YONDELIS- trabectedin injection, powder, lyophilized, for solution
Janssen Products, LP
YONDELIS® is indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen [see Clinical Studies (14)].
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 (bilirubin levels above 3 times the upper limit of normal, and any AST and ALT) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Administer dexamethasone 20 mg intravenously 30 minutes prior to each dose of YONDELIS.
Permanently discontinue YONDELIS for:
- Persistent adverse reactions requiring a delay in dosing 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 at 0.3 mg/m2 for patients with pre-existing moderate hepatic impairment.
- Severe liver dysfunction: bilirubin two times the upper limit of normal, and AST or ALT three times the upper limit of normal, and alkaline phosphatase less than two 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.
- Capillary leak syndrome.
- Grade 3 or 4 cardiac adverse events (AEs) indicative of cardiomyopathy or for subjects with an LVEF that decreases below the lower limit of normal.
The recommended dose modifications for adverse reactions are listed in Table 1. Once reduced, the dose of YONDELIS should not be increased in subsequent treatment cycles.
|Laboratory Result or Adverse Reaction||DELAY next dose of YONDELIS for up to 3 weeks||REDUCE next dose of YONDELIS by one dose level for adverse reaction(s) during prior cycle|
|Platelets||Less than 100,000 platelets/microliter||Less than 25,000 platelets/microliter|
|Absolute neutrophil count||Less than 1,500 neutrophils/microliter|| |
|Total bilirubin||Greater than the upper limit of normal||Greater than the upper limit of normal|
|Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)||More than 2.5 times the upper limit of normal||More than 5 times the upper limit of normal|
|Alkaline phosphatase (ALP)||More than 2.5 times the upper limit of normal||More than 2.5 times the upper limit of normal|
|Creatine phosphokinase||More than 2.5 times the upper limit of normal||More than 5 times the upper limit of normal|
|Other non-hematologic adverse reactions||Grade 3 or 4||Grade 3 or 4|
The recommended starting doses and dose reductions for YONDELIS are listed in Table 2:
|Starting Dose and Dose Reduction||For patients with normal hepatic function or mild hepatic impairment * prior to initiation of YONDELIS treatment||For patients with moderate hepatic impairment † prior to initiation of YONDELIS treatment|
|Starting Dose||1.5 mg/m2||0.9 mg/m2|
|First dose reduction||1.2 mg/m2||0.6 mg/m2|
|Second dose reduction||1.0 mg/m2||0.3 mg/m2|
- YONDELIS is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
- 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.
- Discard any remaining solution within 30 hours of reconstituting the lyophilized powder.
- 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.
- 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.
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