Trilacicilib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Trilacicilib is a kinase inhibitor that is FDA approved for the treatment 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.. Common adverse reactions include fatigue, hypocalcemia,hypokalemia,hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
COSELA is a kinase inhibitor 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.
- COSELA is for intravenous use only.
- The recommended dose of COSELA is 240 mg/m2 as a 30-minute intravenous infusion completed no more than 4 hours prior to the start of chemotherapy on each day chemotherapy is administered.
- Reduce dose in patients with moderate or severe hepatic impairment.
- See Full Prescribing Information for instructions on preparation and administration.
- DOSAGE FORMS AND STRENGTHS
For injection: 300 mg of trilaciclib as a lyophilized cake in a single-dose vial.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Trilacicilib in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Trilacicilib in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Trilacicilib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Trilacicilib in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Trilacicilib in pediatric patients.
Contraindications
- COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis
Warnings
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.
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)].
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.
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
Clinical Trials Experience
There is limited information regarding Trilacicilib Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Trilacicilib Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Trilacicilib Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Trilacicilib in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Trilacicilib in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Trilacicilib during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Trilacicilib in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Trilacicilib in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Trilacicilib in geriatric settings.
Gender
There is no FDA guidance on the use of Trilacicilib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Trilacicilib with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Trilacicilib in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Trilacicilib in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Trilacicilib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Trilacicilib in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Trilacicilib Administration in the drug label.
Monitoring
There is limited information regarding Trilacicilib Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Trilacicilib and IV administrations.
Overdosage
There is limited information regarding Trilacicilib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Trilacicilib Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Trilacicilib Mechanism of Action in the drug label.
Structure
There is limited information regarding Trilacicilib Structure in the drug label.
Pharmacodynamics
There is limited information regarding Trilacicilib Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Trilacicilib Pharmacokinetics in the drug label.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Carcinogenesis studies have not been conducted with trilaciclib.
- Trilaciclib was negative for mutagenic potential in a bacterial reverse mutation (Ames) assay and negative for clastogenic potential in an in vitro histone H2AX phosphorylation assay in primary human fibroblasts. Trilaciclib increased the frequency of micronucleus formation in human lymphocytes in vitro. Clastogenic potential of trilaciclib was not assessed in vivo.
- Fertility studies have not been performed to evaluate the effects of trilaciclib. Treatment with trilaciclib in female rats and dogs resulted in reductions in mean ovary and uterus weights at clinically relevant exposures, which were reversible after a two-week drug-free recovery period.
Clinical Studies
- The efficacy of COSELA was established in three randomized, double-blind, placebo-controlled trials in patients with extensive stage-small cell lung cancer (ES-SCLC). Study 1 (G1T28-05; NCT03041311) enrolled adult patients receiving carboplatin, etoposide, and atezolizumab for newly diagnosed ES-SCLC. Study 2 (G1T28-02; NCT02499770) enrolled adult patients receiving etoposide/carboplatin for newly diagnosed ES-SCLC. Study 3 (G1T28-03; NCT02514447) enrolled adult patients receiving topotecan for previously treated ES-SCLC.
- During Cycle 1, all three studies prohibited primary prophylactic granulocyte-colony stimulating factor (G-CSF) and erythropoiesis-stimulating agent (ESA) use. Both ESAs and prophylactic G-CSF were allowed from Cycle 2 onwards as clinically indicated. Therapeutic G-CSF, RBC, and platelet transfusions were allowed at any time during the studies as clinically indicated.
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) was a 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.
- A total of 107 patients were randomized to receive COSELA (n=54) or placebo (n=53) prior to administration of E/P/A; patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1 vs 2) and the presence of brain metastases. Carboplatin (AUC 5) and atezolizumab (1200 mg) were administered on Day 1 and etoposide (100 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1, 2, and 3 of a 21-day cycle for a maximum of 4 cycles (induction). After induction, maintenance atezolizumab (1200 mg) monotherapy on Day 1 of a 21-day cycle continued until disease progression or unacceptable toxicity. COSELA was not administered during maintenance.
- The study population characteristics were: median age 64 years (range: 45 to 83); 70% male; 97% white; 14% ECOG performance status 2; 28% with a history of brain metastases; 38% current smokers; 46% lactate dehydrogenase (LDH) >ULN.
- The mean relative dose intensities (RDIs) for E/P/A in patients receiving COSELA were 93%, 95%, and 93%, respectively. The mean RDIs for E/P/A in patients receiving placebo were 88%, 89%, and 91%, respectively. Dose reductions of carboplatin occurred in 2% of patients receiving COSELA and in 25% of patients receiving placebo; dose reductions of etoposide occurred in 6% of patients receiving COSELA and in 26% of patients receiving placebo. No dose reduction was allowed for COSELA or atezolizumab.
- The study demonstrated a statistically significantly shorter duration of severe neutropenia (DSN) in Cycle 1 (0 vs 4 days) and a lower proportion of patients with severe neutropenia (SN) (2% vs 49%) in patients receiving COSELA compared with placebo (TABLE 5). Nineteen percent of patients receiving COSELA had Grade 3 or 4 decreased hemoglobin compared with 28% of patients receiving placebo (adjusted relative risk 0.663 [95% CI: 0.336, 1.310]). The rate of RBC transfusions over time was 1.7/100 weeks for patients receiving COSELA and 2.6/100 weeks for patients receiving placebo (adjusted relative risk was not estimable). Six percent of patients receiving COSELA received erythropoiesis-stimulating agents (ESAs) compared with 11% of patients receiving placebo (adjusted relative risk 0.529 [95% CI: 0.145, 1.927]).
- ANCOVA=analysis of covariance; CI=confidence interval; DSN=duration of severe neutropenia; G-CSF=granulocyte colony-stimulating factor; N=total number of patients in each treatment group; RBC=red blood cell; SD=standard deviation
- The following statistical models were used to assess treatment effects: non-parametric ANCOVA (DSN in Cycle 1); modified Poisson regression (occurrence of SN and RBC transfusion on/after 5 weeks); negative binomial regression (number of all-cause dose reductions). All models included the following as covariates: ECOG status, presence of brain metastases, and the corresponding baseline laboratory values.
- One-sided adjusted p-value obtained from a Hochberg-based gatekeeping procedure.
Study 2: COSELA Prior to Etoposide and Carboplatin
Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy
- Study 2 (G1T28-02) was a randomized (1:1), double-blind, placebo-controlled evaluation of COSELA or placebo administered prior to treatment with etoposide and carboplatin (E/P) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. A total of 77 patients were randomized to COSELA (n=39) or placebo (n=38) and stratified by ECOG performance status (0 to 1 vs 2). Carboplatin (AUC 5) was administered on Day 1 and etoposide (100 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1, 2, and 3 of a 21-day cycle until disease progression or unacceptable toxicity.
- Ten percent of patients receiving COSELA had Grade 3 or 4 decreased hemoglobin compared with 18% of patients receiving placebo. The rate of RBC transfusions over time was 0.5/100 weeks for patients receiving COSELA and 1.9/100 weeks for patients receiving placebo. Three percent of patients receiving COSELA received ESAs compared with 5% of patients receiving placebo.
- DSN=duration of severe neutropenia; G-CSF=granulocyte colony-stimulating factor; N=total number of patients in each treatment group; RBC=red blood cell; SD=standard deviation
Study 3: COSELA Prior to Topotecan
Patients with ES-SCLC previously treated with chemotherapy
- Study 3 (G1T28-03) included a randomized, double-blind, placebo-controlled evaluation of COSELA or placebo administered prior to topotecan in patients with ES-SCLC previously treated with chemotherapy. A total of 61 patients were randomized to COSELA (n=32) or placebo (n=29). Patients were stratified by ECOG performance status (0 to 1 vs 2) and sensitivity to first-line treatment. Topotecan (1.5 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1-5 of a 21-day cycle. Treatment was administered until disease progression or unacceptable toxicity.
- Thirty-eight percent of patients receiving COSELA had Grade 3 or 4 decreased hemoglobin compared with 59% of patients receiving placebo. The rate of RBC transfusions over time was 2.6/100 weeks for patients receiving COSELA and 6.3/100 weeks for patients receiving placebo. Three percent of patients receiving COSELA received ESAs compared with 21% of patients receiving placebo.
DSN=duration of severe neutropenia; G-CSF=granulocyte colony-stimulating factor; N=total number of patients in each treatment group; RBC=red blood cell; SD=standard deviation
Patient Subgroups
- Treatment efficacy was examined across different subgroups, including those quantifying the risk of febrile neutropenia, anemia, and RBC transfusions; results were consistent across subgroups.
How Supplied
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.
Storage
- 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.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Injection-Site Reactions, Including Phlebitis and Thrombophlebitis
- Inform patients of the signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis. Advise patients to contact their healthcare provider immediately for signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis.
Acute Drug Hypersensitivity Reactions
- Advise patients to contact their healthcare provider immediately for signs and symptoms of acute drug hypersensitivity reactions including facial, eye, and tongue edema, urticaria, pruritis, and anaphylactic reactions.
Interstitial Lung Disease/Pneumonitis
- Advise patients to immediately report new or worsening respiratory symptoms.
Embryo-Fetal Toxicity
- Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
- Advise females of reproductive potential to use effective contraception during treatment with COSELA and for at least 3 weeks after the final dose.
Lactation
- Advise women not to breastfeed during treatment with COSELA and for at least 3 weeks after the final dose of COSELA .
Drug Interactions
- Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.
Precautions with Alcohol
Alcohol-Trilacicilib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
COSELA
Look-Alike Drug Names
There is limited information regarding Trilacicilib Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.