Overview
11 DESCRIPTION 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 C 24 H 30 N 8 O•2HCl, a molecular...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Bone Marrow Trilaciclib exhibited dose-dependent inhibition of CD45+/CD3+ lymphocyte proliferation following administration of single-dose COSELA 96 or 192 mg/m 2 (0.4 or 0.8 times the approved recommended dose) in healthy subjects. Trilaciclib increased the percentage of cells arrested in G1 up to 32 hours post-infusion for all bone marrow progenitor subsets evaluated (hematopoietic stem cell/multipotent progenitor, oligopotent progenitor, monocyte lineage, granulocyte lineage, erythroid...
Indications
- 1 INDICATIONS AND USAGE 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 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. ( 1 )
Common Doses
- 240 mg
- 170 mg
- 300 mg
- 19.5 mL
Dosage
2 DOSAGE AND ADMINISTRATION COSELA is for intravenous use only. The recommended dose of COSELA is 240 mg/m 2 as a 30-minute intravenous infusion completed no more than 4 hours prior to the start of chemotherapy on each day chemotherapy is administered. ( 2.1 ) Reduce dose in patients with moderate or severe hepatic impairment. ( 2.2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.3 ) 2.1 Recommended Dosage The recommended dose of COSELA is 240 mg/m 2 per dose.
Contraindications
- 4 CONTRAINDICATIONS COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.2 )] . Patients with a history of serious hypersensitivity reactions to COSELA. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the label: Injection-Site Reactions, including phlebitis and thrombophlebitis [ s ee Warnings and Precautions ( 5.1 )] Acute Drug Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] ILD/Pneumonitis [see Warnings and Precautions ( 5.3 )] 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.
Interactions
- 7 DRUG INTERACTIONS Certain OCT2, MATE1, and MATE-2K substrates: Avoid concomitant use with certain OCT2, MATE1, and MATE-2K substrates where minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.1 ) 7.1 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) [see Clinical Pharmacology ( 12.3 )].