\r\n
Selected Safety Information
\r\n
Severe and Fatal Immune-Mediated Adverse Reactions
\r\n
\r\n - \r\n KEYTRUDA is a monoclonal antibody that belongs to a class of\r\n drugs that bind to either the programmed death receptor-1 (PD-1)\r\n or the programmed death ligand 1 (PD-L1), blocking the\r\n PD-1/PD-L1 pathway, thereby removing inhibition of the immune\r\n response, potentially breaking peripheral tolerance and inducing\r\n immune-mediated adverse reactions. Immune-mediated adverse\r\n reactions, which may be severe or fatal, can occur in any organ\r\n system or tissue, can affect more than one body system\r\n simultaneously, and can occur at any time after starting\r\n treatment or after discontinuation of treatment. Important\r\n immune-mediated adverse reactions listed here may not include\r\n all possible severe and fatal immune-mediated adverse reactions.\r\n
\r\n - \r\n Monitor patients closely for symptoms and signs that may be\r\n clinical manifestations of underlying immune-mediated adverse\r\n reactions. Early identification and management are essential to\r\n ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver\r\n enzymes, creatinine, and thyroid function at baseline and\r\n periodically during treatment. In cases of suspected\r\n immune-mediated adverse reactions, initiate appropriate workup\r\n to exclude alternative etiologies, including infection.\r\n Institute medical management promptly, including specialty\r\n consultation as appropriate.\r\n
\r\n\r\n - \r\n Withhold or permanently discontinue KEYTRUDA depending on\r\n severity of the immune-mediated adverse reaction. In general, if\r\n KEYTRUDA requires interruption or discontinuation, administer\r\n systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or\r\n equivalent) until improvement to Grade 1 or less. Upon\r\n improvement to Grade 1 or less, initiate corticosteroid taper\r\n and continue to taper over at least 1 month. Consider\r\n administration of other systemic immunosuppressants in patients\r\n whose adverse reactions are not controlled with corticosteroid\r\n therapy.\r\n
\r\n
\r\n\r\n
Immune-Mediated Pneumonitis
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated pneumonitis. The incidence is\r\n higher in patients who have received prior thoracic radiation.\r\n Immune-mediated pneumonitis occurred in 3.4% (94/2799) of\r\n patients receiving KEYTRUDA, including fatal (0.1%), Grade 4\r\n (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic\r\n corticosteroids were required in 67% (63/94) of patients.\r\n Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3%\r\n (36) and withholding in 0.9% (26) of patients. All patients who\r\n were withheld reinitiated KEYTRUDA after symptom improvement; of\r\n these, 23% had recurrence. Pneumonitis resolved in 59% of the 94\r\n patients.\r\n
\r\n
\r\n\r\n
Immune-Mediated Colitis
\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated colitis, which may present\r\n with diarrhea. Cytomegalovirus infection/reactivation has been\r\n reported in patients with corticosteroid-refractory\r\n immune-mediated colitis. In cases of corticosteroid-refractory\r\n colitis, consider repeating infectious workup to exclude\r\n alternative etiologies. Immune-mediated colitis occurred in 1.7%\r\n (48/2799) of patients receiving KEYTRUDA, including Grade 4\r\n (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions.\r\n Systemic corticosteroids were required in 69% (33/48);\r\n additional immunosuppressant therapy was required in 4.2% of\r\n patients. Colitis led to permanent discontinuation of KEYTRUDA\r\n in 0.5% (15) and withholding in 0.5% (13) of patients. All\r\n patients who were withheld reinitiated KEYTRUDA after symptom\r\n improvement; of these, 23% had recurrence. Colitis resolved in\r\n 85% of the 48 patients.\r\n
\r\n
\r\n\r\n
Hepatotoxicity and Immune-Mediated Hepatitis
\r\n
KEYTRUDA as a Single Agent
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated\r\n hepatitis occurred in 0.7% (19/2799) of patients receiving\r\n KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and\r\n Grade 2 (0.1%) reactions. Systemic corticosteroids were required\r\n in 68% (13/19) of patients; additional immunosuppressant therapy\r\n was required in 11% of patients. Hepatitis led to permanent\r\n discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3%\r\n (9) of patients. All patients who were withheld reinitiated\r\n KEYTRUDA after symptom improvement; of these, none had\r\n recurrence. Hepatitis resolved in 79% of the 19 patients.\r\n
\r\n
\r\n\r\n
Immune-Mediated Endocrinopathies
\r\n
Adrenal Insufficiency
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause primary or secondary adrenal insufficiency.\r\n For Grade 2 or higher, initiate symptomatic treatment, including\r\n hormone replacement as clinically indicated. Withhold KEYTRUDA\r\n depending on severity. Adrenal insufficiency occurred in 0.8%\r\n (22/2799) of patients receiving KEYTRUDA, including Grade 4\r\n (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions.\r\n Systemic corticosteroids were required in 77% (17/22) of\r\n patients; of these, the majority remained on systemic\r\n corticosteroids. Adrenal insufficiency led to permanent\r\n discontinuation of KEYTRUDA in <0.1% (1) and withholding in\r\n 0.3% (8) of patients. All patients who were withheld reinitiated\r\n KEYTRUDA after symptom improvement.\r\n
\r\n
\r\n\r\n
Hypophysitis
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis\r\n can present with acute symptoms associated with mass effect such\r\n as headache, photophobia, or visual field defects. Hypophysitis\r\n can cause hypopituitarism. Initiate hormone replacement as\r\n indicated. Withhold or permanently discontinue KEYTRUDA\r\n depending on severity. Hypophysitis occurred in 0.6% (17/2799)\r\n of patients receiving KEYTRUDA, including Grade 4 (<0.1%),\r\n Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic\r\n corticosteroids were required in 94% (16/17) of patients; of\r\n these, the majority remained on systemic corticosteroids.\r\n Hypophysitis led to permanent discontinuation of KEYTRUDA in\r\n 0.1% (4) and withholding in 0.3% (7) of patients. All patients\r\n who were withheld reinitiated KEYTRUDA after symptom\r\n improvement.\r\n
\r\n
\r\n\r\n
Thyroid Disorders
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated thyroid disorders.\r\n Thyroiditis can present with or without endocrinopathy.\r\n Hypothyroidism can follow hyperthyroidism. Initiate hormone\r\n replacement for hypothyroidism or institute medical management\r\n of hyperthyroidism as clinically indicated. Withhold or\r\n permanently discontinue KEYTRUDA depending on severity.\r\n Thyroiditis occurred in 0.6% (16/2799) of patients receiving\r\n KEYTRUDA, including Grade 2 (0.3%). None discontinued, but\r\n KEYTRUDA was withheld in <0.1% (1) of patients.\r\n
\r\n - \r\n Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving\r\n KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to\r\n permanent discontinuation of KEYTRUDA in <0.1% (2) and\r\n withholding in 0.3% (7) of patients. All patients who were\r\n withheld reinitiated KEYTRUDA after symptom improvement.\r\n Hypothyroidism occurred in 8% (237/2799) of patients receiving\r\n KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to\r\n permanent discontinuation of KEYTRUDA in <0.1% (1) and\r\n withholding in 0.5% (14) of patients. All patients who were\r\n withheld reinitiated KEYTRUDA after symptom improvement. The\r\n majority of patients with hypothyroidism required long-term\r\n thyroid hormone replacement.\r\n
\r\n
\r\n\r\n
\r\n Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic\r\n Ketoacidosis\r\n
\r\n\r\n
\r\n - \r\n Monitor patients for hyperglycemia or other signs and symptoms\r\n of diabetes. Initiate treatment with insulin as clinically\r\n indicated. Withhold KEYTRUDA depending on severity. Type 1 DM\r\n occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led\r\n to permanent discontinuation in <0.1% (1) and withholding of\r\n KEYTRUDA in <0.1% (1) of patients. All patients who were\r\n withheld reinitiated KEYTRUDA after symptom improvement.\r\n
\r\n
\r\n\r\n
Immune-Mediated Nephritis With Renal Dysfunction
\r\n\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated nephritis. Immune-mediated\r\n nephritis occurred in 0.3% (9/2799) of patients receiving\r\n KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and\r\n Grade 2 (0.1%) reactions. Systemic corticosteroids were required\r\n in 89% (8/9) of patients. Nephritis led to permanent\r\n discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1%\r\n (3) of patients. All patients who were withheld reinitiated\r\n KEYTRUDA after symptom improvement; of these, none had\r\n recurrence. Nephritis resolved in 56% of the 9 patients.\r\n
\r\n
\r\n\r\n
Immune-Mediated Dermatologic Adverse Reactions
\r\n
\r\n - \r\n KEYTRUDA can cause immune-mediated rash or dermatitis.\r\n Exfoliative dermatitis, including Stevens-Johnson syndrome, drug\r\n rash with eosinophilia and systemic symptoms, and toxic\r\n epidermal necrolysis, has occurred with anti–PD-1/PD-L1\r\n treatments. Topical emollients and/or topical corticosteroids\r\n may be adequate to treat mild to moderate nonexfoliative rashes.\r\n Withhold or permanently discontinue KEYTRUDA depending on\r\n severity. Immune-mediated dermatologic adverse reactions\r\n occurred in 1.4% (38/2799) of patients receiving KEYTRUDA,\r\n including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic\r\n corticosteroids were required in 40% (15/38) of patients. These\r\n reactions led to permanent discontinuation in 0.1% (2) and\r\n withholding of KEYTRUDA in 0.6% (16) of patients. All patients\r\n who were withheld reinitiated KEYTRUDA after symptom\r\n improvement; of these, 6% had recurrence. The reactions resolved\r\n in 79% of the 38 patients.\r\n
\r\n
\r\n\r\n
Other Immune-Mediated Adverse Reactions
\r\n
\r\n - \r\n The following clinically significant immune-mediated adverse\r\n reactions occurred at an incidence of <1% (unless otherwise\r\n noted) in patients who received KEYTRUDA or were reported with\r\n the use of other anti–PD-1/PD-L1 treatments. Severe or fatal\r\n cases have been reported for some of these adverse reactions.\r\n Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous\r\n System: Meningitis, encephalitis, myelitis and demyelination,\r\n myasthenic syndrome/myasthenia gravis (including exacerbation),\r\n Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy;\r\n Ocular: Uveitis, iritis and other ocular inflammatory toxicities\r\n can occur. Some cases can be associated with retinal detachment.\r\n Various grades of visual impairment, including blindness, can\r\n occur. If uveitis occurs in combination with other\r\n immune-mediated adverse reactions, consider a\r\n Vogt-Koyanagi-Harada-like syndrome, as this may require\r\n treatment with systemic steroids to reduce the risk of permanent\r\n vision loss; Gastrointestinal: Pancreatitis, to include\r\n increases in serum amylase and lipase levels, gastritis,\r\n duodenitis; Musculoskeletal and Connective Tissue:\r\n Myositis/polymyositis, rhabdomyolysis (and associated sequelae,\r\n including renal failure), arthritis (1.5%), polymyalgia\r\n rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune:\r\n Hemolytic anemia, aplastic anemia, hemophagocytic\r\n lymphohistiocytosis, systemic inflammatory response syndrome,\r\n histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis),\r\n sarcoidosis, immune thrombocytopenic purpura, solid organ\r\n transplant rejection.\r\n
\r\n
\r\n\r\n
Infusion-Related Reactions
\r\n
\r\n - \r\n KEYTRUDA can cause severe or life-threatening infusion-related\r\n reactions, including hypersensitivity and anaphylaxis, which\r\n have been reported in 0.2% of 2799 patients receiving KEYTRUDA.\r\n Monitor for signs and symptoms of infusion-related reactions.\r\n Interrupt or slow the rate of infusion for Grade 1 or Grade 2\r\n reactions. For Grade 3 or Grade 4 reactions, stop infusion and\r\n permanently discontinue KEYTRUDA.\r\n
\r\n
\r\n\r\n
\r\n Complications of Allogeneic Hematopoietic Stem Cell\r\n Transplantation (HSCT)\r\n
\r\n
\r\n - \r\n Fatal and other serious complications can occur in patients who\r\n receive allogeneic HSCT before or after anti–PD-1/PD-L1\r\n treatments. Transplant-related complications include hyperacute\r\n graft-versus-host disease (GVHD), acute and chronic GVHD,\r\n hepatic veno-occlusive disease after reduced intensity\r\n conditioning, and steroid-requiring febrile syndrome (without an\r\n identified infectious cause). These complications may occur\r\n despite intervening therapy between anti–PD-1/PD-L1 treatments\r\n and allogeneic HSCT. Follow patients closely for evidence of\r\n these complications and intervene promptly. Consider the benefit\r\n vs risks of using anti–PD-1/PD-L1 treatments prior to or after\r\n an allogeneic HSCT.\r\n
\r\n
\r\n\r\n
Increased Mortality in Patients With Multiple Myeloma
\r\n
\r\n - \r\n In trials in patients with multiple myeloma, the addition of\r\n KEYTRUDA to a thalidomide analogue plus dexamethasone resulted\r\n in increased mortality. Treatment of these patients with an\r\n anti–PD-1/PD-L1 treatment in this combination is not recommended\r\n outside of controlled trials.\r\n
\r\n
\r\n\r\n
Embryofetal Toxicity
\r\n
\r\n - \r\n Based on its mechanism of action, KEYTRUDA can cause fetal harm\r\n when administered to a pregnant woman. Advise women of this\r\n potential risk. In females of reproductive potential, verify\r\n pregnancy status prior to initiating KEYTRUDA and advise them to\r\n use effective contraception during treatment and for 4 months\r\n after the last dose.\r\n
\r\n
\r\n\r\n
Adverse Reactions
\r\n
\r\n - \r\n In KEYNOTE-564, when KEYTRUDA was administered as a single agent\r\n for the adjuvant treatment of renal cell carcinoma, serious\r\n adverse reactions occurred in 20% of patients receiving\r\n KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney\r\n injury, adrenal insufficiency, pneumonia, colitis, and diabetic\r\n ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2%\r\n including 1 case of pneumonia. Discontinuation of KEYTRUDA due\r\n to adverse reactions occurred in 21% of 488 patients; the most\r\n common (≥1%) were increased ALT (1.6%), colitis (1%), and\r\n adrenal insufficiency (1%). The most common adverse reactions\r\n (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash\r\n (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).\r\n
\r\n
\r\n\r\n
Lactation
\r\n
\r\n - \r\n Because of the potential for serious adverse reactions in\r\n breastfed children, advise women not to breastfeed during\r\n treatment and for 4 months after the final dose.\r\n
\r\n
\r\n\r\n
\r\n Before prescribing KEYTRUDA, please read the accompanying\r\n Prescribing Information. The Medication Guide also is available.\r\n
\r\n\r\n \r\n
![\"Keytruda-RCC-Patient-Journey\"](\"@/Assets/Img/CTA-Logo.svg\")
\r\n ![\"Keytruda-RCC-Patient-Journey\"](\"@/Assets/Img/PJ-Logo.svg\")
\r\n ![\"Ask](\"@/Assets/Img/Keytruda-Logo.svg\"){kind=logo}
![\"Prescribing](\"@/Assets/Img/pdf-icon.svg\"){kind=icon}
Prescribing Information\r\n ![\"Medication](\"@/Assets/Img/medical-Cross-Icon.svg\"){kind=icon}
Medication Guide\r\n ![\"\"](\"@/Assets/Img/Merck-Logo.svg\"){kind=logo}
\r\n ![\"\"](\"@/Assets/Img/Patient-Image-Hero-LG.png\")
\r\n ![\"\"/](\"@/Assets/Img/mobile-table-view.png\")
\r\n