IV Dilution &
Medication Reference

COSELA™ (trilaciclib) for injection

Usual Diluents Return to article top

Standard Dilutions [Amt of drug] [Infusion vol] [Infusion rate] Return to article top

The recommended dose of COSELA is 240 mg/m² per dose. Administer as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy on each day chemotherapy is administered. Modification of dose based on adverse effects.

The interval between doses of COSELA on sequential days should not be greater than 28 hours.

Administration

• Administer diluted COSELA solution as a 30-minute intravenous infusion completed within 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 polyethylene sulfone, polyvinylidene fluoride, and cellulose acetate.
• Do not administer diluted COSELA solution with a polytetrafluorethylene (PTFE) in-line filter. PTFE in-line filters are not compatible with diluted COSELA solution.
• 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.

Preparation:

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.

WARNINGS Return to article top

DESCRIPTION Return to article top

The chemical name for trilaciclib is 2'-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one.

Trilaciclib dihydrochloride is a water-soluble yellow solid, with molecular formula of C24H30N8O•2HCl, a molecular weight of 519.48 g/mol (Free base: 446.56 g/mol).

Chemical Structure
COSELA (trilaciclib) for injection is a sterile, preservative-free, yellow lyophilized cake in a single-dose vial for intravenous infusion after reconstitution and dilution.

Each single-dose vial contains the equivalent of 300 mg of trilaciclib (provided as 349 mg of trilaciclib dihydrochloride) and the following inactive ingredients: citric acid monohydrate (75.6 mg) and mannitol (300 mg); hydrochloric acid and sodium hydroxide to adjust pH.

CLINICAL PHARMACOLOGY: Return to article top

Trilaciclib is a transient inhibitor of CDK 4 and 6. Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow give rise to circulating neutrophils, RBCs, and platelets. HSPC proliferation is dependent on CDK4/6 activity.

INDICATIONS AND USAGE Return to article top

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).

CONTRAINDICATIONS Return to article top

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

PRECAUTIONS Return to article top

5.1 Injection-Site Reactions, Including Phlebitis and Thrombophlebitis
COSELA administration can cause injection-site reactions including phlebitis and thrombophlebitis. Injection-site reactions including phlebitis and thrombophlebitis occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions (ARs). The median time to onset from start of COSELA was 15 days (range 1 to 542) and from the preceding dose of COSELA was 1 day (1 to 15).The median duration was 1 day (range 1 to 151 for the resolved cases). Injection-site reactions including phlebitis and thrombophlebitis resolved in 49 (88%) of the 56 patients and led to discontinuation of treatment in 3 (1%) of the 272 patients.

Monitor patients for signs and symptoms of injection-site reactions, phlebitis, and thrombophlebitis, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA [see Dosage and Administration (2.2)].

5.2 Acute Drug Hypersensitivity Reactions
COSELA administration can cause acute drug hypersensitivity reactions, including facial edema and urticaria. Acute drug hypersensitivity reactions occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). One patient experienced a Grade 2 anaphylactic reaction 4 days after receiving COSELA, which resolved with epinephrine, and treatment with COSELA was continued. The median time to onset from start of COSELA was 77 days (range 2 to 256) and from the preceding dose of COSELA was 1 day (range 1 to 28). The median duration was 6 days (range 1 to 69 for the resolved cases). Acute drug hypersensitivity reactions resolved in 12 (75%) of the 16 patients.

Monitor patients for signs and symptoms of acute drug hypersensitivity reactions including facial, eye, and tongue edema, urticaria, pruritus, and anaphylactic reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA [see Dosage and Administration (2.2)].

5.3 Interstitial Lung Disease/Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, the same drug class as COSELA. ILD/pneumonitis occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. The adverse reaction was Grade 3 and reported 2 months after discontinuing COSELA, in a patient receiving a confounding medication. The adverse reaction did not resolve.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis such as cough, dyspnea, and hypoxia. For recurrent moderate (Grade 2) ILD/pneumonitis, permanently discontinue COSELA. For severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA [see Dosage and Administration (2.2)].

5.4 Embryo-Fetal Toxicity
Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose

ADVERSE REACTIONS Return to article top

The most common adverse reactions (≥10% of patients with ≥2% difference in incidence compared to placebo) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact G1 Therapeutics, Inc., at 1-800-790-4189 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. [Drug information (pdf)]

DOSAGE AND ADMINISTRATION Return to article top

HOW SUPPLIED Return to article top

For injection: Contains the equivalent of 300 mg of trilaciclib (provided as 349 mg of trilaciclib dihydrochloride) as a sterile, preservative-free, yellow, lyophilized cake in a single-dose vial for reconstitution and further dilution.

Storage and Stability Return to article top

16.2 Storage and Handling
Store COSELA vials at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

The vial stopper is not made with natural rubber latex.