COSELA™ (trilaciclib) for injection
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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.
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.
- If needed, the unused 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.
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* To ensure product stability, do not exceed specified storage durations. |
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| Intravenous Infusion Bag Material | Diluent | Diluted COSELA Storage Duration* |
| Polyvinyl chloride (PVC), Ethylene vinyl acetate (EVA), Polyolefin (PO), or Polyolefin/polyamide (PO/PA) |
5% Dextrose for Injection, USP | Up to 12 hours at 20°C to 25°C (68°F to 77°F) |
| PVC, EVA, or PO | 0.9% Sodium Chloride Injection, USP | Up to 8 hours at 20°C to 25°C (68°F to 77°F) |
| PO/PA | 0.9% Sodium Chloride Injection, USP | Up to 4 hours at 20°C to 25°C (68°F to 77°F) |
COSELA for injection contains trilaciclib dihydrochloride, a kinase inhibitor.
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.
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.
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).
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis.
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
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)]
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.
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.
Withhold, discontinue, or alter the administration of COSELA to manage adverse reactions as described in TABLE 1 [see Warnings and Precautions (5)].
| Adverse Reaction | Severity Grade* | Recommended Action |
|---|---|---|
|
* National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03x |
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| Injection-site reactions including phlebitis and thrombophlebitis | Grade 1: Tenderness with or without symptoms (e.g., warmth, erythema, itching) | Interrupt or slow infusion of COSELA. If 0.9% Sodium Chloride Injection, USP is being used as a diluent/flush, consider changing to 5% Dextrose Injection, USP as appropriate for subsequent infusions. |
| Grade 2: Pain; lipodystrophy; edema; phlebitis | Interrupt infusion of COSELA. If pain not severe, follow instructions for Grade 1. Otherwise, stop infusion in extremity and rotate site of infusion to site in alternative extremity. If 0.9% Sodium Chloride Injection, USP is being used as a diluent/flush, consider changing to 5% Dextrose Injection, USP as appropriate for subsequent infusions. Central access may also be considered. | |
| Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated. OR Grade 4: Life-threatening consequences; urgent interventions indicated. |
Stop infusion and permanently discontinue COSELA. | |
| Acute drug hypersensitivity reactions | Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting Activities of Daily Living (ADL). | Stop infusion and hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA. If Grade 2 recurs, permanently discontinue COSELA. |
| Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. OR Grade 4: Life-threatening consequences; urgent intervention indicated. |
Permanently discontinue COSELA. | |
| 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. |
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.
- If needed, the unused 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.
|
* To ensure product stability, do not exceed specified storage durations. |
||
| Intravenous Infusion Bag Material | Diluent | Diluted COSELA Storage Duration* |
| Polyvinyl chloride (PVC), Ethylene vinyl acetate (EVA), Polyolefin (PO), or Polyolefin/polyamide (PO/PA) |
5% Dextrose for Injection, USP | Up to 12 hours at 20°C to 25°C (68°F to 77°F) |
| PVC, EVA, or PO | 0.9% Sodium Chloride Injection, USP | Up to 8 hours at 20°C to 25°C (68°F to 77°F) |
| PO/PA | 0.9% Sodium Chloride Injection, USP | Up to 4 hours at 20°C to 25°C (68°F to 77°F) |
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.
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.
COSELA (trilaciclib) for injection is a yellow lyophilized cake supplied in a single-dose vial. Each carton (NDC 73462-101-01) contains one 300 mg strength single-dose vial.
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.
