YONDELIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).
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.
| 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. |
| Molecular Weight | 784.96 |
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. |
| 1st trimester | Avoid; teratogenic in animal studies, no human data. |
| 2nd trimester | Avoid; potential fetal harm. |
| 3rd trimester | Avoid; potential fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for YONDELIS (YONDELIS).
| Placental transfer | Likely crosses placenta based on low molecular weight and animal studies demonstrating fetal toxicity. |
| Breastfeeding | It is not known if YONDELIS is excreted in human milk. Due to potential serious adverse reactions in nursing infants, breast-feeding should be discontinued during treatment and for at least 1 month after the last dose. |
| Lactation Rating |
■ FDA Black Box Warning
Neutropenic sepsis, rhabdomyolysis, and hepatotoxicity. Requires monitoring of neutrophil counts, creatine kinase, and liver function.
| Serious Effects |
Hypersensitivity to trabectedin or any excipientsSevere hepatic impairment (Child-Pugh class C)Pregnancy
| Precautions | Hepatotoxicity, neutropenia (including febrile neutropenia), rhabdomyolysis, cardiomyopathy, extravasation, embryo-fetal toxicity, and hypersensitivity reactions. Avoid live vaccines during treatment. |
| Food/Dietary | Grapefruit, grapefruit juice, starfruit, and Seville oranges should be avoided as they inhibit CYP3A4 and can increase trabectedin exposure. No other specific food restrictions are documented, but a balanced diet is recommended to maintain nutritional status during treatment. |
Loading safety data…
| L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (AST, ALT, alkaline phosphatase, bilirubin), creatine phosphokinase (CPK), and renal function. Assess for signs of neutropenic sepsis, hepatotoxicity, rhabdomyolysis, and cardiotoxicity. Perform fetal ultrasound if pregnancy occurs. |
| Fertility Effects | Trabectedin may impair male and female fertility based on animal studies. In humans, it can cause amenorrhea and oligospermia. Advise patients on fertility preservation options prior to treatment. |
| Clinical Pearls | YONDELIS (trabectedin) is a DNA-alkylating agent derived from the sea squirt Ecteinascidia turbinata. It is indicated for unresectable or metastatic liposarcoma or leiomyosarcoma after prior anthracycline. Administer through a central line; premedicate with dexamethasone to reduce hepatotoxicity. Monitor liver function, creatine kinase, and neutrophil count closely. Dose reductions for moderate hepatic impairment (bilirubin > ULN to ≤3x ULN) decrease risk of severe hepatotoxicity. Use with strong CYP3A4 inhibitors requires dose reduction; avoid with strong CYP3A4 inducers. Infusion site reactions are common; extravasation risk is low if properly diluted. Rhabdomyolysis risk; advise patients to report unexplained muscle pain. |
| Patient Advice | Take dexamethasone as prescribed before each infusion to protect your liver. · Report any unusual bruising, bleeding, or signs of infection (fever) immediately. · Inform your doctor about new or worsening muscle pain, weakness, or dark urine. · Avoid grapefruit, starfruit, and Seville oranges during treatment as they interact with trabectedin. · Tell all healthcare providers you are taking YONDELIS before starting any new medications or supplements. · Do not drive or operate heavy machinery if you experience fatigue or dizziness after treatment. · Use effective contraception during and for 2 months after treatment; avoid breastfeeding. |