Dosing & Uses
Dosage Forms & Strengths
IV solution
- 10mg/mL (4mL, 10mL)
- Further dilution required before administration
Adjuvant Treatment of Melanoma
Indicated for melanoma in patients with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity for up to 1 year
Unresectable or Metastatic Melanoma
Indicated as a single agent or in combination with ipilimumab
Single agent
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
- Nivolumab 1 mg/kg IV q3Weeks PLUS
- Ipilimumab 3 mg/kg IV on the same day for maximum of 4 doses
- After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Non-Small Cell Lung Cancer (NSCLC)
Resectable NSCLC
- Indicated as neoadjuvant treatment in combination with platinum-doublet chemotherapy for resectable (tumors ≥4 cm or node positive) NSCLC
- Nivolumab 360 mg IV q3Weeks, PLUS
- Platinum-doublet chemotherapy q3Weeks for 3 cycles
-
Platinum-doublet chemotherapy consists of the following
- Paclitaxel 175-200 mg/m2 and carboplatin AUC 5 or 6 (any histology): OR
- Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 (non-squamous histology); OR
- Gemcitabine 1000-1250 mg/m2 and cisplatin 75 mg/m2 (squamous histology)
Metastatic NSCLC
-
Monotherapy
- Indicated for metastatic NSCLC with progression in patients on or after platinum-based chemotherapy
- Patients with EGFR or ALK genomic tumor aberrations should have disease progression prior to initiation
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
-
Combination therapy with ipilimumab
- Indicated in combination with ipilimumab for first-line treatment of metastatic NSCLC in adults whose tumors express PD-L1 (≥1%) with no EGFR or ALK genomic tumor aberrations
- Nivolumab 360 mg IV q3Weeks, PLUS
- Ipilimumab 1 mg/kg IV q6Weeks
- Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
-
Combination with ipilimumab and platinum chemotherapy
- Indicated in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment of metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic tumor aberrations
- Nivolumab 360 mg IV q3Weeks, PLUS
- Ipilimumab 1 mg/kg IV q6Weeks, PLUS
- Histology-based platinum doublet chemotherapy q3Weeks for 2 cycles
- Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Malignant Pleural Mesothelioma
Indicated as first-line treatment for unresectable malignant pleural mesothelioma in combination with ipilimumab
Nivolumab 360 mg IV q3Weeks, PLUS
Ipilimumab 1 mg/kg IV q6Weeks
Continue in combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Renal Cell Carcinoma
First-line treatment
-
Combination with cabozantinib
- Indicated in combination with cabozantinib for first-line treatment of advanced renal cell carcinoma (RCC)
- 240 mg IV q2Weeks or 480 mg IV q4Weeks plus cabozantinib (Cabometyx) 40 mg PO qDay
- Nivolumab: Continue until disease progression or unacceptable toxicity, or up to 2 years
- Cabozantinib: Continue until disease progression or unacceptable toxicity
- Note: Do not substitute Cabometyx tablets with Cometriq capsules
-
Combination with ipilimumab
- Indicated for patients with intermediate or poor risk, previously untreated advanced RCC
- Nivolumab 3 mg/kg IV q3Weeks PLUS
- Ipilimumab 1 mg/kg IV on the same day for 4 doses
- After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
- Also see ipilimumab drug monograph for dose
Prior antiangiogenic therapy
- Indicated as a single agent for advanced RCC in patients who have received prior antiangiogenic therapy
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Hodgkin Lymphoma
Indicated for classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin, or ≥3 lines of systemic therapy (eg, autologous HSCT)
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Recurrent of Metastatic Squamous Head & Neck Carcinoma
Indicated for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in patients with disease progression on or after a platinum-based therapy
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Urothelial Carcinoma
Locally advanced or metastatic
- Indicated for locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Adjuvant treatment
- Indicated for adjuvant treatment of UC in patients at high risk of recurrence after undergoing radical resection
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity for up to 1 year
Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer
Indicated as a single agent or in combination with ipilimumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan
Single agent
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
- Nivolumab 3 mg/kg IV q3Weeks PLUS
- Ipilimumab 1 mg/kg IV on the same day for 4 doses
- After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Hepatocellular Carcinoma
Indicated in combination with ipilimumab for hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib
Single agent: Indication was voluntarily withdrawn in the U.S. by manufacturer in July 2021 based on failure of showing a statistically significant benefit in overall survival compared to nivolumab and sorafenib combined
Combination with ipilimumab
- Nivolumab 1 mg/kg IV q3Weeks PLUS
- Ipilimumab 3 mg/kg IV on the same day for 4 doses
- After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Esophageal Cancer
Previously treated
- Indicated for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in patients previously treated with fluoropyrimidine- and platinum-based chemotherapy
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
First-line treatment
- Indicated for first-line treatment of unresectable advanced or metastatic ESCC in combination with fluoropyrimidine- and platinum-based chemotherapy or ipilimumab
-
Combination with fluoropyrimidine and platinum chemotherapy
- 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue fluoropyrimidine- and platinum-based chemotherapy until disease progression or unacceptable toxicity
- Continue nivolumab until disease progression, unacceptable toxicity, or up to 2 yr
-
Combination with ipilimumab
- 3 mg/kg IV q2Weeks or 360 mg IV q3Weeks plus ipilimumab 1 mg/kg IV q6Weeks
- Continue until disease progression, unacceptable toxicity, or up to 2 yr
Completely resected
- Indicated for completely resected esophageal or gastroesophageal junction cancer in patients with residual pathologic disease who have received neoadjuvant chemoradiotherapy
- 240 mg IV q2Weeks or 480 mg q4Weeks
- Continue until disease progression or unacceptable toxicity for up to 1 yr
Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma
Indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy, for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma
240 mg IV q2Weeks or 360 mg IV q3Weeks plus a platinum-containing therapy (eg, oxaliplatin) and a fluoropyrimidine (eg, fluorouracil, capecitabine)
Continue until disease progression, unacceptable toxicity, or up to 2 yr
Dosage Modifications
No dose reductions are recommended
Hypothyroidism or hyperthyroidism: No recommended dose modifications
Note: When administered in combination with ipilimumab, if nivolumab is withheld, ipilimumab should also be withheld
Renal impairment
- All severities: No dosage modifications required
Hepatic impairment
- Mild or moderate: No dosage modifications required
- Severe: Not studied
Pneumonitis
- Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Colitis
- Grade 2 or 3: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4: Permanently discontinue
Hepatitis with no tumor involvement of the liver
- AST or ALT increases to >3 and ≤8x ULN or total bilirubin increases to >1.5 and <3x ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- AST or ALT increases to >8x ULN or total bilirubin increases to >3x ULN: Permanently discontinue
Hepatitis with tumor involvement of the liver
-
Withhold therapy
- Baseline AST or ALT >1 and ≤3x ULN and increases to >5 and ≤10x ULN
- Baseline AST or ALT >3 and ≤5x ULN and increases to >8 and ≤10x ULN
- Resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
-
Permanently discontinue
- AST or ALT increases to >10x ULN or total bilirubin increases to >3x ULN
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 therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4 increased blood creatinine: Permanently discontinue
Exfoliative dermatologic conditions
- Suspected Steven Johnson Syndrome (SJS), toxic epidermal necrosis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Withhold therapy
- Confirmed SJS, TEN, or DRESS: Permanently discontinue
Myocarditis
- Grade 2, 3, or 4: Permanently discontinue
Neurologic toxicities
- Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Infusion-related reactions
- Grade 1 or 2: Interrupt or slow infusion rate
- Grade 3 or 4: Permanently discontinue
Dosing Considerations
Patient selection
- For the MSI-H/dMMR indications, select patients for treatment as a single agent based on MSI-H/dMMR status in tumor specimens
- For the TMB-H indication, select patients for treatment as a single agent based on TMB-H status in tumor specimens
- An FDA-approved test for the detection of MSI-H or dMMR is not currently available
-
Select patients for treatment based on the presence of positive PD-L1 expression in
- NSCLC
- HNSCC
- Metastatic urothelial carcinoma
- Metastatic gastric cancer
- Metastatic esophageal cancer
- Recurrent or metastatic cervical cancer
- Information on FDA-approved tests for the detection of PD-L1 expression and TMB status is available at: http://www.fda.gov/CompanionDiagnostics
Orphan Designations
Glioblastoma
Anal cancer
Primary mediastinal B-cell lymphoma
Orphan sponsor
- Bristol-Myers Squibb Company; P. O. Box 4000; Princeton, New Jersey 08543
Dosage Forms & Strengths
IV solution
- 10mg/mL (4mL, 10mL)
- Further dilution required before administration
Adjuvant Treatment of Melanoma
Indicated for melanoma in adults and pediatric patients aged ≥12 years with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting
≥12 years and <40 kg: 3 mg/kg mg IV q2Weeks or 6 mg/kg IV q4Weeks
≥12 years and ≥40 kg: 240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Unresectable or Metastatic Melanoma
Indicated as a single agent or in combination with ipilimumab in adults and pediatric patients aged ≥12 years
Single agent
- ≥12 years and <40 kg: 3 mg/kg IV q2Weeks or 6 mg/kg IV q4Weeks
- ≥12 years and ≥40 kg: 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
- Nivolumab 1 mg/kg IV q3Weeks PLUS
- Ipilimumab 3 mg/kg IV on the same day for maximum of 4 doses or until unacceptable toxicity, whichever comes first
-
After completing 4 doses of combination therapy, administer nivolumab
- ≥12 years and <40 kg: 3 mg/kg mg IV q2Weeks or 6 mg/kg IV q4Weeks
- ≥12 years and ≥40 kg: 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
Microsatellite Instability-High Cancer
Indicated as a single agent or in combination with ipilimumab for patients aged ≥12 years with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan
<12 years: Safety and efficacy not established
≥12 year
-
Single agent
-
Combination with ipilimumab
- Nivolumab 3 mg/kg IV q3Weeks PLUS
- Ipilimumab 1 mg/kg IV on the same day for 4 doses
- After completing 4 doses of combination therapy: Administer nivolumab 3 mg/kg IV q2Weeks (patients <40 kg); 240 mg IV q2Weeks or 480 mg IV q4Weeks (patients ≥40 kg)
- Continue until disease progression or unacceptable toxicity
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (15)
- axicabtagene ciloleucel
nivolumab, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- brexucabtagene autoleucel
nivolumab, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ciltacabtagene autoleucel
nivolumab, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dexamethasone
dexamethasone increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.
- idecabtagene vicleucel
nivolumab, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ifosfamide
ifosfamide, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.
- lisocabtagene maraleucel
nivolumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- lomustine
lomustine and nivolumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.
- mechlorethamine
mechlorethamine, nivolumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.
- melphalan
melphalan, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.
- palifermin
palifermin increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- procarbazine
procarbazine, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.
- selinexor
selinexor, nivolumab. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
- thalidomide
thalidomide increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.
- tisagenlecleucel
nivolumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
Monitor Closely (8)
- cholera vaccine
nivolumab decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- dengue vaccine
nivolumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- dichlorphenamide
dichlorphenamide and nivolumab both decrease serum potassium. Use Caution/Monitor.
- efgartigimod alfa
efgartigimod alfa will decrease the level or effect of nivolumab by receptor binding competition. Use Caution/Monitor. Coadministration of efgartigimod with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- oxaliplatin
oxaliplatin and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.
- ponesimod
ponesimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- siponimod
siponimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- ublituximab
ublituximab and nivolumab both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered
Minor (0)
Adverse Effects
>10% (All grades)
Melanoma
- Increased AST (28%)
- Hyponatremia (25%)
- Increased alkaline phosphatase (22%)
- Rash (21%)
- Pruritus (19%)
- Cough (17%)
- Increased ALT (16%)
- Hyperkalemia (15%)
- URTI (11%)
NSCLC
- Fatigue (50%)
- Lymphopenia (47%)
- Dyspnea, hyponatremia (38%)
- Musculoskeletal pain (36%)
- Cough (32%)
- Nausea (29%)
- Increases creatinine (22%)
- Hypercalcemia, hypokalemia, hypomagnesemia (20%)
- Vomiting, asthenia (19%)
- Hypocalcemia, hyperkalemia, diarrhea (18%)
- Edema, pyrexia (17%)
- Abdominal pain, rash, increased AST (16%)
- Increased alkaline phosphatase, thrombocytopenia (14%)
- Chest pain, arthralgia, decreased appetite and weight (13%)
- Increased ALT (12%)
1-10% (all grades)
Melanoma
- Peripheral edema (10%)
NSCLC
- Pneumonia (10%)
- Pain (10%)
1-10% (grades 3-4)
Melanoma
- Hyponatremia (5%)
- Increased AST (2.4%)
- Increased alkaline phosphatase (2.4%)
- Hyperkalemia (2%)
- Increased ALT (1.6%)
NSCLC
- Dyspnea (9%)
- Fatigue (7%)
- Musculoskeletal pain (6%)
- Pneumonia (5%)
- Decreased appetite (2.6%)
- Pain (2.6%)
- Nausea (1.7%)
- Abdominal pain (1.7%)
- Asthenia (1.7%)
- Edema (1.7%)
- Cough (1.7%)
1-10% (other clinically important adverse effects)
Melanoma
- Cardiac disorders: Ventricular arrhythmia
- Eye disorders: Iridocyclitis
- General disorders and administration site conditions: Infusion-related reactions
- Immune-mediated disorders: Severe pneumonitis or interstitial lung disease, including fatal cases; colitis; hepatitis; nephritis; thyroid disorders; other immune disorders (pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal insufficiency, facial and abducens nerve paresis, hypophysitis, polymyalgia rheumatica, diabetic ketoacidosis, hypopituitarism, Guillain-Barré syndrome, myasthenic syndrome)
- Investigations: Increased amylase, increased lipase
- Nervous system disorders: Dizziness, peripheral and sensory neuropathy
- Skin and subcutaneous tissue disorders: Exfoliative dermatitis, erythema multiforme, vitiligo, psoriasis
NSCLC
- General disorders and administration site conditions: Stomatitis
- Nervous system disorders: Peripheral neuropathy
- Infections and infestations: Bronchitis, upper respiratory tract infection
Postmarketing Reports
Eye disorders: Vogt-Koyanagi-Harada (VKH) syndrome
Complications of treatment after allogeneic HSCT: Treatment refractory, severe acute and chronic graft versus host disease (GVHD)
Pyrexia
Ascites
Back pain
General physical health deterioration
Abdominal pain
Pneumonia
Anemia
Hemophagocytic lymphohistiocytosis (HLH)
Autoimmune hemolytic anemia
Warnings
Contraindications
None
Cautions
Severe infusion-related reactions can occur; discontinue in patients with severe or life-threatening infusion reactions
Fatal or serious graft-versus-host disease (GVHD) can occur in patients who receive a CTLA-4 receptor blocking antibody either before or after allogeneic hematopoietic stem cell transplantation (HSCT); closely monitor for evidence of GVHD and intervene promptly; consider benefit versus risks of treatment with a CTLA-4 receptor blocking antibody after allogeneic HSCT
May cause fetal harm when administered to pregnant females
When used in combination with ipilimumab, refer to prescribing information for additional risk information that applies to the combination use treatment
In clinical trials in multiple myeloma patients, the addition of a PD-1 blocking antibody to a thalidomide analog plus dexamethasone resulted in increased mortality
Hepatotoxicity
- In combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to drug alone
- Monitor liver enzymes before initiation of and periodically throughout treatment; consider more frequent monitoring of liver enzymes as compared to when drugs are administered as single agents
- For elevated liver enzymes, interrupt combination with cabozantinib and consider administering corticosteroids
Immune-mediated adverse reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction; reactions may be severe or fatal; monitor for early identification and management; evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
- Immune-mediated encephalitis can occur; withhold therapy in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out infectious or other causes of moderate to severe neurologic deterioration
- Other clinically significant and potentially fatal immune-mediated adverse reactions (eg, myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis) can occur after discontinuation
-
Immune-mediated endocrinopathies
- Immune-mediated hypophysitis; monitor
- Immune-mediated hypothyroidism and hyperthyroidism reported; monitor for changes in thyroid function and initiate thyroid hormone replacement as needed; administer hormone-replacement therapy for hypothyroidism; initiate medical management for control of hyperthyroidism
- Adrenal insufficiency may occur; monitor for signs and symptoms of adrenal insufficiency during and after treatment
- May cause type 1 diabetes mellitus; monitor for hyperglycemia
-
Immune-mediated skin reactions
- May cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); for symptoms or signs of SJS or TEN, withhold therapy and refer patient for specialized care for assessment and treatment
- Immune-mediated rash reported in combination with ipilimumab; withhold for severe and permanently discontinue for life-threatening rash
-
Immune-mediated colitis
- Therapy can cause immune-mediated colitis, defined as requiring use of corticosteroids and no clear alternate etiology; common symptom in definition of colitis reported to be diarrhea
- Cytomegalovirus (CMV) infection/reactivation reported in patients with corticosteroid refractory immune-mediated colitis; in cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action and data from animal studies, fetal harm may occur when administered to a pregnant woman
There are no available human data informing the drug-associated risk
Animal data
- 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
- 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
- Effects of nivolumab are likely to be greater during the second and third trimesters of pregnancy
Contraception
- Females of reproductive potential: Verify pregnancy status prior to initiating therapy; use effective contraception during treatment with nivolumab and for at least 5 months following last dose of therapy
Lactation
Unknown if distributed in human breast milk; advise women to discontinue breastfeeding during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2
PD-1 and PD-L1
- PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions; PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound
- This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
- Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells
Absorption
Time to steady state: 12 wk (monotherapy)
Distribution
Vd: 6.8L (monotherapy); 7.92 L (combined with ipilimumab)
Elimination
Clearance: 8.2 mL/h (monotherapy); 10 mL/hr (combined with ipilimumab)
Half-life: 25 days (monotherapy); 24.8 days (combined with ipilimumab)
Administration
IV Preparation
Visually inspect drug for particulate matter and discoloration; it should be a clear to opalescent, colorless to pale-yellow solution
Discard vial if the solution is cloudy, discolored, or contains extraneous particulate matter other than a few translucent-to-white, proteinaceous particles
Do not shake the vial
Admixture
- Withdraw required volume for calculated dose and transfer to an IV container
- Dilute with either 0.9% NaCl or D5W to a final concentration ranging from 1-10 mg/mL
- Total volume of infusion must not exceed 160 mL
- Mix diluted solution by gentle inversion; do NOT shake
- Discard partially used vials or empty vials
IV Administration
Infuse IV over 30-60 min in an IV line containing a sterile, nonpyrogenic, low protein-binding inline filter (pore size of 0.2-1.2 microns)
For adult and pediatric patients (<40 kg): Total volume of infusion must not exceed 4 mL/kg of body weigh
Do not coadminister other drugs through the same IV line
Combined with ipilimumab: Infuse nivolumab first over 30 min followed by ipilimumab over 30 min on the same day; use separate infusion bags and filters for each infusion
Combined with chemotherapy on the same day: Administer prior to chemotherapy
Flush the IV line at end of infusion
Storage
Does not contain preservatives
Unopened vials
- Refrigerate at 2-8°C (36-46°F)
- Protect from light by storing in the original package
- Do not freeze
Diluted admixture
- Room temperature: Store for up to 8 hr from time of preparation; this includes room temperature storage of the admixture in the IV container and time for administration of the infusion OR
- Refrigerate at 2-8°C (36-46°F) for no more than 24 hr from the time of admixture preparation
- Do not freeze
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Opdivo intravenous - | 100 mg/10 mL vial |  | |
| Opdivo intravenous - | 40 mg/4 mL vial |  |
Copyright © 2010 First DataBank, Inc.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
