Usual Adult Dose for Malignant Melanoma

Recommended dose: 480 mg nivolumab and 160 mg relatlimab IV every 4 hours

Duration of therapy: Until disease progression or unacceptable toxicity occurs

Use: Unresectable or metastatic melanoma

Usual Pediatric Dose for Malignant Melanoma

Recommended dose: 480 mg nivolumab and 160 mg relatlimab IV every 4 hours in pediatric patients 12 years of age or older who weight at least 40 kg

Duration of therapy: Until disease progression or unacceptable toxicity occurs

Use: Unresectable or metastatic melanoma

Renal Dose Adjustments

Mild and Moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction: Data not available

Liver Dose Adjustments

Mild and Moderate liver dysfunction: No adjustment recommended.
Severe liver dysfunction: Data not available

Dose Adjustments

No dose reduction of this drug is recommended.

General Guidelines:

• Withhold treatment for: Severe (Grade 3) immune-mediated adverse reactions (IMARs)
• Permanently discontinue for: Life-threatening (Grade 4) IMARs, recurrent Grade 3 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 or initiating steroids.

• Grade 2: Withhold (resume in patients with complete or partial resolution [Grade 0 to 1] after corticosteroid taper; or 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 equivalent] or less within 12 weeks of initiating steroids).
• Grade 3 or 4: Permanently discontinue

• Grade 2 or 3: Withhold (resume in patients with complete or partial resolution [Grade 0 to 1] after corticosteroid taper; or 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 equivalent] or less within 12 weeks of initiating steroids).
• Grade 4: Permanently discontinue

• Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) increases more than 3 and up to 8 times upper limit of normal (ULN) OR total bilirubin increases to more than 1.5 and up to 3 times ULN: Withhold (resume in patients with complete or partial resolution [Grade 0 to 1] after corticosteroid taper; or 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 equivalent] or less within 12 weeks of initiating steroids).
• AST/ALT increases more than 8 times ULN regardless of baseline OR total bilirubin increases to more than 3 times ULN: Permanently discontinue

• Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity. (Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.)

• Grade 2 or 3 increased blood creatinine: Withhold (resume in patients with complete or partial resolution [Grade 0 to 1] after corticosteroid taper; or 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 equivalent] or less within 12 weeks of initiating steroids).
• Grade 4 increased blood creatinine: Permanently discontinue

• Suspected TEN, SJS or DRESS: Withhold
• Confirmed TEN, SJS or DRESS: Permanently discontinue

• Grade 2, 3 or 4: Permanently discontinue

• Grade 2: Withhold (resume in patients with complete or partial resolution [Grade 0 to 1] after corticosteroid taper; or 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 equivalent] or less within 12 weeks of initiating steroids).
• Grade 3 or 4: Permanently discontinue

• Grade 1 or 2: Interrupt or slow the rate of infusion
• Grade 3 or 4: Permanently discontinue

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

CONTRAINDICATIONS:

• None

Dialysis

Data not available.

Other Comments

Administration advice:

• Administer as an IV infusion over 30 minutes (IV line should contain a sterile, non-pyrogenic, low protein binding in-line polyethersulfone (PES), nylon, or polyvinylidene fluoride (PVDF) filter (pore size of 0.2 micrometer to 1.2 micrometer).
• Inspect the solution visually for particulate matter or discoloration prior to administration.
• Discard if cloudy, discolored, or if it contains extraneous or translucent to white particles.
• Flush the IV line at the end of the infusion.
• Do not coadminister other drugs through the same IV line.

• Store the prepared solution either:
• At room temperature and room light for no more than 8 hours from the time of preparation to the end of the infusion. Discard any prepared solution not used within 8 hours from preparation.
• Under refrigeration at 2C to 8C (36F to 46F) with protection from light for no more than 24 hours from the time of preparation (including the time allowed for equilibration of the infusion bag to room temperature and the duration of the infusion). Discard the prepared solution if not used within 24 hours from the time of preparation.
• Do not freeze or shake.

• The manufacturer product information should be consulted.

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Contact immediately your health care provider if you have:
• any new or worsening cough, chest pain, shortness of breath, palpitations, or fatigue
• diarrhea or severe abdominal pain
• jaundice, severe nausea or vomiting, pain on the right side of the abdomen, lethargy, easy bruising or bleeding
• decreased urine output, blood in urine, swelling in ankles, loss of appetite
• rash, itching, skin blistering or peeling
• Contact your health care provider If you are a woman of reproductive potential and become pregnant or suspect a pregnancy.
• Women of reproductive potential should use effective contraception during treatment and for at least 5 months after the last dose.
• Do not breastfeed during treatment and for 5 months after the last dose.