Avelumab Disease Interactions

No clinically meaningful differences in pharmacokinetics were observed in the clearance of avelumab based on mild or moderate hepatic impairment. Caution should be exercised when avelumab is used in patients with severe hepatic impairment as there are limited data from patients. The effect of severe hepatic impairment on the pharmacokinetics of avelumab is unknown.

Avelumab can cause immune-mediated adrenal insufficiency. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients with prolonged periods of stress due to major surgery, intensive care, etc. It is recommended to administer corticosteroids as appropriate for adrenal insufficiency. Monitor patients for clinical signs and symptoms of adrenal insufficiency and institute appropriate measures as necessary. Withhold avelumab for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. If appropriate modify the dose according to manufacturer recommendations. Monitor as clinically indicated prior to and periodically during treatment. Care should be taken when using avelumab in these patients.

Immune-mediated colitis has been reported with the use of avelumab. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents followed by corticosteroid taper for moderate or severe or life-threatening colitis. If appropriate modify the dose according to manufacturer recommendations. Monitor patients for signs and symptoms of colitis. Permanently discontinue avelumab for life-threatening or for recurrent colitis. Care should be taken when using avelumab in patients with inflammatory bowel disease.

Avelumab can cause type 1 diabetes mellitus. Monitor for hyperglycemia or other signs and symptoms of diabetes. Withhold treatment in cases of severe hyperglycemia until metabolic control is achieved. Permanently discontinue avelumab for life-threatening hyperglycemia. If appropriate modify the dose according to manufacturer recommendations. Care should be exercised when using avelumab in diabetic patients.

Immune-mediated pneumonitis, including fatal cases have been reported with the use of avelumab. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for moderate or more severe pneumonitis, followed by corticosteroid taper. Withhold treatment with avelumab for moderate pneumonitis and permanently discontinue therapy for severe, life-threatening, or recurrent moderate pneumonitis. If appropriate modify the dose according to manufacturer recommendations. Care should be taken when using avelumab in patients with pulmonary infections.

Avelumab can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. It is recommended to administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents followed by corticosteroid taper for life-threatening increased serum creatinine. Withhold avelumab for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to <= Grade 1. Permanently discontinue avelumab for life-threatening (Grade 4) nephritis. If appropriate modify the dose according to manufacturer recommendations. Care should be taken when using avelumab in patients with renal dysfunction.

Avelumab can cause autoimmune thyroid disorders. Monitor thyroid function prior to and periodically during treatment. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. It is recommended to withhold avelumab for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Care should be taken when using this agent in patients with thyroid disease.

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. It is recommended to follow patients closely for evidence of transplant-related complications and intervene promptly. The benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT should be considered.

Myasthenic syndrome/myasthenia gravis (including exacerbation) has been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. Care should be exercised when using PD-1/PD-L1 blocking antibodies in patients with myasthenia gravis.

Solid organ transplant rejection and other transplant (including corneal graft) rejection have been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. Care should be exercised when using PD-1/PD-L1 blocking antibodies in patients who have received a solid organ or other transplant.