YONDELIS® (trabectedin) Dosing and Administration

Prior to administration: patients should receive premedication before YONDELIS® infusion

Administer dexamethasone 20 mg intravenously 30 minutes prior to each dose of YONDELIS®.1

 

Recommended starting dose and schedule1

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, in patients with normal bilirubin and AST or ALT less than or equal to 2.5 times the upper limit of normal

Moderate hepatic impairment:
The recommended dose is 0.9 mg/m2 in patients with bilirubin levels 1.5 times to 3 times the upper limit of normal, and AST and ALT less than 8 times the upper limit of normal

Severe hepatic impairment:
Do not administer to patients with bilirubin levels above 3 times to 10 times the upper limit of normal, and any AST and ALT

ALT = alanine aminotransferase; AST = aspartate aminotransferase.

The recommended starting doses and dose reductions for YONDELIS® are listed in the table below.1

Recommended Starting Doses and Dose Reductions

Starting Dose and Dose Reduction

For patients with normal hepatic function or mild hepatic impairment*

Starting Dose 1.5 mg/m2
Dose Reduction
First dose reduction 1.2 mg/m2
Second dose reduction 1.0 mg/m2

Starting Dose and Dose Reduction

For patients with moderate hepatic impairment prior to initiation of YONDELIS® treatment

Starting Dose 0.9 mg/m2
Dose Reduction
First dose reduction 0.6 mg/m2
Second dose reduction 0.3 mg/m2

*Including patients with bilirubin 1 to 1.5 times the upper limit of normal, and any AST or ALT.

 

Abnormal laboratory results or adverse events may require dose modifications1

The recommended dose modifications for adverse reactions are listed in the table below. Once reduced, the dose of YONDELIS® should not be increased in subsequent treatment cycles.

 

Recommended Dose Modifications

Laboratory Result or Adverse Reaction

DELAY Next Dose for Up to 3 Weeks

Platelets <100,000 platelets/microliter
Absolute neutrophil count <1,500 neutrophils/microliter
Total bilirubin > upper limit of normal
AST or ALT >2.5 times the upper limit of normal
ALP >2.5 times the upper limit of normal
Creatine phosphokinase >2.5 times the upper limit of normal
Decreased left ventricular ejection fraction >2.5 times the upper limit of normal
Other & non-hematologic adverse reactions Grades 3 or 4

Laboratory Result or Adverse Reaction

REDUCE next dose by 1 Dose level for Adverse Reaction(s) during prior cycle

Platelets <25,000 platelets/microliter
Absolute neutrophil count • <1000 neutrophils/microliter with fever/infection
• <500 neutrophils/microliter lasting more than 5 days
Total bilirubin >upper limit of normal
AST or ALT >5 times the upper limit of normal
ALP >2.5 times the upper limit of normal
Creatine phosphokinase >5 times the upper limit of normal
Decreased left ventricular ejection fraction • Absolute decrease of 10% or more from baseline and <lower limit of normal; or
• Clinical evidence of cardiomyopathy
Other nonhematologic adverse reactions Grades 3 or 4

ALP = alkaline phosphatase.

Permanently discontinue YONDELIS® when liver dysfunction is exacerbated for patients with pre-existing moderate hepatic impairment.

 

Conditions that require permanent discontinuation of YONDELIS®1

permanent discontinuation

  • Persistent adverse reactions requiring a dose delay of more than 3 weeks
  • Adverse reactions requiring dose reduction following YONDELIS® administered at 1.0 mg/m2 for patients with normal hepatic function or 0.3 mg/m2 for patients with pre-existing moderate hepatic impairment
  • Severe liver dysfunction (all of the following): bilirubin 2 times the upper limit of normal and AST or ALT 3 times the upper limit of normal with alkaline phosphatase less than 2 times the upper limit of normal in the prior treatment cycle for patients with normal liver function at baseline
  • Exacerbation of liver dysfunction in patients with pre-existing moderate hepatic impairment

 

 

YONDELIS® may be infused in both inpatient and outpatient sites of care1

YONDELIS® is administered as an intravenous infusion over 24 hours through a central venous line every 21 days (3 weeks), until disease progression or unacceptable toxicity. YONDELIS® may be administered to inpatients or outpatients, via stationary or ambulatory pump, at the physician’s discretion. Extravasation of YONDELIS®, resulting in tissue necrosis requiring debridement, can occur. Evidence of tissue necrosis can occur more than 1 week after the extravasation. There is no specific antidote for extravasation of YONDELIS®. For additional safety considerations, please see the full Prescribing Information.

 

 

Administration1

  • Infuse the reconstituted, diluted solution over 24 hours through a central venous line using an infusion set with a 0.2-micron polyethersulfone (PES) in-line filter to reduce the risk of exposure to adventitious pathogens that may be introduced during solution preparation
  • Complete infusion within 30 hours of initial reconstitution. Discard any unused portion of the reconstituted product or of the infusion solution

 

Preparation and Administration Checklist

The purpose of this checklist is to give an overview of the preparation and infusion process for YONDELIS®.

It is not intended to be a comprehensive checklist to cover all clinical scenarios, or a substitute for the healthcare professional’s expertise and clinical judgment. Please refer to the full Prescribing Information for complete preparation and administration instructions.

Assess clinical status

  • In addition to a clinical assessment, it is recommended that laboratory values are monitored before and during administration (complete blood count [CBC] with platelets and absolute neutrophil count; liver function tests; creatine phosphokinase)
  • Assess left ventricular ejection fraction by echocardiogram or multigated acquisition scan before initiation of YONDELIS® and at 2- to 3-month intervals until YONDELIS® is discontinued

For more information, please see the full Prescribing Information.

Premedicate

  • Premedicate with dexamethasone 20 mg intravenously 30 minutes prior to administration

For more information, please see the full Prescribing Information.

Determine dosage

  • In patients with normal bilirubin and AST or ALT less than or equal to 2.5 times the upper limit of normal, the recommended dose is 1.5 mg/m2 until disease progression or unacceptable toxicity
    • In patients with moderate hepatic impairment, the recommended dose is 0.9 mg/m2
    • Do not administer YONDELIS® to patients with severe hepatic impairment§
    • Avoid the use of concomitant strong CYP3A inducers and inhibitors
  • For additional dose modifications based on abnormal laboratory results and/or adverse events, refer to Table 1 and Table 2 in the full Prescribing Information
  • Conditions that warrant permanent discontinuation of YONDELIS® can be found in section 2.3 of the full Prescribing Information (See Prescribing Information section 2.3 [Dose Modification])

For more information, please see the full Prescribing Information.

Prepare YONDELIS®

  • Using aseptic technique, inject 20 mL of Sterile Water for Injection, USP into the vial
  • Shake the vial until complete dissolution
  • The reconstituted solution is clear, colorless to pale brownish-yellow, and contains 0.05 mg/mL of trabectedin
  • Inspect for particulate matter and discoloration prior to further dilution
  • Discard vial if particles or discoloration are observed
  • Immediately following reconstitution, withdraw the calculated volume of trabectedin and further dilute in 500 mL of 0.9% Sodium Chloride, USP or 5% Dextrose Injection, USP
  • Do not mix YONDELIS® with other drugs
  • YONDELIS® diluted solution is compatible with Type I colorless glass vials, polyvinylchloride (PVC) and polyethylene (PE) bags and tubing, PE and polypropylene (PP) mixture bags, polyethersulfone (PES) in-line filters, titanium, platinum or plastic ports, silicone and polyurethane catheters, and pumps having contact surfaces made of PVC, PE, or PE/PP

For more information, please see the full Prescribing Information.

Administer

  • Infuse YONDELIS® solution over 24 hours through a central venous line using an infusion set with a 0.2 micron PES in-line filter
  • Complete infusion within 30 hours of initial reconstitution
  • Discard any unused portion of the reconstituted product or of the infusion solution

For more information, please see the full Prescribing Information.

Bilirubin levels 1.5 times to 3 times the upper limit of normal, and AST and ALT less than 8 times the upper limit of normal.

§Bilirubin levels above 3 times to 10 times the upper limit of normal, and any AST and ALT.

 

Reference:

  1. YONDELIS® (trabectedin) [package insert]. Horsham, PA: Janssen Products, LP; 2017.