trabectedin (Rx)

Brand and Other Names:Yondelis
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

lyophilized powder for reconstitution

  • 1mg/vial

Soft Tissue Sarcoma

Indicated for unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received a prior anthracycline-containing regimen

Premedicate with dexamethasone prior to each dose

1.5 mg/m² IV q3wk until disease progression or unacceptable toxicity

Infuse over 24 hr via a central venous line

Note: Patients must have normal bilirubin and AST or ALT ≤2.5 x ULN; there is no recommended dose in patients with serum bilirubin levels above the institutional ULN

Dosage Modifications

Bilirubin >ULN: Not studied

Hepatic impairment

  • Moderate hepatic impairment (bilirubin levels 1.5 times to 3 times upper limit of normal, and AST and ALT < 8 times upper limit of normal): 0.9 mg/ m²

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dose adjustment required
  • Severe (CrCl <30 mL/min) or ESRD: Not studied

Permanently discontinue

  • Persistent adverse reactions requiring a delay in dosing of >3 weeks
  • Adverse reactions requiring dose reduction following dose of 1 mg/m²
  • Severe liver dysfunction including all of the following in the prior treatment cycle
    • Severe hepatic impairment (bilirubin levels >3 times to 10 times upper limit of normal, AND
    • AST or ALT 3 x ULN, WITH
    • Alkaline phosphatase <2 x ULN

Dose reductions

  • First dose reduction: 1.2 mg/m² q3wk
  • Second dose reduction: 1 mg/m² q3wk

Delay next dose for up to 3 weeks

  • Platelets: <100,000 platelets/mc
  • Absolute neutrophil count (ANC): <1500 neutrophils/mcL
  • Total bilirubin: >ULN AST or ALT: >2.5 x ULN
  • Alkaline phosphatase: >2.5 x ULN
  • Creatinine phosphate (CPK): >2.5 x ULN
  • Decreased LVEF: Less than lower limit of normal or clinical evidence of cardiomyopathy
  • Other nonhematologic adverse reactions: Grade 3 or 4

Reduce next dose by one dose level for adverse reaction(s) during prior cycle

  • Platelets: <25,000 platelets/mcL
  • ANC: <1000 neutrophils/mcL with fever/infection
  • ANC: <500 neutrophils/mcL lasting >5 days
  • AST or ALT: >5 x ULN Total bilirubin: >ULN
  • Alkaline phosphatase: >5 x ULN
  • CPK: >5 x ULN
  • Decreased LVEF: Absolute decrease of ≥10% from baseline and less than lower limit of normal, or clinical evidence of cardiomyopathy
  • Other nonhematologic adverse reactions: Grade 3 or 4

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and trabectedin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Nausea, all grades (75%)

            Fatigue, all grades (69%)

            Vomiting, all grades (46%)

            Constipation, all grades (37%)

            Decreased appetite, all grades (37%)

            Diarrhea, all grades (35%)

            Peripheral edema, all grades (28%)

            Dyspnea, all grades (25%)

            Headache, all grades (25%)

            Arthralgia, all grades (15%)

            Insomnia, all grades (15%)

            Myalgia, all grades (12%)

            Laboratory abnormalities

            • Anemia, all grades (96%)
            • Increased ALT, all grades (90%)
            • Increased AST, all grades (84%)
            • Increased alkaline phosphatase, all grades (70%)
            • Neutropenia, all grades (66%)
            • Hypoalbuminemia, all grades (63%)
            • Thrombocytopenia, all grades (59%)
            • Increased creatinine, all grades (46%)
            • Neutropenia, grades 3-4 (43%)
            • Increased CPK, all grades (33%)
            • Increased ALT, grades 3-4 (31%)
            • Thrombocytopenia, grades 3-4 (21%)
            • Anemia, grades 3-4 (19%)
            • Increased AST, grades 3-4 (17%)
            • Hyperbilirubinemia, all grades (13%)

            1-10%

            Fatigue, grades 3-4 (8%)

            Nausea, grades 3-4 (7%)

            Increased CPK, grades 3-4 (6.4%)

            Vomiting, grades 3-4 (6%)

            Dyspnea, grades 3-4 (4.2%)

            Increased creatinine, grades 3-4 (4.2%)

            Hypoalbuminemia, grades 3-4 (3.7%)

            Decreased appetite, grades 3-4 (1.9%)

            Hyperbilirubinemia, grades 3-4 (1.9%)

            Diarrhea, grades 3-4 (1.6%)

            Increased alkaline phosphatase, grades 3-4 (1.6%)

            <1%

            Constipation, grades 3-4

            Peripheral edema, grades 3-4

            Headache, grades 3-4

            Insomnia, grades 3-4

            Postmarketing Reports

            Capillary leak syndrome

            Previous
            Next:

            Warnings

            Contraindications

            Known hypersensitivity, including anaphylaxis, to trabectedin

            Cautions

            Neutropenic sepsis, including fatal cases, were reported during clinical trials; assess neutrophil count prior to administration of each dose and periodically throughout the treatment cycle (see Dosage Modifications)

            May cause rhabdomyolysis and musculoskeletal toxicity; assess CPK levels prior to each administration; reduce dose, or permanently discontinue based on severity of adverse reaction (see Dosage Modifications)

            Hepatotoxicity, including hepatic failure, reported during clinical trials (see Dosage Modifications)

            Assess LFTs prior to each administration and as clinically indicated based on underlying severity of pre-existing hepatic impairment; manage elevated LFTs with treatment interruption, dose reduction, or permanent discontinuation based on severity and duration of LFT abnormality; not for administration to patients with severe hepatic impairment (bilirubin levels above 3 times to 10 times the upper limit of normal, and any AST and ALT); reduce dose in patients with moderate hepatic impairment

            Cardiomyopathy, including cardiac failure, congestive heart failure, ejection fraction decreased, diastolic dysfunction, or right ventricular dysfunction, can occur; discontinue treatment based on severity of adverse reaction (also see Dosage Modifications)

            Extravasation, resulting in tissue necrosis, requiring debridement, can occur; evidence of tissue necrosis can occur >1 week after the extravasation; there is no specific antidote for extravasation of trabectedin; administer through a central venous line (see Administration)

            Capillary leak syndrome (CLS) characterized by hypotension, edema, and hypoalbuminemia reported, including serious CLS resulting in death; monitor for signs and symptoms of CLS; discontinue therapy and promptly initiate standard management for patients with CLS, which may include a need for intensive care

            Based on its mechanism of action, can cause fetal harm when administered to a pregnant woman (see Pregnancy)

            Coadministration with strong CYP3A inhibitors and inducers

            • Trabectedin is a CYP3A substrate
            • Avoid coadministration with strong CYP3A inhibitors or inducers
            • Clinical trials showed systemic exposure of trabectedin by increased by 66% with ketoconazole, a strong CYP3A inhibitor
            • Coadministration with rifampin, a strong CYP3A inducer, decreased systemic exposure of trabectedin by 31%
            Previous
            Next:

            Pregnancy

            Pregnancy

            Based on its mechanism of action, trabectedin can cause fetal harm when administered during pregnancy

            There are no available data on trabectedin use 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

            Contraception

            • Females: Advise female patients of reproductive potential to use effective contraception during and for 2 months after the last dose
            • Males: May damage spermatozoa, resulting in possible genetic and fetal abnormalities; advise males with a female sexual partner of reproductive potential to use effective contraception during and for 5 months after the last dose

            Infertility

            • May result in decreased fertility in males and females

            Lactation

            Unknown if distributed in human breast milk

            Because of the potential for serious adverse reactions from trabectedin in breastfed infants, advise a nursing woman to discontinue nursing during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix toward 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

            Distribution

            Protein bound: ~97%

            Vd: >5,000 L

            Metabolism

            Extensively metabolized in liver, predominantly by CYP3A

            Elimination

            Half-life: 175 hr

            Clearance: 31.5 L/hr

            Excretion

            • Extensively metabolized, with negligible unchanged drug in urine and feces following administration
            • Collection over 24 days: 58% in feces; 6% in urine
            Previous
            Next:

            Administration

            IV Compatibilities

            Dextrose 5% water

            0.9% NaCl

            IV Preparation

            Cytotoxic drug; follow applicable special handling and disposal

            Using aseptic technique, inject 20 mL of sterile water for injection into the vial

            Shake the vial until complete dissolution

            The reconstituted solution is clear, colorless to pale brownish-yellow

            Resulting concentration following reconstitution is 0.05 mg/mL

            Immediately following reconstitution, withdraw the calculated volume of trabectedin and further dilute in 500 mL of 0.9% NaCl or D5W

            Do not mix with other drugs

            Discard any remaining solution within 30 hr of reconstituting the lyophilized powder

            Diluted solution compatibility with containers, filters, and infusion lines

            • Type I colorless glass vials
            • Polyvinylchloride (PVC) bags
            • Polyethylene (PE) bags, mixture bags, and tubing
            • Polypropylene (PP) mixture bags
            • Polyethersulfone (PES) in-line filters
            • Titanium, platinum, or plastic ports
            • Silicone and polyurethane catheters
            • Pumps with contact surfaces made of PVC, PE, or PE/PP

            IV Administration

            Administer dexamethasone 20 mg IV 30 minutes prior to each dose

            Administer trabectedin by IV infusion over 24 hr

            Use an infusion set with a 0.2-micron polyethersulfone (PES) in-line filter to reduce the risk of exposure to adventitious pathogens that may be introduced during solution preparation

            Complete infusion within 30 hr of initial reconstitution

            Discard any unused portion of the reconstituted product or of the infusion solution

            Storage

            Cytoxic agent; follow applicable special handling and disposal procedures

            Refrigerate unopened vials at 2-8ºC (36-46ºF)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.