Version May 2024
Note: Prior to each treatment cycle, ANC should be ≥1,500/mm3, platelets ≥100,000/mm3 total bilirubin ≤ ULN, and alkaline phosphatase, ALT, AST, and CPK ≤2.5 times ULN.
Premedications: Administer dexamethasone 20 mg IV 30 minutes prior to each infusion. Trabectedin is associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting.
Ovarian cancer, relapsed, platinum sensitive (off-label use): IV: 1.1 mg/m2 over 3 hours every 3 weeks (in combination with doxorubicin liposomal); continue as long as clinical benefit is demonstrated or until disease progression or confirmed complete response or for 2 or more cycles beyond complete response (Monk 2010; Monk 2012; Poveda 2011). Delay treatment and/or reduce the trabectedin dose (to 0.9 mg/m2, then to 0.75 mg/m2) for toxicities (doxorubicin liposomal may also require modification); consider discontinuing if a second dose reduction is not tolerated (Monk 2010).
Soft tissue sarcoma, unresectable/metastatic liposarcoma or leiomyosarcoma:
Previously treated unresectable/metastatic liposarcoma or leiomyosarcoma : IV: 1.5 mg/m2 as a continuous infusion over 24 hours once every 3 weeks; continue until disease progression or unacceptable toxicity (Demetri 2016).
Previously untreated unresectable/metastatic leiomyosarcoma (off-label use/combination) : IV: 1.1 mg/m2 over 3 hours once every 3 weeks (in combination with doxorubicin and pegfilgrastim) for a maximum of 6 combination cycles, followed by single-agent trabectedin maintenance therapy of 1.1 mg/m2 over 3 hours once every 3 weeks until disease progression or unacceptable toxicity for up to a maximum of 17 maintenance cycles (Pautier 2022).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment is necessary.
CrCl <30 mL/minute or end-stage kidney disease: There is no dosage adjustment provided in the manufacturer's labeling (effects are unknown); however, no need for dosage adjustment is expected (Krens 2019).
Hemodialysis: Hemodialysis is not expected to enhance elimination of trabectedin. No need for dosage adjustment is expected (Krens 2019).
Hepatic impairment prior to treatment (per the manufacturer's labeling ):
Mild impairment (bilirubin >1 to 1.5 times ULN and any AST or ALT): No initial dosage adjustment necessary.
Moderate impairment (bilirubin >1.5 to 3 times ULN and AST or ALT <8 times ULN): Reduce dose from 1.5 mg/m2 to 0.9 mg/m2.
Severe impairment: (bilirubin >3 times ULN and any AST or ALT): Do not administer.
Hepatotoxicity during treatment:
Recommended dose reduction levels in patients with mild or moderate hepatic impairment at baseline (once a dose is reduced it should not be increased in subsequent cycles):
Mild impairment:
First dose reduction: 1.2 mg/m2 once every 3 weeks.
Second dose reduction: 1 mg/m2 once every 3 weeks.
Moderate impairment:
First dose reduction: 0.6 mg/m2 once every 3 weeks.
Second dose reduction: 0.3 mg/m2 once every 3 weeks.
Total bilirubin >ULN: Delay dose for up to 3 weeks and reduce the next dose by one dose level
AST or ALT >2.5 times ULN: Delay dose for up to 3 weeks
AST or ALT >5 times ULN during prior cycle: Delay dose for up to 3 weeks and reduce the next dose by one dose level
Alkaline phosphatase >2.5 times ULN: Delay dose for up to 3 weeks and reduce the next dose by one dose level
Severe liver dysfunction (bilirubin 2 times ULN and AST or ALT 3 times ULN and alkaline phosphatase <2 times ULN in prior treatment cycle in patients with normal hepatic function at baseline): Permanently discontinue trabectedin.
Exacerbation of hepatic dysfunction in patients with preexisting moderate impairment: Permanently discontinue trabectedin.
Adverse reactions with trabectedin administered at 1 mg/m2 (in patients with normal hepatic function or preexisting mild hepatic impairment) or at 0.3 mg/m2 (in patients with preexisting moderate hepatic impairment) and requiring further dose reduction: Permanently discontinue trabectedin.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2 (ASCO [Griggs 2021]). Note: According to the prescribing information, if a dose is reduced due to toxicity, do not re-escalate the dose.
Soft tissue sarcoma:
Recommended dose reduction levels (once a dose is reduced it should not be increased in subsequent cycles):
First dose reduction: 1.2 mg/m2 once every 3 weeks
Second dose reduction: 1 mg/m2 once every 3 weeks
Hematologic toxicity:
ANC <1,500/mm3: Delay trabectedin dose for up to 3 weeks
ANC <1,000/mm3 with fever or infection or <500/mm3 lasting >5 days during prior cycle: Delay trabectedin dose for up to 3 weeks and reduce the next dose by one dose level
Platelets <100,000/mm3: Delay trabectedin dose for up to 3 weeks
Platelets <25,000/mm3 during prior cycle: Delay trabectedin dose for up to 3 weeks and reduce the next dose by one dose level
Nonhematologic toxicity:
Capillary leak syndrome: Permanently discontinue trabectedin and manage as clinically appropriate.
Cardiotoxicity, grade 3 or 4 cardiac adverse events indicative of cardiomyopathy or decreased left ventricular ejection fraction (LVEF) below the lower limit of normal (LLN): Permanently discontinue trabectedin.
Creatine phosphokinase >2.5 times ULN: Delay trabectedin dose for up to 3 weeks
Creatine phosphokinase >5 times ULN during prior cycle: Delay trabectedin dose for up to 3 weeks and reduce the next dose by one dose level
Persistent adverse events requiring a delay of more than 3 weeks: Permanently discontinue trabectedin.
Rhabdomyolysis: Permanently discontinue trabectedin.
Other nonhematologic toxicity: Grade 3 or 4: Delay trabectedin dose for up to 3 weeks and reduce the next dose by one dose level
Adverse reactions with trabectedin administered at 1 mg/m2 (in patients with normal hepatic function or preexisting mild hepatic impairment) or 0.3 mg/m2 (in patients with preexisting moderate hepatic impairment; refer to dosing in hepatic impairment) and requiring further dose reduction: Permanently discontinue trabectedin.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (28%)
Endocrine & metabolic: Hypoalbuminemia (63%)
Gastrointestinal: Constipation (37%), decreased appetite (37%), diarrhea (35%), nausea (75%), vomiting (46%)
Hematologic & oncologic: Anemia (96%; grades 3/4: 19%), neutropenia (66%; grades 3/4: 43%), thrombocytopenia (59%; grades 3/4: 21%)
Hepatic: Hyperbilirubinemia (13%), increased serum alanine aminotransferase (90%), increased serum alkaline phosphokinase (70%), increased serum aspartate aminotransferase (84%)
Nervous system: Fatigue (≤69%), headache (25%), insomnia (15%), malaise (≤69%)
Neuromuscular & skeletal: Arthralgia (15%), asthenia (≤69%), increased creatine phosphokinase in blood specimen (32% to 33%), myalgia (12%)
Renal: Increased serum creatinine (46%)
Respiratory: Dyspnea (25%)
1% to 10%:
Cardiovascular: Cardiomyopathy (6%), pulmonary embolism (<10%)
Gastrointestinal: Stomatitis (<10%)
Hematologic & oncologic: Febrile neutropenia (5%)
Hepatic: Hepatic injury (1%)
Infection: Neutropenic sepsis (≤3%)
Nervous system: Hypoesthesia (<10%), paresthesia (<10%), peripheral neuropathy (<10%)
Postmarketing:
Cardiovascular: Capillary leak syndrome
Neuromuscular & skeletal: Rhabdomyolysis
Known, severe hypersensitivity (including anaphylaxis) to trabectedin or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Active serious or uncontrolled infection; breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Anemia, neutropenia, and thrombocytopenia commonly occur; neutropenic fever and neutropenic sepsis (with fatalities) have been reported. The median onset for first occurrence of grade 3/4 neutropenia was 16 days (range: 8 days to ~10 months) and median time to recovery was 13 days (range: 3 days to ~2 months).
• Capillary leak syndrome: Capillary leak syndrome (CLS) has been reported, including serious cases resulting in death. Symptoms include hypotension, edema, and hypoalbuminemia.
• Cardiovascular events: Cardiomyopathy, including HF, decreased ejection fraction, diastolic dysfunction, or right ventricular dysfunction, has been observed; some events were grades 3 and 4. The median time to development of grades 3 and 4 cardiomyopathy was ~5 months (range: 1 to 15 months). Risk of cardiac dysfunction may be increased in patients with left ventricular ejection fraction (LVEF) below lower limit of normal, prior cumulative (lifetime) anthracycline dose ≥300 mg/m2, age ≥65, or history of cardiovascular disease. Permanently discontinue treatment for grade 3 or 4 cardiac events indicative of cardiomyopathy or for LVEF decreased below the lower limit of normal. Patients with a history of New York Heart Association class II, III, or IV heart failure or abnormal LVEF were excluded from the sarcoma study.
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Infuse through a central line. Avoid extravasation. Extravasation of trabectedin with subsequent tissue necrosis requiring debridement has been reported; evidence of necrosis may be delayed up to 1 week after extravasation. There are no specific antidotes for trabectedin extravasation.
• Hepatotoxicity: Hepatotoxicity (including hepatic failure) may occur with trabectedin. Grade 3 and 4 LFT elevations (AST, ALT, total bilirubin, or alkaline phosphatase) occurred in over one-third of patients. The median onset for grade 3/4 ALT or AST elevations was 29 days (range: 3 days to 11.5 months) and the median time to resolution was 13 days (range: 4 days to ~4 months); some patients experienced complete resolution. Drug-induced liver injury (ALT or AST elevation >3 times ULN, alkaline phosphatase <2 times ULN, and total bilirubin ≥2 times ULN) and ALT or AST elevations >8 times ULN have been reported. Premedication with dexamethasone (4 mg twice daily the day prior to administration) has been reported to reduce the incidence of hepatotoxicity (Grosso 2006). Patients with bilirubin above the ULN or AST or ALT >2.5 times the ULN were excluded from the sarcoma clinical trial.
• Hypersensitivity: Symptoms of hypersensitivity reactions have been reported.
• Rhabdomyolysis: Trabectedin may cause rhabdomyolysis and musculoskeletal toxicity (some fatal). Creatine phosphokinase (CPK) elevations occurred in nearly one-third of patients receiving trabectedin; grade 3 and 4 CPK elevations, some complicated by renal failure, occurred. The median time to first occurrence of grade 3 or 4 CPK elevation was 2 months (range: 1 to 11.5 months) and the median time to complete resolution was 14 days (range: 5 to 30 days).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Yondelis: 1 mg (1 ea)
No
Solution (reconstituted) (Yondelis Intravenous)
1 mg (per each): $3,866.89
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Yondelis: 0.25 mg (1 ea); 1 mg (1 ea)
Trabectedin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: Infuse through a central line with a 0.2 micron polyethersulfone filter. Infusion must be completed within 30 hours of reconstitution. Premedicate with a corticosteroid (eg, dexamethasone 20 mg IV) 30 minutes prior to treatment; additional antiemetics may be needed.
Soft tissue sarcoma:
Single-agent therapy: Infuse as a continuous infusion over 24 hours.
Off-label combination therapy with doxorubicin: Administer doxorubicin first, followed by trabectedin infused over 3 hours (Pautier 2022).
Ovarian cancer (off-label use): Combination therapy with doxorubicin liposomal: Administer doxorubicin liposomal first (flush line with D5W) then follow with trabectedin infusion over 3 hours (Monk 2010).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207953s004lbl.pdf#page=20, must be dispensed with this medication.
Soft tissue sarcoma, unresectable or metastatic liposarcoma or leiomyosarcoma: Treatment of unresectable or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) in patients who have received a prior anthracycline-containing regimen.
Ovarian cancer, relapsed, platinum sensitive
Trabectedin may be confused with lurbenectedin.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Alcohol (Ethyl): May enhance the hepatotoxic effect of Trabectedin. Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Trabectedin. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Trabectedin. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Trabectedin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Trabectedin. Risk X: Avoid combination
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
HMG-CoA Reductase Inhibitors (Statins): May enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Trabectedin. Risk X: Avoid combination
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 2 months after the last trabectedin dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 5 months after the last trabectedin dose.
Based on the mechanism of action, trabectedin may cause fetal harm if administered during pregnancy.
It is not known if trabectedin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during trabectedin treatment.
CBC with differential (baseline, prior to each dose, and periodically throughout treatment cycles); total bilirubin (prior to each cycle; more frequently if clinically indicated), ALT, AST, and alkaline phosphatase (prior to each dose; more frequently if clinically indicated); renal function (baseline and during treatment); CPK (prior to each dose). Evaluate pregnancy status (prior to treatment in patients who could become pregnant). Evaluate LVEF via MUGA or echocardiogram (baseline and every 2 to 3 months until trabectedin is discontinued). Monitor for signs/symptoms of capillary leak syndrome and hypersensitivity reactions; monitor infusion site for signs/symptoms of extravasation.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Trabectedin is a marine-derived compound (alkylating agent) which blocks the cell cycle at the G2/M phase by covalently binding to the minor DNA groove, bending the helix toward the major groove and altering DNA transcription (Garcia-Carbonero 2005). Affects activity of DNA binding proteins, transcription factors and DNA repair mechanism, leading to cell death.
Distribution: Vdss: >5,000 L
Protein binding: ~97%; to plasma proteins
Metabolism: Extensively hepatic; via CYP3A4
Half-life elimination: ~175 hours
Excretion: Feces (58%; only negligible amounts as unchanged drug); urine (6%; only negligible amounts as unchanged drug)
Hepatic function impairment: Following a single dose of 0.58 mg/m2 or 0.9 mg/m2 in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and AST and ALT <8 times ULN), trabectedin AUC increased by 97% (90% CI: 20%, 222%) compared with patients with normal liver function who received a single dose of 1.3 mg/m2.
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