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RECOMMENDED DOSAGE

Recommended dose of BAVENCIO® (avelumab)

800 MG IV INFUSION 

OVER 60 MINUTES

EVERY 2 WEEKS

Management of some adverse reactions may require temporary interruption or permanent discontinuation.

PREMEDICATION

Prior to BAVENCIO administration

First 4 infusions

Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions

After 4th infusion

Administer premedication for subsequent BAVENCIO doses based on clinical judgement and presence and severity of prior infusion reactions

DOSE MODIFICATIONS

Recommended dose modifications for adverse reactions

Severe and fatal immune-mediated adverse reactions

  • BAVENCIO is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1(PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions
  • Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immunemediated reactions
  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and at any time after starting treatment with a PD-1/PD-L1 blocking antibody
  • While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, they can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies

Monitor and assess

  • Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies
  • Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions
  • Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
  • In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate

General dose modifications

  • No dose reduction for BAVENCIO is recommended
  • In general, withhold BAVENCIO for severe (Grade 3) immune-mediated adverse reactions
  • Permanently discontinue BAVENCIO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids
    • Dosage modifications for BAVENCIO for adverse reactions that require management different from these general guidelines are summarized in the table below

General corticosteroid management

  • In general, if BAVENCIO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less
    • Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month
    • Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy
    • Toxicity management guidelines for adverse reactions that do not necessarily require systemic corticosteroids (eg, endocrinopathies and dermatologic reactions) are discussed in the table below

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Modify treatment based on severity

Withhold* Permanently discontinue
For Grade 2 For Grade 3 or 4

*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

Modify treatment based on severity

Withhold* Permanently discontinue
For Grade 2 or 3 For Grade 4

*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce rednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

Liver enzyme elevations in patients being treated with BAVENCIO as monotherapy:

Modify treatment based on severity

  Withhold* Permanently discontinue
Hepatitis with no tumor involvement of the liver For AST or ALT increases >3 and up to 8 times ULN, or total bilirubin increases >1.5 and up to 3 times ULN For AST or ALT >8 times ULN or total bilirubin >3 times ULN
Hepatitis with tumor involvement of the liver If baseline AST or ALT is >1 and up to 3 times ULN and increases to >5 and up to 10 times ULN, or baseline AST or ALT is >3 and up to 5 times ULN and increases to >8 and up to 10 times ULN For AST or ALT increases to >10 times ULN, or total bilirubin increases to >3 times ULN
  Hepatitis with no tumor involvement of the liver Hepatitis with tumor involvement of the liver
Withhold* For AST or ALT increases >3 and up to 8 times ULN, or total bilirubin increases >1.5 and up to 3 times ULN If baseline AST or ALT is >1 and up to 3 times ULN and increases to >5 and up to 10 times ULN, or baseline AST or ALT is >3 and up to 5 times ULN and increases to >8 and up to 10 times ULN
Permanently discontinue For AST or ALT >8 times ULN, or total bilirubin >3 times ULN For AST or ALT increases to >10 times ULN, or total bilirubin increases to >3 times ULN

*In patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue BAVENCIO based on recommendations for hepatitis where there is no tumor involvement of the liver.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal.

Modify treatment based on severity

Grade 2 or higher Grade 3-4
Initiate symptomatic treatment, including hormone replacement, as clinically indicated Withhold BAVENCIO for adrenal insufficiency until clinically stable, or permanently discontinue depending on severity

Modify treatment based on severity

Any grade Grade 3-4
Initiate hormone replacement, as clinically indicated Withhold BAVENCIO until clinically stable, or permanently discontinue depending on severity

Modify treatment based on severity

Any grade hypothyroidism or hyperthyroidism Grade 3-4
Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism, as clinically indicated Withhold BAVENCIO until clinically stable, or permanently discontinue depending on severity

Modify treatment based on severity

Hyperglycemia
Initiate treatment with insulin, as clinically indicated. Withhold BAVENCIO until clinically stable, or permanently discontinue depending on severity

Modify treatment based on severity

Withhold* Permanently discontinue
For Grade 2 or 3 increased blood creatinine For Grade 4 increased blood creatinine

*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

Modify treatment based on severity

Withhold* Permanently discontinue
For suspected Stevens Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) For confirmed SJS, TEN, or DRESS
  • Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions

*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

For myocarditis, permanently discontinue BAVENCIO for Grade 2, Grade 3, or Grade 4 adverse reactions
For neurological toxicities, withhold* BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4 adverse reactions

*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids.

Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT

Learn more about managing adverse reactions

DOSING AND TREATMENT MANAGEMENT GUIDE

PREPARATION, STORAGE & ADMINISTRATION

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 and 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 diluted solution

Administration

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

 

 

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