Nivolumab
FDA Drug Information • Also known as: Opdivo
- Brand Names
- Opdivo
- Drug Class
- Programmed Death Receptor-1 Blocking Antibody [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
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.
What Is Nivolumab Used For?
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-approved 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 patients with classical Hodgkin lymphoma that has relapsed or progressed after a : (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,...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 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...Side Effects (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) 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 . 6.1 Clinical 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); and OPDIVO 240 mg with cabozantinib 40 mg in patients enrolled in CHECKMATE-9ER (n=320). 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 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, patients with a condition requiring chronic systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications, a...Contraindications
4 CONTRAINDICATIONS None.
None. (4)Pregnancy and Breastfeeding
8.1 Pregnancy 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...
How Supplied
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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.