BAVENCIO® (avelumab) Dosing Information

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BAVENCIO® (avelumab) dosing and administration

800 mg
IV INFUSION
GIVEN OVER
60 MINUTES
EVERY
2 WEEKS

  • BAVENCIO is administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
  • Management of some adverse reactions may require temporary interruption or permanent discontinuation

Premedication

  • Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions of BAVENCIO
    • Premedication should be administered for subsequent BAVENCIO doses based upon clinical judgment and presence/severity of prior infusion reactions

Preparation

  • Visually inspect vial for particulate matter and discoloration. BAVENCIO is a clear, colorless to slightly yellow solution. Discard vial if the solution is cloudy, discolored, or contains particulate matter
  • Withdraw the required volume of BAVENCIO from the vial(s) and inject it into a 250 mL infusion bag containing either 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection
  • Gently invert the bag to mix the diluted solution; avoid foaming or excessive shearing
  • Inspect the solution to ensure it is clear, colorless, and free of visible particles
  • Discard any partially used or empty vials

Storage of diluted solution

  • Protect from light
  • Store diluted BAVENCIO solution at room temperature up to 77°F (25°C) for no more than 4 hours from the time of dilution, or
  • Under refrigeration at 36°F to 46°F (2°C to 8°C) for no more than 24 hours from the time of dilution. If refrigerated, allow the diluted solution to come to room temperature prior to administration
  • Do not freeze or shake the diluted solution

Administration

  • Administer the diluted solution over 60 minutes through an intravenous line containing a sterile, nonpyrogenic, low protein binding in-line filter (pore size of 0.2 micron)
  • Do not coadminister other drugs through the same intravenous line

Pharmacodynamics

  • Based on exposure efficacy and exposure safety relationships, there are no expected clinically meaningful differences in the safety or efficacy of BAVENCIO administered every 2 weeks at 800 mg or 10 mg/kg in patients with metastatic Merkel cell carcinoma or in patients with urothelial carcinoma

Pharmacokinetics

  • The pharmacokinetics of BAVENCIO was studied in 1629 patients who received doses ranging from 1 to 20 mg/kg every 2 weeks
  • Exposure of BAVENCIO increased dose proportionally in the dose range of 10 to 20 mg/kg once every 2 weeks
  • The terminal half-life was 6.1 days in patients receiving 10 mg/kg
  • The steady-state concentrations of BAVENCIO were reached after approximately 4 to 6 weeks (2 to 3 cycles) of repeated dosing, and the systemic accumulation was approximately 1.25-fold
  • Based on a population PK analysis, there are no expected clinically meaningful differences in exposure of BAVENCIO administered every 2 weeks at 800 mg or 10 mg/kg

Renal impairment  

  • No clinically meaningful differences in pharmacokinetics were observed in the clearance of BAVENCIO based on renal impairment

Hepatic impairment 

  • No clinically meaningful differences in pharmacokinetics were observed in the clearance of BAVENCIO based on mild or moderate hepatic impairment
  • There are limited data from patients with severe hepatic impairment (defined as bilirubin > 3 times ULN, n=1) and the effect of severe hepatic impairment on the pharmacokinetics of BAVENCIO is unknown

ULN, upper limit of normal.

Helping manage immune-mediated adverse reactions for patients receiving BAVENCIO

Immune-mediated pneumonitis

  • Monitor patients for signs and symptoms of pneumonitis
    • Suspected pneumonitis should be confirmed with radiographic imaging
  • For Grade ≥ 2 pneumonitis, administer corticosteroids (initial dose 1-2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper)
  • For Grade 2 pneumonitis, withhold BAVENCIO until resolution
  • For Grade ≥ 3 or recurrent Grade 2 pneumonitis, permanently discontinue BAVENCIO

Immune-mediated hepatitis

  • Monitor patients for abnormal liver tests prior to and periodically during treatment
  • For Grade ≥ 2 immune-mediated hepatitis, administer corticosteroids (initial dose 1-2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper)
  • For Grade 2 immune-mediated hepatitis, withhold BAVENCIO until resolution
  • For Grade ≥ 3 immune-mediated hepatitis, permanently discontinue BAVENCIO

Immune-mediated colitis

  • Monitor patients for signs and symptoms of colitis
  • For Grade ≥ 2 immune-related colitis, administer corticosteroids (initial dose 1-2 mg/kg/day prednisone or equivalent followed by a corticosteroid taper)
  • For Grade 2-3 immune-related colitis, withhold BAVENCIO until resolution
  • For Grade 4 or recurrent Grade 3 immune-related colitis, permanently discontinue BAVENCIO

Immune-mediated endocrinopathies (adrenal insufficiency)

  • Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment
  • Administer corticosteroids as appropriate for adrenal insufficiency
  • For Grade ≥ 3 adrenal insufficiency, withhold BAVENCIO

Immune-mediated endocrinopathies (thyroid disorders)

  • Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation
  • Manage hypothyroidism with hormone replacement therapy and initiate medical management for control of hyperthyroidism
  • For Grade ≥ 3 thyroid disorders, withhold BAVENCIO

Immune-mediated endocrinopathies (type 1 diabetes mellitus)

  • Monitor patients for hyperglycemia or other signs and symptoms of diabetes
  • Initiate treatment with insulin for type 1 diabetes mellitus
  • For Grade ≥ 3 hyperglycemia, withhold BAVENCIO and administer antihyperglycemics or insulin
  • Resume treatment with BAVENCIO when metabolic control is achieved on insulin replacement or antihyperglycemics

Immune-mediated nephritis and renal dysfunction

  • Monitor patients for elevated serum creatinine prior to and periodically during treatment
  • For Grade ≥ 2 nephritis, administer corticosteroids (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a corticosteroid taper)
  • For Grade 2 or 3 nephritis, withhold BAVENCIO until resolution to ≤ Grade 1
  • For Grade 4 nephritis, permanently discontinue BAVENCIO

Other immune-mediated adverse reactions

  • For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes
  • Depending upon the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids and, if appropriate, initiate hormone replacement therapy
    • Upon improvement to Grade 1 or below, initiate corticosteroid taper
    • Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or below following corticosteroid taper
  • For any Grade 3 immune-mediated adverse reaction that recurs, and for any life-threatening immune-mediated adverse reaction, permanently discontinue BAVENCIO

Infusion-related reactions

  • Premedicate with antihistamine and acetaminophen prior to the first 4 infusions
  • Monitor patients for signs and symptoms of infusion-related reactions including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria
  • Interrupt or slow the rate of infusion for mild or moderate infusion-related reactions
  • For ≥ Grade 3 infusion-related reactions, stop the infusion and permanently discontinue BAVENCIO

Embryo-fetal toxicity

  • Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death
  • If BAVENCIO is used during pregnancy, or if the patient becomes pregnant while taking BAVENCIO, inform the patient of the potential risk to a fetus
  • Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO