opdivo qvantig

Important safety information

Immune-Mediated Adverse Reactions : (5.1) o Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction. o Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. o Withhold or permanently discontinue based on severity and type of reaction. (2.4) • Complications of allogeneic HSCT : Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. (5.2) • Embryo-Fetal toxicity : Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. (5.3 , 8.1 , 8.3) • Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. (5.4) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions OPDIVO QVANTIG is a combination of a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance, and inducing immune-mediated adverse reactions, and an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD‑1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue OPDIVO QVANTIG depending on severity [see Dosage and Administration (2.4) ] . In general, if OPDIVO QVANTIG requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis OPDIVO QVANTIG can cause immune-mediated pneumonitis, which is defined as requiring use of steroids and no clear alternate etiology. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 2.8% (7/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (0.8%) and Grade 2 (2.0%) adverse reactions. Pneumonitis led to permanent discontinuation of OPDIVO QVANTIG in 1.6% and withholding of OPDIVO QVANTIG in 1.6% of patients. Systemic corticosteroids were required in 100% (7/7) of patients with pneumonitis. Pneumonitis resolved in 27% of the 7 patients. Of the 4 patients in whom OPDIVO QVANTIG was withheld for pneumonitis, 2 reinitiated OPDIVO QVANTIG after symptom improvement; of these, 1 (50%) had recurrence of pneumonitis. Immune-Mediated Colitis OPDIVO QVANTIG can cause immune-mediated colitis, defined as requiring use of corticosteroids and no clear alternate etiology. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2.8% (7/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (0.4%) and Grade 2 (2.4%) adverse reactions. Colitis led to withholding of OPDIVO QVANTIG in 2.0% of patients. Systemic corticosteroids were required in 100% (7/7) of patients with colitis. Colitis resolved in 71% of the 7 patients. Of the 5 patients in whom OPDIVO QVANTIG was withheld for colitis, 3 reinitiated OPDIVO QVANTIG after symptom improvement; of these, 2 (67%) had recurrence of colitis. Immune-Mediated Hepatitis and Hepatotoxicity OPDIVO QVANTIG can cause immune-mediated hepatitis, defined as requiring the use of corticosteroids and no clear alternate etiology. Immune-mediated hepatitis occurred in 2.4% (6/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (1.6%), and Grade 2 (0.8%) adverse reactions. Hepatitis led to permanent discontinuation of OPDIVO QVANTIG in 0.8% and withholding of OPDIVO QVANTIG in 1.6% of patients. Systemic corticosteroids were required in 100% (6/6) of patients with hepatitis. Hepatitis resolved in 67% of the 6 patients. Of the 2 patients in whom OPDIVO QVANTIG was withheld for hepatitis, 2 reinitiated OPDIVO QVANTIG after symptom improvement; of these, 1 (50%) had recurrence of hepatitis. Intravenous Nivolumab with Cabozantinib Nivolumab in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to nivolumab alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt nivolumab and cabozantinib and consider administering corticosteroids [see Dosage and Administration (2.4) ] . With the combination of intravenous nivolumab and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% (35/320) of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either intravenous nivolumab (n=11) or cabozantinib (n=9) administered as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving intravenous nivolumab, 2 patients receiving cabozantinib, and 7 patients receiving both intravenous nivolumab and cabozantinib. Immune-Mediated Endocrinopathies Adrenal Insufficiency OPDIVO QVANTIG can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold OPDIVO QVANTIG depending on severity [see Dosage and Administration (2.4) ] . Adrenal insufficiency occurred in…