Trabectedin

The standard dose of Trabectedin is 1.5 mg/m2 which should be administered as an intravenous infusion over 24 hours through a central venous line every 3 weeks or 21 days, until the disease is progressive or unacceptable toxicity occurred, in patients with normal bilirubin and AST or ALT less than or equal to 2.5 times the upper limit of normal.

Commonly reported trabectedin side effects include: constipation, nausea, fatigue, decreased appetite, peripheral edema, vomiting, diarrhea, dyspnea, headache.

• Administer the dexamethasone 20 mg intravenously 30 minutes before each dose of Trabectedin.
• Trabectedin 1 mg is contraindicated in patients with severe hypersensitivity, including anaphylaxis, to trabectedin.
• Neutrophil count needs to be assessed before the administration of each dose of Trabectedin and then periodically throughout the therapy.
• Assess LFTs before each administration of trabectedin injection. Manage the elevated LFTs with interruption of therapy, dose reduction, or permanent discontinuation based on severity and duration of LFT abnormality.
• Assess left ventricular ejection fraction (LVEF) by echocardiogram or MUGA (Multigated Acquisition) scan prior to beginning of trabectedin and at 2-3 month intervals thereafter until the therapy is discontinued.
• Based on its mechanism of action, trabectedin injection can cause fetal harm in cases administered to a pregnant woman.
• Due to potential for severe adverse events from trabectedin in breastfed infants, nursing women are advised to interrupt nursing while on trabectedin treatment.

Store Trabectedin vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Trabectedin is a cytotoxic drug. Follow applicable special handling and disposal procedures.

• Coadministration of Trabectedin with ketoconazole, a strong CYP3A inhibitor, increases systemic exposure of trabectedin by 66%. Avoid use of strong CYP3A inhibitors (e.g., oral ketoconazole, posaconazole, ritonavir, itraconazole, voriconazole, lopinavir, telithromycin, clarithromycin, indinavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan) in patients with therapy of Trabectedin. Do not take grapefruit or grapefruit juice while on Trabectedin therapy. In case a strong CYP3A inhibitor for short-term use (i.e., less than 14 days) must be used, administer the strong CYP3A inhibitor 7 days after the Trabectedin infusion, and discontinue it the day prior to the next Trabectedin infusion.
• Coadministration of Trabectedin with rifampin, a strong CYP3A inducer, decreased systemic exposure of trabectedin by 31 percent. Do not administer strong CYP3A inducers (e.g., phenobarbital, rifampin, St. John’s wort) to patients with Trabectedin.