ONIVYDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONIVYDE (ONIVYDE).

How it works

Topoisomerase I inhibitor; irinotecan and its active metabolite SN-38 bind to topoisomerase I-DNA complexes, preventing religation of single-strand breaks and leading to double-strand DNA damage and cell death.

What the body does with it

Metabolism	Irinotecan is hydrolyzed by carboxylesterases to SN-38 (active metabolite). SN-38 undergoes glucuronidation by UGT1A1. Both irinotecan and SN-38 are also metabolized by CYP3A4 to inactive metabolites.
Excretion	Renal: <1% as unchanged irinotecan; biliary/fecal: major route, with 50-66% of dose recovered as irinotecan and metabolites (SN-38, SN-38G) in feces.
Half-life	Terminal elimination half-life: total irinotecan ~6-12 hours; SN-38 active metabolite ~10-20 hours; prolonged in patients with UGT1A1*28 homozygosity or hepatic impairment.
Protein binding	Irinotecan: ~50% bound (primarily to albumin); SN-38: ~95% bound (albumin).
Volume of Distribution	Volume of distribution: irinotecan ~150 L/m² (approximately 3-4 L/kg); large Vd indicates extensive tissue distribution, including into tumors.
Bioavailability	IV administration only; oral bioavailability not applicable. Administered as intravenous infusion.
Onset of Action	IV administration: clinical effect (reduction in tumor size or symptom improvement) typically observed after 4-6 weeks of treatment (2-3 cycles).
Duration of Action	Duration of neutropenia and diarrhea risk persists for 3-4 weeks after each dose; antitumor effect may continue for months with repeated cycles.

Classification & Brands

Dosing & administration

70 mg/m² intravenously over 90 minutes every 2 weeks, in combination with 5-fluorouracil and leucovorin.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No specific dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min).
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 50 mg/m². Child-Pugh Class C: not recommended.
Pediatric use	Not approved for pediatric use; no established dosing in patients <18 years.
Geriatric use	No specific dose adjustment for elderly; consider increased risk of toxicity (e.g., diarrhea, neutropenia) and monitor closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ONIVYDE (ONIVYDE).

Breastfeeding	It is unknown whether irinotecan or its metabolites are excreted in human milk. Due to potential serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 1 month after the last dose. The M/P ratio is not available.
Teratogenic Risk	ONIVYDE (irinotecan liposome) is embryotoxic and teratogenic in animal studies. Use during pregnancy, especially in the first trimester, carries a high risk of fetal harm, including malformations and miscarriage. Avoid during pregnancy; effective contraception is required during treatment and for at least 1 month after the last dose in women of childbearing potential.

Warnings & precautions

■ FDA Black Box Warning

WARNING: SEVERE NEUTROPENIA AND SEVERE DIARRHEA. Fatal neutropenic sepsis and fatal cases of diarrhea have occurred. Do not administer ONIVYDE to patients with severe neutropenia or severe diarrhea. Monitor blood cell counts and bowel movements closely.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe neutropenia (absolute neutrophil count < 1500/mm^3)","Severe diarrhea","History of severe hypersensitivity reaction to irinotecan or liposomal irinotecan","Breastfeeding"]

Clinical Precautions

Precautions

["Severe neutropenia and febrile neutropenia","Severe diarrhea (early and late-onset)","Interstitial lung disease","Embryo-fetal toxicity","Severe hypersensitivity reactions including anaphylaxis","Increased toxicity in patients with reduced UGT1A1 activity (e.g., Gilbert's syndrome)"]

Clinical Tips & Counseling

Drug interactions

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ONIVYDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONIVYDE (ONIVYDE).

How it works

What the body does with it

Metabolism	Irinotecan is hydrolyzed by carboxylesterases to SN-38 (active metabolite). SN-38 undergoes glucuronidation by UGT1A1. Both irinotecan and SN-38 are also metabolized by CYP3A4 to inactive metabolites.
Excretion	Renal: <1% as unchanged irinotecan; biliary/fecal: major route, with 50-66% of dose recovered as irinotecan and metabolites (SN-38, SN-38G) in feces.
Half-life	Terminal elimination half-life: total irinotecan ~6-12 hours; SN-38 active metabolite ~10-20 hours; prolonged in patients with UGT1A1*28 homozygosity or hepatic impairment.
Protein binding	Irinotecan: ~50% bound (primarily to albumin); SN-38: ~95% bound (albumin).
Volume of Distribution	Volume of distribution: irinotecan ~150 L/m² (approximately 3-4 L/kg); large Vd indicates extensive tissue distribution, including into tumors.
Bioavailability	IV administration only; oral bioavailability not applicable. Administered as intravenous infusion.
Onset of Action	IV administration: clinical effect (reduction in tumor size or symptom improvement) typically observed after 4-6 weeks of treatment (2-3 cycles).
Duration of Action	Duration of neutropenia and diarrhea risk persists for 3-4 weeks after each dose; antitumor effect may continue for months with repeated cycles.

Classification & Brands

Dosing & administration

70 mg/m² intravenously over 90 minutes every 2 weeks, in combination with 5-fluorouracil and leucovorin.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No specific dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min).
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 50 mg/m². Child-Pugh Class C: not recommended.
Pediatric use	Not approved for pediatric use; no established dosing in patients <18 years.
Geriatric use	No specific dose adjustment for elderly; consider increased risk of toxicity (e.g., diarrhea, neutropenia) and monitor closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ONIVYDE (ONIVYDE).

Breastfeeding	It is unknown whether irinotecan or its metabolites are excreted in human milk. Due to potential serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 1 month after the last dose. The M/P ratio is not available.
Teratogenic Risk	ONIVYDE (irinotecan liposome) is embryotoxic and teratogenic in animal studies. Use during pregnancy, especially in the first trimester, carries a high risk of fetal harm, including malformations and miscarriage. Avoid during pregnancy; effective contraception is required during treatment and for at least 1 month after the last dose in women of childbearing potential.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe neutropenia (absolute neutrophil count < 1500/mm^3)","Severe diarrhea","History of severe hypersensitivity reaction to irinotecan or liposomal irinotecan","Breastfeeding"]