TRYE-la-SYE-klib

Therapeutic Classification:

Pharmacologic Classification: kinase inhibitors

• To decrease the incidence of chemotherapy-induced myelosuppression in patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

• Acts as a reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, which leads to hematopoietic stem and progenitor cell G1 cell cycle arrest, thereby preventing the cells from proliferating in the presence of cytotoxic chemotherapy. This effect results in myelopreservation.

• Decreased incidence of chemotherapy-induced myelosuppression.

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism/Excretion: Extensively metabolized. Primarily excreted in feces (7% as unchanged drug), with 14% being excreted in urine (2% as unchanged drug).

Half-life: 14 hr.

(plasma concentrations)

Contraindicated in:

• Hypersensitivity
• Moderate or severe hepatic impairment (total bilirubin >1.5x ULN)
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: peripheral edema.

Derm: rash.

Endo: hyperglycemia.

F and E: hypocalcemia, hypokalemia, hypophosphatemia.

GI: ↑liver enzymes, upper abdominal pain.

Hemat: BLEEDING, NEUTROPENIA, THROMBOSIS, anemia, thrombocytopenia, leukopenia.

Local: injection site reactions.

Neuro: STROKE, fatigue, headache.

Resp: pneumonia, INTERSTITIAL LUNG DISEASE/PNEUMONITIS, RESPIRATORY FAILURE.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), INFUSION REACTIONS.

Drug-Drug:

• May ↑ dofetilide levels and risk of toxicity, including QT interval prolongation.
• May ↑ dalfampridine levels and risk of toxicity, including seizures.
• May ↑ cisplatin levels and risk of toxicity, including nephrotoxicity.

• IV (Adults): 240 mg/m² administered within 4 hr prior to the start of chemotherapy on each day chemotherapy is administered. Do not exceed an interval of more than 28 days between doses.

• Lyophilized powder for injection: 300 mg/vial;

• Monitor for signs and symptoms of injection-site reactions, phlebitis, and thrombophlebitis, including infusion-site pain and erythema during infusion. If Grade 1 reactions: Tenderness with or without symptoms (warmth, erythema, itching) occur, hold or slow infusion. If 0.9% NaCl is being used as a diluent/flush, consider changing to D5W for subsequent infusions. Flush line/cannula with at least 20 mL of 0.9% NaCl or D5W after end of infusion.If Grade 2 reactions: Pain; lipodystrophy; edema; phlebitis occur, hold infusion. If pain not severe, follow instructions for Grade 1. Otherwise, stop infusion in extremity and rotate site of infusion to site in alternative extremity. If 0.9% NaCl is being used as a diluent/flush, consider changing to D5W for subsequent infusions. Central access may also be considered. Flush line/cannula with at least 20 mL of 0.9% NaCl or D5W after end of infusion.If Grade 3 reactions: Ulceration or necrosis; severe tissue damage; operative intervention indicated OR Grade 4 reactions: Life-threatening; urgent interventions indicated occur, stop infusion and permanently discontinue trilaciclib.
• Monitor for signs and symptoms of hypersensitivity reactions (facial, eye, and tongue edema, urticaria, pruritus, anaphylactic reactions). For Grade 2 reactions: Moderate; minimal, local, or noninvasive intervention indicated; limiting activities of daily living (ADL), stop infusion and hold therapy until recovery to Grade 1. For Grade 3 reactions: Severe 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, stop infusion and permanently discontinue trilaciclib.
• Monitor for signs and symptoms of interstitial lung disease (ILD)/pneumonitis (cough, dyspnea, hypoxia) during therapy. If Grade 2 symptoms (symptomatic) occur, hold trilaciclib until recovery to Grade 1 or baseline, then consider resuming therapy. If Grade 2 symptoms recur, permanently discontinue trilaciclib. If Grade 3 symptoms: Severe symptoms; limiting self-care ADL; oxygen indicated OR Grade 4 symptoms: Life-threatening respiratory compromise; urgent intervention indicated (tracheotomy or intubation) occur, permanently discontinue trilaciclib.

• Verify negative pregnancy test before starting therapy.

• High Alert:Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations, and infusion pump settings.
• Infusion must be completed 4 hr before start of chemotherapy on each day chemotherapy is administered. The interval between doses of trilaciclib on sequential days should not be >28 hr.
• If trilaciclib dose is missed, discontinue chemotherapy on the day trilaciclib dose was missed. Consider resuming both trilaciclib and chemotherapy on next scheduled day for chemotherapy. If trilaciclib is discontinued, wait 96 hr from last dose of trilaciclib before resumption of chemotherapy only.

IV Administration:

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
• Intermittent Infusion: Reconstitution: Reconstitute each 300 mg vial with 19.5 mL of 0.9% NaCl or D5W. Concentration: 15 mg/mL. Gently swirl vial for up to 3 minutes until the sterile lyophilized cake is completely dissolved. Do not shake. Solution is clear and yellow; do not use solutions that are discolored, cloudy, or contains visible particulates. Unused reconstituted solution in the vial is stable for up to 4 hr at room temperature prior to transfer to infusion bag; do not refrigerate or freeze. Discard any unused solution.
  Diluent: Dilute solution with 0.9% NaCl or D5W. Concentration: Final concentration of diluted trilaciclib solution should be between 0.5 mg/mL and 3 mg/mL. Mix diluted solution by gentle inversion; do not shake. Diluted solution is clear and yellow. Diluted solution in polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyolefin (PO), or polyolefin/polyamide (PO/PA) bag diluted with D5W is stable for up to 12 hr at room temperature; in PVC, EVA, or PO diluted with 0.9% NaCl is stable for up to 8 hr at room temperature; in PO/PA diluted with 0.9 NaCl is stable for up to 4 hr at room temperature. Discard if storage time exceeds limits. Do not refrigerate or freeze.
• Rate: Infuse over 30 min via a 0.2 or 0.22 micron in-line filter of polyethylene sulfone, polyvinylidene fluoride, or cellulose acetate. Infusion must be completed within 4 hr before start of chemotherapy. Flush line with at least 20 mL of 0.9% NaCl or D5W at completion of infusion.
• Y-Site Incompatibility: Do not co-administer other drugs through a central access device unless the device supports co-administration of incompatible drugs.
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• Explain purpose of trilaciclib to patient.
• Advise patient to notify health care professional if signs and symptoms of injection-site reactions, hypersensitivity reactions, or interstitial lung disease/pneumonitis occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 3 wk after last dose of trilaciclib. Inform patient that trilaciclib may impair fertility in females.

• Decreased incidence of chemotherapy-induced myelosuppression.

Cosela