igns or symptoms of endocrinopathies should be considered immune-mediated.
Monitor thyroid function tests and clinical chemistries at the start of treatment, before each dose, and as clinically indicated based on symptoms. In a limited number of patients, hypophysitis was diagnosed by imaging studies through enlargement of the pituitary gland.
Withhold Yervoy dosing in symptomatic patients. Initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent, and initiate appropriate hormone replacement therapy. [See Dosage and Administration (2.2).]
Other Immune-mediated Adverse Reactions, Including Ocular Manifestations
The following clinically significant immune-mediated adverse reactions were seen in less than 1% of Yervoy-treated patients in Study 1: nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia.
Across the clinical development program for Yervoy, the following likely immune-mediated adverse reactions were also reported with less than 1% incidence: myocarditis, angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis, leukocytoclastic vasculitis, erythema multiforme, psoriasis, pancreatitis, arthritis, autoimmune thyroiditis, sarcoidosis, neurosensory hypoacusis, autoimmune central neuropathy (encephalitis), myositis, polymyositis, and ocular myositis.
Permanently discontinue Yervoy for clinically significant or severe immune-mediated adverse reactions. Initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day prednisone or equivalent for severe immune-mediated adverse reactions.
Administer corticosteroid eye drops to patients who develop uveitis, iritis, or episcleritis. Permanently discontinue Yervoy for immune-mediated ocular disease that is unresponsive to local immunosuppressive therapy. [See Dosage and Administration (2.2).]
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling.
Immune-mediated enterocolitis [see Warnings and Precautions (5.1)].
Immune-mediated hepatitis [see Warnings and Precautions (5.2)].
Immune-mediated dermatitis [see Warnings and Precautions (5.3)].
Immune-mediated neuropathies [see Warnings and Precautions (5.4)].
Immune-mediated endocrinopathies [see Warnings and Precautions (5.5)].
Other immune-mediated adverse reactions, including ocular manifestations [see Warnings and Precautions (5.6)].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared with rates in other clinical trials or experience with therapeutics in the same class and may not reflect the rates observed in clinical practice.
The clinical development program excluded patients with active autoimmune disease or those receiving systemic immunosuppression for organ transplantation. Exposure to Yervoy 3 mg/kg for 4 doses given by intravenous infusion in previously treated patients with unresectable or metastatic melanoma was assessed in a randomized, double-blind clinical study (Study 1). [See Clinical Studies (14).] One hundred thirty-one patients (median age 57 years, 60% male) received Yervoy as a single agent, 380 patients (median age 56 years, 61% male) received Yervoy w |
