• Unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have previously received an anthracycline-containing regimen.

Contraindicated in:

• Severe hypersensitivity
• Severe hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors or inducers
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Moderate hepatic impairment (↓ dose)
• Severe renal impairment
• Ejection fraction <40%, prior cumulative doxorubicin dose ≥300 mg/m², or cardiovascular disease (↑ risk of cardiomyopathy)
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: peripheral edema, HF, CAPILLARY LEAK SYNDROME.

GI: ↓ appetite, constipation, diarrhea, hepatotoxicity, nausea, vomiting.

GU: ↑ serum creatinine, ↓ fertility, renal failure.

Hemat: anemia, neutropenia, thrombocytopenia.

Local: extravasation.

MS: ↑ creatine kinase, arthralgia, myalgia, RHABDOMYOLYSIS.

Neuro: fatigue, headache, insomnia.

Resp: dyspnea.

Drug-Drug:

• Strong CYP3A4 inhibitors, including clarithromycin, conivaptan, itraconazole, ketoconazole (oral), lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, or voriconazole may ↑ levels and risk for toxicity; avoid concurrent use.
• Strong CYP3A4 inducers, including phenobarbital or rifampin may ↓ levels and effectiveness; avoid concurrent use.

Drug-Natural Products:

• St. John's wortmay ↓ levels and effectiveness; avoid concurrent use.

• Lyophilized powder for injection: 1 mg/vial;

• IV (Adults): 1.5 mg/m² every 21 days; continue until disease progression or unacceptable toxicity.

Yondelis

• Interferes with DNA transcription, ultimately disrupting protein synthesis and causing cell death.

• Death of rapidly replicating cells, particularly malignant ones. Significantly improves progression-free survival rates.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed.

Protein Binding: 97%.

Metabolism/Excretion: Primarily metabolized via CYP3A in liver to inactive metabolites. 58% excreted in feces and 6% in urine (primarily as metabolites).

Half-life: 175 hr.

(blood levels)

• Explain purpose of trabectedin to patient. Advise patient to read Patient Information before starting therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of myelosuppression (fever, unusual bruising, bleeding, tiredness, paleness), rhabdomyolysis (severe muscle pain or weakness), hepatotoxicity (yellowing of skin and eyes, pain in upper right quadrant, severe nausea or vomiting, difficulty concentrating, disorientation, or confusion) cardiomyopathy (new onset chest pain, shortness of breath, fatigue, lower extremity edema, heart palpitations), hypersensitivity (difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips, skin rash) extravasation (redness, swelling, itchiness and discomfort or leakage at infusion site) or capillary leak syndrome (edema with or without hypotension) occur.
• Advise parents to notify health care professional of all Rx or OTC medications, vitamins, or herbal products, especially St. John's Wort, being taken and to consult with health care professional before taking other medications.
• May be teratogenic. Advise female patients of reproductive potential of the need for effective contraception and to avoid breast feeding during and for 2 mo following final dose. Advise male patients with female partners of reproductive potential to use effective contraception during and for at least 5 mo after last dose. May damage spermatozoa, leading to potential genetic and fetal abnormalities. May decrease fertility in males and females. Advise patient to notify health care professional if pregnancy is planned or suspected.
• Emphasize the need for periodic lab tests to monitor for side effects.

tra-BEK-te-din