trabectedin (Rx)

Brand and Other Names:Yondelis
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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

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Interactions

Interaction Checker

and trabectedin

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            Contraindicated (0)

              Serious - Use Alternative (60)

              • abametapir

                abametapir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • apalutamide

                apalutamide will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • atazanavir

                atazanavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • bosentan

                bosentan will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • carbamazepine

                carbamazepine will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • chloramphenicol

                chloramphenicol will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • clarithromycin

                clarithromycin will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • cobicistat

                cobicistat will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • conivaptan

                conivaptan will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • dabrafenib

                dabrafenib will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • darunavir

                darunavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • deferiprone

                deferiprone, trabectedin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

              • dexamethasone

                dexamethasone will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • efavirenz

                efavirenz will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • enzalutamide

                enzalutamide will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • erdafitinib

                erdafitinib will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • etravirine

                etravirine will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • fexinidazole

                fexinidazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              • fosamprenavir

                fosamprenavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • fosphenytoin

                fosphenytoin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • grapefruit

                grapefruit will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • idelalisib

                idelalisib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • imatinib

                imatinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • indinavir

                indinavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • isoniazid

                isoniazid will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • itraconazole

                itraconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • ivosidenib

                ivosidenib will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • ketoconazole

                ketoconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • lasmiditan

                lasmiditan increases levels of trabectedin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • lonafarnib

                lonafarnib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

              • lopinavir

                lopinavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • mifepristone

                mifepristone will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • mitotane

                mitotane will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nafcillin

                nafcillin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nefazodone

                nefazodone will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • nelfinavir

                nelfinavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • nevirapine

                nevirapine will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nicardipine

                nicardipine will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • oxcarbazepine

                oxcarbazepine will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • palifermin

                palifermin increases toxicity of trabectedin by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hrbefore, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

              • pentobarbital

                pentobarbital will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • phenobarbital

                phenobarbital will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • phenytoin

                phenytoin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • posaconazole

                posaconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • primidone

                primidone will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ribociclib

                ribociclib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifabutin

                rifabutin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifampin

                rifampin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifapentine

                rifapentine will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ritonavir

                ritonavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • saquinavir

                saquinavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • sotorasib

                sotorasib will decrease the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • St John's Wort

                St John's Wort will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • tepotinib

                tepotinib will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

              • tipranavir

                tipranavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • tucatinib

                tucatinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              • voriconazole

                voriconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

              • voxelotor

                voxelotor will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (51)

              • amiodarone

                amiodarone will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • aprepitant

                aprepitant will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • armodafinil

                armodafinil will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • berotralstat

                berotralstat will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              • bicalutamide

                bicalutamide will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ceritinib

                ceritinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • cholera vaccine

                trabectedin decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

              • clobazam

                clobazam will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clotrimazole

                clotrimazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clozapine

                clozapine will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • crizotinib

                crizotinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • cyclosporine

                cyclosporine will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dengue vaccine

                trabectedin decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

              • desipramine

                desipramine will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • diltiazem

                diltiazem will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • doxycycline

                doxycycline will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dronedarone

                dronedarone will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • duvelisib

                duvelisib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

              • elagolix

                elagolix will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

                elagolix decreases levels of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • encorafenib

                encorafenib, trabectedin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              • erythromycin base

                erythromycin base will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin ethylsuccinate

                erythromycin ethylsuccinate will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin lactobionate

                erythromycin lactobionate will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin stearate

                erythromycin stearate will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fedratinib

                fedratinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              • fluconazole

                fluconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • glecaprevir/pibrentasvir

                glecaprevir/pibrentasvir will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • haloperidol

                haloperidol will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ifosfamide

                ifosfamide, trabectedin. Other (see comment). Use Caution/Monitor. Comment: Risk of developing cardiotoxic effects increase in patients with prior or concomitant treatment with other cardiotoxic agents.

              • iloperidone

                iloperidone will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • isavuconazonium sulfate

                trabectedin and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.

              • istradefylline

                istradefylline will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

                istradefylline will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

              • lapatinib

                lapatinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lonafarnib

                lonafarnib will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

              • lorlatinib

                lorlatinib will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • metronidazole

                metronidazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • netupitant/palonosetron

                netupitant/palonosetron will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ofatumumab SC

                ofatumumab SC, trabectedin. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

              • rucaparib

                rucaparib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • sarecycline

                sarecycline will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

              • schisandra

                schisandra will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • sertraline

                sertraline will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • siponimod

                siponimod and trabectedin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • stiripentol

                stiripentol, trabectedin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

                stiripentol will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              • tazemetostat

                tazemetostat will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tecovirimat

                tecovirimat will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              • tetracycline

                tetracycline will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • trastuzumab

                trastuzumab, trabectedin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • trastuzumab deruxtecan

                trastuzumab deruxtecan, trabectedin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • tucatinib

                tucatinib will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

              • verapamil

                verapamil will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              Minor (0)

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                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

                Mucosal inflammation at administration site

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                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%
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                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.

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                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
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                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)

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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Yondelis intravenous
                -
                1 mg vial

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                A Patient Handout is not currently available for this monograph.
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                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.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.