Opdualag
Generic Name: nivolumab and relatlimab-rmbw
Dosage Form: injection, for intravenous use
What is Opdualag?
Opdualag (Nivolumab and relatlimab-rmbw) are two IgG4 kappa monoclonal antibodies that come in a fixed-dose combination (mAbs). Nivolumab is a PD-1 blocking antibody that is expressed in a recombinant Chinese Hamster ovary cell line (CHO) and has an estimated molecular mass of 146 kDa.
OPDUALAG (nivolumab and relatlimab-rmbw) injection is a sterile, preservative-free, clear to
opalescent, colorless to a slightly yellow solution that may contain few translucent-to-white
particles. OPDUALAG is supplied as 240 mg of nivolumab and 80 mg of relatlimab in a 20 mL
single-dose vial for intravenous use. Each mL of OPDUALAG solution contains 12 mg of
nivolumab, 4 mg of relatlimab, and histidine (1.1 mg), L-histidine hydrochloride monohydrate
(2.7 mg), pentetic acid (0.008 mg), polysorbate 80 (0.5 mg), sucrose (85.6 mg), and Water for
Injection, USP. The pH is 5.8.
It is used to treat:
- adults and children 12 years of age or older with a type of skin cancer called melanoma that has spread or cannot be removed by surgery.
It is not known if this medicine is safe and effective when used:
- in children 12 years of age or older who weigh less than 88 pounds (40 kg), or
- in children younger than 12 years of age.
Important information to know
Opdualag is a drug that works with your immune system to treat melanoma, a kind of skin cancer. Opdualag can make your immune system attack healthy organs and tissues in any part of your body, causing them to malfunction. These issues can sometimes become life-threatening or even fatal. These issues can arise at any time throughout your therapy or even after it has been completed. You could be dealing with more than one of these issues at the same time.
If you notice any new or worsening symptoms, call or contact your healthcare professional right away, including:
Lung problems.
- new or worsening cough
- shortness of breath
- chest pain
Intestinal problems.
- diarrhea (loose stools) or more frequent bowel movements than usual
- stool that are black, tarry, sticky, or have blood or mucus
- severe stomach-area (abdominal) pain or tenderness
Liver problems.
- yellowing of your skin or the whites of your eyes dark urine (tea colored)
- severe nausea or vomiting
- bleeding or bruising more easily than normal
- pain on the right side of your stomach area (abdomen)
Hormone gland problems.
- headaches that will not go away or unusual
- urinating more often than usual headaches
- hair loss
- eye sensitivity to light
- feeling cold
- eye problems
- constipation
- rapid heartbeat
- your voice gets deeper
- increased sweating
- dizziness or fainting
- extreme tiredness
- changes in mood or behavior, such as
- weight gain or weight loss decreased sex drive, irritability, or forgetfulness
- feeling more hungry or thirsty than usual
Kidney problems.
- decrease in your amount of urine
- swelling in your ankles
- blood in your urine
- loss of appetite
Skin problems.
- rash
- skin blistering or peeling
- itching painful sore or ulcers in mouth or nose, throat, or genital area
Heart problems.
- new or worse chest pain tiredness
- irregular heartbeat or feel like your heart is racing
- swelling in your ankles
- shortness of breath
Problems that can also happen in other organs.
These aren’t the only signs and symptoms of immune system issues that OPDUALAG might cause. If you see any new or worsening signs or symptoms, call or contact your healthcare professional straight away.
- Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
- Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
- Persistent or severe muscle pain or weakness, muscle cramps
- Low red blood cells, bruising
Getting medical treatment right away may keep these problems from becoming more serious.
During your therapy with OPDUALAG, your healthcare professional will check for these issues. Your doctor may prescribe corticosteroid or hormone replacement therapy for you. If you encounter severe adverse effects, your healthcare professional may need to postpone or stop your treatment with OPDUALAG.
Before you receive Opdualag
Tell your healthcare practitioner if you have any of the following conditions before receiving treatment:
- have Crohn’s disease, ulcerative colitis, or lupus;
- have undergone or plan to get an organ transplant; have received or plan to have a stem cell transplant using donor stem cells (allogeneic)
- have a nervous system disorder such as myasthenia gravis or Guillain-Barré syndrome
are expecting a child or plan to have a child Opdualag can cause harm to your unborn child.
Females who are able to conceive include:
- Before you begin therapy, your healthcare professional should perform a pregnancy test.
- During and for at least 5 months following the final dose, you should utilize an effective method of birth control. Consult your doctor about birth control options that you can use during this period.
- If you become pregnant while undergoing treatment, notify your healthcare practitioner straight away.
- You are breastfeeding or intend to nurse their children. Opdualag does not appear to enter into breast milk. Breastfeeding is not recommended during therapy or for 5 months after the final dosage.
How will I receive OPDUALAG?
- Over the course of 30 minutes, your healthcare professional will inject OPDUALAG into your vein using an intravenous (IV) line.
- OPDUALAG is typically administered every four weeks.
- The number of treatments you require will be determined by your healthcare professional.
- Blood tests will be performed by your healthcare practitioner to check for adverse effects.
- If you forget an appointment, phone your healthcare practitioner as soon as possible to reschedule.
Dosage and administration
Recommended Dosage
Adult patients and pediatric patients 12 years of age and older who weigh at least 40 kg should receive 480 mg nivolumab and 160 mg relatlimab intravenously every 4 weeks until disease progression or unacceptable toxicity occurs.
There is no recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg.
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.
Table 1: Recommended Dosage Modifications for Adverse Reactions¶
| Adverse Reaction | Severity | Dose Modification |
| Immune-Mediated Adverse Reactions | ||
| Pneumonitis | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
| 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. |
Withhold |
Table 1: Recommended Dosage Modifications for Adverse Reactions
| Adverse Reaction | Severity | Dose Modification |
| Immune-Mediated Adverse Reactions | ||
| 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 | |
| Endocrinopathies | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Infusion-Related Reactions
[see Warnings and Precautions (5.2)] |
Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
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
Preparation and Administration
OPDUALAG is a fixed-dose combination of nivolumab and relatlimab.
Prior to administration, visually inspect the solution in the drug product container for particle matter and discoloration. OPDUALAG is a colorless to slightly yellow solution that is transparent to opalescent.
If the solution is hazy, discolored, or includes particulate matter other than a few translucent-to-white particles, discard the bottle.
Preparation
- During the preparation of the infusion solution, use an aseptic technique to assure sterility, as the product does not contain a preservative.
- OPDUALAG can be administered diluted or undiluted and administered at a final concentration as specified in Table 2 below.
- Withdraw the required volume of OPDUALAG and transfer it 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.
- If diluting OPDUALAG prior to administration:
− 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.
− Then mix the diluted solution by gentle inversion. Do not shake.
- Discard partially used vials or empty vials following infusion preparation.
Table 2: Maximum Infusion Volumes and Concentration Ranges by Patient Group
| Patient Group | Maximum Infusion Volume
(mL or mL/kg) |
Concentration Range (mg/mL)* |
| 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 |
| 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 |
* 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.
Storage of prepared solution
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 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
- 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).
- Flush the intravenous line at the end of the infusion.
- Do not coadminister other drugs through the same intravenous line.
DOSAGE FORMS AND STRENGTHS
Injection: 240 mg nivolumab and 80 mg relatlimab per 20 mL (12 mg and 4 mg per mL) as a clear to opalescent, colorless to slightly yellow solution in a single-dose vial.
Opdualag side effects
Opdualag can cause serious side effects, including:
- See Important information
- Severe infusion reactions. Tell your healthcare provider or nurse right away if you get these symptoms during an infusion of Opdualag:
- chills or shaking
- itching or rash
- flushing
- shortness of breath
- dizziness
- feel like passing out
- fever
- nausea
- back or neck pain
- Complications of stem cell transplant that uses donor stem cells (allogeneic). These consequences are serious and can result in death. If you had a transplant before or after being treated with Opdualag, you may experience these problems. If you receive an allogeneic stem cell transplant, your healthcare professional will keep an eye on you for signs of problems.
The most common side effects include:
- muscle and bone pain
- rash
- tiredness
- itching
- chest pain
- decreased red blood cell and white blood cell counts
- diarrhea
- increased liver function test results
- decreased salt (sodium) in your blood
These are not all the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Additional information
Always check with your healthcare practitioner to make sure the information on this page pertains to your specific situation.