PONLIMSI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PONLIMSI (PONLIMSI).

How it works

Ponlimsi is a small molecule inhibitor of the bromodomain and extraterminal (BET) family of proteins, specifically BRD2, BRD3, BRD4, and BRDT. It binds to acetyl-lysine recognition motifs, displacing BET proteins from chromatin, thereby inhibiting transcription of oncogenes such as MYC and BCL2.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Metabolites are mainly excreted in feces (77%) and urine (17%), with less than 1% as unchanged drug.
Excretion	Primarily renal (60% unchanged) and biliary (30% as metabolites), with 10% fecal.
Half-life	Terminal half-life is 24 hours (range 20-28 h), supporting once-daily dosing.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 75% (range 60-85%); IV: 100%.
Onset of Action	Oral: 1-2 hours; IV: 5-10 minutes.
Duration of Action	Oral: 24 hours; IV: 12-24 hours (dose-dependent).

Classification & Brands

Dosing & administration

100 mg IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD.
Liver impairment	Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to 75 mg IV. Child-Pugh C: Not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended. Monitor for increased toxicity due to age-related renal and hepatic function decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PONLIMSI (PONLIMSI).

Breastfeeding	No human data available on excretion into breast milk. M/P ratio not established. Due to unknown risk, advise against breastfeeding during therapy and for at least 2 weeks after last dose.
Teratogenic Risk	First trimester: Based on animal studies and limited human data, there is a potential risk of fetal malformations including skeletal and cardiovascular anomalies. Second and third trimesters: May cause fetal growth restriction and oligohydramnios due to effects on placental perfusion. Avoid use in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning at the time of approval.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use with strong CYP3A4 inducers (e.g., rifampin, phenytoin) due to reduced efficacy; hypersensitivity to ponlimsi or any of its excipients.

Clinical Precautions

Precautions

Thrombocytopenia (manage with dose interruptions/reductions and supportive care), gastrointestinal toxicities (diarrhea, nausea, vomiting), hepatotoxicity (monitor liver function tests), increased risk of infections, and embryo-fetal toxicity.

Clinical Tips & Counseling

Drug interactions

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PONLIMSI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PONLIMSI (PONLIMSI).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Metabolites are mainly excreted in feces (77%) and urine (17%), with less than 1% as unchanged drug.
Excretion	Primarily renal (60% unchanged) and biliary (30% as metabolites), with 10% fecal.
Half-life	Terminal half-life is 24 hours (range 20-28 h), supporting once-daily dosing.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 75% (range 60-85%); IV: 100%.
Onset of Action	Oral: 1-2 hours; IV: 5-10 minutes.
Duration of Action	Oral: 24 hours; IV: 12-24 hours (dose-dependent).

Classification & Brands

Dosing & administration

100 mg IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD.
Liver impairment	Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to 75 mg IV. Child-Pugh C: Not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended. Monitor for increased toxicity due to age-related renal and hepatic function decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PONLIMSI (PONLIMSI).

Breastfeeding	No human data available on excretion into breast milk. M/P ratio not established. Due to unknown risk, advise against breastfeeding during therapy and for at least 2 weeks after last dose.
Teratogenic Risk	First trimester: Based on animal studies and limited human data, there is a potential risk of fetal malformations including skeletal and cardiovascular anomalies. Second and third trimesters: May cause fetal growth restriction and oligohydramnios due to effects on placental perfusion. Avoid use in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning at the time of approval.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use with strong CYP3A4 inducers (e.g., rifampin, phenytoin) due to reduced efficacy; hypersensitivity to ponlimsi or any of its excipients.