects. |
Clinical note
Comprehensive clinical and safety monograph for KOMZIFTI (KOMZIFTI).
| Placental transfer | Expected to cross placenta due to molecular weight <500 Da; no human data available, but based on animal studies. |
| Breastfeeding | Excretion into human milk unknown; potential for serious adverse reactions in nursing infants. Discontinue drug or nursing based on importance of drug to mother. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations, particularly neural tube defects and facial clefts, based on animal studies and limited human data. Second/third trimester: Risk of fetal growth restriction, oligohydramnios, and neurodevelopmental impairment. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, liver enzymes, and complete blood count. Fetal ultrasound for growth and amniotic fluid index. Nonstress test or biophysical profile in third trimester. |
| Fertility Effects | In animal studies, reduced fertility and implantation failure observed. Human data insufficient; potential for reversible impairment of spermatogenesis and ovulation. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to Komzifti or any excipientPregnancy
| Precautions | Cardiovascular events, including arterial occlusive events (e.g., myocardial infarction, stroke)., Pancreatic toxicity (elevated lipase/amylase, pancreatitis)., Hepatotoxicity (elevated transaminases, bilirubin)., Myelosuppression (anemia, neutropenia, thrombocytopenia)., Fetal harm: Can cause fetal harm; verify pregnancy status before initiation. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to risk of increased asciminib exposure. No other food restrictions. |
| Clinical Pearls | KOMZIFTI (asciminib) is a BCR-ABL1 inhibitor specific for the ABL myristoyl pocket, effective against T315I mutant CML. Dose reduction required in hepatic impairment (Child-Pugh A/B/C). QT interval monitoring recommended due to concentration-dependent QT prolongation. Avoid concurrent use with strong CYP3A4 inhibitors or inducers. |
| Patient Advice | Take KOMZIFTI exactly as prescribed, with or without food. · Do not crush or chew tablets; swallow whole. · Report any signs of pancreatitis (severe abdominal pain), hypertension, or thrombotic events immediately. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception if of childbearing potential; avoid pregnancy. · Regular monitoring of blood counts, liver function, and ECG is required. |
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