Grade 3 diarrhoea or colitis OPDIVO+ipilimumab Permanently discontinue treatment Grade 4 diarrhoea or colitis Permanently discontinue treatment Immunerelated hepatitis Grade 2 elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin Withhold dose(s) until laboratory values return to baseline and management with corticosteroids, if needed, is complete Grade 3 or 4 elevation in AST, ALT, or total bilirubin Permanently discontinue treatment Immunerelated nephritis and renal dysfunction Grade 2 or 3 creatinine elevation Withhold dose(s) until creatinine returns to baseline and management with corticosteroids is complete Grade 4 creatinine elevation Permanently discontinue treatment Immunerelated endocrinopathies Symptomatic Grade 2 or 3 hypothyroidism, hyperthyroidism, hypophysitis Grade 2 adrenal insufficiency 3 diabetes Grade 4 hypothyroidism Grade 4 hyperthyroidism Grade 4 hypophysitis 3 or 4 adrenal insufficiency Grade 4 diabetes Withhold dose(s) until symptoms resolve and management with corticosteroids (if needed for symptoms of acute inflammation) is complete. OPDIVO should be continued in the presence of hormone replacement therapya as long as no symptoms are present Permanently discontinue treatment Immune-related rash and severe skin reactions Grade 3 rash Grade 4 rash Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Permanently discontinue treatment Encephalitis New onset moderate or severe neurologic signs or symptoms Immune-related encephalitis Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Permanently discontinue treatment Other adverse reactions Other Grade 3 adverse reaction First occurrence Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Recurrence of same Grade 3 adverse reactions Permanently discontinue Life-threatening or Grade 4 adverse reaction Inability to reduce corticosteroid dose to 10 mg prednisone or equivalent per day
Persistent Grade 2 or 3 adverse reactions despite treatment modification Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCICTCAE v4). a Recommendation for the use of hormone replacement therapy is provided inPRECAUTIONS. SPECIAL POPULATIONS Paediatric patients The safety and efficacy of OPDIVO in children below 18 years of age have not been established. No data are available. OPDIVO should not be used in children below 18 years of age. Elderly patients No overall differences in safety or efficacy were reported between elderly (≥ 65 years) and younger patients (< 65 years). No dose adjustment is required for elderly patients (≥ 65 years) (see section PHARMACOKINETICS). Patients with renal impairment The safety and efficacy of OPDIVO have not been studied in patients with severe renal impairment. Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with mild or moderate renal impairment (see section PHARMACOKINETICS). Data from patients with severe renal impairment are too limited to drawn conclusions from this population.. Patients with hepatic impairment The safety and efficacy of OPDIVO have not been studied in patients with moderate or severe hepatic impairment. Based on the population PK results, no dose adjustment is required in patients with mild hepatic impairment (see section PHARMACOKINETICS). Data from patients with moderate or severe hepatic impairment are too limited to draw conclusions on these populations. OPDIVO must be administered with caution in patients with moderate (total bilirubin > 1.5 × to 3 × the upper limit of normal [ULN] and any AST) or severe (total bilirubin > 3 × ULN and any AST) hepatic impairment. PREPARATION AND ADMINISTRATION INSTRUCTIONS Preparation should be performed by trained personnel in accordance with good practices rules, especially with respect to asepsis. Calculating the dose The prescribed dose for the patient is given in mg/kg. Based on this prescribed dose, calculate the total dose to be given. More than one vial of OPDIVO concentrate may be needed to give the total dose for the patient.