Trilaciclib

• Approved Indications:
• Prophylactic use to reduce the incidence of chemotherapy-induced myelosuppression (particularly neutropenia) in adult patients receiving certain myelosuppressive chemotherapy regimens for extensive-stage small cell lung cancer (ES-SCLC).
• Off-label Uses:
• Investigational use in other malignancies undergoing myelosuppressive chemotherapy to protect hematopoietic stem and progenitor cells.
• Potential future use to reduce chemotherapy-induced bone marrow toxicity in other cancers under clinical evaluation.

• Adults:
• Administered intravenously at a dose of 240 mg/m² given as a 30-minute infusion within 4 hours prior to the start of chemotherapy on each chemotherapy treatment day.
• Dosing schedules correspond with the patient’s chemotherapy regimen.
• Pediatrics:
• Safety and efficacy not established in patients under 18 years.
• Elderly:
• No dose adjustment recommended solely based on age; monitor for tolerability.
• Special Populations:
• No specific dosage adjustment recommended for mild to moderate renal or hepatic impairment; data limited for severe impairment.
• Administration Notes:
• Administer intravenously as a separate infusion before chemotherapy.
• Avoid mixing with other drugs; administer through a dedicated intravenous line if possible.

Trilaciclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). By transiently arresting hematopoietic stem and progenitor cells (HSPCs) in the G1 phase of the cell cycle, trilaciclib protects these cells from chemotherapy-induced cytotoxicity, which mainly targets rapidly dividing cells. This mechanism helps to preserve bone marrow function and reduce chemotherapy-induced myelosuppression, leading to decreased rates of neutropenia, anemia, and thrombocytopenia.

• Absorption: Administered intravenously; systemic availability is 100%.
• Distribution: Exhibits moderate plasma protein binding (~70%).
• Metabolism: Primarily metabolized by CYP3A4 in the liver.
• Elimination: Eliminated mainly via feces; minor renal excretion.
• Half-life: Approximately 14 hours, supporting once-per-chemotherapy-cycle dosing.
• Onset of Action: Transient cell cycle arrest occurs rapidly post-infusion, protecting bone marrow during chemotherapy exposure.

• Pregnancy:
• No adequate human data; animal studies indicate potential fetal harm. Use only if benefit justifies risk.
• Lactation:
• Unknown if excreted in human milk. Breastfeeding not recommended during treatment.

• Primary Class: CDK4/6 inhibitor
• Subclass: Myelopreservation agent / Chemoprotective agent

• Known hypersensitivity to trilaciclib or any formulation components.
• Severe hepatic impairment (use with caution).
• Concurrent use with strong CYP3A4 inhibitors or inducers requires caution but not absolute contraindication.

• Monitor for potential hematologic adverse effects despite prophylaxis.
• Use cautiously in patients with active infections due to risk of myelosuppression.
• Monitor liver function tests due to hepatic metabolism.
• Not a substitute for standard supportive measures (e.g., growth factors, transfusions).
• Early signs of severe adverse reactions such as hypersensitivity or infusion reactions require immediate attention.

• Common:
• Fatigue, nausea, decreased appetite.
• Electrolyte abnormalities (e.g., hypokalemia).
• Headache.
• Hematologic:
• Generally reduces severity of neutropenia but possible mild anemia or thrombocytopenia may occur.
• Serious/Rare:
• Hypersensitivity reactions.
• Infusion-related reactions (rare).
• Dose-Dependence & Timing:
• Most side effects occur within days after infusion; severity is generally mild to moderate.

• CYP3A4 metabolism:
• Strong CYP3A4 inhibitors (e.g., ketoconazole) may increase trilaciclib plasma levels, requiring caution.
• Strong CYP3A4 inducers (e.g., rifampin) may reduce trilaciclib efficacy.
• No significant interactions with chemotherapy agents; however, monitor clinical status.
• Avoid grapefruit or grapefruit juice during treatment.

• FDA granted accelerated approval for trilaciclib to reduce chemotherapy-induced myelosuppression in ES-SCLC patients receiving specific regimens.
• Updated oncology guidelines incorporate trilaciclib as a supportive care option for myelopreservation in ES-SCLC.
• Ongoing clinical trials exploring expanded indications and combination therapies.
• Emphasis on monitoring hematologic parameters to optimize dosing and manage toxicities.

• Store at 2°C to 8°C (36°F to 46°F) in a refrigerator.
• Protect from light; keep vial in original carton until use.
• Do not freeze.
• Use immediately after reconstitution as per manufacturer instructions.
• Handle aseptically; do not shake vigorously.