Navigation

Yondelis

Yondelis (Trabectedin for Injection) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Yondelis Side Effects Center

What Is Yondelis?

Yondelis (trabectedin) for injection is an alkylating drug indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen.

What Are Side Effects of Yondelis?

Common side effects of Yondelis include:

Dosage for Yondelis

Administer Yondelis at a dose of 1.5 mg/m2 body surface area as a 24-hour intravenous infusion, every 3 weeks through a central venous line. Premedicate with dexamethasone 20 mg IV, 30 min. before each infusion of Yondelis.

What Drugs, Substances, or Supplements Interact with Yondelis?

Yondelis may interact with strong CYP3A inhibitors (e.g., azole antifungals, clarithromycin, telithromycin, indinavir, lopinavir,ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan), strong CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort), and grapefruit or grapefruit juice. Tell your doctor all medications and supplements you use.

Yondelis During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before taking Yondelis; it may cause fetal harm. Breastfeeding is not recommended while taking Yondelis.

Additional Information

Our Yondelis (trabectedin) for injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Yondelis Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; chest tightness, wheezing, difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Capillary leak syndrome is a rare but serious side effect of trabectedin. Tell your doctor right away if you have signs of this condition: stuffy or runny nose followed by weakness or tired feeling, and sudden swelling in your arms, legs and other parts of the body.

Call your doctor at once if you have:

  • pain, burning, irritation, or skin changes where the injection was given;
  • heart problems--chest pain, fast or pounding heartbeats, shortness of breath (even with mild exertion), swelling, rapid weight gain;
  • breakdown of muscle tissue--unexplained muscle pain, tenderness, or weakness (especially if you also have fever, unusual tiredness, and dark colored urine);
  • liver problems--nausea, upper stomach pain, confusion, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, loss of appetite;
  • diarrhea, constipation;
  • swelling, tiredness;
  • low blood cell counts;
  • abnormal liver or kidney function tests;
  • headache; or
  • feeling short of breath.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Yondelis (Trabectedin for Injection)

 

Yondelis Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Anaphylaxis [see CONTRAINDICATIONS]
  • Neutropenic Sepsis [see WARNINGS AND PRECAUTIONS]
  • Rhabdomyolysis [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Cardiomyopathy [see WARNINGS AND PRECAUTIONS]
  • Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]
  • Extravasation Resulting in Tissue Necrosis [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to YONDELIS in 755 patients with soft tissue sarcoma including 197 (26%) patients exposed to YONDELIS for greater than or equal to 6 months and 57 (8%) patients exposed to YONDELIS for greater than or equal to 1 year. The safety of YONDELIS was evaluated in six open-label, single-arm trials, in which 377 patients received YONDELIS and one open-label, randomized, active-controlled clinical trial in which 378 patients received YONDELIS (Trial ET743-SAR-3007). All patients received YONDELIS at the recommended dosing regimen of 1.5 mg/m2 administered as an intravenous infusion over 24 hours once every 3 weeks (q3wk, 24-h). The median age was 54 years (range: 18 to 81 years), 63% were female, and all patients had metastatic soft tissue sarcoma.

Tables 3 and 4 present selected adverse reactions and laboratory abnormalities, respectively, observed in Trial ET743-SAR-3007, an open-label, randomized (2:1), active-controlled trial in which 550 patients with previously treated leiomyosarcoma or liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) received YONDELIS 1.5 mg/m2 intravenous infusion over 24 hours once every 3 weeks (n=378) or dacarbazine 1000 mg/m2 intravenous infusion over 20 to 120 minutes once every 3 weeks (n=172) [see Clinical Studies]. All patients treated with YONDELIS were required to receive dexamethasone 20 mg intravenous injection 30 minutes prior to start of the YONDELIS infusion.

In Trial ET743-SAR-3007, patients had been previously treated with an anthracycline-and ifosfamide-containing regimen or with an anthracycline-containing regimen and one additional cytotoxic chemotherapy regimen. The trial excluded patients with known central nervous system metastasis, elevated serum bilirubin or significant chronic liver disease, such as cirrhosis or active hepatitis, and history of myocardial infarction within 6 months, history of New York Heart Association Class II to IV heart failure, or abnormal left ventricular ejection fraction at baseline. The median age of patients in Trial ET743-SAR-3007 was 57 years (range: 17 to 81 years), with 69% female, 77% White, 12% Black or African American, 4% Asian, and <1% American Indian or Alaska Native. The median duration of exposure to trabectedin was 13 weeks (range: 1 to 127 weeks) with 30% of patients exposed to YONDELIS for greater than 6 months and 7% of patients exposed to YONDELIS for greater than 1 year.

In Trial ET743-SAR-3007, adverse reactions resulting in permanent discontinuation of YONDELIS occurred in 26% (98/378) of patients; the most common were increased liver tests (defined as ALT, AST, alkaline phosphatase, bilirubin) (5.6%), thrombocytopenia (3.4%), fatigue (1.6%), increased creatine phosphokinase (1.1%), and decreased ejection fraction (1.1%). Adverse reactions that led to dose reductions occurred in 42% (158/378) of patients treated with YONDELIS; the most common were increased liver tests (24%), neutropenia (including febrile neutropenia) (8%), thrombocytopenia (4.2%), fatigue (3.7%), increased creatine phosphokinase (2.4%), nausea (1.1%), and vomiting (1.1%). Adverse reactions led to dose interruptions in 52% (198/378) of patients treated with YONDELIS; the most common were neutropenia (31%), thrombocytopenia (15%), increased liver tests (6%), fatigue (2.9%), anemia (2.6%), increased creatinine (1.1%), and nausea (1.1%).

The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. The most common laboratory abnormalities (≥20%) were increases in AST or ALT, increased alkaline phosphatase, hypoalbuminemia, increased creatinine, increased creatine phosphokinase, anemia, neutropenia, and thrombocytopenia.

Table 3: Selected Adverse Reactionsa Occurring in ≥10% of Patients Receiving YONDELIS and at a Higher Incidence than in the Control Arm -Trial ET743-SAR-3007

System Organ Class Adverse Reaction YONDELIS
(N=378)		 Dacarbazine
(N=172)
All Gradesb
(%)		 Grades 3-4
(%)		 All Grades
(%)		 Grades 3-4
(%)
Gastrointestinal disorders
  Nausea 75 7 50 1.7
  Vomiting 46 6 22 1.2
  Constipation 37 0.8 31 0.6
  Diarrhea 35 1.6 23 0
General disorders and administration site conditions
  Fatiguec 69 8 52 1.7
  Peripheral edema 28 0.8 13 0.6
Metabolism and nutrition disorders
  Decreased appetite 37 1.9 21 0.6
Respiratory, thoracic and mediastinal disorders
  Dyspnea 25 4.2 20 1.2
Nervous system disorders
  Headache 25 0.3 19 0
Musculoskeletal and connective tissue disorders
  Arthralgia 15 0 8 1.2
  Myalgia 12 0 6 0
Psychiatric disorders
  Insomnia 15 0.3 9 0
a Limited to adverse reactions at a rate of ≥10% in the trabectedin arm and at a rate higher in the trabectedin arm compared with dacarbazine arm by ≥5% in overall incidence or by ≥2% for Grade 3-4 adverse reactions.
b Toxicity grade is based on NCI common toxicity criteria, version 4.0.
c Fatigue is a composite of the following adverse event terms: fatigue, asthenia, and malaise.

Other clinically important adverse reactions observed in <10% of patients (N=755) with soft tissue sarcoma receiving YONDELIS were:

Nervous system disorders: peripheral neuropathy, paresthesia, hypoesthesia.

Respiratory, thoracic, and mediastinal disorders: pulmonary embolism.

General disorders and administration site conditions: mucosal inflammation

Table 4: Incidence of Selected Treatment-Emergent Laboratory Abnormalitiesa -Trial ET743-SAR-3007

Laboratory Abnormalities YONDELIS Dacarbazine
All Grades
(%)		 Grades 3-4
(%)		 All Grades
(%)		 Grades 3-4
(%)
Chemistry
  Increased ALT 90 31 33 0.6
  Increased AST 84 17 32 1.2
  Increased alkaline phosphatase 70 1.6 60 0.6
  Hypoalbuminemia 63 3.7 51 3.0
  Increased creatinine 46 4.2 29 1.2
  Increased creatine phosphokinase 33 6.4 9 0.6
  Hyperbilirubinemia 13 1.9 5 0.6
Hematology
  Anemia 96 19 79 12
  Neutropenia 66 43 47 26
  Thrombocytopenia 59 21 57 20
a Treatment-emergent laboratory abnormalities including those higher in the trabectedin arm compared with the dacarbazine arm by ≥5% (all Grades) or by ≥2% (Grade 3-4). Incidence based on number of patients who had both baseline and at least one on-study laboratory measurement.
YONDELIS group (range: 373 to 377 patients) and dacarbazine group (range: 166 to 168 patients).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of YONDELIS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Vascular disorders: capillary leak syndrome

DRUG INTERACTIONS

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, 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 [see CLINICAL PHARMACOLOGY].

Effect Of Cytochrome CYP3A Inducers

Coadministration of YONDELIS with rifampin, a strong CYP3A inducer, decreased systemic exposure of trabectedin by 31%. Avoid using strong CYP3A inducers (e.g., rifampin, phenobarbital, St. John’s wort) in patients taking YONDELIS [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Yondelis (Trabectedin for Injection)

&Copy; Yondelis Patient Information is supplied by Cerner Multum, Inc. and Yondelis Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.