On February 12, 2021, the U.S. Food and Drug Administration approved trilaciclib (CoselaTM), a parenteral inhibitor of cyclin-dependent kinase (CDK), to prevent myelosuppression when administered prior to chemotherapy administration. The approval is currently limited to the use of trilaciclib before treatment with platinum- and etoposide-containing regimens and topotecan-containing regimens for treatment of extensive-stage small cell lung cancer.
CDK4/6 inhibitor, targeted therapy kinase inhibitor, chemoprotectant
Mechanism of Action
Trilaciclib is a transient inhibitor of CDK 4 and 6 in cells, an activity that the proliferation of hematopoietic stem cells and progenitor cells depends on. It temporarily stops the reproduction of stem cells to mitigate the impact of myelosuppressive chemotherapy. With fewer stem cells reproducing during chemotherapy administration, hematopoietic stem cells and progenitor cells are protected from chemotherapy damage.
Trilaciclib is indicated for use in adult patients to decrease the incidence of chemotherapy-induced myelosuppression following platinum- and etoposide-containing regimens or topotecan-containing regimens for extensive-stage small cell lung cancer. It must be administered prior to chemotherapy.
240 mg/m2 given as a 30-minute IV infusion prior to chemotherapy administration on each day of treatment
Trilaciclib is administered through a 0.2- or 0.22-micron inline filter and should be completed within four hours prior to the initiation of chemotherapy.
Do not use a polytetrafluorethylene inline filter.
Do not coadminister with other drugs in the same infusion line, peripheral or central.
After infusion is complete, flush with at least 20 ml of sterile 0.9% sodium chloride or 5% dextrose solution.
Trilaciclib is contraindicated in patients with a history of serious hypersensitivity reactions to the drug. Monitor for signs and symptoms of injection site reactions. Severe phlebitis and thrombophlebitis can occur. Permanently discontinue for grade 3 or 4 reactions.
Hypersensitivity reactions may occur, including anaphylaxis. Monitor for face, eye, and tongue edema; urticaria; pruritus; and anaphylactic reactions. Hold trilaciclib for moderate reactions, and permanently discontinue for severe reactions.
Patients may develop interstitial lung disease or pneumonitis, and trilaciclib is associated with embryo-fetal toxicity.
Monitor for signs and symptoms of injection site reactions, including severe phlebitis and thrombophlebitis. For grade 1 reactions, interrupt or slow the infusion. If using a saline flush, consider changing to 5% dextrose in water for subsequent infusions. For grade 2 reactions, consider changing the fluid, stop the infusion, and rotate the infusion site or give centrally. Permanently discontinue with grade 3 or 4 reactions (e.g., ulceration, necrosis, severe tissue damage, life-threatening consequences). Watch for hypersensitivity reactions.
Monitor for signs of pneumonitis. Hold the drug for grade 1 symptoms, and permanently discontinue it for grade 2 or higher. Advise patients about the risk of embryo-fetal toxicity.
Teach patients about the signs and symptoms of injection site reactions and when and how to notify their nurse or others in the healthcare team. Immediately report any signs and symptoms of acute drug hypersensitivity reactions, including facial, eye, and tongue edema; urticaria; pruritis; and anaphylactic reactions. Monitor for and report new or worsening respiratory symptoms.
Discuss the potential risk to a fetus, using effective contraception, and avoiding breastfeeding during treatment with trilaciclib and for at least three weeks after the final dose or longer depending on the embryo-fetal toxicity potential of the concurrent chemotherapy. Have them inform their healthcare provider of a known or suspected pregnancy.
Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.
No differences in safety or effectiveness were noted in patients older than 65.
Trilaciclib is considered a hazardous drug because of its reproductive risk, as is the chemotherapy used in the regimen. Both agents can cause fetal harm and potentially impair fertility.