Adult Dosing
Melanoma
- As a single agent:
- Recommended dose: 3 mg/kg IV (infused over 60 mins) q2wks until disease progression or unacceptable toxicity
- In combination with ipilimumab:
- Initial dose: nivolumab 1 mg/kg IV (infused over 60 mins), followed by ipilimumab (infused over 90 min) on the same day, q3wks x 4 doses
- Subsequent dose: nivolumab as a single agent: 3 mg/kg IV (infused over 60 mins) q2wks until disease progression or unacceptable toxicity
Note:
- Refer package insert for full prescribing information for ipilimumab prior to initiation
- Refer package insert for preparation and administration instructions
Non-Small Cell Lung Cancer
- Recommended dose: 3 mg/kg IV (infused over 60 mins) q2wks until disease progression or unacceptable toxicity
Renal Cell Carcinoma (RCC)
- Recommended dose: 3 mg/kg IV (infused over 60 mins) q2wks until disease progression or unacceptable toxicity
Dose Modifications
- Hypothyroidism and hyperthyroidism: No recommended dose modifications
Withhold dose and resume treatment when adverse reaction returns to grade 0 or 1 for the following adverse reactions:- Diarrhea or colitis, Grade 2
- Diarrhea or colitis with single agent nivolumab, Grade 3
- Pneumonitis, Grade 2
- Hepatitis with AST or ALT > 3 up to 5 x ULN or total bilirubin > 1.5 up to 3 x ULN
- Hypophysitis, Grade 2 or 3
- Adrenal insufficiency, Grade 2
- Type 1 diabetes mellitus, hyperglycemia Grade 3
- Nephritis and renal dysfunction with serum creatinine > 1.5 up to 6 x ULN
- Rash, Grade 3
- Encephalitis, new-onset moderate-severe neurologic signs/symptoms
- Other treatment-associated adverse reactions, first occurrence, Grade 3
Note:
- If nivolumab is withheld, ipilimumab should also be withheld when used as combination therapy
Permanently discontinue nivolumab for the following adverse reactions: - Diarrhea or colitis with nivolumab plus ipilimumab, Grade 3
- Diarrhea or colitis, Grade 4
- Pneumonitis, Grade 3 or 4
- Hepatitis with AST or ALT > 5 x ULN or total bilirubin > 3 x ULN
- Hypophysitis, Grade 4
- Adrenal insufficiency, Grade 3 or 4
- Type 1 diabetes mellitus, hyperglycemia Grade 4
- Nephritis and renal dysfunction with serum creatinine > 6 x ULN
- Rash, Grade 4
- Encephalitis, immune-mediated
- Recurrence of Grade 3 other treatment-associated adverse reactions
- Life-threatening or Grade 4 other adverse reactions
- Severe or life-threatening infusion reactions
- Prednisone requirement of
10 mg/day x > 12 or more weeks - Grade 2 or 3 adverse reactions persistent for 12 wks
Pediatric Dosing
- The safety and effectiveness in pediatric patients have not been established
[Outline]
- Immune-mediated pneumonitis or interstitial lung disease, including fatal cases have been reported. Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroid as clinically indicated. Withhold treatment for Grade 2 pneumonitis and discontinue treatment for Grade 3 or 4 pneumonitis
- Immune-mediated colitis has been reported. Monitor patients for signs and symptoms of colitis. Administer corticosteroid as clinically indicated. When nivolumab is administered as a single agent, withhold treatment for Grade 2 or 3 colitis and permanently discontinue if Grade 4 or recurrent colitis occurs. When administered in combination with ipilimumab, withhold nivolumab for Grade 2 colitis and permanently discontinue if Grade 3 or 4 or recurrent colitis occurs
- Immune-mediated hepatitis has been reported. Monitor patients for abnormal LFTs prior to and during treatment. Administer corticosteroid as clinically indicated. Withhold nivolumab for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis
- Immune-mediated nephritis and renal dysfunction may occur. Monitor patients for elevated serum creatinine prior to and during treatment. Withhold nivolumab for increased serum creatinine (Grade 2 or 3) and administer corticosteroids as clinically indicated. If worsening or no improvement occurs, increase dose of corticosteroids and permanently discontinue nivolumab. If Grade 4 increase in serum creatinine occurs, discontinue nivolumab permanently
- Hypophysitis has been reported. Monitor patients for signs and symptoms of hypophysitis. Administer corticosteroids as clinically indicated. Withhold nivolumab for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis
- Adrenal insufficiency has been reported. Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment. Administer corticosteroids as clinically indicated. Withhold nivolumab for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency
- Thyroid disorders have been reported. Monitor thyroid function prior to and during treatment. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. There are no recommended dose adjustments of nivolumab for hypothyroidism or hyperthyroidism
- Type 1 diabetes can occur. Monitor for hyperglycemia. Administer insulin as clinically indicated. Withhold nivolumab if Grade 3 hyperglycemia occurs until metabolic control is achieved and permanently discontinue for Grade 4 hyperglycemia
- Immune-mediated encephalitis has been reported. Withhold therapy in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other etiologies. Administer corticosteroids as clinically indicated. Permanently discontinue therapy for immune-mediated encephalitis
- Immune-mediated rash has been reported, including rare cases of fatal toxic epidermal necrolysis. Monitor patients for rash. Administer corticosteroids for Grade 3 or Grade 4 rash. Withhold nivolumab for Grade 3 rash and permanently discontinue if Grade 4 rash occurs
- Other clinically significant, immune-mediated adverse reactions such as uveitis, pancreatitis, abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, and systemic inflammatory response syndrome have been reported in less than 2% patients. Based on the severity of the condition, permanently discontinue or withhold treatment. Administer corticosteroids as clinically indicated. Restart nivolumab upon improvement of the condition to Grade 1 or 0 and after completion of corticosteroid taper
- Severe infusion reactions have been reported in < 1% patients. Discontinue nivolumab for severe or life-threatening reactions and interrupt or slow the infusion rate for mild or moderate reactions
- Therapy may cause fetal harm when administered to pregnant women. Caution pregnant women of the potential risk to a fetus. Use of effective contraception should be recommended to females of reproductive potential during treatment with nivolumab and for at least 5 months after the last dose
Cautions: Use cautiously in:
- Pneumonitis
- Colitis
- Elevated LFTs
- Elevated serum creatinine
- Adrenal insufficiency
- Hyperglycemia
- Thyroid disorder
- Neurologic signs and symptoms
- Pregnant women
Pregnancy Category: Not rated; there is no available human data regarding drug-associated risk to the fetus, however, because nivolumab is an IgG4 and human IgG4 is known to cross the placental barrier particularly in the second and third trimester of pregnancy, advise pregnant women of the potential risk to the fetus.
Breastfeeding: Unsafe; discontinue breastfeeding during treatment.
Unresectable or metastatic melanoma
Nivolumab as a single agent- CV: Ventricular arrhythmia
- CNS: Dizziness, peripheral and sensory neuropathy
- RESP: Cough, rhinitis, pharyngitis, nasopharyngitis
- GI: Colitis
- GU: Nephritis
- DERM: Rash, pruritus, exfoliative dermatitis, erythema multiforme, vitiligo, psoriasis
- EENT: Iridocyclitis
- METABOLIC: Hyponatremia, hyperkalemia
- LABTEST: Increased AST, ALT, and alkaline phosphatase; increased amylase and lipase
Nivolumab in combination with ipilimumab- CNS: Headache, peripheral neuropathy
- RESP: Pneumonitis
- GI: Vomiting, colitis, stomatitis, colonic perforation
- DERM: Rash, pruritus
- EENT: Blurred vision
- METABOLIC: Dehydration, hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia|ENDCRIN: Hypothyroidism, hypophysitis
- HEMAT: Anemia, lymphopenia, neutropenia
- IMMU: Immune-mediated enterocolitis, hepatitis, dermatitis, neuropathies, and endocrinopathies
- LABTEST: Increased ALT, AST, and alkaline phosphatase; increased amylase and lipase; increased creatinine
Metastatic Non-Squamous Non-Small Cell Lung Cancer
- RESP: Cough, pleural effusion, pulmonary embolism
- GI: Constipation
- MUSC: Musculoskeletal pain, asthenia
- DERM: rash, pruritus, urticaria
- METABOLIC: Hyponatremia, decreased appetite
- MISC: Fatigue, asthenia, polymyalgia rheumatica
- LABTEST: Increases creatinine; increased AST, ALT, and alkaline phosphatase; increased TSH
Renal cell carcinoma
- HEMAT: Anemia, lymphopenia
- CNS: Headache/migraine, peripheral neuropathy|RESP: Cough, dyspnea, nasopharyngitis, pharyngitis, rhinitis, and viral URI
- GI: Nausea, vomiting, diarrhea, constipation, abdominal pain/discomfort
- MUSC: Arthralgia, back pain, extremity pain, musculoskeletal pain
- DERM: Rash, pruritus, palmar-plantar erythrodysesthesia
- METABOLIC; Decreased appetite, decreased weight, hyponatremia, hyperkalemia, hypocalcemia, hypercalcemia
- MISC: Asthenia, decreased activity, fatigue, malaise, pyrexia, peripheral edema
- LABTEST: Increased AST, ALT, and alkaline phosphatase; increased triglycerides and cholesterol; increased creatinine
