tevimbra

Important safety information

Immune-Mediated Adverse Reactions : ( 5.1 ) 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, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue TEVIMBRA based on the severity of reaction. Infusion-Related Reactions : Slow the rate of infusion, interrupt, or permanently discontinue based on severity of infusion reaction. ( 5.2 ) Complications of Allogeneic Hematopoietic Stem Cell Transplantation (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. ( 5.3 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or 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. 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 TEVIMBRA depending on severity [see Dosage and Administration (2.2) ] . In general, if TEVIMBRA 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 corticosteroids. 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 TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. 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 4.7% (113/2390) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (1.4%), and Grade 2 (1.9%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 44 (1.8%) patients and withholding of TEVIMBRA in 40 (1.7%) patients. Eighty-one (71.7%) of the 113 patients received systemic corticosteroids. Seventy-four (65.5%) of the 113 patients received high-dose systemic corticosteroids. Immune-mediated pneumonitis resolved in 48.7% of the 113 patients. Of the 40 patients in whom TEVIMBRA was withheld for pneumonitis, 26 (65%) reinitiated TEVIMBRA after symptom improvement; of these, 5 (19%) patients had recurrence of pneumonitis. Immune-Mediated Colitis TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 0.8% (19/2390) of patients receiving TEVIMBRA, including Grade 3 (0.3%) and Grade 2 (0.4%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 5 (0.2%) patients and withholding of TEVIMBRA in 10 (0.4%) patients. Seventeen (89.5%) of the 19 patients received systemic corticosteroids. Twelve (63.2%) of the 19 patients received high-dose systemic corticosteroids. Two (10.5%) of the 19 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 89.5% of the 19 patients. Of the 10 patients in whom TEVIMBRA was withheld for colitis, 9 (90%) reinitiated TEVIMBRA after symptom improvement; of these, 2 (22%) patients had recurrence of colitis. Immune-Mediated Hepatitis TEVIMBRA can cause immune-mediated hepatitis, which can be fatal. Immune-mediated hepatitis occurred in 1.3% (30/2390) of patients receiving TEVIMBRA, including Grade 4 (0.3%), Grade 3 (0.6%), and Grade 2 (0.3%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 6 (0.3%) patients and withholding of TEVIMBRA in 19 (0.8%) patients. Twenty-five (83.3%) of the 30 patients received systemic corticosteroids. Twenty-four (80%) of the 30 patients received high-dose systemic corticosteroids. Two (6.7%) of the 30 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 66.7% of the 30 patients. Of the 19 patients in whom TEVIMBRA was withheld for hepatitis, 7 (37%) reinitiated TEVIMBRA after symptom improvement; of these, 1 (14%) patient had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity [see Dosage and Administration (2.2) ] . Immune-mediated adrenal insufficiency occurred in 0.5% (12/2390) of patients receiving TEVIMBRA, including Grade 4 (0.04%), Grade 3 (0.2%), and Grade 2 (0.3%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 10 (0.4%) patients. All 12 patients received systemic corticosteroids. Three (25%) of the 12 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 25% of the 12 patients. Of the 10 patients in whom TEVIMBRA was withheld for adrenal insufficiency, 8 (80%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of adrenal insufficiency. Hypophysitis TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity [see Dosage and Administration (2.2) ] . Hypophysitis/hypopituitarism occurred in 0.3% (6/2390) of patients receiving TEVIMBRA; all were Grade 2 (0.3%).…