Opdualag

About Opdualag (Nivolumab and Relatlimab-rmbw)

• Opdualag, marketed as a combination of nivolumab and relatlimab, stands as a fixed-dose medication crafted for the treatment of melanoma. 
• This innovative therapeutic formulation comprises nivolumab, an antibody inhibiting the programmed death receptor-1 (PD-1), and relatlimab, an antibody targeting the lymphocyte activation gene-3 (LAG-3). 
• Administered via intravenous infusion, Opdualag received approval for medical use in the United States on March 18, 2022, and gained authorization in the European Union in September 2022.
• Distinguished as a first-in-class medication by the U.S. Food and Drug Administration (FDA), Opdualag represents a pioneering approach to melanoma treatment.
• Nivolumab’s PD-1 blocking capabilities and relatlimab’s inhibition of LAG-3 collectively contribute to the medication’s therapeutic efficacy. This combination therapy signifies a significant advancement in the medical landscape for addressing unresectable or metastatic melanoma in patients aged 12 and older.
• Melanoma, a form of skin cancer arising from melanocytes, the pigment-producing cells determining skin color, is often identified by distinct signs. 
• Early manifestations commonly involve alterations in existing moles or the appearance of new pigmented or unusual skin growths. 
• These indicators serve as crucial cues for individuals to seek timely medical evaluation and intervention. 
• Regular skin examinations and vigilance for changes can aid in the early detection and effective management of melanoma, contributing to improved outcomes and prognosis.

Strength: 

The injection is available in a single-dose vial, there is a combination of 240 mg of Nivolumab and 80 mg of Relatlimab, with concentrations of 12 mg per mL and 4 mg per mL, respectively, in a total volume of 20 mL.

Recommended Dosage:

During preparation, maintain an aseptic technique for sterility, as the product lacks a preservative. Opdualag can be administered either diluted or undiluted, with compatibility confirmed with specific intravenous bags. If dilution is necessary, use 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, following specified parameters. Finally, discard partially used or empty vials after infusion preparation.

Administer the Opdualag infusion over 30 minutes using an intravenous line equipped with a sterile, non-pyrogenic in-line filter characterized by low protein binding. The suitable filter materials include polyethersulfone (PES), nylon, or polyvinylidene fluoride (PVDF), with a pore size ranging from 0.2 to 1.2 micrometers. Ensure to flush the intravenous line post-infusion. It is crucial to refrain from concurrently administering other medications through the same intravenous line.

• For adult patients and pediatric individuals aged 12 years or older with a body weight of at least 40 kg, the recommended dosage is 480 mg of nivolumab and 160 mg of relatlimab administered intravenously every four weeks.

Important:

Opdualag injection, should undergo visual inspection for particulate matter and discoloration before administration. The solution, appearing clear to opalescent and colorless to slightly yellow, should be discarded if found cloudy, discolored, or containing extraneous particulate matter beyond a few translucent-to-white particles. Dispose of any unused medicinal product or waste material. 

Warnings & Precautions

• Opdualag injection presents potential immune-mediated adverse reactions, some severe or fatal, across various organ systems, including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, and myocarditis. 
• Vigilant monitoring of liver enzymes, creatinine, and thyroid function is paramount at baseline and throughout treatment for early identification and management. Adjustments, such as withholding or permanent discontinuation, are warranted based on the severity and nature of the reaction. 
• Infusion-related reactions call for intervention strategies, including interruption, slowing the infusion rate, or permanent discontinuation of Opdualag depending on the severity. 
• Notably, complications, including fatal outcomes, may arise in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) before or after PD-1/PD-L1 blocking antibody treatment, emphasizing the need for careful consideration and monitoring in this patient population.

Common Opdualag Side Effects:

• Musculoskeletal pain
• Fatigue
• Rash
• Pruritus
• Diarrhea 
• Decreased hemoglobin
• Decreased lymphocytes
• Increased AST (aspartate aminotransferase)
• Increased ALT (alanine aminotransferase)
• Decreased sodium

Use in Specific Population

• Opdualag has the potential to cause harm to the fetus if administered to pregnant women. 
• It is advised not to breastfeed during this treatment because there is a lack of data regarding the presence of nivolumab and relatlimab in human milk, their impact on breastfed infants, or their influence on milk production.
• Due to the possibility of these substances being excreted in human milk and the potential for severe adverse reactions in breastfed infants, it is advisable for patients to refrain from breastfeeding during Opdualag treatment and for a minimum of 5 months after the final dose. 
• Prior to initiating Opdualag, it is crucial to confirm the pregnancy status of females capable of reproduction. 
• Additionally, females of reproductive potential should employ effective contraception throughout the treatment period and for at least 5 months following the last dose of Opdualag. 
• The safety and efficacy of Opdualag have not been established in pediatric patients aged 12 years or older weighing less than 40 kg and in those under 12 years of age. 
• No discernible distinctions in safety or efficacy were observed between elderly and younger patients.

Storage and Handling

• Store the prepared solution at room temperature and ambient light for a maximum of 8 hours from preparation until the end of the infusion. 
• Alternatively, under refrigeration at 2°C to 8°C (36°F to 46°F), shielded from light, for up to 24 hours from preparation, including the infusion bag equilibration period and the infusion duration. 
• Discard any unused solution after the specified timeframes. Avoid freezing the solution.
• Maintain the medication’s effectiveness by ensuring appropriate storage. 
• Shield Opdualag from direct light exposure and prevent freezing. 
• Keep the medicine away from pets and children.