nivolumab

Nivolumab is a medication used in the treatment of many types of cancers, mostly advanced or metastatic, either as monotherapy or in combination with other medications.

Nivolumab is a type of targeted therapy that does not directly kill cancer cells, but targets and alters a specific cell mechanism that promotes cancer growth and spread. Nivolumab works by stimulating the body’s own immune system to fight against cancer cells.

Nivolumab is a lab-made human monoclonal immunoglobulin G4 (IgG4) antibody designed to act against a specific protein expressed in T-cells, which enhances the activity of T-cells against cancer cells. T-cells are immune cells that normally induce programmed death in damaged and mutated (cancer) cells. In many metastatic cancers, cancer cells escape being killed by the T-cells by developing certain cell mechanisms. Nivolumab blocks a specific protein interaction and cell-signaling that cancer cells use to evade death.

Nivolumab belongs to a class of medications known as PD-1/PD-L1 inhibitors, which binds to protein molecules known as programmed death-1 (PD-1) and inhibits their interactions with PD-L1 and PD-L2 molecules. These proteins are normally expressed on T-cells and the interaction of PD-1 with PD-L1 and PD-L2 inhibits the activation of T-cells. Cancer cells escape death by secreting PD-L1 or inducing the T-cells in the tumor microenvironment to produce PD-L1. Inhibition of PD-1 results in increased T-cell activity against cancer cells.

Nivolumab is administered as an intravenous infusion over 30 minutes. Nivolumab is often used in combination with ipilimumab, another antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4), another protein that inhibits T-cell activity. The uses of Nivolumab include the following:

FDA-approved:

Adult:

• Esophageal cancer
• Advanced or metastatic gastric cancer and gastroesophageal junction cancer
• Recurrent or metastatic squamous cell head and neck cancer
• Hepatocellular carcinoma
• Classical Hodgkin lymphoma
• Unresectable malignant pleural mesothelioma
• Metastatic melanoma
• Metastatic non-small cell lung cancer (NSCLC)
• Metastatic small cell lung cancer
• Advanced renal cell carcinoma
• Urothelial carcinoma

Adult and pediatric (12 years and older:

Under accelerated approval, contingent on verification of benefits in clinical trials

• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer

Adult:

Off-label:

• Metastatic melanoma with brain metastases

Orphan designation:

• Glioblastoma
• Anal cancer
• Primary mediastinal B-cell lymphoma

• Nivolumab can cause immune-mediated severe or even fatal inflammatory reactions. In case of moderate reactions, withhold treatment, monitor the patient, and treat appropriately with corticosteroids. Discontinue permanently in case of severe or life-threatening reactions. Immune-mediated adverse reactions may include
  • Pneumonitis
  • Colitis and diarrhea
  • Hepatitis
  • Endocrinopathies including:
    • Hypophysitis
    • Adrenal insufficiency
    • Hyperglycemia and type I diabetes mellitus
    • Hyperthyroidism or hypothyroidism
  • Nephritis and renal dysfunction
  • Encephalitis
  • Dermatologic reactions including:
    • Stevens-Johnson syndrome
    • Toxic epidermal necrolysis
  • Myocarditis and pericarditis
  • Myositis and rhabdomyolysis
  • Pancreatitis
  • Iritis and uveitis
  • Neuropathies
  • Blood and lymphatic disorders
  • Systemic inflammatory response syndrome
• Nivolumab may cause severe infusion reactions. Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions and discontinue for severe and life-threatening infusion reactions.
• In patients who receive donor (allogeneic) hematopoietic stem cell transplantation (HSCT) before or after nivolumab therapy, serious and fatal complications can occur, including graft-versus-host disease (GVHD), veno-occlusive disease and steroid-requiring febrile syndrome without an identified infectious cause. Monitor patients closely and intervene promptly.
• Nivolumab can cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and at least for 5 months following the last dose.
• Increased mortality was observed in patients with multiple myeloma when PD-1 inhibitor antibody, including nivolumab, was added to thalidomide analog and dexamethasone therapy. This combination is not recommended outside of controlled clinical trials.
• When used in combination with ipilimumab, refer to prescribing information for additional risk information that applies to the combination use treatment.

Common side effects of nivolumab include:

• Fatigue
• Headache
• Fever
• Dizziness
• Weakness (asthenia)
• Musculoskeletal pain
• Joint pain (arthralgia)
• Blood disorders including
  • Low red blood cell count (anemia)
  • Low lymphocyte immune cell count (lymphocytopenia)
  • Low leukocyte immune cell count (leukopenia)
  • Low neutrophil immune cell count (neutropenia)
• Increased serum levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
• Increase in serum alkaline phosphatase
• Increase in serum bilirubin
• Liver inflammation (hepatitis)
• Increase in gamma-glutamyl transferase enzyme
• Increase in blood glucose levels (hyperglycemia)
• Increase in serum albumin
• Overactive or underactive thyroid (hyperthyroidism/hypothyroidism)
• Electrolyte disturbances including:
  • Low sodium levels (hyponatremia)
  • High or low calcium levels (hypercalcemia/hypocalcemia)
  • High or low potassium levels (hyperkalemia/hypokalemia)
  • Low magnesium (hypomagnesemia)
• Increase in level of amylase, the enzyme that breaks down carbohydrates
• Increase in serum lipase, the enzyme that breaks down fats
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Reduced appetite
• Weight loss
• Constipation
• Colon inflammation (colitis)
• Intestinal perforation
• Oral inflammation (stomatitis)
• Skin reactions including
  • Rash
  • Redness (erythema)
  • Itching (pruritus)
  • White patches from loss of pigmentation (vitiligo)
• Cough
• Productive cough
• Shortness of breath (dyspnea)
• Dyspnea upon exertion
• Upper respiratory tract infections
• Lung inflammation (pneumonitis)
• Renal insufficiency
• Increase in serum creatinine
• Kidney inflammation (nephritis)
• Swelling of extremities (peripheral edema)
• High blood pressure (hypertension)
• Antibody development
• Sjogren syndrome
• Nerve inflammation (neuritis)
• Peripheral nerve weakness (palsy)
• Peripheral nerve disease (neuropathy)
• Muscle disease (myopathy)
• Muscle inflammation (myositis)
• Skeletal muscle inflammation affecting both sides (polymyositis)
• Rheumatism
• Infusion-related reactions
• Adrenocortical insufficiency

Less common side effects of nivolumab include:

• Heart muscle inflammation (myocarditis)
• Acute coronary syndrome
• Heart failure
• Inflammation of pericardium, membrane around the heart (pericarditis)
• Fluid around the heart (pericardial effusion)
• Blood vessel inflammation (vasculitis)
• Cold fingers and toes with reduced blood flow (acral ischemia)
• Fluid buildup in the chest and around lungs (pleural effusion)
• Gastritis
• Inflammation of esophagus (esophagitis)
• Inflammation of duodenum (duodenitis)
• Inflammation of pancreas (pancreatitis)
• Inflammation of bile ducts (cholangitis) or gall bladder (cholecystitis)
• Dry mouth (xerostomia)
• Oral ulcers
• Type I diabetes mellitus
• Diabetic ketoacidosis
• Thyroid inflammation (thyroiditis)
• Hypoparathyroidism
• Graves’ disease
• Inflammation of the pituitary gland (hypophysitis)
• Solid organ transplant rejection
• Graft-versus-host disease (GVHD), a condition in which transplanted donor cells attack the host cells
• Hepatic veno-occlusive disease, a condition that blocks small veins in the liver, damaging the liver
• Steroid-requiring febrile syndrome
• Cytokine release syndrome
• Systemic inflammatory response syndrome
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Acute kidney injury
• Inflammation of the infrarenal portion of the abdominal aorta (periaortitis)
• Severe skin reactions including:
  • Bullous pemphigoid
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Bluish-gray nail discoloration
• Blood disorders including:
  • Anemia due to inadequate production of red cells (aplastic anemia)
  • Anemia due to autoimmune destruction of red cells (autoimmune hemolytic anemia)
  • Immune-mediated low platelet levels (immune thrombocytopenia)
  • Thrombotic thrombocytopenic purpura
  • Low count of all types of blood cells (pancytopenia)
  • Acquired blood coagulation disorder (hemophilia)
  • Disseminated intravascular coagulation
• Growth of clusters of inflammatory immune cells in the skin (granuloma annulare)
• Granulomas in any part of the body (sarcoidosis)
• Lymph node infection and inflammation (lymphadenitis)
• T-cell lymphoma
• Tumor lysis syndrome, a condition in which large number of tumor cells die and release their contents into the bloodstream
• Demyelinating diseases, conditions that damage the protective layer (myelin sheath) of nerve fibers
• Inflammation of the brain (encephalitis)
• Reversible posterior leukoencephalopathy syndrome, a condition that affects the brain’s white matter
• Inflammation of the membranes covering the brain and spinal cord (meningitis)
• Cerebral hemorrhage
• Autoimmune neuropathy
• Guillain-Barre syndrome
• Muscle weakness due to nerve damage (paresis)
• Muscle weakness (myasthenia)
• Onset or exacerbation of myasthenia gravis
• Inflammation of the spinal cord (myelitis)
• Muscle pain (myalgia)
• Inflammatory muscle disorder (polymyalgia rheumatica)
• Muscle breakdown (rhabdomyolysis)
• Inflammatory muscle disease with skin rash (dermatomyositis)
• Lambert-Eaton syndrome
• Cutaneous lupus erythematosus
• Joint inflammation (arthritis)
• Inflammatory disease of multiple joints (inflammatory polyarthropathy)
• Inflammation of ribs (costochondritis)
• Eye conditions such as:
  • Inflammation of the iris (iritis)
  • Inflammation of the uvea (uveitis)
  • Inflammation of cornea (keratitis)
  • Droopy eyelid (blepharoptosis)
  • Dry eye syndrome
• Vogt-Koyanagi-Harada disease
• Bilateral hearing loss

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Intravenous (IV) Solution

• 10 mg/mL (4mL, 10mL)
• Further dilution required before administration

Adult:

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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 1 mg/kg IV every 3 weeks 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 and larger or node positive) NSCLC
• Nivolumab 360 mg IV every 3 weeks, PLUS
• Platinum-doublet chemotherapy every 3 weeks 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 every 2 weeks or 480 mg IV every 4 weeks
• 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% or greater) with no EGFR or ALK genomic tumor aberrations
• Nivolumab 360 mg IV every 3 weeks, PLUS
• Ipilimumab 1 mg/kg IV every 6 weeks  
• 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 every 3 weeks, PLUS
• Ipilimumab 1 mg/kg IV every 6 weeks, PLUS
• Histology-based platinum doublet chemotherapy every 3 weeks 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 every 3 weeks, PLUS
• Ipilimumab 1 mg/kg IV every 6 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks plus cabozantinib (Cabometyx) 40 mg orally every day
  • 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 every 3 weeks 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 every 2 weeks or 480 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity
  • 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 or more of systemic therapy (e.g., autologous HSCT)
• 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Recurrent of Metastatic Squamous Head and 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 3 mg/kg IV every 3 weeks 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 the 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 every 3 weeks 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
• 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 every 2 weeks or 480 mg IV every 4 weeks
  • Continue fluoropyrimidine- and platinum-based chemotherapy until disease progression or unacceptable toxicity
  • Continue nivolumab until disease progression, unacceptable toxicity, or up to 2 years
• Combination with ipilimumab
  • 3 mg/kg IV every 2 weeks or 360 mg IV every 3 weeks plus ipilimumab 1 mg/kg IV every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or up to 2 years

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 every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity for up to 1 year

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 every 2 weeks or 360 mg IV every 3 weeks plus a platinum-containing therapy (e.g., oxaliplatin) and a fluoropyrimidine (e.g., fluorouracil, capecitabine)
• Continue until disease progression, unacceptable toxicity, or up to 2 years

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 below 1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (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 below 1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (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 above 3 and up to 8 times the upper limits of normal (ULN) or total bilirubin increases to above 1.5 and up to 3 times ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade below 1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (or equivalent) within 12 weeks of initiating steroids
• AST or ALT increases to above 8 times ULN or total bilirubin increases to above 3 times ULN: Permanently discontinue

Hepatitis with tumor involvement of the liver

• Withhold therapy
  • Baseline AST or ALT above 1 and up to 3 times ULN and increases to above 5 and up to 10 times ULN
  • Baseline AST or ALT above 3 and up to 5 times ULN and increases to above 8 and up to 10 times ULN
  • Resume when complete or partial resolution occurs (Grade below 1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (or equivalent) within 12 weeks of initiating steroids
• Permanently discontinue
  • AST or ALT increases to above 10 times ULN or total bilirubin increases to above 3 times 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 below 1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (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 below 1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg/day or less (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

Pediatric:

Microsatellite Instability-High Cancer

• Indicated as a single agent or in combination with ipilimumab for patients aged 12 years or above 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

Children below 12 years: Safety and efficacy not established

Children 12 years and above

Single agent

• Children below 40 kg: 3 mg/kg IV every 2 weeks  
• Children 40 kg and above: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 3 mg/kg IV every 3 weeks 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 every 2 weeks (patients below 40 kg); 240 mg IV every 2 weeks or 480 mg IV every 4 weeks (patients 40 kg or above)
• Continue until disease progression or unacceptable toxicity

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Nivolumab has no known severe interactions with other drugs.
• Serious interactions of nivolumab include:
  • axicabtagene ciloleucel
  • brexucabtagene autoleucel
  • ciltacabtagene autoleucel
  • dexamethasone
  • idecabtagene vicleucel
  • ifosfamide
  • lisocabtagene maraleucel
  • lomustine
  • mechlorethamine
  • melphalan
  • palifermin
  • procarbazine
  • selinexor
  • thalidomide
  • tisagenlecleucel
• Moderate interactions of nivolumab include:
  • cholera vaccine
  • dengue vaccine
  • dichlorphenamide
  • efgartigimod alfa
  • oxaliplatin
  • ponesimod
  • siponimod
• Nivolumab has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Nivolumab can cause fetal harm. Women of pregnancy potential should use effective contraception during therapy and for at least 5 months following the last dose of nivolumab.
• There are no human data available on drug-associated fetal risk, but based on animal reproduction studies and nivolumab’s mechanism of action, administration of nivolumab during pregnancy can:
  • Result in spontaneous abortion or premature infant death. The drug effects are likely to be greater in the second and third trimesters of pregnancy.
  • Increase the risk of the development of fetal immune-mediated disorders or altering of the normal immune response.
• It is not known if nivolumab is present in breast milk, however, many drugs are excreted in breast milk. Nursing mothers should discontinue breastfeeding while on treatment with nivolumab, because of the potential for serious adverse reactions in the breastfed infant.

• While on nivolumab treatment, contact your healthcare provider immediately if you:
  • Develop any symptoms of immune-related inflammatory reactions
  • Experience infusion reactions