trilaciclib

Action and Spectrum

Actions and Spectrum:  

Action: 

The primary action of trilaciclib is its ability to inhibit the CDK4/6 enzymes. CDK4/6 enzymes play a crucial role in cell cycle progression by promoting the transition from the G1 phase to the S phase, where DNA replication occurs. By inhibiting CDK4/6, trilaciclib blocks this transition, leading to cell cycle arrest in the G1 phase. This cell cycle arrest can help protect healthy cells, including hematopoietic stem and progenitor cells in the bone marrow, from the damaging effects of chemotherapy. 

Spectrum: 

The spectrum of trilaciclib’s activity is mainly focused on reducing myelosuppression. Myelosuppression is a common side effect of chemotherapy, characterized by a decrease in the production of blood cells, including white blood cells, red blood cells, and platelets. trilaciclib helps preserve the function of hematopoietic stem and progenitor cells in the bone marrow, reducing the severity and duration of myelosuppression caused by chemotherapy. This can lead to a decrease in the frequency of infections, transfusions, and other complications associated with myelosuppression. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

All grades 

Headache (13%) 

AST increased (17%) 

Hypophosphatemia (21%) 

Hypokalemia (22%) 

Hypocalcemia (24%) 

Fatigue (34%)  

Grade ≥3 

placebo (34%) 

Anemia (16%) 

placebo (33%) 

Thrombocytopenia (18%) 

placebo (69%) 

Neutropenia (32%) 

1-10% 

All grades 

Hyperglycemia (6%) 

Thrombosis (7%) 

Upper abdominal pain (7%) 

Peripheral edema (7%) 

Infusion-related reaction (8%) 

Rash (9%) 

Pneumonia (10%) 

Grade ≥3 H4 

Asthenia (2%) 

Hyperglycemia (2%) 

Respiratory failure (≥2%) 

Hemorrhage (>3%) 

placebo (9%) 

Febrile neutropenia (3%) 

Thrombosis (3%) 

Fatigue (3%) 

placebo (17%) 

Leukopenia (4%) 

Hypokalemia (6%) 

Pneumonia (7%) 

Hypophosphatemia (7%) 

<1% 

Grade ≥3 

Acute respiratory failure (fatal) 

Lymphopenia 

Myositis 

Hemoptysis 

Ischemic stroke 

Cerebrovascular accident 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: trilaciclib should not be used in individuals who have a known hypersensitivity or allergic reaction to trilaciclib or any of its components. 

Severe liver impairment: Since trilaciclib is primarily metabolized in the liver, individuals with severe liver impairment may be at an increased risk of experiencing adverse effects. Therefore, trilaciclib should be used with caution or avoided in patients with severe liver dysfunction. 

Pregnancy and breast-feeding: The safety of trilaciclib during pregnancy and lactation has not been established. It is important to discuss the risks and benefits with a healthcare professional before using trilaciclib in pregnant or breastfeeding individuals. 

Concomitant use with certain medications: trilaciclib may interact with other medications, including strong CYP3A inhibitors or inducers. It is crucial to notify your healthcare professional about the complete list of medications you are currently using to prevent any potential complications arising from drug interactions. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

trilaciclib is a small molecule drug that belongs to the class of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. It is primarily used as a myelopreservation agent in patients undergoing chemotherapy. 

Pharmacodynamics:  

trilaciclib exerts its pharmacological effects by inhibiting CDK4/6 enzymes. CDK4/6 are protein kinases that regulate the cell cycle by promoting cell progression from the G1 phase to the S phase. By inhibiting CDK4/6, trilaciclib slows down the proliferation of hematopoietic stem and progenitor cells (HSPCs) and prevents excessive replication and differentiation. This protective effect on HSPCs helps preserve the bone marrow microenvironment and mitigates chemotherapy-induced myelosuppression.   

Pharmacokinetics: 

Absorption 

Since trilaciclib is administered intravenously, it achieves complete bioavailability. 

Distribution 

trilaciclib has a relatively large volume of distribution, suggesting extensive tissue distribution. The plasma protein binding of trilaciclib is moderate. 

Metabolism 

trilaciclib is primarily metabolized by cytochrome P450 (CYP) enzymes, particularly CYP3A4. The major metabolites formed are pharmacologically inactive. 

Excretion and Elimination 

trilaciclib and its metabolites are predominantly excreted in the feces, with a minor fraction being eliminated in the urine. 

Adminstartion

Administration:  

trilaciclib is administered intravenously (IV) and is usually given as a short infusion before the start of chemotherapy. The exact dosage and schedule may vary depending on the specific chemotherapy regimen being used and the individual patient’s condition. Therefore, it is crucial to follow the instructions given by the prescribing healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trilaciclib 

Why do we use trilaciclib?  

Chemotherapy-induced myelosuppression: trilaciclib is administered to patients undergoing chemotherapy to help protect their bone marrow and hematopoietic stem cells from the toxic effects of chemotherapy. By preserving these cells, trilaciclib aims to reduce the severity and duration of myelosuppression, which is the decrease in blood cell production caused by chemotherapy. This can help prevent or reduce complications such as anemia, infections, and the need for blood transfusions. 

Small cell lung cancer (SCLC): trilaciclib has shown promising results in patients with SCLC. Clinical trials have demonstrated that administering trilaciclib prior to chemotherapy can reduce the occurrence and severity of myelosuppression associated with SCLC treatment. This enables patients to better tolerate chemotherapy and potentially receive more effective treatment regimens. 

Other solid tumors: Apart from SCLC, trilaciclib has also been investigated in other types of solid tumors, including metastatic triple-negative breast cancer and bladder cancer. The aim is to assess its potential benefits in reducing chemotherapy-induced myelosuppression and improving treatment outcomes.