Yondelis

Drug overview for YONDELIS (trabectedin):

Generic name: TRABECTEDIN (tra-BEK-te-din)
Drug class: Antineoplastic - Topoisomerase I Inhibitors
Therapeutic class: Antineoplastics

Trabectedin, a synthetic alkaloid originally isolated from the marine ascidian Ecteinascidia turbinata, is an alkylating antineoplastic agent.

No enhanced Uses information available for this drug.

DRUG IMAGES

YONDELIS 1 MG VIAL

The following indications for YONDELIS (trabectedin) have been approved by the FDA:

Indications:
Leiomyosarcoma
Liposarcoma

Professional Synonyms:
None.

The following dosing information is available for YONDELIS (trabectedin):

Dosing
Administration
YONDELIS
Generic

If adverse reactions occur, interruption of therapy, dosage reduction, and/or permanent discontinuance of trabectedin should be considered. When dosage reduction is necessary, an initial dosage reduction to 1.2 mg/m2 every 3 weeks is recommended.

If further dosage reduction is necessary, the dosage should be reduced to 1 mg/m2 every 3 weeks. If a dosage of 1 mg/m2 every 3 weeks is not tolerated, trabectedin should be permanently discontinued.

Dosage of trabectedin should not be re-escalated following a dosage reduction.

Trabectedin should be permanently discontinued in patients experiencing persistent adverse reactions requiring a treatment delay of more than 3 weeks.

Procedures for proper handling and disposal of antineoplastic agents should be followed. Trabectedin is administered by continuous IV infusion over 24 hours via a central venous line using an infusion set with a 0.2-mcm polyethersulfone inline filter.

Unreconstituted vials of trabectedin powder for injection should be stored at 2-8degreesC. Prior to administration, commercially available trabectedin powder for injection must be reconstituted and diluted using proper aseptic technique. The lyophilized powder is reconstituted by adding 20 mL of sterile water for injection to a vial labeled as containing 1 mg of trabectedin to provide a solution containing 0.05

mg/mL of the drug. The vial should then be shaken until complete dissolution of the powder occurs and inspected visually for particulate matter and discoloration prior to dilution. The solution should be clear and colorless to pale brownish-yellow; the vial should be discarded if particulate matter or discoloration is present.

The reconstituted trabectedin solution should be diluted immediately. Any partially used vials should be discarded. For preparation of the final diluted trabectedin solution for infusion, the appropriate volume of reconstituted solution should be withdrawn from the vial and further diluted in 500 mL of 0.9%

sodium chloride injection or 5% dextrose injection. Final diluted solutions of trabectedin are stable for 30 hours following reconstitution when stored at 2-8degreesC or room temperature in ambient light. Administration of the drug must be completed within 30 hours following reconstitution.

Any unused portion of reconstituted solution or diluted infusion solution should be discarded. Trabectedin should not be admixed with any other drug. Trabectedin may adsorb to certain infusion materials; however, the manufacturer states that diluted solutions of trabectedin are compatible with type I colorless glass vials; polyvinylchloride (PVC) and polyethylene bags and tubing; polyethylene and polypropylene mixture bags; polyethersulfone inline filters; titanium, platinum, or plastic ports; silicone and polyurethane catheters; and infusion pumps having contact surfaces made of PVC, polyethylene, or polyethylene/polypropylene.

Dosing information for YONDELIS
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
YONDELIS 1 MG VIAL	Maintenance	Adults infuse 1.5 mg/m2 over 24 hour(s) by continuous infusion route every 3 weeks

No generic dosing information available.

The following contraindication information is available for YONDELIS (trabectedin):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Trabectedin is contraindicated in patients with known severe hypersensitivity, including anaphylaxis, to the drug. In the European Medicines Agency (EMEA) labeling, the manufacturer states that concurrent use of trabectedin with yellow fever vaccine is contraindicated. (See Live Vaccines under Drug Interactions.)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Lactation
Rhabdomyolysis

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic heart failure
Disease of liver
Infection
Myopathy with CK elevation
Neutropenic disorder
Pregnancy
Thrombocytopenic disorder

There are 0 moderate contraindications.

The following adverse reaction information is available for YONDELIS (trabectedin):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in 10% or more of patients receiving trabectedin for the treatment of advanced leiomyosarcoma or liposarcoma and at an incidence that is at least 2% higher than that reported with dacarbazine include nausea, vomiting, constipation, decreased appetite, diarrhea, fatigue (includes asthenia and malaise), peripheral edema, dyspnea, headache, arthralgia, myalgia, and insomnia. Laboratory abnormalities reported in more than 10% of patients receiving trabectedin for the treatment of advanced leiomyosarcoma or liposarcoma and at an incidence that is at least 2% higher than that reported with dacarbazine include anemia, increased concentrations of alkaline phosphatase, neutropenia, hypoalbuminemia, thrombocytopenia, increased concentrations of serum creatinine, increased concentrations of CK, increased concentrations of aminotransferases (i.e., ALT, AST), and hyperbilirubinemia.

There are 22 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Anemia Increased alanine transaminase Increased aspartate transaminase Neutropenic disorder Thrombocytopenic disorder	Hypokalemia Leukopenia Pulmonary thromboembolism

Rare/Very Rare
Acute renal failure Bacterial sepsis Capillary leak syndrome Cardiomyopathy Chronic heart failure Extravasation injury Hepatic failure Hepatitis Hypersensitivity drug reaction Hypotension Multiple organ failure Pancytopenia Rhabdomyolysis

There are 31 less severe adverse reactions.

More Frequent	Less Frequent
Anorexia Fatigue Headache disorder Hyperbilirubinemia Nausea Vomiting	Acute abdominal pain Alopecia Arthralgia Chest pain Constipation Dehydration Diarrhea Dizziness Dysgeusia Dyspepsia Dyspnea Edema Fever General weakness Injection site sequelae Myalgia Peripheral edema Skin pigmentation enhancement Stomatitis

Rare/Very Rare
Flushing Hypoesthesia Insomnia Paresthesia Peripheral neuropathy Tachycardia

The following precautions are available for YONDELIS (trabectedin):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of trabectedin have not been established in pediatric patients with liposarcoma or leiomyosarcoma. In a phase 2 study evaluating the pharmacokinetics of trabectedin 1.5 mg/m2 by IV infusion over 24 hours in pediatric patients (12-21 years of age) weighing 15 kg or more with rhabdomyosarcoma, Ewing sarcoma, or non-rhabdomyosarcoma soft tissue sarcoma, pharmacokinetic parameters were generally similar to those observed in adults.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Trabectedin may cause fetal harm if administered to pregnant women based on its mechanism of action. (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

It is not known whether trabectedin is distributed into milk. The effects of the drug on nursing infants and on milk production also are unknown. Because of the potential for serious adverse reactions to trabectedin in nursing infants, women should be advised to discontinue nursing while receiving the drug. In the European Union, the manufacturer also recommends discontinuing nursing for 3 months after discontinuance of the drug.

Clinical studies of trabectedin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. (See Dosage and Administration: Special Populations.) Population pharmacokinetic analyses in adults indicate that age (19-83 years) does not have clinically important effects on the pharmacokinetics of trabectedin.