- Unresectable/metastatic melanoma (in combination with ipilimumab).
- BRAF V600 wild-type unresectable/metastatic melanoma (as monotherapy).
- BRAF V600 mutation positive unresectable/metastatic melanoma (as monotherapy).
- Adjuvant treatment of melanoma in patients that have involvement of lymph nodes or metastatic disease and have undergone complete resection.
- Metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
- Advanced renal cell carcinoma in patients who have previously received anti-angiogenic therapy.
- Classic Hodgkin's lymphoma that has relapsed or progressed after either autologous hematopoietic stem cell transplantation (HSCT) and brentuximab or ≥3 lines of systemic therapy that includes autologous HSCT.
- Recurrent or metastatic squamous cell carcinoma of the head and neck with progression on or after platinum-based therapy.
- Locally advanced or metastatic urothelial carcinoma in patients who either have progression during or following platinum-based therapy or progression within 12 mo of neoadjuvant or adjuvant treatment with platinum-based therapy.
- Microsatellite instability-high (MSI-H) or mismatch repair deficient colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
- Hepatocellular carcinoma (HCC) previously treated with sorafenib.
Acts as a human programmed death receptor-1 (PD-1) blocking antibody. Inhibits T-cell proliferation and cytokine production.
- Decreased progression of melanoma, Hodgkin's lymphoma, urothelial carcinoma, colorectal cancer, and HCC.
- Decreased progression of and improved survival with NSCLC and advanced renal cell carcinoma.
- Improved survival with squamous cell carcinoma of head and neck.
Absorption: IV administration results in complete bioavailability.
Metabolism and Excretion: Unknown.
Half-life: 26.7 days.
- OB: Pregnancy (may cause fetal harm);
- Lactation: Discontinue breast feeding.
Use Cautiously in:
- Patients undergoing allogenic HSCT after nivolumab therapy (↑ risk of complications);
- Pedi: Safety and effectiveness not established;
- Rep: Women of reproductive potential (use effective contraception).
Adverse Reactions/Side Effects
CNS: IMMUNE-MEDIATED ENCEPHALITIS
Resp: IMMUNE-MEDIATED PNEUMONITIS, cough
CV: peripheral edema
GI: IMMUNE-MEDIATED COLITIS, IMMUNE-MEDIATED HEPATITIS
GU: immune-mediated nephritis/renal dysfunction
Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash
Endo: ADRENAL INSUFFICIENCY, IMMUNE-MEDIATED HYPOPHYSITIS, hypothyroidism, hyperglycemia, hyperthyroidism
F and E: hyperkalemia
Misc: INFUSION-RELATED REACTIONS
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IV:(Adults)As monotherapy–240 mg every 2 wk or 480 mg every 4 wk until disease progression or unacceptable toxicity; With ipilimumab–1 mg/kg followed by ipilimumab on the same day every 3 wk for 4 doses, then 240 mg as monotherapy every 2 wk or 480 mg every 4 wk until disease progression or unacceptable toxicity.
Adjuvant Treatment of Melanoma
IV:(Adults)240 mg every 2 wk or 480 mg every 4 wk until disease progression or unacceptable toxicity for up to 1 yr.
NSCLC, Classical Hodgkin's Lymphoma, Advanced Renal Cell Carcinoma, Urothelial Carcinoma, Squamous Cell Carcinoma of Head and Neck, and HCC
IV:(Adults)240 mg every 2 wk or 480 mg every 4 wk until disease progression or unacceptable toxicity.
IV:(Adults)240 mg every 2 wk until disease progression or unacceptable toxicity.
Solution for injection: 10 mg/mL
- Monitor for signs and symptoms of immune-mediated pneumonitis (shortness of breath, chest pain, new or worse cough) periodically during therapy. Treat with corticosteroids 1–2 mg/kg/day prednisone equivalents for ≥Grade 2 pneumonitis followed by corticosteroid taper. Withhold nivolumab and monitor symptoms for moderate (Grade 2) pneumonitis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) pneumonitis.
- Assess for signs and symptoms of infusion reactions (chills or shaking, itching or rash, flushing, difficulty breathing, dizziness, fever, feeling faint) periodically during therapy. Withhold or slow infusion for mild to moderate reactions. Discontinue therapy for severe or life-threatening reactions.
- Monitor for signs and symptoms of immune-mediated colitis (diarrhea, abdominal pain, mucus or blood in stool, with or without fever). Treat with corticosteroids at doses of 1–2 mg/kg/day of prednisone or equivalents followed by corticosteroid taper for severe (Grade 3) or life-threatening (Grade 4) colitis. Treat with corticosteroids at a dose of 0.5 mg/kg/day of prednisone or equivalent followed by corticosteroid taper for moderate (Grade 2) colitis or >5 days; if worsening or no improvement despite corticosteroids increase dose to 1–2 mg/kg/day prednisone equivalents. Withhold nivolumab for Grade 2 or 3 colitis; permanently discontinue nivolumab for Grade 4 colitis or for recurrent colitis upon restarting nivolumab. If administered with ipilimumab, withhold for Grad 2 colitis. For moderate or severe (Grade 3 or 4) or recurrent colitis, permanently discontinue nivolumb and ipilimumab.
- Monitor for signs and symptoms of hepatitis (yellowing of skin or whites of eyes, severe nausea or vomiting, right-sided abdominal pain, drowsiness, dark urine, unusual bleeding or bruising, anorexia) periodically during therapy.
- Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). If rash, itching, blistering, or ulcers in mouth or other mucous membranes occur, withhold dose and refer for assessment and treatment. If SJS or TEN occur, permanently discontinue therapy. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia. For immune-mediated rash, administer corticosteroids at doses of 1–2 mg/kg/day of prednisone or equivalents followed by corticosteroid taper for severe (Grade 3) or life-threatening (Grade 4) rash. Withhold for severe rash; permanently discontinue for life threatening rash.
- Monitor for signs and symptoms of hypophysitis (headaches, extreme tiredness, weight gain or loss, dizziness or fainting, mood changes, hair loss, feeling cold, constipation, deepening voice, excessive thirst and urination) periodically during therapy. Administer hormone replacement and corticosteroids at a dose of 1 mg/kg/day prednisone equivalents followed by corticosteroid taper for moderate or severe hypophysitis. Withhold therapy for moderate or severe hypophysitis. Discontinue for life threatening Grade 4.
- Monitor for signs and symptoms of adrenal insufficiency. Administer corticosteroids at a dose of 1–2 mg/kg/day prednisone equivalents followed by corticosteroid taper for severe (Grade 3) or life threatening (Grade 4) symptoms. Withhold for moderate (Grade 2) and permanently discontinue therapy for severe or life-threatening adrenal insufficiency.
- Monitor for signs and symptoms of encephalitis (headache, fever, tiredness or weakness, confusion, memory problems, sleepiness, hallucinations, seizures, stiff neck) periodically during therapy. Withhold therapy for patients with new-onset moderate to severe neurologic symptoms during diagnosis. Permanently discontinue nivolumab and administer corticosteroids at dose of 1–2 mg/kg/day prednisone equivalents for immune-mediated encephalitis, followed by corticosteroid taper.
- Monitor for signs and symptoms of kidney dysfunction (decrease in amount of urine, blood in urine, swelling in ankles, anorexia) periodically during therapy.
Lab Test Considerations:
Monitor for abnormal liver tests prior to and periodically during therapy. Administer corticosteroids at dose of 1–2 mg/kg/day prednisone equivalents for ≥Grade 2 transaminase ↑, with or without ↑ in total bilirubin. Withhold for moderate (Grade 2) and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis.
- Monitor for ↑ serum creatinine prior to and periodically during therapy. Administer corticosteroids at a dose of 1–2 mg/kg/day prednisone equivalents followed by corticosteroid taper for life-threatening (Grade 4) ↑ serum creatinine and permanently discontinue nivolumab. Withhold nivolumab for severe (Grade 3) or moderate (Grade 2) ↑ serum creatinine and administer corticosteroids at a dose of 0.5–1 mg/kg/day prednisone equivalents followed by corticosteroid taper. If worsening or no improvement occurs, increase dose of corticosteroids to 1–2 mg/kg/day prednisolone equivalents and permanently discontinue nivolumab.
- Monitor thyroid function prior to and periodically during therapy. Treat hypothyroidism with replacement therapy. Use medical management for hyperthyroidism. Immune-mediated thyroid dysfunction does not require dose modification of nivolumab.
- Monitor for hyperglycemia. If severe, withhold therapy until metabolic control achieved. If life-threatening, permanently discontinue nivolumab.
- Intermittent Infusion: Diluent: 0.9% NaCl or D5W.Concentration: 1 mg/mL to 10 mg/mL. Mix by gentle inversion; do not shake. Solution is clear to slightly opalescent, colorless to slightly yellow; do not administer solution if discolored or contains particulate matter other than translucent to white proteinaceous particles. Solution is stable at room temperature for up to 8 hr and 24 hr if refrigerated.
- Rate:Infuse through a sterile, non-pyrogenic, low-protein binding 0.2 micrometer to 1.2 micrometer in-line filter over 30 min. Flush line at end of infusion.
- Y-Site Incompatibility: Do not administer other drugs through same infusion line.
- Explain purpose of nivolumab to patient.
- Advise patient to notify health care professional immediately if signs and symptoms of pneumonitis, colitis, hepatitis (jaundice, severe nausea or vomiting, pain on right side of abdomen, lethargy, easy bruising or bleeding), kidney problems (decreased urine output, blood in urine, swollen ankles, loss of appetite), hormone gland problems (rapid heart beat, weight loss, increased sweating, weight gain, hair loss, feeling cold, constipation, deepening of voice, muscle aches, dizziness or fainting, persistent or unusual headache) occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: Advise female patient of reproductive potential to use highly effective contraception during and for 5 mo after last dose; may cause fetal harm. Avoid breast feeding during therapy.
- Emphasize importance of keeping scheduled appointments for blood work or other laboratory tests.
- ↓ spread of melanoma.
- ↓ spread of NSCLC.
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