YONDELIS

The pharmacokinetics of trabectedin is characterized by a rapid decline phase at the end of the infusion and slower exponential phases. Population pharmacokinetic analyses suggest that the pharmacokinetics of trabectedin is dose-proportional (over the dose range of 0.024 to 1.8 mg/m 2 ) and exposure is time-independent. No accumulation of trabectedin in plasma is observed upon repeated administrations every 3 weeks.

DistributionBinding of trabectedin to human plasma proteins was approximately 9...

The clinical efficacy and safety of YONDELIS in patients with metastatic or recurrent leiomyosarcoma or liposarcoma were demonstrated in Trial ET743-SAR-3007 (NCT01343277), a randomized (2:1), open-label, active-controlled trial comparing treatment with YONDELIS 1.5 mg/m 2 as a 24-hour continuous intravenous infusion once every 3 weeks to dacarbazine 1000 mg/m 2 intravenous infusion (20 to 120 minutes) once every 3 weeks. Treatment continued in both arms until disease progression or unacceptable toxicity; all patients in the YONDELIS arm were required to receive dexamethasone 20 mg intravenous...

The following adverse reactions are discussed in more detail in other sections of the labeling: Anaphylaxis [see Contraindications (4) ] Neutropenic Sepsis [see Warnings and Precautions (5.1) ] Rhabdomyolysis [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Cardiomyopathy [see Warnings and Precautions (5.4) ] Capillary Leak Syndrome [see Warnings and Precautions (5.5) ] Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.6) ] The ...

YONDELIS is contraindicated in patients with known severe hypersensitivity, including anaphylaxis, to trabectedin. Known hypersensitivity to trabectedin ( 4 )

Neutropenic sepsis: Severe, and fatal, neutropenic sepsis may occur. Monitor neutrophil count during treatment. Withhold YONDELIS for neutrophil count < 1,500/mcL ( 2.4 , 5.1 ) Rhabdomyolysis: Rhabdomyolysis may occur. Monitor creatine phosphokinase (CPK) levels prior to each administration. Withhold YONDELIS for CPK more than 2.5 times the upper limit of normal. ( 2.4 , 5.2 ) Hepatotoxicity: Hepatotoxicity may occur. Monitor and delay and/or reduce dose if needed ( 5.3 ) Cardiomyopathy: Severe ...

7 DRUG INTERACTIONS CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 7.1 ) CYP3A inducers: Avoid concomitant strong CYP3A inducers ( 7.2 ) 7.1 Effect of Cytochrome CYP3A Inhibitors Coadministration of YONDELIS with ketoconazole, a strong CYP3A inhibitor, increased systemic exposure of trabectedin by 66%. Avoid using strong CYP3A inhibitors (e.g., oral ketoconazole, itraconazole, posac...