Version May 2024
Chemotherapy-induced myelosuppression: IV: 240 mg/m2/dose; administered prior to a platinum/etoposide- or topotecan-based regimen for extensive-stage small cell lung cancer (Hart 2021; Weiss 2019). Trilaciclib infusion should be completed no more than 4 hours prior to the start of chemotherapy; administer trilaciclib on each day chemotherapy is administered.
Note: The interval between trilaciclib doses (on sequential days) should not be >28 hours. If trilaciclib is discontinued, allow 96 hours to elapse after the last trilaciclib dose before resuming chemotherapy. In studies, primary prophylaxis with G-CSF (filgrastim) was not permitted in cycle 1, however, therapeutic use was permitted; beyond cycle 1, G-CSF use according to American Society of Clinical Oncology guidelines was permitted (Hart 2021; Weiss 2019).
Missed dose: If a trilaciclib dose is missed, withhold chemotherapy on that day. Consider resuming both trilaciclib and chemotherapy on the next scheduled day for chemotherapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in trilaciclib pharmacokinetics were noted based on eGFR ≥30 mL/minute/1.73 m2.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease or dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment is necessary.
Moderate to severe impairment (Child-Turcotte-Pugh class B, C): Reduce dose to 170 mg/m2.
|
Adverse reaction |
Severity |
Recommended trilaciclib modification |
|---|---|---|
|
aADL = activities of daily living. | ||
|
Infusion-site reactions (including phlebitis and thrombophlebitis) |
Grade 1: Tenderness with or without symptoms (eg, warmth, erythema, itching) |
Interrupt or slow trilaciclib infusion. If NS was used as the diluent/flush, consider changing to D5W (as appropriate) for subsequent infusions. |
|
Grade 2: Pain, lipodystrophy, edema, phlebitis |
Interrupt trilaciclib infusion. If pain is not severe, follow recommendations for grade 1 toxicity above. Otherwise, stop infusion in extremity and rotate infusion site to alternate extremity. If NS was used as the diluent/flush, consider changing to D5W (as appropriate) for subsequent infusions. Consider central access. | |
|
Grade 3: Ulceration or necrosis, severe tissue damage; operative intervention indicated |
Stop infusion and permanently discontinue trilaciclib. | |
|
Grade 4: Life-threatening consequences; urgent intervention indicated | ||
|
Acute drug hypersensitivity reactions |
Grade 2: Moderate, minimal, local, or noninvasive intervention indicated; limiting ADLa |
Interrupt trilaciclib infusion until recovery to ≤ grade 1 or baseline, then consider resuming infusion. If grade 2 reaction recurs, permanently discontinue trilaciclib. |
|
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADLa |
Permanently discontinue trilaciclib. | |
|
Grade 4: Life-threatening consequences; urgent intervention required | ||
|
Pulmonary toxicity: Interstitial lung disease/pneumonitis |
Grade 2 (symptomatic) |
Interrupt trilaciclib infusion until recovery to ≤ grade 1 or baseline, then consider resuming infusion. If grade 2 reaction recurs, permanently discontinue trilaciclib. |
|
Grade 3: Severe symptoms; limiting self-care ADLa; oxygen indicated |
Permanently discontinue trilaciclib. | |
|
Grade 4: Life-threatening respiratory compromise; urgent intervention indicated (eg, tracheotomy or intubation) | ||
|
Other adverse reactions |
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADLa |
Interrupt trilaciclib infusion until recovery to ≤ grade 1 or baseline, then consider resuming infusion. If grade 3 reaction recurs, permanently discontinue trilaciclib. |
|
Grade 4: Life-threatening consequences; urgent intervention required |
Permanently discontinue trilaciclib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hypocalcemia (24%), hypokalemia (22%), hypophosphatemia (21%)
Hepatic: Increased serum aspartate aminotransferase (17%)
Local: Injection site reaction (21%; including injection site phlebitis, inflammation at injection site)
Nervous system: Fatigue (34%), headache (13%)
1% to 10%:
Cardiovascular: Peripheral edema (7%), thrombosis (7%)
Dermatologic: Skin rash (9%)
Endocrine & metabolic: Hyperglycemia (6%)
Gastrointestinal: Upper abdominal pain (7%)
Hypersensitivity: Hypersensitivity reaction (acute: 6%; including anaphylaxis, facial edema, urticaria)
Respiratory: Pneumonia (10%)
Miscellaneous: Infusion related reaction (8%)
<1%: Respiratory: Interstitial pulmonary disease, pneumonitis
Frequency not defined:
Cardiovascular: Cerebrovascular accident, ischemic stroke
Hematologic & oncologic: Hemorrhage
Neuromuscular & skeletal: Asthenia, myositis
Respiratory: Respiratory failure
Serious hypersensitivity (eg, anaphylaxis) to trilaciclib or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity: Acute hypersensitivity reactions, including facial edema and urticaria, have been reported; anaphylaxis has also been reported. A grade 2 anaphylactic reaction occurred 4 days after trilaciclib infusion in one case; trilaciclib was continued after resolution. The median time to onset of hypersensitivity reactions (from trilaciclib initiation and from the previous trilaciclib dose, respectively) was 77 days (range: 2 to 256 days) and 1 day (range: up to 28 days). The median duration was 6 days (range: 1 to 69 days for resolved cases). Acute hypersensitivity reactions resolved in three-fourths of patients.
• Infusion-site reactions: Infusion-site reactions, including phlebitis and thrombophlebitis, have occurred; grade 2 and 3 events were reported. The median time to onset of infusion-site reactions (from trilaciclib initiation and from the previous trilaciclib dose, respectively) was 15 days (range: 1 to 542 days) and 1 day (range: up to 15 days). The median duration of reactions was 1 day (range: up to 151 days; for resolved cases). Infusion-site reactions resolved in most patients.
• Pulmonary toxicity: Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis may occur with cyclin-dependent kinase 4/6 inhibitors. ILD/pneumonitis occurred rarely in trilaciclib clinical trials; a grade 3 reaction was reported 2 months after trilaciclib discontinuation and did not resolve; concomitant therapy may be involved.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Cosela: 300 mg (1 ea)
No
Solution (reconstituted) (Cosela Intravenous)
300 mg (per each): $1,826.40
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IV: Infuse over 30 minutes; complete trilaciclib infusion no more than 4 hours prior to the start of chemotherapy on each day chemotherapy is administered. Flush the infusion line/cannula with ≥20 mL NS or D5W after the trilaciclib infusion is complete.
Administer trilaciclib with an infusion set that includes an inline 0.2- or 0.22-micron filter. Compatible inline filters include polyethersulfone (PES), polyvinylidene fluoride (PVDF), and cellulose acetate (CA); due to incompatibility, do not use a polytetrafluoroethylene (PTFE) inline filter. PTFE is acceptable for use in air vent filters. Do not concomitantly administer other medications through the same infusion line or through the central access catheter (unless catheter supports concomitant administration of incompatible medications).
Monitor for infusion-site reactions (refer to "Dosing: Adjustment for Toxicity" for infusion-site reaction management).
Chemotherapy-induced myelosuppression: To decrease the incidence of chemotherapy-induced myelosuppression when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC) in adults.
Cosela may be confused with Cosentyx.
Trilaciclib may be confused with abemaciclib, palbociclib, ribociclib, and trametinib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP2C8 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits OCT2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
CISplatin: Trilaciclib may increase the serum concentration of CISplatin. Risk C: Monitor therapy
Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification
Dofetilide: MATE1/2-K Inhibitors may increase the serum concentration of Dofetilide. Risk X: Avoid combination
MetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 3 weeks after the last trilaciclib dose.
Based on the mechanism of action, in utero exposure to trilaciclib may cause fetal harm.
It is not known if trilaciclib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for at least 3 weeks after the last trilaciclib dose.
Hepatic function (at baseline). Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor for signs/symptoms of infusion-site reactions, phlebitis, and thrombophlebitis (including infusion-site pain and erythema). Monitor for signs/symptoms of acute drug hypersensitivity reactions (eg, facial, eye, and tongue edema; urticaria; pruritus; anaphylaxis) and for pulmonary symptoms indicative of interstitial lung disease/pneumonitis (eg, cough, dyspnea, hypoxia).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Trilaciclib is a highly potent, selective, and reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (Weiss 2019). Hematopoietic stem and progenitor cell (HSPC) proliferation is dependent on CDK4/6 activity. Through CDK4/6 inhibition, trilaciclib transiently induces HSPC G1 cell cycle arrest, preventing the cells from proliferating in the presence of cytotoxic chemotherapy and thus resulting in myelopreservation (Hart 2021).
Duration: Following a single trilaciclib 192 mg/m2 dose, the percentage of cells arrested in G1 was increased up to 32 hours post-infusion. Resumption of proliferation of bone marrow progenitor subsets was observed by 32 hours post–trilaciclib dose.
Distribution: Vdss: 1,130 L.
Protein binding: 69%.
Metabolism: Extensively metabolized, primarily via aldehyde oxidase, CYP3A4, and CYP2C8.
Half-life elimination: ~14 hours.
Excretion: Following a single 192 mg/m2 dose: Feces: ~79% (7% as unchanged drug); urine: ~14% (2% unchanged drug).
Clearance: ~158 L/hour.
Hepatic function impairment: Trilaciclib unbound AUCinf is increased by 40% and 63%, respectively, in subjects with moderate and severe hepatic impairment (Child-Turcotte-Pugh classes B and C).
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