Trilaciclib

Hepatic Impairment Reduce the dose of COSELA to 170 mg/m 2 in patients with moderate or severe hepatic impairment (Child-Pugh classes B and C). No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A) [see Dosage and Administration]. Trilaciclib is mainly metabolized in the liver. Trilaciclib exposure increased with moderate and severe hepatic impairment (Child-Pugh classes B and C) [see Clinical Pharmacology].

Dose Modification Dose Modification for Adverse Reactions Withhold, discontinue, or alter the administration of COSELA to manage adverse reactions as described in Table 1 [see Warnings and Precautions]. [See table below.] Interstitial lung disease/pneumonitis Grade 2 (symptomatic) Hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA.

If Grade 2 recurs, permanently discontinue COSELA. Grade 3: Severe symptoms; limiting self-care ADL; oxygen indicated. OR Grade 4: Life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation) Permanently discontinue COSELA. Other toxicities Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.

Hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA. If Grade 3 recurs, permanently discontinue COSELA. Grade 4: Life-threatening consequences; urgent intervention indicated. Permanently discontinue COSELA. Dose Modifications for Hepatic Impairment Reduce the dose of COSELA to 170 mg/m 2 in patients with moderate or severe hepatic impairment (Child-Pugh classes B and C).

No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh class A) [see Use in Specific Populations and Clinical Pharmacology] .

Preparation and Administration Instructions Reconstitute and further dilute COSELA prior to intravenous infusion as outlined below. Use aseptic technique for reconstitution and dilution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstitution of COSELA Calculate the COSELA dose based on the patient's body surface area (BSA), the total volume of reconstituted COSELA solution required, and the number of COSELA vials needed. Reconstitute each 300 mg vial with 19.5 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP using a sterile syringe to obtain a concentration of 15 mg/mL of trilaciclib.

Gently swirl the vial for up to 3 minutes until the sterile lyophilized cake is completely dissolved. Do not shake. Inspect the reconstituted solution for discoloration and particulate matter. Reconstituted COSELA solution should be a clear, yellow solution. Do not use if the reconstituted solution is discolored, cloudy, or contains visible particulates.

Reconstituted solution in the vial can be stored at 20°C to 25°C (68°F to 77°F) for up to 4 hours prior to transfer to the infusion bag. Do not refrigerate or freeze. Discard any unused portion after use. Dilution of Reconstituted COSELA Solution Withdraw the required volume from the vial(s) of reconstituted COSELA solution and dilute into an intravenous infusion bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.

The final concentration of the diluted COSELA solution should be between 0.5 mg/mL and 3 mg/mL Mix diluted solution by gentle inversion. Do not shake. The diluted COSELA solution for infusion is a clear, yellow solution. If not used immediately, store the diluted COSELA solution in the intravenous infusion bag as specified in Table 2 .

Discard if storage time exceeds these limits. Do not refrigerate or freeze. [See table below.] Administration Administer diluted COSELA solution as a 30-minute intravenous infusion completed no more than 4 hours prior to the start of chemotherapy. Diluted COSELA solution must be administered with an infusion set, including an in-line filter (0.2 or 0.22 micron).

Compatible in-line filters include polyethersulfone (PES), polyvinylidene fluoride (PVDF), and cellulose acetate (CA). Do not administer diluted COSELA solution with a polytetrafluorethylene (PTFE) in-line filter as it is not compatible. PTFE is acceptable for use in air vent filters. Do not co-administer other drugs through the same infusion line.

Do not co-administer other drugs through a central access device unless the device supports co-administration of incompatible drugs. Upon completion of infusion of diluted COSELA solution, the infusion line/cannula must be flushed with at least 20 mL sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.