Lurbinectedin

Dosage Modifications for Patients with Severe and Moderate Hepatic Impairment Avoid administration of ZEPZELCA in patients with severe hepatic impairment (total bilirubin > 3 × Upper Limit of Normal (ULN)). If administration of ZEPZELCA cannot be avoided, the recommended dosage is 1.6 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity [see Use In Specific Populations and Clinical Pharmacology ] .

In patients with moderate hepatic impairment (total bilirubin > 1.5 to ≤ 3 × ULN and any AST), the recommended dosage of ZEPZELCA is 1.6 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity .

Dosage Modifications for Use with Strong and Moderate CYP3A Inhibitors Avoid coadministration of ZEPZELCA with strong or moderate CYP3A inhibitors. If coadministration of ZEPZELCA with a strong or moderate CYP3A inhibitor cannot be avoided, reduce the dose of ZEPZELCA by 50% [see Drug Interactions and Clinical Pharmacology ] .

After discontinuation of a strong or moderate CYP3A inhibitor for 5 half-lives of the inhibitor, increase the ZEPZELCA dose to the dose used before starting the inhibitor .

Preparation, Administration and Storage ZEPZELCA is a hazardous drug. Follow applicable special handling and disposal procedures 1 . 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, free of visible particles.

Calculate the required volume of reconstituted solution as follows:

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

Administration via a central venous line is recommended to reduce the risk of extravasation that can cause tissue necrosis requiring debridement [see Warnings and Precautions ] .

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. o 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: o Containers: Polyolefin containers (polyethylene, polypropylene and mixtures). o Infusion sets: Polyvinyl Chloride (PVC) (non-DEHP-containing), polyurethane and polyolefin infusion sets (polyethylene, polypropylene and polybutadiene). o Implantable venous access systems: 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. ZEPZELCA with Intravenous Atezolizumab or atezolizumab and hyaluronidase - tqjs

Administer either atezolizumab or atezolizumab and hyaluronidase-tqjs first, then administer ZEPZELCA. For the recommended dosage of atezolizumab or atezolizumab and hyaluronidase-tqjs refer to the respective Prescribing Information . 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 to 8ºC (36ºF to 46ºF) conditions. volume calculation