OPDUALAG
Clinical safety rating
cautionComprehensive clinical and safety monograph for OPDUALAG (OPDUALAG).
Comprehensive clinical and safety monograph for OPDUALAG (OPDUALAG).
Melanoma (unresectable or metastatic, as monotherapy or in combination with ipilimumab)Non-small cell lung cancer (metastatic, first-line in combination with ipilimumab and platinum-doublet chemotherapy, or as monotherapy for PD-L1>=1%)Malignant pleural mesothelioma (unresectable, first-line in combination with ipilimumab)Renal cell carcinoma (advanced, first-line in combination with ipilimumab, or as monotherapy after prior therapy)Hodgkin lymphoma (classical, relapsed or refractory after autologous HSCT and brentuximab)Squamous cell carcinoma of head and neck (recurrent or metastatic, PD-L1>=1%, first-line in combination with ipilimumab)Urothelial carcinoma (locally advanced or metastatic, after prior platinum-containing therapy, or as first-line for cisplatin-ineligible with PD-L1>=1%)Colorectal cancer (MSI-H or dMMR, metastatic, after prior fluoropyrimidine, oxaliplatin, and irinotecan)Hepatocellular carcinoma (prior sorafenib, in combination with ipilimumab)Esophageal cancer (squamous, after prior therapy, or first-line in combination with fluoropyrimidine and platinum-based chemotherapy)Gastric cancer (advanced, after prior therapy, for PD-L1 CPS>=1)Esophagogastric junction cancer (same as gastric)Small cell lung cancer (extensive-stage, first-line in combination with ipilimumab and platinum-doublet chemotherapy)Triple-negative breast cancer (unresectable locally advanced or metastatic, PD-L1 CPS>=10, first-line in combination with nab-paclitaxel)Cervical cancer (recurrent or metastatic, PD-L1 CPS>=1, first-line in combination with bevacizumab and platinum-based chemotherapy)Thymoma (limited data)Non-Hodgkin lymphoma (off-label)Glioblastoma (recurrent, off-label)
Nivolumab is a human IgG4 monoclonal antibody that binds to PD-1 on activated T-cells, blocking interaction with its ligands PD-L1 and PD-L2, thereby restoring anti-tumor T-cell function.
| Metabolism | Nivolumab is a monoclonal antibody degraded into small peptides and amino acids via general protein catabolism; not metabolized by CYP450 enzymes. |
| Excretion | Primarily eliminated via biliary/fecal route (approximately 80%) and renal excretion accounts for less than 20% as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 23-27 days, allowing for every-4-week dosing intervals. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 6-7 L, indicating limited extravascular distribution and primarily residing in the vascular space. |
| Bioavailability | Intravenous administration yields 100% bioavailability; no other routes are clinically relevant. |
| Onset of Action | Intravenous administration: onset of clinical effect observed within 2-4 weeks based on tumor response assessments. |
| Duration of Action | Duration of action is prolonged, with sustained receptor occupancy for several weeks after a single dose; clinical effects persist through the dosing interval (4 weeks). |
| Molecular Weight | 1435.6 |
For patients with relapsed or refractory classical Hodgkin lymphoma: 2.7 mg/kg (up to 200 mg) intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | SOLUTION |
| Renal impairment | No formal renal adjustment guidelines. Use caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh Class A: No adjustment; Class B: Reduce dose to 1.8 mg/kg (up to 135 mg) every 3 weeks; Class C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. No specific dosing recommendations available. |
| Geriatric use | No specific dose adjustment required; monitor renal function and overall tolerance due to potential age-related organ function decline. |
| 1st trimester | No adequate human data; animal studies show risk. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited human data; potential fetal risk. Use only if clearly needed. |
| 3rd trimester | May cause fetal harm and neonatal toxicity in third trimester. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for OPDUALAG (OPDUALAG).
| Placental transfer | Crosses placenta in animal studies; likely in humans. |
| Breastfeeding | Unknown if secreted in human milk; potential for serious adverse reactions in infants. Discontinue nursing or drug, considering importance to mother. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Opdualag (nivolumab + relatlimab) is an immune checkpoint inhibitor. Based on its mechanism of action (PD-1 and LAG-3 blockade), it can cause fetal harm. In animal studies, inhibition of PD-1 and LAG-3 pathways has been associated with increased risk of immune-mediated rejection of the developing fetus, potentially leading to fetal death or developmental abnormalities. Use is contraindicated in pregnancy unless the benefit outweighs the risk. First trimester: potential for miscarriage or malformation; second and third trimesters: risk of immune-mediated fetal injury. |
| Fetal Monitoring | Monitor maternal thyroid function, liver function, renal function, and complete blood count regularly during treatment. Assess for immune-related adverse events (e.g., pneumonitis, colitis, hepatitis, endocrinopathies) that could affect pregnancy. Fetal monitoring includes ultrasound for growth restriction and assessment for hydrops fetalis if immune-mediated hemolysis occurs. No specific fetal heart rate monitoring required unless complications arise. |
| Fertility Effects | No formal studies on fertility. Based on animal models, immune checkpoint inhibitors may impair female fertility by altering immune tolerance during implantation and early pregnancy. In males, no known direct effect on spermatogenesis, but chronic immune activation could theoretically affect reproductive function. Advise patients of potential reduced fertility. |
■ FDA Black Box Warning
Immune-mediated adverse reactions: including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions. Fatal and serious toxicities can occur. Monitor closely and manage with treatment interruption, corticosteroids, or discontinuation as indicated.
| Serious Effects |
Hypersensitivity to Opdualag or any componentActive severe autoimmune diseaseSevere hepatic impairment (Child-Pugh C)
| Precautions | Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies (hypophysitis, adrenal insufficiency, hypothyroidism, thyroiditis, type 1 diabetes), nephritis, dermatologic reactions, infusion-related reactions, embryo-fetal toxicity, and complications of allogeneic HSCT. Monitor liver function, renal function, thyroid function, and for signs of colitis. |
| Food/Dietary | No known food interactions. No dietary restrictions required. |
| Clinical Pearls | OPDUALAG (nivolumab and relatlimab) is a fixed-dose combination of PD-1 and LAG-3 immune checkpoint inhibitors for unresectable or metastatic melanoma. Monitor for immune-related adverse events (irAEs) including colitis, hepatitis, pneumonitis, endocrinopathies, and dermatologic reactions. Corticosteroids (prednisone 1-2 mg/kg/day) are first-line for moderate to severe irAEs. Do not dose-escalate or de-escalate components; administer fixed dose of 160 mg nivolumab and 80 mg relatlimab every 2 weeks. Hold for Grade 2 or higher irAEs; permanently discontinue for life-threatening or recurrent severe irAEs. |
| Patient Advice | OPDUALAG is a combination immunotherapy that helps your immune system fight melanoma. · You will receive this drug as an IV infusion every 2 weeks. · Common side effects include fatigue, rash, diarrhea, joint pain, and itching. · Call your doctor immediately if you develop new or worsening symptoms such as chest pain, shortness of breath, fever, severe abdominal pain, blood in stool, jaundice, severe headache, or vision changes. · Do not become pregnant while on treatment; effective contraception is needed during and for at least 5 months after the last dose. · Tell your doctor about all medications you take, including over-the-counter drugs and supplements. |
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