trilaciclib (Rx)

Brand and Other Names:Cosela
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized cake for reconstitution

  • 300mg (provided as trilaciclib dihydrochloride 349 mg)

Chemotherapy-Induced Myelosuppression

Indicated for adults with extensive-stage small cell lung cancer to reduce chemotherapy-induced myelosuppression when administered before platinum/etoposide-containing or topotecan-containing regimens

240 mg/m2/dose IV completed within 4 hr before chemotherapy on each day chemotherapy is administered

Interval between doses on sequential days should not be >28 hr

Dosage Modifications

Injection-site reactions

  • Includes phlebitis and thrombophlebitis
  • Grade 1
    • Tenderness with or without symptoms (eg, warmth, erythema, itching)
    • Interrupt or slow infusion
    • If diluent/flush was 0.9% NaCl, consider changing to D5W for subsequent infusions
  • Grade 2
    • Pain, lipodystrophy, edema, phlebitis
    • Interrupt infusion
    • If pain not severe, follow Grade 1; otherwise, stop infusion in extremity and rotate site of infusion to alternative extremity
    • If diluent/flush was 0.9% NaCl, consider changing to D5W for subsequent infusions
    • May also consider central access
  • Grade 3 or 4
    • Grade 3: Ulceration or necrosis, severe tissue damage; operative intervention indicated OR
    • Grade 4: Life-threatening consequences; urgent interventions indicated
    • Stop infusion and permanently discontinue

Acute drug hypersensitivity reactions

  • Grade 2
    • Moderate; minimal, local, or noninvasive intervention indicated; limiting activities of daily living (ADL)
    • Stop infusion and hold until recovery to Grade ≤1 or baseline, then consider resumption
    • If Grade 2 recurs, permanently discontinue
  • Grade 3 or 4
    • Grade 3: Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL OR
    • Grade 4: Life-threatening consequences; urgent intervention indicated
    • Permanently discontinue

Interstitial lung disease/pneumonitis

  • Grade 2 (symptomatic)
    • Hold until recover to Grade ≤1 or baseline
    • Consider resumption
  • Permanently discontinue
    • Grade 2 recurs
    • Grade 3: Severe symptoms; limiting self-care ADL; oxygen indicated
    • Grade 4: Life-threatening respiratory compromise; urgent intervention indicated (eg, tracheotomy or intubation)

Other toxicities

  • Hold until recovery to Grade ≤1 or baseline
    • Grade 3: Severe/medically significant but not immediately life-threatening; require hospitalization or prolonging hospital stay; disabling; limiting self-care ADL
    • Consider resumption
  • Permanently discontinue
    • Grade 3 recurs
    • Grade 4: Life-threatening consequences, urgent intervention indicated

Renal impairment

  • Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment necessary
  • Severe (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or dialysis: Not studied

Hepatic impairment

  • Mild (total bilirubin ≤ULN and AST >ULN OR total bilirubin 1-1.5x ULN and any AST): No dosage adjustment necessary
  • Moderate-to-severe (total bilirubin >1.5x ULN and any AST): Not studied

Dosing Considerations

Females of reproductive potential: Pregnancy test recommended before initiation

Safety and efficacy not established

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Interactions

Interaction Checker

and trilaciclib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All grades

            • Fatigue (34%)
            • Hypocalcemia (24%)
            • Hypokalemia (22%)
            • Hypophosphatemia (21%)
            • AST increased (17%)
            • Headache (13%)

            Grade ≥3

            • Neutropenia (32%); placebo (69%)
            • Thrombocytopenia (18%); placebo (33%)
            • Anemia (16%); placebo (34%)

            1-10%

            All grades

            Pneumonia (10%)

            • Rash (9%)
            • Infusion-related reaction (8%)
            • Peripheral edema (7%)
            • Upper abdominal pain (7%)
            • Thrombosis (7%)
            • Hyperglycemia (6%)
            • Grade ≥3 H4
            • Hypophosphatemia (7%)
            • Pneumonia (7%)
            • Hypokalemia (6%)
            • Leukopenia (4%); placebo (17%)
            • Fatigue (3%)
            • Thrombosis (3%)
            • Febrile neutropenia (3%); placebo (9%)
            • Hemorrhage (>3%)
            • Respiratory failure (≥2%)
            • Hyperglycemia (2%)
            • Asthenia (2%)

            <1%

            Grade ≥3

            • Cerebrovascular accident
            • Ischemic stroke
            • Hemoptysis
            • Myositis
            • Lymphopenia
            • Acute respiratory failure (fatal)
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            Warnings

            Contraindications

            History of serious hypersensitivity to trilaciclib

            Cautions

            Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis reported with cyclin-dependent kinases (CDK)4/6 inhibitors, including trilaciclib; monitor for symptoms (eg, cough, dyspnea, hypoxia)

            May cause fetal harm

            Injection-site reactions

            • Injection-site reactions (eg, phlebitis, thrombophlebitis) may occur
            • Median time to onset: 15 days (from initiation); 1 day (preceding dose)
            • Median duration: 1 day
            • Monitor for signs and symptoms, including infusion-site pain and erythema during infusion

            Acute drug hypersensitivity reactions

            • May cause acute drug hypersensitivity reactions, including facial edema and urticaria
            • Median time to onset: 77 days (from initiation); 1 day (preceding dose)
            • Median duration: 6 day
            • Monitor for signs and symptoms, including facial, eye, and tongue edema, urticaria, pruritus, and anaphylactic reactions

            Drug interaction overview

            • Inhibitor of OCT2, MATE1, MATE-2K
            • Certain OCT2, MATE1, and MATE-2K substrates
              • Avoid coadministration
              • Trilaciclib may increase plasma and/or kidney concentrations of certain OCT2, MATE1, and MATE-2K substrates (eg, dofetilide, dalfampridine, cisplatin)
              • Even minimal changes in concentrations may lead to serious or life-changing toxicities
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            Pregnancy & Lactation

            Pregnancy

            Based on mechanism of action, fetal harm may occur when administer to pregnant females

            No human or animal data are available

            Advise pregnant females of potential risks to fetus

            Pregnancy test recommended in females of reproductive potential

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for at least 3 weeks after final dose

            Infertility

            • No studies performed
            • Based on animal studies, fertility may be impaired in females of reproductive potential

            Lactation

            No data are available

            Advise to not breastfeed during treatment and for at least 3 weeks after last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Transient CDK 4/6 inhibitor

            Hematopoietic stem and progenitor cells (HSPC) in the bone marrow give rise to circulating neutrophils, red blood cells, and platelets

            HSPC proliferation is dependent on CDK4/6 activity

            Distribution

            Blood-to-plasma ratio:1.21-1.53

            Vd: 1,130 L

            Metabolism

            Extensively metabolized

            Trilaciclib is the predominantly circulating compound in plasma following IV administration, representing ~50% of plasma total radioactivity

            Elimination

            Half-life: ~14 hr

            Estimated clearance: 158 L/hr

            Excretion: Feces (79.1% [7% unchanged]); urine (14% [2% unchanged])

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            Administration

            IV Compatibilities

            D5W

            0.9% NaCl

            IV Preparation

            Reconstitution

            • Calculate dose, total drug volume, and number of vials needed
            • Reconstitute each 300-mg vial with 19.5 mL of 0.9% NaCl or D5W, obtaining a concentration of 15 mg/mL
            • Gently swirl vial for up to 3 min until sterile lyophilized cake completely dissolves; do not shake
            • Visually inspect for discoloration and particulate matter; reconstituted solution should be a clear, yellow solution; discard if discolored, cloudy, or contains visible particulates

            Dilution

            • Withdraw required dosage volume from reconstituted vial(s); dilute into 0.9% NaCl or D5W IV infusion bag to obtain final concentration of 0.5-3 mg/mL
            • Gently invert diluted solution to mix; do not shake
            • Visually inspect for particulate matter and discoloration; diluted solution is a clear, yellow solution

            IV Administration

            Infuse over 30 min

            Complete infusion within 4 hr before starting chemotherapy

            Administer with an infusion set, including an in-line 0.2- or 0.22-micron filter; compatible in-line filters include polyethylene sulfone, polyvinylidene fluoride, and cellulose acetate

            Flush infusion line/cannula with sterile 0.9% NaCl or D5W once infusion completes

            Do NOT administer or coadminister with

            • Polytetrafluorethylene (PTFE) in-line filters: Diluted solutions are incompatible with PTFE in-line filters
            • Other drugs through same infusion line
            • Other drugs through a central access device unless device supports coadministration of incompatible drug(s)

            Missed dose

            • Discontinue chemotherapy on day dose was missed
            • Consider resuming both trilaciclib and chemotherapy on next scheduled chemotherapy

            Discontinuing treatment

            • Wait 96 hr from last trilaciclib dose before resumption of chemotherapy only

            Storage

            Unopened vial

            • Store at 20-25ºC (68-77ºF); excursion permitted to 15-30ºC (59-86ºF)

            Reconstituted vial

            • Store at 20-25ºC (68-77ºF) for up to 4 hr before transfer to infusion bag; do not refrigerate or freeze; discard any unused portion after use
            • Do not refrigerate or freeze

            Diluted solution

            • D5W
              • IV infusion bag material (polyvinyl chloride [PVC], ethylene vinyl acetate [EVA], polyolefin [PO], or polyolefin/polyamide [PO/PA])
              • Store at 20-25ºC (68-77ºF) for up to 12 hr
            • 0.9% NaCl
              • IV infusion bag material (PVC, EVA, or PO): Store at 20-25ºC (68-77ºF) for up to 8 hr
              • IV infusion bag material (PO/PA): Store at 20-25ºC (68-77ºF) for up to 4 hr
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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