Brand name: Cosela
Drug class: Protective Agents
Chemical name: 4-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1'-cyclohexane]-10-one
Molecular formula: C₂₄H₃₀N₈O
CAS number: 1374743-00-6

Medically reviewed by Drugs.com on Mar 6, 2023. Written by ASHP.

Introduction

Trilaciclib dihydrochloride is a protective agent.

Uses for Trilaciclib

Trilaciclib dihydrochloride has the following uses:

Trilaciclib dihydrochloride is a kinase inhibitor indicated 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.

Trilaciclib Dosage and Administration

General

Trilaciclib dihydrochloride is available in the following dosage form(s) and strength(s):

For injection: 300 mg of trilaciclib as a lyophilized cake in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Trilaciclib dihydrochloride is for intravenous use only.

The recommended dose of trilaciclib dihydrochloride is 240 mg/m² as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy on each day chemotherapy is administered.

See full prescribing information for instructions on preparation and administration.

Cautions for Trilaciclib

Contraindications

Patients with a history of serious hypersensitivity reactions to trilaciclib dihydrochloride.

Warnings/Precautions

Injection-site Reactions, Including Phlebitis and Thrombophlebitis

Trilaciclib dihydrochloride administration can cause injection-site reactions including phlebitis and thrombophlebitis. Injection-site reactions including phlebitis and thrombophlebitis occurred in 56 (21%) of 272 patients receiving trilaciclib dihydrochloride in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. The median time to onset from start of trilaciclib dihydrochloride was 15 days (range 1 to 542) and from the preceding dose of trilaciclib dihydrochloride was 1 day (1 to 15). The median duration was 1 day (range 1 to 151 for the resolved cases). Injection-site reactions including phlebitis and thrombophlebitis resolved in 49 (88%) of the 56 patients and led to discontinuation of treatment in 3 (1%) of the 272 patients.

Monitor patients for signs and symptoms of injection-site reactions, phlebitis, and thrombophlebitis, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% sodium chloride injection or 5% dextrose injection after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue trilaciclib dihydrochloride.

Acute Drug Hypersensitivity Reactions

Trilaciclib dihydrochloride administration can cause acute drug hypersensitivity reactions, including facial edema and urticaria. Acute drug hypersensitivity reactions occurred in 16 (6%) of 272 patients receiving trilaciclib dihydrochloride in clinical trials, including Grade 2 reactions (2%). One patient experienced a Grade 2 anaphylactic reaction 4 days after receiving trilaciclib dihydrochloride, which resolved with epinephrine, and treatment with trilaciclib dihydrochloride was continued. The median time to onset from start of trilaciclib dihydrochloride was 77 days (range 2 to 256) and from the preceding dose of trilaciclib dihydrochloride was 1 day (range 1 to 28). The median duration was 6 days (range 1 to 69 for the resolved cases). Acute drug hypersensitivity reactions resolved in 12 (75%) of the 16 patients.

Monitor patients for signs and symptoms of acute drug hypersensitivity reactions including facial, eye, and tongue edema, urticaria, pruritus, and anaphylactic reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold trilaciclib dihydrochloride until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue trilaciclib dihydrochloride.

Interstitial Lung Disease/Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK) 4/6 inhibitors, the same drug class as trilaciclib dihydrochloride. ILD/pneumonitis occurred in 1 (0.4%) of 272 patients receiving trilaciclib dihydrochloride in clinical trials. The adverse reaction was Grade 3 and was reported 2 months after discontinuing trilaciclib dihydrochloride in a patient receiving a confounding medication. The adverse reaction did not resolve.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis such as cough, dyspnea, and hypoxia. For recurrent moderate (Grade 2) ILD/pneumonitis, permanently discontinue trilaciclib dihydrochloride. For severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue trilaciclib dihydrochloride.

Embryofetal Toxicity

Based on its mechanism of action, trilaciclib dihydrochloride can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with trilaciclib dihydrochloride and for at least 3 weeks after the final dose.

Specific Populations

Pregnancy

Risk Summary: Based on its mechanism of action, trilaciclib dihydrochloride can cause fetal harm when administered to a pregnant woman. There are no available human or animal data on trilaciclib dihydrochloride use to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. However, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the United States general population.

Lactation

Risk Summary: There are no data on the presence of trilaciclib in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise lactating women to not breastfeed while taking trilaciclib dihydrochloride and for at least 3 weeks after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action, trilaciclib dihydrochloride can cause fetal harm if administered to a pregnant woman. Pregnancy testing is recommended for females of reproductive potential prior to initiating trilaciclib dihydrochloride.

Trilaciclib dihydrochloride can cause fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with trilaciclib dihydrochloride and for at least 3 weeks after the final dose.

No studies have been performed in humans to evaluate the effects of trilaciclib dihydrochloride on fertility in either sex.

Based on animal toxicology studies, trilaciclib dihydrochloride may impair fertility in females of reproductive potential.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In the pooled efficacy dataset from Studies 1, 2, and 3, 46% of 123 patients randomized to trilaciclib dihydrochloride were ≥65 years of age, and 49% of 119 patients randomized to placebo were ≥65 years of age. No overall differences in safety or effectiveness of trilaciclib dihydrochloride were observed between these patients and younger patients.

Hepatic Impairment

Use of trilaciclib dihydrochloride is not recommended in patients with moderate or severe hepatic impairment. No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN, or total bilirubin >1.0 to 1.5 × ULN, irrespective of AST). The pharmacokinetics of trilaciclib dihydrochloride have not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN, irrespective of AST).

Common Adverse Effects

The most common adverse reactions (≥10% of patients with ≥2% difference in incidence compared to placebo) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Certain organic cation transporter (OCT) 2, multidrug and toxin extrusion (MATE) transporter 1, and MATE-2K substrates: Avoid concomitant use with certain OCT2, MATE1, and MATE-2K substrates where minimal concentration changes may lead to serious or life-threatening toxicities.

Actions

Mechanism of Action

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, erythrocytes, and platelets. HSPC proliferation is dependent on CDK4/6 activity.

Advice to Patients

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis

Inform patients of the signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis. Advise patients to contact their healthcare provider immediately for signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis.

Acute Drug Hypersensitivity Reactions

Advise patients to contact their healthcare provider immediately for signs and symptoms of acute drug hypersensitivity reactions including facial, eye, and tongue edema, urticaria, pruritis, and anaphylactic reactions.

Interstitial Lung Disease/Pneumonitis

Advise patients to immediately report new or worsening respiratory symptoms.

Embryofetal Toxicity

Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.

Advise females of reproductive potential to use effective contraception during treatment with trilaciclib dihydrochloride and for at least 3 weeks after the final dose.

Lactation

Advise women not to breastfeed during treatment with trilaciclib dihydrochloride and for at least 3 weeks after the final dose of trilaciclib dihydrochloride.

Drug Interactions

Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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