Nivolumab

Nivolumab is a prescription medication indicated for the treatment of:

• Adjuvant treatment of melanoma 
• Unresectable or metastatic melanoma
• Non-small cell lung cancer (NSCLC)
• Malignant pleural mesothelioma
• Renal cell carcinoma (RCC)
• Classical Hodgkin lymphoma
• Recurrent or metastatic squamous head & neck carcinoma
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer
• Hepatocellular carcinoma (HCC)
• Esophageal cancer
• Gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma

Nivolumab is available under the following different brand names: Opdivo.

Common side effects of Nivolumab include:

• feeling tired
• rash
• pain in muscles, bones, and joints
• itching
• diarrhea
• nausea
• weakness
• cough
• shortness of breath
• constipation
• decreased appetite
• back pain
• upper respiratory tract infection
• fever
• headache
• abdominal pain
• vomiting
• urinary tract infection
• hypothyroidism
• joint pain
• weight loss
• dizziness
• numbness, pain, tingling, or burning in your hands or feet
• mouth sores
• change in sense of taste
• rash, redness, pain, swelling, or blisters on the palms of the hands or soles of the feet
• high blood pressure

Serious side effects of Nivolumab include:

• lung problems causing symptoms like cough
• intestinal problems causing symptoms like diarrhea, black or tarry stools, and severe abdominal pain
• liver problems causing symptoms like yellowing of the skin and white of the eyes, dark urine, severe nausea and vomiting, bleeding or bruising more than normal, pain on the right side of the abdomen
• hormone gland problems causing symptoms like unusual headaches, eye problems, sensitivity to light, 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, voice getting deeper, dizziness or fainting, changes in mood or behavior, such as decreased sex drive, irritability or forgetfulness
• kidney problems causing symptoms like decrease in urine output, blood in the urine, swelling of the ankles, loss of appetite
• skin problems causing symptoms like rash, itching, skin blistering or peeling, swollen lymph nodes, painful sores or ulcers in the mouth, nose, throat, or genital area, and fever
• severe infusion reactions causing chills or shaking, itching or rash, flushing, or wheezing, dizziness, fainting, fever, and back or neck pain
• risk of organ or tissue transplant rejection
• complications of stem cell transplant that uses donor stem cells

Rare side effects of Nivolumab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

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

Adult and pediatric dosage
IV solution

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

Adjuvant treatment of melanoma
Adult dosage

• 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

Pediatric dosage

• Children aged  12 years and older and weighing less than 40 kg: 3 mg/kg mg IV every 2 weeks or 6 mg/kg IV every 4 weeks
• Children aged  12 years and older and weighing 40 kg and more: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Unresectable or metastatic melanoma
Adult dosage
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 a 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

Pediatric dosage
Single agent

• Children aged 12 years and older and weighing less than 40 kg: 3 mg/kg IV every 2 weeks or 6 mg/kg IV every 4 weeks
• Children aged  12 years and older and weighing 40 kg and more: 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 a maximum of 4 doses or until unacceptable toxicity, whichever comes first
• After completing 4 doses of combination therapy, administer nivolumab
• Children aged  12 years and older and weighing  less than 40 kg: 3 mg/kg mg IV every 2 weeks or 6 mg/kg IV every 4 weeks
• Children aged  12 years and older and weighing 40 kg and more: 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)
Adult dosage

• Neoadjuvant treatment of resectable (tumors sized 4 cm and greater or node positive) NSCLC
  • Nivolumab 360 mg IV every 3 weeks, plus
  • Platinum-doublet chemotherapy every 3 weeks for 3 cycles consisting of 
    • 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)
• Neoadjuvant and adjuvant treatment of resectable NSCLC
  • Nivolumab 360 mg IV every 3 weeks, plus
  • Platinum-doublet chemotherapy on Day 1 every 3 weeks for up to 4 cycles consisting of 
    • Paclitaxel 175 or 200 mg/m2 and carboplatin AUC 5 or 6 (any histology); or
    • Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 or 6 (non-squamous histology); or
    • Cisplatin 75 mg/m2 and docetaxel 75 mg/m2 (squamous histology)
    • Adjuvant therapy: Nivolumab 480 mg IV every 4 weeks starting within 90 days after surgery until disease progression, recurrence, or unacceptable toxicity for up to 13 cycles (approximately 1 year)
• Metastatic NSCLC
  • Monotherapy
    • Patients with EGFR or ALK genomic tumor aberrations should have disease progression before 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
    • 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
    • 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
Adult dosage

• 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
Adult dosage

• First-line treatment
• Combination with cabozantinib
  • 240 mg IV every 2 weeks or 480 mg IV every 4 weeks plus cabozantinib (Cabometyx) 40 mg orally once a day
  • Nivolumab: Continue until disease progression or unacceptable toxicity, or up to 2 years
  • Cabozantinib: Continue until disease progression or unacceptable toxicity
  • Do not substitute cabometyx tablets with Cometriq capsules
• 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
• 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
Adult dosage

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

Recurrent or metastatic squamous head & neck carcinoma
Adult dosage

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

Urothelial carcinoma
Adult dosage

• First-line treatment
  • Each cycle is 21 days
  • Nivolumab 360 mg IV on Day 1
  • Cisplatin 70 mg/m2 on Day 1
  • Gemcitabine 1000 mg/m2 on Days 1 and 8
  • For up to 6 cycles
• After completing up to 6 cycles
  • Nivolumab 240 mg IV every 2 weeks or 480 mg every 4 weeks as a single agent
  • Continue until disease progression, unacceptable toxicity, or up to 2 years from the first dose
• Locally advanced or metastatic
  • 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity
• Adjuvant treatment
  • 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
Adult dosage

• 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
  • 240 mg IV every 3 weeks plus ipilimumab 1 mg/kg IV every 3 weeks for a maximum of 4 doses, followed by
  • Single-agent nivolumab 240 mg IV every 2 weeks or480 mg IV every 4 weeks until disease progression, unacceptable toxicity, or up to 2 years

Pediatric dosage

• Children younger than 12 years: Safety and efficacy not established
• Children aged 12 years and older
• Single agent
  • Children weighing less than 40 kg: 3 mg/kg IV every 2 weeks  
  • Children weighing 40 kg and more: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity
• Combination with ipilimumab
  • Children weighing 40 kg and more:
    • 240 mg IV every 3 weeks plus ipilimumab 1 mg/kg IV every 3 weeks for maximum of 4 doses, followed by
    • Single-agent nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression, unacceptable toxicity, or up to 2 years
  • Children weighing less than 40 kg:
    • 3 mg/kg IV every 3 weeks plus ipilimumab 1 mg/kg IV every 3 weeks for maximum of 4 doses, followed by
    • Single-agent nivolumab 3 mg/kg IV every 2 weeks or 6 mg/kg IV every 4 weeks until disease progression, unacceptable toxicity, or up to 2 years

Hepatocellular carcinoma
Adult dosage

• Single agent: Indication was voluntarily withdrawn in the U.S. by the manufacturer in July 2021 based on failure to show a statistically significant benefit in overall survival compared to nivolumab and sorafenib combined
• Combination with ipilimumab
  • 1 mg/kg IV every 3 weeks plus ipilimumab 3 mg/kg IV every 3 weeks for a maximum of 4 doses, followed by
  • Single-agent nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression, unacceptable toxicity, or up to 2 years

Esophageal cancer
Adult dosage

• Previously treated
  • 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity
• First-line treatment
  • 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
  • 240 mg IV every 2 weeks or 480 mg every 4 weeks
  • Continue until disease progression or unacceptable toxicity for up to 1 year

Gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma
Adult dosage

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

Dosage Considerations – Should be Given as Follows: 
See “Dosages

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Nivolumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Nivolumab?”

Cautions

Immune-mediated adverse reactions

• Severe and fatal immune-mediated reactions reported
• May occur in any organ system or tissue and at any time after starting therapy including after discontinuation
• For suspected reactions, initiate appropriate workup to exclude alternative etiologies (eg, infection)
• Institute medical management promptly; consult specialists as appropriate
• Hold or permanently discontinue based on severity
• Administer systemic corticosteroids (eg, 1-2 mg/kg/day prednisone or equivalent) until improvement to Grade of 1and less, then taper corticosteroids over at least 1 month
• Other systemic immunosuppressants may be required if reactions not controlled with corticosteroids
• Immune-mediated pneumonitis
  • Incidence of pneumonitis is higher following prior thoracic radiation
• Immune-mediated colitis
  • Frequently associated with diarrhea
  • Cytomegalovirus (CMV) infection/reactivation reported with corticosteroid-refractory immune-mediated colitis
  • For corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
• Immune-mediated hepatitis
  • Evaluate liver enzymes prior to initiating and periodically during therapy
• Immune-mediated endocrinopathies
  • Immune-mediated adrenal insufficiency, hypophysitis, thyroiditis, hyperthyroidism, hypothyroidism, and type 1 diabetes mellitus (may present with diabetic ketoacidosis) reported
  • Initiate symptomatic treatment (eg, hormone replacement, insulin) as clinically indicated
  • Evaluate thyroid function prior to initiation and periodically during therapy
  • Monitor for hyperglycemia and other signs of diabetes
• Immune-mediated nephritis
  • May occur with renal dysfunction
  • Evaluate renal function prior to initiation and periodically during therapy
  • Immune-mediated dermatologic reactions
  • Exfoliative dermatitis may occur (eg, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis)
  • Treat mild to moderate nonexfoliative rashes with topical emollients and/or topical corticosteroids
  • Hold or permanently discontinue depending on severity
• Infusion-related reactions
  • Severe infusion-related reactions reported
  • Monitor for signs and symptoms
  • Interrupt, reduce the rate, or permanently discontinue based on the severity
• Complications of allogeneic HSCT
  • Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1 blocking antibody
  • Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
  • These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT
  • Follow patients closely for evidence of transplant-related complications and intervene promptly; consider the benefit versus risks of treatment with a PD-1 blocking antibody prior to or after an allogeneic HSCT
• Combination therapy with a thalidomide analogue and dexamethasone
  • Use not recommended
  • Increased mortality reported in patients with multiple myeloma who received nivolumab in combination with a thalidomide analogue and dexamethasone
• Embryo-fetal toxicity
  • Fetal harm may occur if used during pregnancy
  • Advise pregnant patients of the potential risk to the fetus
  • Effective contraception recommended during and after therapy in females of reproductive potential

Pregnancy and Lactation

• Based on its mechanism of action and data from animal studies, fetal harm may occur when administered to a pregnant woman
• No available human data are informing the drug-associated risk
• Contraception
  • Women of reproductive potential: Verify pregnancy status before initiating therapy; use effective contraception during treatment with Nivolumab and for at least 5 months following the last dose of therapy
• Lactation
  • Unknown if distributed in human breast milk; advise women to discontinue breastfeeding during treatment