Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (69)
- 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
- axicabtagene ciloleucel
trabectedin, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- bosentan
bosentan will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- brexucabtagene autoleucel
trabectedin, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. 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.
- ceritinib
ceritinib will increase 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.
- ciltacabtagene autoleucel
trabectedin, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. 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
- idecabtagene vicleucel
trabectedin, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- 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.
- levoketoconazole
levoketoconazole 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
- lisocabtagene maraleucel
trabectedin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. 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
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, trabectedin. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- 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
- tisagenlecleucel
trabectedin, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- 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 (50)
- 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.
- 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.
- 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.
- 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.
- fosaprepitant
fosaprepitant 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.
- lenacapavir
lenacapavir will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- 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 (4)
- acetazolamide
acetazolamide will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
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
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%
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.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
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Yondelis intravenous - | 1 mg vial |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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