Drug Detail:Opdualag ( nivolumab and relatlimab-rmbw)
Generic Name: NIVOLUMAB 12mg in 1mL, RELATLIMAB 4mg in 1mL
Dosage Form: injection
Drug Class: Antineoplastic combinations
Recommended Dosage
The recommended dosage of OPDUALAG for adult patients and pediatric patients 12 years of age or older who weigh at least 40 kg is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks until disease progression or unacceptable toxicity occurs.
The recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg has not been established [see Use in Specific Populations (8.4)].
Dosage Modifications
No dose reduction for OPDUALAG is recommended. In general, withhold OPDUALAG for severe (Grade 3) immune-mediated adverse reactions (IMARs). Permanently discontinue OPDUALAG for life-threatening (Grade 4) IMARs, recurrent severe (Grade 3) IMARs 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 steroids.
Dosage modifications for adverse reactions that require management different from these general guidelines are summarized in Table 1.
| * Based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. a 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 equivalent) or less within 12 weeks of initiating steroids. b Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal |
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Adverse Reaction |
Severity* |
Dose Modification |
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Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] |
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Pneumonitis |
Grade 2 |
Withholda |
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Grade 3 or 4 |
Permanently discontinue |
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Colitis |
Grade 2 or 3 |
Withholda |
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Grade 4 |
Permanently discontinue |
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Hepatitis |
AST/ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN. |
Withholda |
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AST or ALT increases to more than 8 times ULN regardless of baseline. or Total bilirubin increases to more than 3 times ULN. |
Permanently discontinue |
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Endocrinopathiesb |
Grade 3 or 4 |
Withhold until clinically stable or permanently discontinue depending on severity |
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Nephritis with Renal Dysfunction |
Grade 2 or 3 increased blood creatinine |
Withholda |
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Grade 4 increased blood creatinine |
Permanently discontinue |
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Exfoliative Dermatologic Conditions |
Suspected SJS, TEN, or DRESS |
Withhold |
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Confirmed SJS, TEN, or DRESS |
Permanently discontinue |
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Myocarditis |
Grade 2, 3, or 4 |
Permanently discontinue |
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Neurological Toxicities |
Grade 2 |
Withholda |
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Grade 3 or 4 |
Permanently discontinue |
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Other Adverse Reactions |
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Infusion-Related Reactions [see Warnings and Precautions (5.2)] |
Grade 1 or 2 |
Interrupt or slow the rate of infusion |
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Grade 3 or 4 |
Permanently discontinue |
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Preparation and Administration
OPDUALAG is a fixed-dose combination of nivolumab and relatlimab.
Visually inspect the solution in the drug product vial for particulate matter and discoloration prior to administration. OPDUALAG is a clear to opalescent, colorless to slightly yellow solution. Discard the vial if the solution is cloudy, discolored, or contains extraneous particulate matter other than a few translucent-to-white particles.
Preparation
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- During preparation of the infusion solution, use aseptic technique to assure sterility, as the product does not contain a preservative.
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- OPDUALAG can be administered diluted or undiluted and administered at a final concentration as specified in Table 2 below.
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- Withdraw the required volume of OPDUALAG and transfer into an intravenous container. OPDUALAG is compatible with di(2-ethylhexyl)phthalate (DEHP)-plasticized polyvinyl chloride (PVC), ethyl vinyl acetate (EVA), and polyolefin (PO) intravenous bags.
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- If diluting OPDUALAG prior to administration:
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- Dilute OPDUALAG solution with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to prepare an infusion meeting the final concentration and maximum infusion volume parameters as specified in Table 2 below.
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- Then mix the diluted solution by gentle inversion. Do not shake.
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- Discard partially used vials or empty vials following infusion preparation.
| * The concentration range in each group includes 12 mg/mL nivolumab and 4 mg/mL relatlimab as the upper limit, which represents a scenario in which the drug product is infused without dilution. | ||
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Patient Group |
Maximum Infusion Volume (mL or mL/kg) |
Concentration Range (mg/mL)* |
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Adult patients who weigh at least 40 kg and pediatric patients 12 years of age or older who weigh at least 40 kg |
160 mL |
Nivolumab: 3 mg/mL to 12 mg/mL Relatlimab: 1 mg/mL to 4 mg/mL |
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Adult patients who weigh less than 40 kg |
4 mL/kg |
Nivolumab: 3 mg/mL to 12 mg/mL Relatlimab: 1 mg/mL to 4 mg/mL |
Storage of Prepared Solution
Store the prepared solution either:
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- at room temperature and room light for no more than 8 hours from the time of preparation to the end of the infusion. Discard the prepared solution if not used within 8 hours from the time of preparation;
-or-
- under refrigeration at 2°C to 8°C (36°F to 46°F) with protection from light for no more than 24 hours from the time of preparation, which includes 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.
Administration
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- Administer the infusion over 30 minutes through an intravenous line containing 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).
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- Flush the intravenous line at the end of the infusion.
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- Do not coadminister other drugs through the same intravenous line.
