OPDIVO nivolumab 10 mg/mL Injection — NDC 0003-3734-13 (Billing 00003-3734-13)
This is a package of OPDIVO nivolumab 10 mg/mL Injection from E.R. Squibb & Sons, L.L.C., marketed since Dec 2017 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 0003-3734-13 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 0003 labeler · 3734 product · 13 package
- Package marketed since
- Dec 8, 2017
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Barcode (UPC-A, from the NDC)
- 3 0003373413 3
- Medicaid fills, this package
- 17,733 prescriptions in the last four reported quarters
- FDA record last changed
- Sep 10, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 078045
- GCN: 44267
- HICL (First Databank): 041654
- AHFS class code: 10:00.00.00
- RxCUI (RxNorm): 1657190
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Programmed Death Receptor-1 Blocking Antibody class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Nivolumab injection is used to treat a variety of cancers. Nivolumab is in a class of medications called monoclonal antibodies. It works by helping your immune system to slow or stop the growth of cancer cells.
Read the full MedlinePlus article ↗- Opdivo is used for many cancers, including melanoma, lung, kidney, bladder, colorectal, liver, esophageal and stomach cancers, and classical Hodgkin lymphoma. Which use applies to...
- It is given through an IV in a vein by a healthcare professional, usually as a 30-minute infusion. Your visits may be every few weeks depending on your plan. Your team will tell yo...
- Common ones are tiredness, rash, itching, aches and pains, diarrhea, nausea and decreased appetite. Many people can manage these with help from their team. Tell them about anything...
- Call right away for new cough or trouble breathing, severe diarrhea or belly pain, signs of liver or hormone problems, severe skin reactions, or any reaction during an infusion. Th...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Nivolumab — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $287.14 | $287.14 / 1 vial |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9299 | $34.222 / J9299 unit | — |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Billing & reimbursement
Where does this data come from?
- CMS ASP NDC-HCPCS crosswalk · refreshed Sep 22, 2026
- DMEPDAC NDC-HCPCS crosswalk
- openFDA NSDE billing units · refreshed Sep 7, 2026
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00003-3734-13 You're viewing this Main listing | 1 VIAL, SINGLE-DOSE in 1 CARTON / 24 mL in 1 VIAL, SINGLE-DOSE | 2017-12-08 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Opdivo 10 mg/mLthis 00003-3734-13 | E.R. | 1 vial | — | — | FDA listed | — |
| Opdivo 10 mg/mL 00003-3772-11 | E.R. | 1 vial | — | — | FDA listed | — |
| Opdivo 10 mg/mL 00003-3774-12 | E.R. | 1 vial | — | — | FDA listed | — |
| Opdivo 10 mg/mL 00003-3756-14 | E.R. | 1 vial | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Purple Book · refreshed Oct 5, 2026
- CMS NADAC weekly file
Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Dec 22, 2026 |
Is there a biosimilar for OPDIVO 240 MG/24 ML VIAL?
Why do different websites show different biosimilar dates?
Can a biosimilar launch before the last patent expires?
What does “current Purple Book estimate” mean?
What does “FDA listed” mean?
What does a patent or protection date mean here?
Where does this data come from?
- FDA Purple Book · refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Nivolumab Injection inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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30 mg / 1 mL
UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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0.008 mg / 1 mL
UNII 7A314HQM0I
Pentetic acid is a chelating agent, a chemical that binds to metals. It's used in some medicines to prevent metal ions from interfering with drug stability or effectiveness.
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0.2 mg / 1 mL
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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2.92 mg / 1 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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5.88 mg / 1 mL
UNII B22547B95K
A salt derived from citric acid that helps maintain the proper acid-base balance in the medicine. It's used as a buffer to keep the product stable and at the right pH level.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
8 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from E.R. Squibb & Sons, L.L.C. labeler code 00003
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- Reyataz Atazanavir 300 mg Capsule, Gelatin Coated NDC 0003-3622-12
- Reyataz Atazanavir 200 mg Capsule, Gelatin Coated NDC 0003-3631-12
- Reyataz Atazanavir 50 mg Powder NDC 0003-3638-10
- Evotaz atazanavir and cobicistat 300 mg; 150 mg Tablet NDC 0003-3641-11
- OPDIVO nivolumab 10 mg/mL Injection NDC 0003-3756-14
- ELIQUIS 30-Day Starter Pack apixaban Kit NDC 0003-3764-74
- OPDIVO nivolumab 10 mg/mL Injection NDC 0003-3772-11
- OPDIVO nivolumab 10 mg/mL Injection NDC 0003-3774-12
- Augtyro repotrectinib 40 mg Capsule NDC 0003-4040-12
- Augtyro repotrectinib 160 mg Capsule NDC 0003-4160-14
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE OPDIVO is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of: Melanoma • adult and pediatric (12 years and older) patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab. (1.1) • for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. (1.2) Non-Small Cell Lung Cancer (NSCLC) • adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer in the neoadjuvant setting, in combination with platinum-doublet chemotherapy.
(1.3) • adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer and no known EGFR mutations or ALK rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by single-agent OPDIVO as adjuvant treatment after surgery. (1.4) • adult patients with metastatic non-small cell lung cancer expressing PD‑L1 (≥1%) as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab.
(1.5) • adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy. (1.5) • adult patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
(1.5) Malignant Pleural Mesothelioma • adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with ipilimumab. (1.6) Renal Cell Carcinoma (RCC) • adult patients with intermediate or poor risk advanced renal cell carcinoma, as a first-line treatment in combination with ipilimumab. (1.7) • adult patients with advanced renal cell carcinoma, as a first-line treatment in combination with cabozantinib.
(1.7) • adult patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy. (1.7) Classical Hodgkin Lymphoma (cHL) • adult and pediatric (12 years and older) patients with previously untreated, Stage III or IV classical Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine (AVD). (1.8) • adult patients with classical Hodgkin lymphoma that has relapsed or progressed after: (1.8) • autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or • 3 or more lines of systemic therapy that includes autologous HSCT.
Squamous Cell Carcinoma of the Head and Neck (SCCHN) • adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. (1.9) Urothelial Carcinoma • adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. (1.10) • adult patients with unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine.
(1.10) • adult patients with locally advanced or metastatic urothelial carcinoma who: • have disease progression during or following platinum-containing chemotherapy. • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (1.10) Colorectal Cancer • adult and pediatric (12 years and older) patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) in combination with ipilimumab.
(1.11) • adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatmen… [Excerpted — this section continues on DailyMed.]
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Administer by intravenous infusion after dilution based upon recommended infusion rate for each indication. (2) • Unresectable or metastatic melanoma • Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
(2.2) • Adult and pediatric patients weighing 40 kg or greater: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Pediatric patients weighing less than 40 kg: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. (2.2) • Adjuvant treatment of melanoma • Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks.
(2.2) • Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. (2.2) • Neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) non-small cell lung cancer • 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles. (2.2) • Neoadjuvant and adjuvant treatment of resectable non-small cell lung cancer • 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for up to 4 cycles, then continued as single-agent OPDIVO 480 mg every 4 weeks after surgery for up to 13 cycles (~1 year).
(2.2) • Metastatic non-small cell lung cancer • 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks. (2.2) • 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy. (2.2) • 240 mg every 2 weeks or 480 mg every 4 weeks.
(2.2) • Malignant pleural mesothelioma • 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks. (2.2) • Advanced renal cell carcinoma • 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • 240 mg every 2 weeks or 480 mg every 4 weeks administered in combination with cabozantinib 40 mg once daily without food.
(2.2) • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Classical Hodgkin lymphoma • Adult and pediatric patients weighing 40 kg or greater: 240 mg in combination with doxorubicin, vinblastine, and dacarbazine (AVD) every 2 weeks for 6 cycles. (2.2) • Pediatric patients weighing less than 40 kg: 3 mg/kg in combination with AVD every 2 weeks for 6 cycles.
(2.2) • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Recurrent or metastatic squamous cell carcinoma of the head and neck • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Adjuvant treatment of urothelial carcinoma • 240 mg every 2 weeks or 480 mg every 4 weeks.
(2.2) • First-line unresectable or metastatic urothelial carcinoma • 360 mg every 3 weeks with cisplatin and gemcitabine on the same day for up to 6 cycles, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Previously treated locally advanced or metastatic urothelial carcinoma • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer • Adult and pediatric patients weighing 40 kg or greater: 240 mg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for a maximum of 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
( 2.2 ) • Pediatric patients weighing less than 40 kg: 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for a maximum of 4 doses, then 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. ( 2.2 ) • Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following prior treatment for metastatic disease. • Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks. ( 2.2 ) • Pediatric patients weighing less than 4… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 40 mg/4 mL (10 mg/mL), 100 mg/10 mL (10 mg/mL), 120 mg/12 mL (10 mg/mL), and 240 mg/24 mL (10 mg/mL) clear to opalescent, colorless to pale-yellow solution in a single-dose vial. • Injection: 40 mg/4 mL (10 mg/mL), 100 mg/10 mL (10 mg/mL), 120 mg/12 mL (10 mg/mL), and 240 mg/24 mL (10 mg/mL) solution in a single-dose vial. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. • None. (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Immune-Mediated Adverse Reactions: (5.1) • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction. • Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. • Withhold or permanently discontinue based on severity and type of reaction.
(2.3) • Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue OPDIVO based on severity of reaction. (5.2) • Complications of allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. (5.3) • Embryo-Fetal toxicity: Can cause fetal harm.
Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. (5.4 , 8.1 , 8.3) • Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. (5.5)
5.1Severe and Fatal Immune-Mediated Adverse Reactions OPDIVO is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD‑1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue OPDIVO depending on severity [see Dosage and Administration (2.3) ] .
In general, if OPDIVO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis OPDIVO can cause immune-mediated pneumonitis, which is defined as requiring use of steroids and no clear alternate etiology. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who ha… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling. • Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] • Infusion-Related Reactions [see Warnings and Precautions (5.2) ] • Complications of Allogeneic HSCT [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥20%) in patients were: • As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection.
(6.1) • In combination with ipilimumab: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness. (6.1) • In combination with platinum-doublet chemotherapy: nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. (6.1) • In combination with ipilimumab and platinum-doublet chemotherapy: fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.
(6.1) • In combination with cabozantinib: diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection. (6.1) • In combination with fluoropyrimidine- and platinum-containing chemotherapy: nausea, peripheral neuropathy, decreased appetite, fatigue, constipation, stomatitis, diarrhea, vomiting, abdominal pain, and musculoskeletal pain.
(6.1) Most common adverse reactions (incidence ≥30%) in patients were: • In combination with AVD: nausea, neutropenia, fatigue, anemia, constipation, leukopenia, musculoskeletal pain, peripheral neuropathy, transaminases increase, vomiting, and stomatitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in WARNINGS AND PRECAUTIONS reflect exposure to OPDIVO as a single agent in 1994 patients enrolled in CHECKMATE-037, CHECKMATE-017, CHECKMATE-057, CHECKMATE-066, CHECKMATE-025, CHECKMATE-067, CHECKMATE-205, CHECKMATE-039 or a single-arm trial in NSCLC (n=117); OPDIVO 1 mg/kg with ipilimumab 3 mg/kg in patients enrolled in CHECKMATE-067 (n=313), CHECKMATE-040 (n=49), or another randomized trial (n=94); OPDIVO 3 mg/kg administered with ipilimumab 1 mg/kg (n=666) in patients enrolled in CHECKMATE-214 or CHECKMATE-142; OPDIVO 3 mg/kg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks in patients enrolled in CHECKMATE-227 (n=576) or CHECKMATE-743 (n=300); OPDIVO 360 mg with ipilimumab 1 mg/kg and 2 cycles of platinum-doublet chemotherapy in CHECKMATE-9LA (n=361); OPDIVO 240 mg with cabozantinib 40 mg in patients enrolled in CHECKMATE-9ER (n=320); and OPDIVO 240 mg or 3 mg/kg with AVD in patients enrolled in CA209-8UT (SWOG 1826) (n=490).
Unresectable or Metastatic Melanoma Previously Treated Metastatic Melanoma The safety of OPDIVO was evaluated in CHECKMATE-037, a randomized, open-label trial in 370 patients with unresectable or metastatic melanoma [see Clinical Studies (14.1) ] . Patients had documented disease progression following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. The trial excluded patients with autoimmune disease, prior ipilimumab-related Grade 4 adverse reaction… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed. (8.2)
8.1Pregnancy Risk Summary Based on data from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , OPDIVO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see Data) . Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus.
The effects of OPDIVO are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDIVO use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus.
The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss.
The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. Based on its mechanism of action, fetal exposure to nivolumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice.
In surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period.
8.2Lactation Risk Summary There are no data on the presence of nivolumab in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 5 months after the last dose of OPDIVO.
8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating OPDIVO [see Use in Specific Populations (8.1) ] . Contraception OPDIVO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for 5 months following the last dose.
8.4Pediatric Use The safety and effectiveness of OPDIVO have been established in pediatric patients aged 12 years and older for the following indications: as a single agent and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma, as a single agent for the adjuvant treatment of completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma in combination with ipilimumab for the treatment of MSI-H or dMMR unresectable and metastatic CRC, and as a single agent for the treatment of MSI-H or dMMR mCRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Use of OPDIVO for these indications is supported by evidence from adequate and well-controlled studies in adults with melanoma or MSI-H or dMMR mCRC and additional pharmacokinetic data in pediatric patients. Nivolumab exposure in pediatric patients 12 years and older… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on data from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , OPDIVO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see Data) . Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus.
The effects of OPDIVO are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDIVO use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus.
The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss.
The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. Based on its mechanism of action, fetal exposure to nivolumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice.
In surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of OPDIVO have been established in pediatric patients aged 12 years and older for the following indications: as a single agent and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma, as a single agent for the adjuvant treatment of completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma in combination with ipilimumab for the treatment of MSI-H or dMMR unresectable and metastatic CRC, and as a single agent for the treatment of MSI-H or dMMR mCRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Use of OPDIVO for these indications is supported by evidence from adequate and well-controlled studies in adults with melanoma or MSI-H or dMMR mCRC and additional pharmacokinetic data in pediatric patients. Nivolumab exposure in pediatric patients 12 years and older is comparable to that of adults and the courses of melanoma and MSI-H or dMMR mCRC are similar in pediatric patients aged 12 years and older to that of adults to allow extrapolation of safety and efficacy [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.1 , 14.11) ] .
The safety and effectiveness of OPDIVO in combination with AVD have been established in patients aged 12 years and older for the treatment of cHL. Use of OPDIVO for this indication is supported by evidence from Study CA209-8UT, which included 120 pediatric patients ages ≥12 to <18 with previously untreated cHL treated with OPDIVO plus AVD. Adverse reactions reported with ≥10% higher frequency in pediatric compared to adult patients included nausea, anemia, increased transaminases, vomiting, lymphopenia, pyrexia, hyperphosphatemia, and eosinophilia [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.8) ] .
The safety and effectiveness of OPDIVO have not been established for pediatric patients younger than 12 years old with melanoma, MSI-H or dMMR mCRC, or cHL. The safety and effectiveness of OPDIVO have not been established in pediatric patients with non-small cell lung cancer, malignant pleural mesothelioma, advanced renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, hepatocellular carcinoma, esophageal cancer, gastric cancer, gastroesophageal cancer and esophageal adenocarcinoma.
🧓 Geriatric Use ▾
8.5Geriatric Use Single Agent Of 3569 patients with melanoma, NSCLC, renal cell carcinoma, urothelial carcinoma, ESCC, and esophageal or gastroesophageal junction cancer who were randomized to single agent OPDIVO in clinical studies, 41% were 65 years and over and 10% were 75 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients [see Clinical Studies (14.1 , 14.2 , 14.5 , 14.7 , 14.10 , 14.13 , 14.14) ]. In patients with cHL, recurrent head and neck SCC, or dMMR or MSI-H metastatic CRC (mCRC) who were treated with single agent OPDIVO in clinical studies did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients [see Clinical Studies (14.8 , 14.9 , 14.11) ].
OPDIVO in Combination with Ipilimumab Of the 314 patients with melanoma who were randomized to OPDIVO in combination with ipilimumab, 41% were 65 years or older and 11% were 75 years or older. No overall differences in safety or effectiveness were reported between elderly patients and younger patients [see Clinical Studies (14.1) ]. Of the 576 patients with NSCLC who were randomized to OPDIVO in combination with ipilimumab, 48% were 65 years or older and 10% were 75 years or older.
No overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (29%) relative to all patients who received OPDIVO with ipilimumab (18%). Of the 396 patients in the primary efficacy population (PD-L1 ≥1%) randomized to OPDIVO in combination with ipilimumab, the hazard ratio for overall survival was 0.70 (95% CI: 0.55, 0.89) in the 199 patients younger than 65 years compared to 0.91 (95% CI: 0.72, 1.15) in the 197 patients 65 years or older [see Clinical Studies (14.3) ].
Of the 303 patients with malignant pleural mesothelioma who were randomized to OPDIVO in combination with ipilimumab, 77% were 65 years old or older and 26% were 75 years or older. No overall difference in safety was reported between older patients and younger patients; however, there were higher rates of serious adverse reactions and discontinuation due to adverse reactions in patients aged 75 years or older (68% and 35%, respectively) relative to all patients who received OPDIVO with ipilimumab (54% and 28%, respectively).
For patients aged 75 years or older who received chemotherapy, the rate of serious adverse reactions was 34% and the discontinuation rate due to adverse reactions was 26% relative to 28% and 19% respectively for all patients. The hazard ratio for overall survival was 0.76 (95% CI: 0.52, 1.11) in the 71 patients younger than 65 years compared to 0.74 (95% CI: 0.59, 0.93) in the 232 patients 65 years or older randomized to OPDIVO in combination with ipilimumab [see Clinical Studies (14.6) ]. Of the 550 patients with renal cell carcinoma who were randomized to OPDIVO in combination with ipilimumab, 38% were 65 years or older and 8% were 75 years or older.
No overall difference in safety was reported between elderly patients and younger patients. In elderly patients with intermediate or poor risk, no overall difference in effectiveness was reported [see Clinical Studies (14.7) ]. Of the 354 patients with dMMR or MSI-H metastatic CRC (mCRC) who were randomized to OPDIVO in combination with ipilimumab, 44% were 65 years or older and 14% were 75 years or older.
Of the 353 patients randomized to OPDIVO, as a single agent, 45% were 65 years or older and 13% were 75 years or older. There was a higher incidence of any Grade 3 or 4 adverse reactions (55%) in patients aged 65 years or older receiving OPDIVO in combination with ipilimumab compared to those younger than 65 receiving the combination (42%). There was also a higher incidence of any Grade 3 or 4 adverse reactions (55%) in patients aged 65 years or older receiving OPDIVO in combin… [Excerpted — this section continues on DailyMed.]
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma and advanced RCC. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity.
12.2Pharmacodynamics There are no clinically significant exposure-response relationships for efficacy or safety for nivolumab monotherapy across the approved dosing regimens, regardless of cancer type.
12.3Pharmacokinetics Nivolumab pharmacokinetics (PK) was assessed using a population PK approach for both single agent OPDIVO and OPDIVO with ipilimumab. The PK of nivolumab was studied in patients over a dose range of 0.1 mg/kg to 20 mg/kg administered as a single dose or as multiple doses of OPDIVO as a 60-minute intravenous infusion every 2 or 3 weeks. The exposure to nivolumab increases dose proportionally over the dose range of 0.1 to 10 mg/kg administered every 2 weeks.
The predicted exposure of nivolumab after a 30-minute infusion is comparable to that observed with a 60-minute infusion. Steady-state concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg every 2 weeks, and systemic accumulation was 3.7-fold. Distribution The geometric mean volume of distribution at steady state (Vss) and coefficient of variation (CV%) is
6.8L (27.3%). Elimination Nivolumab clearance (CL) decreases over time, with a mean maximal reduction from baseline values (CV%) of 24.5% (47.6%) resulting in a geometric mean steady-state clearance (CLss) (CV%) of 8.2 mL/h (53.9%) in patients with metastatic tumors; the decrease in CLss is not considered clinically relevant. Nivolumab clearance does not decrease over time in patients with completely resected melanoma, as the geometric mean population clearance is 24% lower in this patient population compared with patients with metastatic melanoma at steady state.
The geometric mean elimination half-life (t 1/2 ) is 25 days (77.5%). Specific Populations The following factors had no clinically important effect on the clearance of nivolumab: age (29 to 87 years), weight (35 to 160 kg), sex, race, baseline LDH, PD-L1 expression, solid tumor type, tumor size, renal impairment (eGFR ≥15 mL/min/1.73 m 2 ), and mild (total bilirubin [TB] less than or equal to the ULN and AST greater than ULN or TB greater than 1 to 1.5 times ULN and any AST) or moderate hepatic impairment (TB greater than 1.5 to 3 times ULN and any AST).
Nivolumab has not been studied in patients with severe hepatic impairment (TB greater than 3 times ULN and any AST). Pediatric Patients The exposures of nivolumab, as monotherapy or in combination with ipilimumab, in pediatric patients 12 years of age or older are within range of those in adults at the recommended dosage [see Dosage and Administration (2.2) ]. Drug Interaction Studies When OPDIVO 3 mg/kg every 3 weeks was administered in combination with ipilimumab 1 mg/kg every 3 weeks, the CL of nivolumab and ipilimumab were unchanged compared to nivolumab or ipilimumab administered alone.
When OPDIVO 1 mg/kg every 3 weeks was administered in combination with ipilimumab 3 mg/kg every 3 weeks, the CL of nivolumab… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma and advanced RCC. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING OPDIVO ® (nivolumab) Injection is a clear to opalescent, colorless to pale-yellow solution in a single-dose vial available as follows: Carton Contents NDC 40 mg/4 mL (10 mg/mL) single-dose vial 0003-3772-11 100 mg/10 mL (10 mg/mL) single-dose vial 0003-3774-12 120 mg/12 mL (10 mg/mL) single-dose vial 0003-3756-14 240 mg/24 mL (10 mg/mL) single-dose vial 0003-3734-13 Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light by storing in the original package until time of use.
Do not freeze or shake.
📋 Description ▾
11 DESCRIPTION Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody. Nivolumab is an IgG4 kappa immunoglobulin that has a calculated molecular mass of 146 kDa. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line.
OPDIVO is a sterile, preservative-free, non-pyrogenic, clear to opalescent, colorless to pale-yellow liquid that may contain light (few) particles. OPDIVO (nivolumab) injection for intravenous use is supplied in single-dose vials. Each mL of OPDIVO solution contains nivolumab 10 mg, mannitol (30 mg), pentetic acid (0.008 mg), polysorbate 80 (0.2 mg), sodium chloride (2.92 mg), sodium citrate dihydrate (5.88 mg), and Water for Injection, USP.
May contain hydrochloric acid and/or sodium hydroxide to adjust pH to 6.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) . Immune-Mediated Adverse Reactions Inform patients of the risk of immune-mediated adverse reactions that may require corticosteroid treatment and withholding or discontinuation of OPDIVO, including: • Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1) ] . • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1) ] . • Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding [see Warnings and Precautions (5.1) ] . • Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, and diabetes mellitus [see Warnings and Precautions (5.1) ] . • Nephritis and Renal Dysfunction: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis including decreased urine output, blood in urine, swelling in ankles, loss of appetite, and any other symptoms of renal dysfunction [see Warnings and Precautions (5.1) ] . • Skin Adverse Reactions: Advise patients to contact their healthcare provider immediately for rash [see Warnings and Precautions (5.1) ] .
Infusion-Related Reactions • Advise patients of the potential risk of infusion-related reactions [see Warnings and Precautions (5.2) ] . Complications of Allogeneic HSCT • Advise patients of potential risk of post-transplant complications [see Warnings and Precautions (5.3) ]. Embryo-Fetal Toxicity • Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] . • Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months following the last dose [see Use in Specific Populations (8.3) ] .
Lactation • Advise women not to breastfeed during treatment with OPDIVO and for 5 months after the last dose [see Use in Specific Populations (8.2) ] . Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA U.S. License No.
1713
💬 Medication Guide ▾
MEDICATION GUIDE OPDIVO ® (op-DEE-voh) (nivolumab) injection Read this Medication Guide before you start receiving OPDIVO and before each infusion. There may be new information. If your healthcare provider prescribes OPDIVO in combination with ipilimumab, also read the Medication Guide that comes with ipilimumab.
If your healthcare provider prescribes OPDIVO in combination with cabozantinib, also read the Patient Information that comes with cabozantinib. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about OPDIVO?
OPDIVO is a medicine that may treat certain cancers by working with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death.
These problems may happen anytime during treatment or even after your treatment has ended. You may have more than one of these problems at the same time. Some of these problems may happen more often when OPDIVO is used in combination with another therapy.
Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems. • cough • shortness of breath • chest pain Intestinal problems. • diarrhea (loose stools) or more frequent bowel movements than usual • stools 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 • severe nausea or vomiting • pain on the right side of your stomach area (abdomen) • dark urine (tea colored) • bleeding or bruising more easily than normal Hormone gland problems. • headaches that will not go away or unusual headaches • eye sensitivity to light • eye problems • rapid heartbeat • increased sweating • extreme tiredness • weight gain or weight loss • feeling more hungry or thirsty than usual • urinating more often than usual • hair loss • feeling cold • constipation • your voice gets deeper • dizziness or fainting • changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems. • decrease in your amount of urine • blood in your urine • swelling of your ankles • loss of appetite Skin problems. • rash • itching • skin blistering or peeling • swollen lymph nodes • painful sore or ulcers in mouth or nose, throat, or genital area • fever or flu-like symptoms Problems can also happen in other organs and tissues.
These are not all of the signs and symptoms of immune system problems that can happen with OPDIVO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: • chest pain, irregular heartbeat, shortness of breath or swelling of ankles • 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 Rejection of a transplanted organ or tissue.
Your healthcare provider should tell you what signs and symptoms you should report and monitor you depending on the type of organ or tissue transplant that you have had. Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during treatment with OPDIVO.
Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with OPDIVO, if you have severe side effects. What is OPDIVO?
OPDIVO is a prescription medicine used to treat: • adults and children 12 years of age and older with a type of ski… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Nivolumab pharmacokinetics (PK) was assessed using a population PK approach for both single agent OPDIVO and OPDIVO with ipilimumab. The PK of nivolumab was studied in patients over a dose range of 0.1 mg/kg to 20 mg/kg administered as a single dose or as multiple doses of OPDIVO as a 60-minute intravenous infusion every 2 or 3 weeks. The exposure to nivolumab increases dose proportionally over the dose range of 0.1 to 10 mg/kg administered every 2 weeks.
The predicted exposure of nivolumab after a 30-minute infusion is comparable to that observed with a 60-minute infusion. Steady-state concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg every 2 weeks, and systemic accumulation was 3.7-fold. Distribution The geometric mean volume of distribution at steady state (Vss) and coefficient of variation (CV%) is
6.8L (27.3%). Elimination Nivolumab clearance (CL) decreases over time, with a mean maximal reduction from baseline values (CV%) of 24.5% (47.6%) resulting in a geometric mean steady-state clearance (CLss) (CV%) of 8.2 mL/h (53.9%) in patients with metastatic tumors; the decrease in CLss is not considered clinically relevant. Nivolumab clearance does not decrease over time in patients with completely resected melanoma, as the geometric mean population clearance is 24% lower in this patient population compared with patients with metastatic melanoma at steady state.
The geometric mean elimination half-life (t 1/2 ) is 25 days (77.5%). Specific Populations The following factors had no clinically important effect on the clearance of nivolumab: age (29 to 87 years), weight (35 to 160 kg), sex, race, baseline LDH, PD-L1 expression, solid tumor type, tumor size, renal impairment (eGFR ≥15 mL/min/1.73 m 2 ), and mild (total bilirubin [TB] less than or equal to the ULN and AST greater than ULN or TB greater than 1 to 1.5 times ULN and any AST) or moderate hepatic impairment (TB greater than 1.5 to 3 times ULN and any AST).
Nivolumab has not been studied in patients with severe hepatic impairment (TB greater than 3 times ULN and any AST). Pediatric Patients The exposures of nivolumab, as monotherapy or in combination with ipilimumab, in pediatric patients 12 years of age or older are within range of those in adults at the recommended dosage [see Dosage and Administration (2.2) ]. Drug Interaction Studies When OPDIVO 3 mg/kg every 3 weeks was administered in combination with ipilimumab 1 mg/kg every 3 weeks, the CL of nivolumab and ipilimumab were unchanged compared to nivolumab or ipilimumab administered alone.
When OPDIVO 1 mg/kg every 3 weeks was administered in combination with ipilimumab 3 mg/kg every 3 weeks, the CL of nivolumab was increased by 29% compared to OPDIVO administered alone and the CL of ipilimumab was unchanged compared to ipilimumab administered alone. When OPDIVO 3 mg/kg every 2 weeks was administered in combination with ipilimumab 1 mg/kg every 6 weeks, the CL of nivolumab was unchanged compared to OPDIVO administered alone and the CL of ipilimumab was increased by 30% compared to ipilimumab administered alone.
When OPDIVO 360 mg every 3 weeks was administered in combination with ipilimumab 1 mg/kg every 6 weeks and chemotherapy, the CL of nivolumab was unchanged compared to OPDIVO administered alone and the CL of ipilimumab increased by 22% compared to ipilimumab administered alone.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics There are no clinically significant exposure-response relationships for efficacy or safety for nivolumab monotherapy across the approved dosing regimens, regardless of cancer type.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Unresectable or Metastatic Melanoma Previously Treated Metastatic Melanoma CHECKMATE-037 (NCT01721746) was a multicenter, open-label trial that randomized (2:1) patients with unresectable or metastatic melanoma to receive OPDIVO 3 mg/kg intravenously every 2 weeks or investigator’s choice of chemotherapy, either single-agent dacarbazine 1000 mg/m 2 every 3 weeks or the combination of carboplatin AUC 6 intravenously every 3 weeks and paclitaxel 175 mg/m 2 intravenously every 3 weeks. Patients were required to have progression of disease on or following ipilimumab treatment and, if BRAF V600 mutation positive, a BRAF inhibitor.
The trial excluded patients with autoimmune disease, medical conditions requiring systemic immunosuppression, ocular melanoma, active brain metastasis, or a history of Grade 4 ipilimumab-related adverse reactions (except for endocrinopathies) or Grade 3 ipilimumab-related adverse reactions that had not resolved or were inadequately controlled within 12 weeks of the initiating event. Tumor assessments were conducted 9 weeks after randomization then every 6 weeks for the first year, and every 12 weeks thereafter. Efficacy was evaluated in a single-arm, non-comparative, planned interim analysis of the first 120 patients who received OPDIVO in CHECKMATE-037 and in whom the minimum duration of follow-up was 6 months.
The major efficacy outcome measures in this population were confirmed overall response rate (ORR) as measured by blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and duration of response. Among the 120 patients treated with OPDIVO, the median age was 58 years (range: 25 to 88), 65% of patients were male, 98% were White, and the ECOG performance score was 0 (58%) or 1 (42%). Disease characteristics were M1c disease (76%), BRAF V600 mutation positive (22%), elevated LDH (56%), history of brain metastases (18%), and two or more prior systemic therapies for metastatic disease (68%).
The ORR was 32% (95% confidence interval [CI]: 23, 41), consisting of 4 complete responses and 34 partial responses in OPDIVO-treated patients. Of 38 patients with responses, 87% had ongoing responses with durations ranging from 2.6+ to 10+ months, which included 13 patients with ongoing responses of 6 months or longer. There were responses in patients with and without BRAF V600 mutation-positive melanoma.
A total of 405 patients were randomized and the median duration of OS was 15.7 months (95% CI: 12.9, 19.9) in OPDIVO-treated patients compared to 14.4 months (95% CI: 11.7, 18.2) (HR 0.95; 95.54% CI: 0.73, 1.24) in patients assigned to investigator’s choice of treatment. Figure 1 summarizes the OS results. Figure 1: Overall Survival - CHECKMATE-037* * The primary OS analysis was not adjusted to account for subsequent therapies, with 54 (40.6%) patients in the chemotherapy arm subsequently receiving an anti-PD1 treatment.
OS may be confounded by dropout, imbalance of subsequent therapies, and differences in baseline factors. opdivo-os-checkmate-037.jpg Previously Untreated Metastatic Melanoma CHECKMATE-066 CHECKMATE-066 (NCT01721772) was a multicenter, double-blind, randomized (1:1) trial in 418 patients with BRAF V600 wild-type unresectable or metastatic melanoma. Patients were randomized to receive either OPDIVO 3 mg/kg by intravenous infusion every 2 weeks or dacarbazine 1000 mg/m 2 intravenously every 3 weeks until disease progression or unacceptable toxicity.
Randomization was stratified by PD-L1 status (≥5% of tumor cell membrane staining by immunohistochemistry vs. <5% or indeterminate result) and M stage (M0/M1a/M1b versus M1c). Key eligibility criteria included histologically confirmed, unresectable or metastatic, cutaneous, mucosal, or acral melanoma; no prior therapy for metastatic disease; completion of prior adjuvant or neoadjuvant therapy at least 6 weeks prior to randomization; ECOG performance status 0 or 1; absence of autoimmune di… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to assess the potential of nivolumab for carcinogenicity or genotoxicity. Fertility studies have not been performed with nivolumab. In 1-month and 3-month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, most animals in these studies were not sexually mature.
13.2Animal Toxicology and/or Pharmacology In animal models, inhibition of PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. M. tuberculosis–infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 knockout mice have also shown decreased survival following infection with lymphocytic choriomeningitis virus.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to assess the potential of nivolumab for carcinogenicity or genotoxicity. Fertility studies have not been performed with nivolumab. In 1-month and 3-month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, most animals in these studies were not sexually mature.
📄 Recent Major Changes ▾
Indications and Usage (1) 3/2026 Dosage and Administration (2) 3/2026 Warnings and Precautions (5) 5/2026
📄 Package Label / Principal Display Panel ▾
OPDIVO 40 mg/4 mL Representative Packaging See How Supplied section for a complete list of available packages of OPDIVO. NDC 0003-3772-11 Rx only Opdivo ® (nivolumab) injection 40 mg/4 mL (10 mg/mL) For intravenous Infusion Only Single-dose vial; Discard unused portion. Please provide enclosed Medication Guide to the patient. Bristol Myers Squibb opdivo-40mg-4ml-ctn.jpg
OPDIVO 100 mg/10 mL Representative Packaging NDC 0003-3774-12 Rx only Opdivo ® (nivolumab) injection 100 mg/10 mL (10 mg/mL) For Intravenous Infusion Only Single-dose vial; Discard unused portion. Please provide enclosed Medication Guide to the patient. Bristol Myers Squibb opdivo-100mg-10ml-ctn.jpg
OPDIVO 120 mg/12 mL Representative Packaging NDC 0003-3756-14 Rx only Opdivo ® (nivolumab) injection 120 mg/12 mL (10 mg/mL) For Intravenous Infusion Only Single-dose vial; Discard unused portion. Please provide enclosed Medication Guide to the patient. Bristol Myers Squibb opdivo-120mg-12ml-ctn.jpg
OPDIVO 240 mg/24 mL Representative Packaging NDC 0003-3734-13 Rx only Opdivo ® (nivolumab) injection 240 mg/24 mL (10 mg/mL) For Intravenous Infusion Only Single-dose vial; Discard unused portion. Please provide enclosed Medication Guide to the patient. Bristol Myers Squibb opdivo-240mg-24ml-ctn.jpg
Medicaid utilization & spend
Medicare Part D spend CMS · PART D · 2026 (Q1)
Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |