Names and pronunciation
(ip-i-lim′ue-mab) Yervoy
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Drug reference
(ip-i-lim′ue-mab) Yervoy
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Func. class.: Antineoplastic; biologic response modifier
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Chem. class.: CTLA-4-directed blocking antibody
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ACTION: Human IgGIk monoclonal antibody that binds to the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4); action is indirect, possibly through T-cell–mediated antitumor immune responses
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USES: Colorectal cancer, metastatic (microsatellite instability-high or mismatch repair deficient), hepatocellular carci- noma, adjuvant treatment, melanoma, unresectable or metastatic, non-small cell lung cancer (metastatic), non-small cell lung cancer (metastatic or recurrent), advanced renal cell carcinoma
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CONTRAINDICATIONS: Hypersensitivity Precautions: Pregnancy, breastfeeding, Crohn’s disease, hepatitis, immunosup- pression, inflammatory bowel disease, iritis, ocular disease, organ transplant, pancreatitis, renal disease, rheumatoid arthritis, sarcoidosis, systemic lupus ery- thematosus, thyroid disease, ulcerative colitis, uveitis
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Black Box Warning: Adrenal insufficien- cy, diarrhea, Guillain-Barré syndrome, hepatic disease, myasthenia gravis, hypo/hyperthyroidism, hypopituitarism, peripheral neuropathy, serious rash, hypophysitis Black Box Warning: Immune-mediated reactions: before starting treatment, as- sess for enterocolitis, hepatitis, dermatitis, neuropathy, endocrinopathy; take LFTs, ACTH, and thyroid function tests; perma- nently discontinue if these conditions occur • Hepatotoxicity: LFTs baseline and be fore each dose; increase the frequency of liver function test monitoring until resolution; permanently discontinue in grade 3-5 toxicity; give systemic cortico steroids at a dose of 1-2 mg/kg/day of predniSONE or equivalent • Neuropathy: monitor for motor or sen sory neuropathy (unilateral or bilateral weakness, sensory alterations, or pares thesias) before each dose; permanently discontinue if severe neuropathy (inter fering with daily activities), such as Guil lain-Barré–like syndromes, occurs • Endocrinopathy: monitor thyroid func tion tests at baseline and before each dose; monitor hypophysitis, adrenal insuf ficiency, adrenal crisis, hypo/hyperthy roidism (fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, hypotension, or nonspecific symp toms that may resemble other causes) • Vision changes: uveitis, iritis, episcle- ritis; corticosteroids may be used Black Box Warning: Pregnancy/ breastfeeding: do not use in pregnancy, breastfeeding
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SIDE EFFECTS CNS: Severe and fatal immune-mediated neuropathies, fatigue, headache, fever EENT: Uveitis, iritis, episcleritis ENDO: Severe and fatal immune-mediated endocrinopathies GI: Severe and fatal immune-mediated pancreatitis, enterocolitis, hepatitis, abdominal pain, nausea, diarrhea, appe- tite decreased, vomiting, constipation, colitis INTEG: Severe and fatal immune-mediated dermatitis, pruritus, rash, urticaria MISC: Cough, dyspnea, anemia, eosino- philia, nephritis SYST: Antibody formation, Stevens- Johnson syndrome, toxic epidermal necrolysis
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DOSAGE AND ROUTES When given in combination with nivolum- ab, if nivolumab is withheld, ipilimumab should also be withheld, and if ipilim- umab is withheld, nivolumab should be withheld Colorectal cancer, metastatic Adult IV: 1 mg/kg every 3 wk (in com- bination with nivolumab) for 4 combina- tion doses, followed by nivolumab mono- therapy until disease progression or unacceptable toxicity Hepatocellular carcinoma Adult: IV: 3 mg/kg once every 3 wk (in combination with nivolumab) for 4 com- bination doses, followed by nivolumab monotherapy until disease progression or unacceptable toxicity Melanoma, metastatic with brain metastases (unlabeled) Adult: IV: 3 mg/kg once every 3 wk (in combination with nivolumab) for 4 com- bination doses, followed by nivolumab monotherapy; total duration of nivolumab therapy is up to 24 mo, or until disease progression or unacceptable toxicity Melanoma, unresectable or metastatic Adult: IV: 3 mg/kg every 3 wk for a maximum of 4 doses Children ≥12 yr and adolescents: IV: 3 mg/kg every 3 wk for a maximum of 4 doses; doses may be delayed due to tox- icity, but all doses must be administered within 16 wk of the initial dose Non-small cell lung cancer, meta- I static, PD-L1 expressing Adult: IV: 1 mg/kg once every 6 wk (in combination with nivolumab; refer to nivolumab monograph for nivolumab dos- ing information) until disease progres- sion, unacceptable toxicity, or up to 2 yr in patients without disease progression Non-small cell lung cancer, meta- static or recurrent Adult: IV: 1 mg/kg once every 6 wk (in combination with nivolumab and 2 cycles of histology-based platinum-doublet che- motherapy; refer to nivolumab mono- graph for nivolumab dosing information) until disease progression, unacceptable toxicity, or up to 2 yr in patients without disease progression Renal cell cancer, advanced, combi- nation therapy Adult: IV: 1 mg/kg once every 3 wk (in combination with nivolumab) for 4 com- bination doses, followed by nivolumab monotherapy (refer to nivolumab mono- graph for nivolumab dosing information) until disease progression or unacceptable toxicity. Small cell lung cancer, pro- gressive (off-label use): IV: 3 mg/kg every 3 wk (in combination with nivolumab) for 4 combination doses, fol- lowed by nivolumab monotherapy Colorectal cancer, metastatic (micro- satellite instability-high [MSI-H]) or mismatch repair deficient (dMMR) Children ≥12 yr and adolescents: IV: 1 mg/kg/dose once every 3 wk (in combi- nation with nivolumab) for up to 4 doses
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Available forms: Sol for inj 50 mg/10 mL, 200 mg/40 mL
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Administer: Intermittent IV INFUSION route • Visually inspect parenteral products for particulate matter and discoloration be- fore using; sol may have a pale yellow color and have translucent to white, amor- phous particles; discard the vial if sol is cloudy, if there is pronounced discolor- ation, or if particulate matter is present • Allow to stand at room temperature for 5 min before infusion preparation; withdraw the required volume and transfer into an IV bag; discard partially used vials or empty vials; dilute with 0.9% sodium chloride in- jection or 5% dextrose injection to a final concentration (1-2 mg/mL); mix diluted sol by gentle inversion; do not admix • Give infusion over 90 min through an IV line with a low-protein binding in-line filter, do not give with other products; after each infusion, flush the line with 0.9% sodium chloride injection or 0.5% dextrose injection • Store once diluted for no more than 24 hr refrigerated or at room temperature
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Assess: • Serious skin disorders: Stevens-John- son syndrome, toxic epidermal necroly- sis: permanently discontinue in these or rash complicated by full-thickness dermal ulceration; give systemic corticosteroids at a dose of 1-2 mg/kg/day of predniSONE or equivalent; when dermatitis is controlled, taper corticosteroids over at least 1 mo, withhold in patients with moderate to se vere reactions; for mild to moderate derma titis (localized rash and pruritus), give topi cal or systemic corticosteroids
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Evaluate: • Decreasing spread or recurrence of malignant melanoma
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To immediately report allergic reac tions, skin rash, severe abdominal pain, yellowing of skin or eyes, tingling of ex tremities, change in bowel habits • About the reason for treatment and expected results; to read medication guide provided • Pregnancy/breastfeeding: to notify prescriber if pregnancy is planned or sus pected or if breastfeeding; to use contra ception during and for 3 mo after final dose
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PHARMACOKINETICS: Steady- state by 3rd dose; terminal half-life 15.4 days
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