Nivolumab (Opdivo)


Indications for Programmed Cell Death Protein 1 (PD-1) Checkpoint Inhibitors (see Programmed Cell Death Protein 1 Checkpoint Inhibitors)

Castration-Resistant Prostate Cancer (see Prostate Cancer)

Colorectal Cancer (see Colorectal Cancer)

Melanoma (see Melanoma)

Non-Small Cell Lung Cancer with Progression On/After Platinum-Based Chemotherapy (see Lung Cancer)

Renal Cell Carcinoma with Prior Anti-Angiogenic Therapy (see Renal Cancer)

Urothelial Cell Carcinoma (see Urothelial Cell Carcinoma)


Pharmacology

Background

Metabolism


Administration

Dosage

Dose Adjustment


Adverse Effects

Cardiovascular Adverse Effects

Autoimmune Myocarditis (see Myocarditis)

  • Epidemiology
  • Physiology
    • PD-1 and PD-L1 Can Be Expressed in Rodent and Human Cardiac Myocytes
  • Clinical

Heart Block

  • Epidemiology
    • Case Reports (Neurology, 2017) [MEDLINE]

Dermatologic Adverse Effects

Pruritus (see Pruritus)

  • Epidemiology
    • Occurs in 11-23% of Cases

Rash

  • Epidemiology
    • Occurs in 9-40% of Cases
  • Management
    • Grade 4 Rash: discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids)

Vitiligo (see Vitiligo)

  • Epidemiology
    • Occurs in <11% of Cases

Endocrinologic Adverse Effects

Adrenal insufficiency (see Adrenal insufficiency)

  • Epidemiology
    • Occurs in <2% of Cases
    • Median time to onset 3-5.8 mo (range: 15 days to 20.9 mo)
  • Management
    • Grade 2 Adrenal Insufficiency: discontinue nivolumab (and ipilimumab, if also being given)
    • Grade 3-4 Adrenal Insufficiency: discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids)

Diabetes Mellitus (DM) (see Diabetes Mellitus)

  • Epidemiology
    • Occurs in <2% of Cases
    • Median Time of Onset: 1.3-21.8 mo
  • Management
    • Type I Diabetes Mellitus: discontinue nivolumab permanently

Hyperthyroidism (see Hyperthyroidism)

  • Epidemiology
    • Occurs in 1-4% of Cases

Hypertriglyceridemia (see Hypertriglyceridemia)

  • Epidemiology
    • Occurs in 32% of Cases

Hypophysitis

  • Epidemiology
    • May Occur
    • Median Latency to Onset: 27 days-11 mo
  • Management
    • Grade 4 Hypophysitis: discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids)

Hypothyroidism (see Hypothyroidism)

  • Epidemiology
    • Occurs in 7-9% of Cases
    • Median Latency to Onset: 2-5 mo (range: 1 day-13.8 mo)

Thyroiditis (see Thyroiditis)

  • Epidemiology: may occur

Gastrointestinal/Hepatic Adverse Effects

Anorexia (see Anorexia)

  • Epidemiology
    • Occurs in 23-29% of Cases

Colitis (see Colitis)

  • Epidemiology
    • Fatal Cases Have Been Reported (JAMA Oncol, 2018) [MEDLINE]
  • Management
    • Grade 3 Colitis/Diarrhea (If Used with Ipilimumab): discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids)
    • Grade 4 Colitis/Diarrhea (If Used without Ipilimumab): discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids, [[Corticosteroids]])

Constipation (see Constipation)

  • Epidemiology
    • Occurs in 23% of Cases

Diarrhea (see Diarrhea)

  • Management
    • Grade 3 Colitis/Diarrhea (If Used with Ipilimumab): discontinue nivolumab permanently
    • Grade 4 Colitis/Diarrhea (If Used without Ipilimumab): discontinue nivolumab permanently

Hepatitis (see Drug-Induced Hepatotoxicity)

  • Management
    • AST or ALT >3-5x Upper Limit of Normal or Total Bilirubin >1-5-3x Upper Limit of Normal: withhold nivolumab -> may resume nivolumab upon recovery to grade 0-1 toxicity

Nausea/Vomiting (see Nausea and Vomiting)

  • Epidemiology
    • Nausea Occurs in 28% of Cases
    • Vomiting Occurs in 16-17% of Cases

Hematologic Adverse Effects

Anemia (see Anemia)

  • Epidemiology
    • Occurs in 39% of Cases

Lymphocytopenia

  • Epidemiology
    • Occurs in 42% of Cases

Neurologic Adverse Effects

Fatigue (see Fatigue)

  • Epidemiology
    • Occurs in 49-56% of Cases

Headache (see Headache)

  • Epidemiology: may occur

Immune-Mediated Encephalitis (see Encephalitis)

  • Epidemiology
    • May Occur (JAMA Oncol, 2018) [MEDLINE]
  • Management
    • Discontinue Nivolumab Permanently and Administer High-Dose Corticosteroids (see Corticosteroids)

Myasthenia Gravis (see Myasthenia Gravis)

  • Epidemiology
    • Case Reports (Neurology, 2017) [MEDLINE]

Pulmonary Adverse Effects

Pulmonary Toxicity

  • Epidemiology
    • Median Latency to Onset: 1.6-7.2 mo (range: 2 days-22.3 mo)
  • Physiology
    • Immune-Mediated Toxic Effect
  • Clinical Patterns
  • Treatment
    • Grade 2 Pneumonitis: administer high-dose corticosteroids (see Corticosteroids)
    • Grade 3-4 Pneumonitis: discontinue nivolumab permanently and administer high-dose corticosteroids (see Corticosteroids)

Renal Adverse Effects

Acute Kidney Injury (AKI) (see Acute Kidney Injury)

  • Epidemiology:
    • Occurs in 11-42% of Cases
  • Management
    • Cr >1.5-6x Upper Limit of Normal: withhold nivolumab, administer corticosteroids (with taper) -> may resume nivolumab upon recovery to grade 0-1 toxicity
    • Cr >6x Upper Limit of Normal: permanently discontinue nivolumab

Hypercalcemia (see Hypercalcemia)

  • Epidemiology
    • Occurs in 19% of Cases

Hypocalcemia (see Hypocalcemia)

  • Epidemiology
    • Occurs in 13-23% of Cases

Hyponatremia (see Hyponatremia)

  • Epidemiology
    • Occurs in 20-35% of Cases

Rheumatologic Adverse Effects

Myositis (see Myositis)

  • Epidemiology
    • Case Reports (Neurology, 2017) [MEDLINE]

Peripheral Edema (see Peripheral Edema)

  • Epidemiology
    • Occurs in 12% of Cases

Other Adverse Effects

Fever (see Fever)

  • Epidemiology
    • Occurs in 17% of Cases

References