Usual Adult Dose for Merkel Cell Carcinoma

800 mg IV over 60 minutes every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions.

Use: For metastatic Merkel cell carcinoma (MCC)

Usual Adult Dose for Urothelial Carcinoma

800 mg IV over 60 minutes every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions.

Uses:

• For maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy
• Previously treated urothelial carcinoma: For treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who: Have disease progression during or following platinum-containing chemotherapy OR have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Usual Adult Dose for Renal Cell Carcinoma

800 mg IV over 60 minutes every 2 weeks in combination with axitinib 5 mg orally 2 times a day (12 hours apart) with or without food
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions.

Use: In combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC)

Usual Pediatric Dose for Merkel Cell Carcinoma

12 years and older:
800 mg IV over 60 minutes every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions.

Use: For metastatic Merkel cell carcinoma (MCC) in pediatric patients 12 years and older

Renal Dose Adjustments

• Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
• Serum creatinine more than 6 x ULN: Permanently discontinue therapy.

Liver Dose Adjustments

• Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper
• AST or ALT more than 5 x ULN or total bilirubin more than 3 X ULN: Permanently discontinue therapy.

Dose Adjustments

DOSE ADJUSTMENTS FOR ADVERSE REACTIONS:
PNEUMONITIS:

• Grade 2: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of pneumonitis after corticosteroid taper
• Grade 3 or 4 or recurrent Grade 2: Permanently discontinue therapy

HEPATITIS:

• Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper
• AST or ALT more than 5 x ULN or total bilirubin more than 3 X ULN: Permanently discontinue therapy

COLITIS:

• Grade 2 or 3 diarrhea or colitis: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
• Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis: Permanently discontinue therapy

ENDOCRINOPATHIES:
Endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, hyperglycemia):

• Grade 3 or 4: Withhold therapy; administer corticosteroids as appropriate for adrenal insufficiency; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of endocrinopathies after corticosteroid taper

NEPHRITIS AND RENAL DYSFUNCTION:

• Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
• Serum creatinine more than 6 x ULN: Permanently discontinue therapy.

OTHER IMMUNE-MEDIATED ADVERSE REACTIONS (e.g., myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barre syndrome, bullous dermatitis, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, encephalitis):

• For moderate or severe signs of an immune-mediated adverse reaction not previously described: Withhold therapy; administer high dose corticosteroids, and if appropriate, initiate hormone replacement; resume therapy in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper
• For any of the following: Life threatening adverse reaction (excluding endocrinopathies); recurrent severe immune-mediated adverse reactions; requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks; persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or longer: Permanently discontinue therapy

INFUSION-RELATED REACTIONS:
Grade 1 or 2: Interrupt or slow the rate of infusion
Grade 3 or 4: Permanently discontinue therapy

COMBINATION THERAPY:
In patients with RCC being treated with this drug in combination with axitinib:

• If ALT or AST is 3 times upper limit of normal (ULN) or greater but less than 5 x ULN or total bilirubin is 1.5 x ULN or greater but less than 3 x ULN: Withhold both this drug and axitinib until adverse reactions recover to Grade 0 or 1. If persistent (greater than 5 days), consider corticosteroid therapy (initial dose of 0.5 to 1 mg/kg/day) prednisone or equivalent followed by a taper. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery. Dose reduce per the axitinib Full Prescribing Information if rechallenging with axitinib.
• If ALT or AST is 5 x ULN or greater or greater than 3 x ULN with concurrent total bilirubin 2 x ULN or greater or total bilirubin is 3 x ULN or greater, permanently discontinue both this drug and axitinib and consider corticosteroid therapy (initial dose 1 to 2 mg/kg/day prednisone or equivalent followed by a taper).
• When this drug is administered in combination with axitinib, review the axitinib Full Prescribing Information for recommended dose modifications for axitinib.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do not freeze or shake diluted solution.
• Administer the diluted solution over 60 minutes through an IV 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 IV line.

Storage requirements:

• Store diluted solution at room temperature up to 77F (25C) for no more than 4 hours from the time of dilution or under refrigeration at 36F to 46F (2C to 8C) 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.

Reconstitution/preparation techniques:

• Visually inspect vial for particulate matter and discoloration; it should be a clear, colorless to slightly yellow solution. Discard vial if the solution is cloudy, discolored, or contains particulate matter.
• Withdraw the required volume of drug 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.

IV compatibility:

• This drug may be used with 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection.

Frequently asked questions

• Who makes Bavencio and where is it made?
• What type of drug is Bavencio?