Trabectedin

What is Trabectedin?

• Trabectedin (Yondelis) is an alkylating drug used to treat specific soft tissue sarcomas (STS) – liposarcoma and leiomyosarcoma – that cannot be removed by surgery (unresectable) or is advanced (metastatic).

What are the uses of this medicine?

This medicine is used to treat people with liposarcoma or leiomyosarcoma that:

• cannot be treated with surgery or has spread to other areas of the body, and
• who have received treatment with certain other medicines.

How does this medicine work?

• Trabectedin (tra bek' te din) is a novel antineoplastic agent initially derived from extracts of the Caribbean sea squirt, Ecteinascideia turbinata or mangrove tunicate.
• It was the first drug to be isolated from a sea animal.
• Trabectedin binds to the minor groove of DNA, allowing for alkylation of guanine and resulting in DNA damage.
• Biosynthesis of the active product allowed for clinical trials of trabectedin which demonstrated evidence of cytotoxic activity against soft tissue sarcomas.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with known severe hypersensitivity, including anaphylaxis, to trabectedin.

What drug interactions can this medicine cause?

• Avoid using strong CYP3A inhibitors (e.g., oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan) in patients taking Yondelis. If a strong CYP3A inhibitor for short-term use (i.e., less than 14 days) must be used, administer the strong CYP3A inhibitor 1 week after the Yondelis infusion, and discontinue it the day prior to the next Yondelis infusion.
• Avoid using strong CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort) in patients taking Yondelis.

Is this medicine FDA approved?

• It was approved for use in the United States in 2015.

How should this medicine be used?

• Administer dexamethasone 20 mg intravenously 30 minutes prior to each dose of Yondelis.

Recommended Dosage:

• The recommended dose is 1.5 mg/m2 administered as an intravenous infusion over 24 hours through a central venous line every 21 days (3 weeks), until disease progression or unacceptable toxicity.

Hepatic Impairment: The recommended dose is 0.9 mg/m2 in patients with moderate hepatic impairment (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal, and AST and ALT less than 8 times the upper limit of normal). Do not administer Yondelis to patients with severe hepatic impairment.

Administration

• Yondelis is given by an intravenous (IV) infusion into a vein over 24 hours. To help avoid irritation at the site where it is infused, Yondelis is given to you into a large vein through a type of IV line called a central venous line.
• Yondelis is usually given every 3 weeks.
• Your healthcare provider may decrease your dose or delay doses if you have certain side effects. If you have any side effects that are severe, your healthcare provider may stop your treatment with Yondelis.
• Before each treatment with Yondelis, you will receive a steroid medicine to help reduce your risk of getting certain side effects.
• Your healthcare provider will decide how long you will continue treatment with Yondelis.
• Your healthcare provider may do certain tests while you are receiving Yondelis to check you for side effects, and to see how well you respond to the treatment.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 1 mg sterile lyophilized powder in a single-dose vial

This medicine is available in fallowing brand namesː

• Yondelis

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• tiredness
• vomiting
• constipation
• decreased appetite
• diarrhea
• swelling of your hands, ankles, or feet
• shortness of breath
• headache
• decreased red cell count (cells which carry oxygen in the blood). Tell your healthcare provider if you feel more tired than usual or look pale.
• decreased platelet cell counts (cells which help blood to clot). Tell your healthcare provider if you bruise easily or have bleeding.
• changes in liver and kidney function blood tests

Yondelis may cause serious side effects, including:

• Severe infections due to decreased white blood cells
• Severe muscle problems (rhabdomyolysis)
• Liver problems, including liver failure
• Heart muscle problems, including heart failure
• Leakage of Yondelis out of your vein during the infusion
• Capillary leak syndrome

What special precautions should I follow?

• Neutropenic sepsis, including fatal cases, can occur with Yondelis. Monitor neutrophil count during treatment. Withhold Yondelis for neutrophil count < 1,500/mcL.
• 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.
• Hepatotoxicity may occur. Monitor and delay and/or reduce dose if needed.
• Severe and fatal cardiomyopathy can occur. Patients with left ventricular ejection fraction (LVEF) < lower limit of normal, prior cumulative anthracycline dose of ≥300 mg/m2, age ≥65 years, or a history of cardiovascular disease may be at increased risk of developing new or worsening cardiac dysfunction. Discontinue Yondelis in patients who develop decreased LVEF or cardiomyopathy.
• Capillary leak syndrome (CLS) characterized by hypotension, edema, and hypoalbuminemia has been reported with Yondelis. Monitor and discontinue Yondelis for capillary leak syndrome.
• Yondelis Can cause fetal harm. Advise of potential risk to a fetus and use effective contraception.

What to do in case of emergency/overdose?

Management of overdosage:

• There is no specific antidote for Yondelis.
• Hemodialysis is not expected to enhance the elimination of Yondelis because trabectedin is highly bound to plasma proteins (97%) and not significantly renally excreted.

Can this medicine be used in pregnancy?

• Based on its mechanism of action, trabectedin can cause fetal harm when administered during pregnancy.
• There are no available data with the use of Yondelis during pregnancy.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: trabectedin
• Inactive ingredients: potassium dihydrogen phosphate, sucrose, phosphoric acid and potassium hydroxide.

Who manufactures and distributes this medicine?

• Manufactured by: Baxter Oncology GmbH, Halle/Westfalen Germany
• Manufactured for: Janssen Products, LP, Horsham, PA

What should I know about storage and disposal of this medication?

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

• Dailymed label info on Trabectedin
• FDA Trabectedin

Trabectedin Resources
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