Trabectedin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Yondelis: 1 mg (1 ea)

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_dss: >5,000 L

Metabolism

Extensively hepatic; via CYP3A4

Excretion

Feces (58%; only negligible amounts as unchanged drug); urine (6%; only negligible amounts as unchanged drug)

Half-Life Elimination

~175 hours

Protein Binding

~97%; to plasma proteins

Use in Specific Populations

Special Populations: 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.

Use: Labeled Indications

Soft tissue sarcoma: Treatment of unresectable or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) in patients who have received a prior anthracycline-containing regimen.

Use: Off Label

Ovarian cancer, relapsed (platinum sensitive)b

Data from a phase III study support the use of trabectedin (in combination with doxorubicin liposomal) in the treatment of recurrent, platinum-sensitive ovarian cancer in patients with a platinum-free interval of 6 to 12 months (based on a subgroup analysis) Monk 2010, Monk 2012, Poveda 2011.

Contraindications

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

Dosage and Administration

Dosing: Adult

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 (Hesketh 2017; Roila 2016); additional antiemetics may be necessary.

Soft tissue sarcoma, unresectable/metastatic: 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).

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).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

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 dose for up to 3 weeks

ANC <1,000/mm³ with fever or infection or <500/mm³ lasting >5 days during prior cycle: Delay dose for up to 3 weeks and reduce the next dose by one dose level

Platelets <100,000/mm³: Delay dose for up to 3 weeks

Platelets <25,000/mm³ during prior cycle: Delay dose for up to 3 weeks and reduce the next dose by one dose level

Nonhematologic toxicity:

Capillary leak syndrome: Permanently discontinue treatment.

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 treatment.

Creatine phosphokinase >2.5 times ULN: Delay dose for up to 3 weeks

Creatine phosphokinase >5 times ULN during prior cycle: Delay 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 treatment.

Rhabdomyolysis: Permanently discontinue treatment.

Other nonhematologic toxicity: Grade 3 or 4: Delay 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 treatment.

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Reconstitution

Reconstitute the 1 mg vial with 20 mL SWFI resulting in a reconstituted concentration of 0.05 mg/mL. Shake until completely dissolved. Immediately after reconstitution, further dilute for infusion in 500 mL NS or D5W. Diluted solution is compatible in type I glass, polyvinyl chloride (PVC) and polyethylene (PE) bags and tubing, PE and polypropylene (PP) mixture bags, polyethersulfone (PES) inline filters, titanium, platinum, or plastic ports, silicone and polyurethane catheters, and pumps with PVC, PE, or PE/PP contact surfaces. Do not mix with other medications.

Administration

Trabectedin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; 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

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.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Solutions diluted for infusion in NS or D5W should be used within 30 hours of reconstitution (infusion should be completed within that 30 hours).

Drug Interactions

Alcohol (Ethyl): May enhance the hepatotoxic effect of Trabectedin. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Trabectedin. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Trabectedin. Exceptions: Grapefruit Juice. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Trabectedin. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

HMG-CoA Reductase Inhibitors (Statins): May enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. 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. 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. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

St John's Wort: May decrease the serum concentration of Trabectedin. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (28%)

Central nervous system: Fatigue (69%), headache (25%), insomnia (15%)

Endocrine & metabolic: Hypoalbuminemia (63%)

Gastrointestinal: Nausea (75%), vomiting (46%), constipation (37%), decreased appetite (37%), diarrhea (35%)

Hematologic & oncologic: Anemia (96%; grades 3/4: 19%), neutropenia (66%; grades 3/4: 43%), thrombocytopenia (59%; grades 3/4: 21%)

Hepatic: Increased serum ALT (90%), increased serum AST (84%), increased serum alkaline phosphokinase (70%), hyperbilirubinemia (13%)

Neuromuscular & skeletal: Increased creatine phosphokinase (32% to 33%), arthralgia (15%), myalgia (12%)

Renal: Increased serum creatinine (46%)

Respiratory: Dyspnea (25%)

1% to 10%:

Cardiovascular: Pulmonary embolism (<10%), cardiomyopathy (6%)

Central nervous system: Hypoesthesia (<10%), paresthesia (<10%), peripheral neuropathy (<10%)

Frequency not defined:

Hepatic: Hepatic failure

Hypersensitivity: Anaphylaxis

<1%, postmarketing, and/or case reports: Capillary leak syndrome, hepatotoxicity, rhabdomyolysis

Warnings/Precautions

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). Monitor blood counts prior to each dose and periodically throughout treatment cycle. Hematologic toxicity may require treatment interruption and/or dose reduction.
• Capillary leak syndrome: Capillary leak syndrome (CLS) has been reported, including serious cases resulting in death. Symptoms include hypotension, edema, and hypoalbuminemia; monitor for signs/symptoms of CLS. Discontinue if CLS develops and manage as appropriate.
• 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. Monitor LVEF by echocardiogram or MUGA scan prior to treatment initiation and every 2 to 3 months until trabectedin is discontinued. 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.
• GI events: Trabectedin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016). Nausea and vomiting are common; corticosteroid premedication (eg, dexamethasone) is recommended; other antiemetics may also be needed. Constipation and diarrhea (generally mild) also commonly occur.
• 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. Monitor LFTs prior to each dose (more frequently if clinically indicated); elevated LFTs may require treatment interruption, dose reduction, and/or discontinuation (based on severity and duration). 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). Monitor CPK levels prior to each dose; may require treatment interruption, dose reduction, and/or permanent discontinuation.
• Thromboembolic events: Pulmonary embolism has been reported.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

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 cycle; more frequently if clinically indicated); renal function (baseline and during treatment); CPK (prior to each treatment cycle); pregnancy test (prior to treatment in females of reproductive potential); evaluate LVEF via MUGA or echocardiogram (baseline and every 2 to 3 months); monitor for signs/symptoms of capillary leak syndrome; monitor infusion site for signs/symptoms of extravasation

Pregnancy

Pregnancy Considerations

Based on the mechanism of action, trabectedin may cause fetal harm if administered during pregnancy. Verify pregnancy status prior to treatment in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for at least 2 months after the last trabectedin dose. Males with partners of reproductive potential should use effective contraception during treatment and for at least 5 months after the last trabectedin dose.

Patient Education

What is this drug used for?

• It is used to treat soft tissue sarcoma.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Headache
• Constipation
• Diarrhea
• Lack of appetite
• Joint pain
• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Capillary leak syndrome like abnormal heartbeat; chest pain; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; unable to pass urine or change in amount of urine passed; or blood in the urine.
• Infection
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out.
• Trouble focusing
• Confusion
• Severe loss of strength and energy
• Bleeding
• Bruising
• Pale skin
• Dizziness
• Passing out
• Swelling
• Muscle pain
• Muscle weakness
• Severe injection site pain, redness, burning, swelling, blisters, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.