ZEPZELCA Powder for solution for injection Ref.[50657] Active ingredients:

2.1 Recommended Dosage

The recommended dosage of ZEPZELCA is 3.2 mg/m² by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.

Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is at least 1,500 cells/mm³ and platelet count is at least 100,000/mm³.

2.2 Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions are listed in Table 1. Permanently discontinue ZEPZELCA in patients who are unable to tolerate 2 mg/m² or require a dose delay greater than two weeks.

Table 1. Dose Reduction for ZEPZELCA for Adverse Reactions:

Discontinue ZEPZELCA if patients are unable to tolerate 2 mg/m² every 21 days.

Dosage modifications for ZEPZELCA for adverse reactions are presented in Table 2.

Table 2. Dosage Modifications for ZEPZELCA for Adverse Reactions:

^a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
^b Patients with isolated Grade 4 neutropenia (neutrophil count less than 500 cells/mm³) may receive G-CSF prophylaxis rather than undergo lurbinectedin dose reduction.

2.3 Premedication

Consider administering the following pre-infusion medications for antiemetic prophylaxis [see Adverse Reactions (6.1)]:

• Corticosteroids (dexamethasone 8 mg intravenously or equivalent)
• Serotonin antagonists (ondansetron 8 mg intravenously or equivalent)

2.4 Preparation, Administration and Storage

ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures¹.

Preparation:

• Inject 8 mL of Sterile Water for Injection USP into the vial, yielding a solution containing 0.5 mg/mL lurbinectedin. Shake the vial until complete dissolution.
• Visually inspect the solution for particulate matter and discoloration. The reconstituted solution is a clear, colorless or slightly yellowish solution, essentially free of visible particles.
• Calculate the required volume of reconstituted solution as follows:

Volume (mL) = Body Surface Area (m²) x Individual Dose (mg/m²) / 0.5 mg/mL

• For administration through a central venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 100 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP).
• For administration through a peripheral venous line, withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 250 mL of diluent (0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP).

Administration:

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is observed, do not administer.
• ZEPZELCA can be administered with or without an in-line filter. If infusion lines containing in-line filters are utilized for administration of ZEPZELCA, Polyethersulfone (PES) in-line filters with pore sizes of 0.22 micron are recommended.
  • Do not use in-line nylon membrane filters when the reconstituted ZEPZELCA solution is diluted using 0.9% Sodium Chloride Injection USP. Adsorption of ZEPZELCA to the Nylon membrane filters has been observed when 0.9% Sodium Chloride Injection, USP is used as the diluent.
• Compatibility with other intravenous administration materials and the diluted ZEPZELCA solution has been demonstrated in the following materials:
  • Polyolefin containers (polyethylene, polypropylene and mixtures).
  • Polyvinyl Chloride (PVC) (non-DEHP-containing), polyurethane and polyolefin infusion sets (polyethylene, polypropylene and polybutadiene).
  • Implantable venous access systems with titanium and plastic resin ports and with polyurethane or silicone intravenous catheters.
• Do not co-administer ZEPZELCA and other intravenous drugs concurrently within the same intravenous line.

Storage of Infusion Solution:

• If not used immediately after reconstitution or dilution, the ZEPZELCA solution can be stored prior to administration for up to 24 hours following reconstitution, including infusion time, at either room temperature/ambient light or under refrigeration at 2ºC-8ºC (36ºF-46ºF) conditions.

Store refrigerated at 2° to 8°C (36° to 46°F).

ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures¹.