Trilaciclib is indicated to reduce the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or a topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

Trilaciclib is a transient inhibitor of CDK 4 and 6. Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are responsible for producing neutrophils, red blood cells, and platelets, and their proliferation depends on CDK4/6 activity.

Bone Marrow: Trilaciclib showed dose-dependent inhibition of lymphocyte proliferation (CD45+/CD3+) in healthy subjects. It increased G1 phase cell arrest in various bone marrow progenitor cells up to 32 hours after infusion. Partial recovery of bone marrow activity was observed by 32 hours post-dose, with resumption of cell proliferation. This temporary G1 arrest of hematopoietic stem cells contributes to its myeloprotective effect.

Cardiac Electrophysiology: Trilaciclib is associated with a dose-dependent and delayed increase in QTc interval. The exact mechanism is unknown. At the clinical dose of 240 mg/m², no clinically significant QTc prolongation (>10 msec) was observed, although higher doses showed QTc prolongation.

The recommended dose of Trilaciclib is 240 mg/m² per dose. It should be administered as a 30-minute intravenous infusion, completed within 4 hours before the start of chemotherapy on each chemotherapy day. The interval between consecutive doses on sequential days should not exceed 28 hours.

Missed treatment session(s): If a dose of Trilaciclib is missed, chemotherapy should also be withheld on that day. Both Trilaciclib and chemotherapy may be resumed on the next scheduled chemotherapy day.

Discontinuation of treatment: If Trilaciclib is discontinued, chemotherapy should not be restarted until at least 96 hours after the last dose of Trilaciclib.

Preparation and administration: Trilaciclib must be reconstituted and further diluted before intravenous infusion using aseptic technique. The solution should be visually inspected for particulate matter and discoloration prior to administration.

Administer diluted Trilaciclib solution as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy. Diluted Trilaciclib 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 Trilaciclib solution with a polytetrafluorethylene (PTFE) in-line filter. PTFE in-line filters are not compatible with diluted Trilaciclib 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 Trilaciclib 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.

Trilaciclib is an inhibitor of OCT2, MATE1, and MATE-2K transporters. Co-administration may increase plasma or renal exposure of drugs that are substrates of these transporters, such as dofetilide, dalfampridine, and cisplatin.

Trilaciclib is contraindicated in patients with a history of severe hypersensitivity reactions to the drug, including anaphylaxis.

Common adverse reactions include 

• injection-site reactions (phlebitis and thrombophlebitis), 
• acute hypersensitivity reactions, 
• and interstitial lung disease (ILD)/pneumonitis.

Based on its mechanism of action, Trilaciclib may cause fetal harm when used during pregnancy. There are no sufficient human or animal data. Pregnant women should be informed of potential risks. Breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose due to potential serious adverse effects in infants.

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis: Trilaciclib administration may lead to injection-site reactions such as phlebitis and thrombophlebitis. In clinical studies, these reactions occurred in 56 (21%) of 272 patients, including Grade 2 (10%) and Grade 3 (0.4%) events. Median onset was 15 days from treatment initiation and 1 day from the previous dose. Median duration was 1 day. Most cases (88%) resolved, while 1% required discontinuation. Patients should be monitored for pain, redness, and swelling at the infusion site. Mild to moderate reactions may be managed with flushing using sterile saline or dextrose solution. Severe or life-threatening reactions require stopping the infusion and permanent discontinuation of Trilaciclib.

Acute Drug Hypersensitivity Reactions: Trilaciclib may cause acute hypersensitivity reactions such as facial edema, urticaria, and anaphylaxis. In trials, these occurred in 16 (6%) of 272 patients, including Grade 2 reactions (2%). One case of Grade 2 anaphylaxis resolved with epinephrine. Most cases resolved within a median of 6 days. Patients should be monitored for signs of allergic reactions, including swelling, itching, and anaphylaxis. Moderate reactions require temporary interruption, while severe reactions require permanent discontinuation.

Interstitial Lung Disease/Pneumonitis: Serious or fatal interstitial lung disease (ILD) and pneumonitis have been reported with CDK4/6 inhibitors, including Trilaciclib. In clinical trials, 1 patient (0.4%) developed Grade 3 ILD/pneumonitis. Patients should be monitored for respiratory symptoms such as cough, dyspnea, and hypoxia. Severe or recurrent cases require permanent discontinuation of treatment.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trilaciclib may cause fetal harm when administered during pregnancy. Females of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose.

Symptoms of overdose may include drowsiness, disorientation, and extrapyramidal reactions. Management is mainly supportive. Anticholinergic drugs, antiparkinsonian agents, or antihistamines with anticholinergic properties may help control extrapyramidal symptoms. Symptoms are usually self-limiting and resolve within 24 hours.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.