pharmacopeia
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/api/v1/drug/trabectedin

Mechanism of action

Sourced from openFDA

Trabectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.

Indications

Sourced from openFDA
  • YONDELIS ® is indicated for the treatment of adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen [see Clinical Studies (14) ] .

Contraindications

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  • YONDELIS is contraindicated in patients with known severe hypersensitivity, including anaphylaxis, to trabectedin.contraindicated

Dosage & administration

Sourced from openFDA

Administer at 1.5 mg/m 2 as a 24-hour intravenous infusion, every 3 weeks through a central venous line ( 2.1 , 2.6 ) Premedication: dexamethasone 20 mg intravenously, 30 min before each infusion ( 2.3 ) Hepatic Impairment: Administer at 0.9 mg/m 2 as a 24-hour intravenous infusion, every 3 weeks through a central venous line in patients with moderate hepatic impairment ( 2.2 ) 2.1 Recommended Dosage The recommended dose is 1.5 mg/m 2 administered as an intravenous infusion over 24 hours through a central venous line every 21 days (3 weeks), until disease progression or unacceptable toxicity. 2.2 Recommended Dosage in Patients with Hepatic Impairment The recommended dosage of YONDELIS in patients with moderate hepatic impairment (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal, and AST and ALT less than 8 times the upper limit of normal) is 0.9 mg/m 2 every 21 days (3 weeks). Do not administer YONDELIS to patients with severe hepatic impairment (bilirubin levels above 3 times the upper limit of normal, and any AST and ALT) [ see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 2.3 Premedication Administer dexamethasone 20 mg intravenously 30 minutes prior to each dose of YONDELIS. 2.4 Dosage Modifications for Adverse Reactions Permanently discontinue YONDELIS for: Persistent adverse reactions requiring a delay in dosing of more than 3 weeks.

Warnings & precautions

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Neutropenic sepsis: Severe, and fatal, neutropenic sepsis may occur. Monitor neutrophil count during treatment. Withhold YONDELIS for neutrophil count < 1,500/mcL ( 2.4 , 5.1 ) Rhabdomyolysis: Rhabdomyolysis may occur. Monitor creatine phosphokinase (CPK) levels prior to each administration. Withhold YONDELIS for CPK more than 2.5 times the upper limit of normal. ( 2.4 , 5.2 ) Hepatotoxicity: Hepatotoxicity may occur. Monitor and delay and/or reduce dose if needed ( 5.3 ) Cardiomyopathy: Severe and fatal cardiomyopathy can occur. Patients with left ventricular ejection fraction (LVEF) < lower limit of normal, prior cumulative anthracycline dose of ≥300 mg/m 2 , age ≥65 years, or a history of cardiovascular disease may be at increased risk of developing new or worsening cardiac dysfunction. Discontinue YONDELIS in patients who develop decreased LVEF or cardiomyopathy ( 2.4 , 5.4 ) Capillary leak syndrome: Monitor and discontinue YONDELIS for capillary leak syndrome ( 5.5 ) Embryo-fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use effective contraception ( 5.7 , 8.1 , 8.3 ) 5.1 Neutropenic Sepsis Neutropenic sepsis, including fatal cases, can occur with YONDELIS. In Trial ET743-SAR-3007, the incidence of Grade 3 or 4 neutropenia, based on laboratory values, in patients receiving YONDELIS was 43% (161/378). The median time to the first occurrence of Grade 3 or 4 neutropenia was 16 days (range: 8 days to 9.7 months); the median time to complete resolution of neutropenia was 13 days (range: 3 days to 2.3 months).

Adverse reactions

Sourced from openFDA

The following adverse reactions are discussed in more detail in other sections of the labeling: Anaphylaxis [see Contraindications (4) ] Neutropenic Sepsis [see Warnings and Precautions (5.1) ] Rhabdomyolysis [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Cardiomyopathy [see Warnings and Precautions (5.4) ] Capillary Leak Syndrome [see Warnings and Precautions (5.5) ] Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.6) ] The most common (≥20%) adverse reactions are nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. The most common (≥5%) grades 3–4 laboratory abnormalities are: neutropenia, increased ALT, thrombocytopenia, anemia, increased AST, and increased creatine phosphokinase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Products, LP at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to YONDELIS in 755 patients with soft tissue sarcoma including 197 (26%) patients exposed to YONDELIS for greater than or equal to 6 months and 57 (8%) patients exposed to YONDELIS for greater than or equal to 1 year.

Use in specific populations

Sourced from openFDA

Lactation: Advise not to breastfeed ( 8.2 ) Hepatic Impairment: Do not administer YONDELIS to patients with severe hepatic impairment ( 8.6 , 12.3 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, trabectedin can cause fetal harm when administered during pregnancy [see Clinical Pharmacology (12.1) ] . There are no available data with the use of YONDELIS during pregnancy. Animal reproductive and developmental studies at relevant doses have not been conducted with trabectedin; however, placental transfer of trabectedin was demonstrated in pregnant rats. Advise pregnant woman of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population are unknown; however, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. 8.2 Lactation Risk Summary There are no data on the presence of trabectedin in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions from YONDELIS in a breastfed child, advise a nursing woman to discontinue nursing during treatment with and for 3 months after the last dose of YONDELIS.

Pharmacokinetics

Sourced from openFDA
Metabolism
The pharmacokinetics of trabectedin is characterized by a rapid decline phase at the end of the infusion and slower exponential phases. Population pharmacokinetic analyses suggest that the pharmacokinetics of trabectedin is dose-proportional (over the dose range of 0.024 to 1.8 mg/m 2 ) and exposure is time-independent.

Overdosage

Sourced from openFDA

There is no specific antidote for YONDELIS. Hemodialysis is not expected to enhance the elimination of YONDELIS because trabectedin is highly bound to plasma proteins (97%) and not significantly renally excreted.

Approval history

Sourced from openFDA
  • Oct 23, 2015NDANDA207953Janssen Prods

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
2,260 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Neutropenia24411%
  2. 2Anaemia2109.3%
  3. 3Nausea1988.8%
  4. 4Thrombocytopenia1988.8%
  5. 5Febrile Neutropenia1597.0%
  6. 6Pancytopenia1566.9%
  7. 7Vomiting1496.6%
  8. 8Off Label Use1366.0%
  9. 9Rhabdomyolysis1305.8%
  10. 10Alanine Aminotransferase Increased1245.5%
  11. 11Disease Progression1225.4%
  12. 12Aspartate Aminotransferase Increased1054.6%
  13. 13Asthenia1044.6%
  14. 14Pyrexia1024.5%
  15. 15Acute Kidney Injury984.3%

Literature

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Recent PubMed references pinned to Trabectedin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 111 ClinicalTrials.gov registrations naming Trabectedin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Trabectedin work?
Trabectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.
What is Trabectedin used for?
According to FDA labeling, Trabectedin carries indications including: YONDELIS ® is indicated for the treatment of adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen [see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Trabectedin?
Trabectedin is classified as Other plant alkaloids and natural products, Alkylating Drug, Alkylating Activity, Decreased DNA Integrity.
What are the brand names for Trabectedin?
Trabectedin is marketed under brand names including Yondelis.
What are the contraindications for Trabectedin?
Trabectedin labeling lists contraindications including: YONDELIS is contraindicated in patients with known severe hypersensitivity, including anaphylaxis, to trabectedin.. Always consult the full prescribing information and a clinician.
Note. Data for trabectedin is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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