Cosela Drug Information

COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

Recommended Dosage

The recommended dose of COSELA is 240 mg/m 2 per dose. Administer as a 30-minute intravenous infusion completed no more than 4 hours prior to the start of chemotherapy on each day chemotherapy is administered. The interval between doses of COSELA on sequential days should not be greater than 28 hours.

Missed Treatment Session(s) If the COSELA dose is missed, discontinue chemotherapy on the day the COSELA dose was missed. Consider resuming both COSELA and chemotherapy on the next scheduled day for chemotherapy. Discontinuation of Treatment If COSELA is discontinued, wait 96 hours from the last dose of COSELA before resumption of chemotherapy only.

Dose Modification Dose Modification for Adverse Reactions

Withhold, discontinue, or alter the administration of COSELA to manage adverse reactions as described in Table 1. Table 1: 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).

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. 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. Table 2: Diluted COSELA Solution Storage Conditions 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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of COSELA was evaluated in Studies 1, 2, and 3. Patients received COSELA 240 mg/m 2 by 30-minute intravenous infusion prior to chemotherapy on each chemotherapy day.

Study 1: COSELA Prior to Etoposide, Carboplatin, and Atezolizumab (E/P/A) Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy Study 1 (G1T28-05; NCT03041311) was an international, randomized (1:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with etoposide, carboplatin, and atezolizumab (E/P/A) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. The data presented below are for the 105 patients who received study treatment. Eighty-five percent of patients receiving COSELA and 91% receiving placebo completed 4 cycles of induction therapy.

Seventy-six percent of patients in the COSELA group and 87% of patients in the placebo group completed at least 4 cycles of therapy. The median duration of treatment was 6 cycles in each treatment group. Study 3: COSELA Prior to Topotecan Patients with ES-SCLC previously treated with chemotherapy Study 3 (G1T28-03; NCT02514447) was an international, randomized (2:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with topotecan for patients with ES-SCLC previously treated with chemotherapy.

Thirty-eight percent of patients receiving COSELA and 29% of patients receiving placebo completed 5 or more cycles of therapy. The patients included in the pooling are those randomized patients that received at least 1 dose of COSELA (122 patients) or placebo (118 patients). Seventy-one percent of patients receiving COSELA and 78% of patients receiving placebo completed at least 4 cycles of therapy.

The median duration of treatment was the same (4 cycles) for patients receiving COSELA and placebo. Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each). Fatal adverse reactions were observed in 5% of patients receiving COSELA.

Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA. The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. The most frequently reported Grade ≥3 adverse reaction (≥5%) in patients receiving COSELA occurring at the same or higher incidence than in patients receiving placebo was hypophosphatemia.

The most common adverse reactions reported in at least 5% of patients receiving COSELA with a ≥2% higher incidence compared to patients receiving placebo are shown in Table 3.

Effect of COSELA on Other Drugs, Certain OCT2, MATE1, and MATE-2K Substrates COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin). Refer to the prescribing information for these concomitant medications for assessing the benefit and risk of concomitant use of COSELA.

Table 4: Potentially Significant Drug Interactions with COSELA

Pregnancy Risk Summary Based on the mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. There are no available human or animal data on COSELA use to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis.