YONDELIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).

How it works

Trabectedin (Yondelis) is a marine-derived alkylating agent that binds to the minor groove of DNA, forming adducts that inhibit transcription and DNA repair. It also modulates the tumor microenvironment by reducing cytokine production and angiogenesis.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2J2, CYP2C9, and CYP2C19.
Excretion	Primarily fecal (approximately 60%) and renal (approximately 22%) as unchanged drug and metabolites. Biliary excretion is a minor route.
Half-life	Terminal elimination half-life is approximately 40 hours (range 27-60 hours), supporting a weekly dosing schedule.
Protein binding	Approximately 96-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution at steady state (Vdss) is approximately 500-600 L/m² (or 10-15 L/kg), indicating extensive tissue distribution and binding.
Bioavailability	Bioavailability is 100% via intravenous route; oral bioavailability is negligible and not used clinically.
Onset of Action	Intravenous administration: Clinical effects (e.g., tumor response) typically observed after 2-3 cycles (6-9 weeks) of treatment. No other routes are clinically relevant.
Duration of Action	Duration of antitumor effect varies; treatment continues until disease progression or unacceptable toxicity. Pharmacodynamic effects persist beyond the infusion period.

Classification & Brands

Dosing & administration

1.5 mg/m2 intravenously over 24 hours every 21 days.

Dosage form	POWDER
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh A: 1.2 mg/m2 every 21 days. Child-Pugh B: Not recommended. Child-Pugh C: Not studied.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	Elderly patients >65 years have higher incidence of severe neutropenia and thrombocytopenia; monitor blood counts closely. No specific dose adjustment recommended based on age alone.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).

Breastfeeding	No human data on trabectedin excretion in breast milk; M/P ratio unknown. Due to potential adverse effects in the nursing infant, breastfeeding is contraindicated during treatment and for at least 3 months after the last dose.
Teratogenic Risk	YONDELIS (trabectedin) is embryotoxic and teratogenic in animals. First trimester: high risk of major malformations and spontaneous abortion. Second and third trimesters: risk of fetal growth restriction and adverse effects due to maternal toxicity. Avoid use during pregnancy unless no alternative and benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Neutropenic sepsis, rhabdomyolysis, and hepatotoxicity. Requires monitoring of neutrophil counts, creatine kinase, and liver function.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to trabectedin or any component; severe hepatic impairment (Child-Pugh class C); concomitant use with strong CYP3A4 inhibitors or inducers.

Clinical Precautions

Precautions

Hepatotoxicity, neutropenia (including febrile neutropenia), rhabdomyolysis, cardiomyopathy, extravasation, embryo-fetal toxicity, and hypersensitivity reactions. Avoid live vaccines during treatment.

Clinical Tips & Counseling

Drug interactions

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YONDELIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2J2, CYP2C9, and CYP2C19.
Excretion	Primarily fecal (approximately 60%) and renal (approximately 22%) as unchanged drug and metabolites. Biliary excretion is a minor route.
Half-life	Terminal elimination half-life is approximately 40 hours (range 27-60 hours), supporting a weekly dosing schedule.
Protein binding	Approximately 96-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution at steady state (Vdss) is approximately 500-600 L/m² (or 10-15 L/kg), indicating extensive tissue distribution and binding.
Bioavailability	Bioavailability is 100% via intravenous route; oral bioavailability is negligible and not used clinically.
Onset of Action	Intravenous administration: Clinical effects (e.g., tumor response) typically observed after 2-3 cycles (6-9 weeks) of treatment. No other routes are clinically relevant.
Duration of Action	Duration of antitumor effect varies; treatment continues until disease progression or unacceptable toxicity. Pharmacodynamic effects persist beyond the infusion period.

Classification & Brands

Dosing & administration

1.5 mg/m2 intravenously over 24 hours every 21 days.

Dosage form	POWDER
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh A: 1.2 mg/m2 every 21 days. Child-Pugh B: Not recommended. Child-Pugh C: Not studied.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	Elderly patients >65 years have higher incidence of severe neutropenia and thrombocytopenia; monitor blood counts closely. No specific dose adjustment recommended based on age alone.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).

Breastfeeding	No human data on trabectedin excretion in breast milk; M/P ratio unknown. Due to potential adverse effects in the nursing infant, breastfeeding is contraindicated during treatment and for at least 3 months after the last dose.
Teratogenic Risk	YONDELIS (trabectedin) is embryotoxic and teratogenic in animals. First trimester: high risk of major malformations and spontaneous abortion. Second and third trimesters: risk of fetal growth restriction and adverse effects due to maternal toxicity. Avoid use during pregnancy unless no alternative and benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Neutropenic sepsis, rhabdomyolysis, and hepatotoxicity. Requires monitoring of neutrophil counts, creatine kinase, and liver function.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to trabectedin or any component; severe hepatic impairment (Child-Pugh class C); concomitant use with strong CYP3A4 inhibitors or inducers.