Trilaciclib
What is Trilacicilib?[edit | edit source]
Trilacicilib (COSELA) is a kinase inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression.
What are the uses of this medicine?[edit | edit source]
This medicine is used 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).
How does this medicine work?[edit | edit source]
- 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.
Who Should Not Use this medicine ?[edit | edit source]
This medicine cannot be used in patients with:
- with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis.
What drug interactions can this medicine cause?[edit | edit source]
- Avoid concomitant use with certain OCT2, MATE1, and MATE-2K substrates (e.g., dofetilide, dalfampridine, and cisplatin) where minimal concentration changes may lead to serious or life-threatening toxicities.
Is this medicine FDA approved?[edit | edit source]
- It was approved for use in the United States in 2021.
How should this medicine be used?[edit | edit source]
Recommended Dosage
- The recommended dose of COSELA is 240 mg/m2 per dose as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy on each day chemotherapy is administered.
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.
What are the dosage forms and brand names of this medicine?[edit | edit source]
This medicine is available in fallowing doasage form:
- As injection: 300 mg of trilaciclib as a lyophilized cake in a single-dose vial.
This medicine is available in fallowing brand namesː
- COSELA
What side effects can this medication cause?[edit | edit source]
The most common side effects of this medicine include:
- fatigue
- hypocalcemia
- hypokalemia
- hypophosphatemia
- aspartate aminotransferase increased
- headache
- pneumonia
What special precautions should I follow?[edit | edit source]
- Monitor for signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis during infusion. Stop infusion and permanently discontinue COSELA for severe or life-threatening reactions.
- Monitor for signs and symptoms of acute drug hypersensitivity reactions, including edema (facial, eye, and tongue), urticaria, pruritus, and anaphylactic reactions. Withhold COSELA for moderate reactions, and permanently
- Patients treated with this medicine should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Interrupt and evaluate patients with new or worsening symptoms suspected to be due to ILD/pneumonitis. Permanently discontinue COSELA in patients with recurrent symptomatic or severe/life-threatening ILD/pneumonitis.
- This medicine Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
What to do in case of emergency/overdose?[edit | edit source]
- In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.
- Overdose related information is also available online at poisonhelp.org/help.
- In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
Can this medicine be used in pregnancy?[edit | edit source]
- 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.
Can this medicine be used in children?[edit | edit source]
- Safety and effectiveness in pediatric patients have not been established.
What should I know about storage and disposal of this medication?[edit | edit source]
- 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).
- The vial stopper is not made with natural rubber latex.
Summary[edit | edit source]
Trilaciclib is a small molecule, competitive inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), with potential antineoplastic and chemoprotective activities. Upon intravenous administration, trilaciclib binds to and inhibits the activity of CDK4/6, thereby blocking the phosphorylation of the retinoblastoma protein (Rb) in early G1. This prevents G1/S phase transition, causes cell cycle arrest in the G1 phase, induces apoptosis, and inhibits the proliferation of CDK4/6-overexpressing tumor cells. In patients with CDK4/6-independent tumor cells, G1T28 may protect against multi-lineage chemotherapy-induced myelosuppression (CIM) by transiently and reversibly inducing G1 cell cycle arrest in hematopoietic stem and progenitor cells (HSPCs) and preventing transition to the S phase. This protects all hematopoietic lineages, including red blood cells, platelets, neutrophils and lymphocytes, from the DNA-damaging effects of certain chemotherapeutics and preserves the function of the bone marrow and the immune system. CDKs are serine/threonine kinases involved in the regulation of the cell cycle and may be overexpressed in certain cancer cell types. HSPCs are dependent upon CDK4/6 for proliferation.
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