Note: This document contains side effect information about pembrolizumab. Some dosage forms listed on this page may not apply to the brand name Keytruda.
Applies to pembrolizumab: parenteral injection concentrate, parenteral powder for injection.
Side effects include:
Unresectable or metastatic melanoma: Pruritus, rash, constipation, fatigue, arthralgia, cough, decreased appetite, pyrexia, abdominal pain, vitiligo, back pain, dyspnea, asthenia, hypothyroidism, nausea, hyperglycemia, hypertriglyceridemia, hypoalbuminemia, hyponatremia, anemia, lymphopenia, elevated ALT/AST concentrations, elevated alkaline phosphatase concentrations, decreased bicarbonate concentrations, hypocalcemia, hypercholesterolemia.
Adjuvant therapy for advanced melanoma with regional lymph node involvement: Diarrhea, pruritus, nausea, arthralgia, hypothyroidism, cough, rash, asthenia, influenza-like illness, weight loss, hyperthyroidism, elevated ALT/AST concentrations, lymphopenia.
Combination therapy with pemetrexed and a platinum-containing antineoplastic agent (carboplatin or cisplatin) in patients with previously untreated metastatic nonsquamous NSCLC: Nausea, fatigue, constipation, diarrhea, rash, pyrexia, anemia, hyperglycemia, neutropenia, elevated ALT/AST concentrations, elevated Scr, hyponatremia, hypophosphatemia, hypocalcemia, hyperkalemia.
Combination therapy with carboplatin and paclitaxel (conventional or albumin-bound) in patients with previously untreated metastatic squamous NSCLC: Alopecia, peripheral neuropathy; other adverse effects generally similar to those reported in patients receiving pembrolizumab (the active ingredient contained in Keytruda) in combination with pemetrexed and a platinum-containing antineoplastic agent for treatment of previously untreated metastatic nonsquamous NSCLC.
Monotherapy in patients with previously treated PD-L1-positive metastatic NSCLC: Decreased appetite, dyspnea, nausea, cough, rash, constipation, vomiting, arthralgia, back pain, pruritus, hyponatremia, elevated alkaline phosphatase concentrations, elevated ALT/AST concentrations.
Head and neck squamous cell carcinoma: Fatigue, decreased appetite, dyspnea. Increased frequency of facial edema and new or worsening hypothyroidism compared with patients with melanoma or NSCLC.
cHL: Fatigue, cough, pyrexia, musculoskeletal pain, diarrhea, rash, vomiting, hypothyroidism, nausea, upper respiratory tract infection, dyspnea, headache, pruritus, arthralgia, peripheral neuropathy, elevated ALT/AST concentrations, anemia, thrombocytopenia, neutropenia.
PMBL: Musculoskeletal pain, upper respiratory tract infection, pyrexia, cough, fatigue, dyspnea, abdominal pain, diarrhea, arrhythmia, headache, nausea, anemia, hyperglycemia, leukopenia, lymphopenia, neutropenia, hypophosphatemia, elevated ALT/AST concentrations, hypoglycemia, elevated alkaline phosphatase concentrations, elevated Scr, hypocalcemia, hypokalemia.
Locally advanced or metastatic urothelial carcinoma in cisplatin-ineligible patients: Fatigue, musculoskeletal pain, decreased appetite, constipation, rash, diarrhea, pruritus, urinary tract infection, abdominal pain, nausea, cough, peripheral edema, hematuria, vomiting, dyspnea, pyrexia, arthralgia, weight loss, anemia, elevated ALT/AST concentrations, elevated Scr, hyponatremia.
Previously treated locally advanced or metastatic urothelial carcinoma: Musculoskeletal pain, pruritus, rash, cough, vomiting, dyspnea, hematuria, elevated alkaline phosphatase concentrations, elevated Scr, elevated AST concentrations.
Gastric cancer: Adverse effects similar to those in patients with melanoma or NSCLC.
Cervical cancer: Fatigue, musculoskeletal pain, diarrhea, abdominal pain, pain, decreased appetite, hemorrhage, nausea, pyrexia, vomiting, infection (including urinary tract infection), rash, peripheral edema, constipation, headache, hypothyroidism, dyspnea, anemia, lymphopenia, hypoalbuminemia, elevated alkaline phosphatase concentrations, hyperglycemia, hyponatremia, elevated ALT/AST concentrations, elevated Scr, hypocalcemia, hypokalemia.
Hepatocellular carcinoma: Adverse effects generally similar to those in patients with melanoma or NSCLC; however, ascites, immune-mediated hepatitis, elevated ALT/AST concentrations, and hyperbilirubinemia more common in patients with hepatocellular carcinoma.
Merkel cell carcinoma: Adverse effects similar to those in patients with melanoma or NSCLC; however, hyperglycemia and elevated AST concentrations more common in patients with Merkel cell carcinoma.
For Healthcare Professionals
Applies to pembrolizumab: intravenous powder for injection, intravenous solution.
General
The most common adverse reactions reported with this drug as a single agent were fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.
The most common adverse reactions reported with this drug in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.
The most common adverse reactions reported with this drug in combination with chemotherapy and bevacizumab were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.
The most common adverse reactions reported with this drug in combination with axitinib were diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.
The most common adverse reactions reported with this drug in combination with lenvatinib were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, rash, hepatotoxicity, and acute kidney injury.
The most common adverse reactions reported with this drug in combination with enfortumab vedotin were rash, peripheral neuropathy, fatigue, alopecia, weight loss, diarrhea, pruritus, decreased appetite, nausea, dysgeusia, urinary tract infection, constipation, peripheral edema, dry eye, dizziness, arthralgia, and dry skin.
The manufacturer product information for the concomitant therapies should be consulted.[Ref]
Cardiovascular
Clinically significant immune-mediated cardiovascular adverse reactions (including myocarditis, pericarditis, vasculitis) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies; severe or fatal cases have been reported for some of these adverse reactions.
Very common (10% or more): Hypertension (includes hypertension, increased blood pressure, hypertensive crisis, labile hypertension, essential hypertension, increased diastolic blood pressure, hypertensive retinopathy, labile blood pressure, secondary hypertension, abnormal blood pressure, hypertensive encephalopathy, blood pressure fluctuation; up to 67%), hemorrhage/hemorrhagic events (includes all hemorrhage terms [including anal hemorrhage, ruptured aneurysm, blood blister, blood loss anemia, blood urine present, catheter site hematoma, cerebral hemorrhage, cerebral microhemorrhage, conjunctival hemorrhage, contusion, hemorrhagic diarrhea, disseminated intravascular coagulation, ecchymosis, epistaxis, eye hemorrhage, gastric hemorrhage, gastrointestinal hemorrhage, hemorrhagic gastritis, gingival bleeding, urinary tract hemorrhage, hemothorax, hematemesis, hematoma, hematochezia, hematuria, hemoptysis, hemorrhagic stroke, hemorrhoidal hemorrhage, hepatic hematoma, increased tendency to bruise, injection site hematoma, injection site bruising, injection site hemorrhage, intestinal hemorrhage, intra-abdominal hemorrhage, intracranial hemorrhage, lower gastrointestinal hemorrhage, laryngeal hemorrhage, Mallory-Weiss syndrome, melena, metrorrhagia, mouth hemorrhage, petechiae, pulmonary hemorrhage, rectal hemorrhage, renal hemorrhage, retroperitoneal hemorrhage, small intestinal hemorrhage, splinter hemorrhages, stoma site hemorrhage, subcutaneous hematoma, subcutaneous hemorrhage, subdural hematoma, subarachnoid hemorrhage, thrombotic thrombocytopenic purpura, tumor hemorrhage, traumatic hematoma, upper gastrointestinal hemorrhage, umbilical hemorrhage, uterine hemorrhage, vaginal hemorrhage, vessel puncture site bruise, wound hemorrhage]; up to 27%), arrhythmia (includes atrial fibrillation, sinus tachycardia, supraventricular tachycardia, tachycardia; up to 11%)
Common (1% to 10%): Myocarditis (includes autoimmune myocarditis), cardiac tamponade, myocardial infarction, pericardial effusion, pericarditis, hypotension, cardiac ischemia, angina pectoris, cardiac arrhythmia (including atrial fibrillation)
Uncommon (0.1% to 1%): Cardiac failure, cardiorespiratory arrest, hypertensive crisis, ruptured aneurysm, vasculitis (includes central nervous system vasculitis, aortitis, giant cell arteritis)
Frequency not reported: Cardiac arrest, right ventricular dysfunction, hypovolemic shock
Dermatologic
Very common (10% or more): Rash (includes rash, erythematous rash, follicular rash, generalized rash, macular rash, maculopapular rash, papular rash, pruritic rash, exfoliative rash, genital rash, pustular rash, dermatitis, acneiform dermatitis, allergic dermatitis, bullous dermatitis, contact dermatitis, exfoliative dermatitis, drug eruption, erythema, erythema multiforme, seborrheic dermatitis, atopic dermatitis, psoriasiform dermatitis, eczema, toxic skin eruption, asteatotic eczema, blister, conjunctivitis, generalized exfoliative dermatitis, palmar-plantar erythrodysesthesia syndrome, pemphigoid, vesicular rash, skin exfoliation, stomatitis, skin reaction, seborrheic keratosis, lichenoid keratosis, urticaria, butterfly rash, skin discoloration, perineal rash, infusion site rash, penile rash, lichen planus, Stevens-Johnson syndrome, application site rash, incision site rash, injection site rash, morbilliform rash, rubelliform rash, skin toxicity, vasculitic rash, viral rash, eyelid rash; up to 71%), alopecia (up to 61%), pruritus (includes urticaria, papular urticaria, genital pruritus; up to 40%), palmar-plantar erythrodysesthesia (includes palmar erythema, palmar-plantar erythrodysesthesia syndrome, plantar erythema; up to 29%), stomatitis/mucosal inflammation (up to 27%), dry skin (up to 21%), vitiligo (includes skin hypopigmentation, skin depigmentation, hypopigmentation of the eyelid; up to 13%)
Common (1% to 10%): Immune-mediated dermatologic adverse reactions, severe skin reactions (includes exfoliative rash, pemphigus), erythema, dermatitis, eczema, acneiform dermatitis
Uncommon (0.1% to 1%): Bullous dermatitis, psoriasis, lichenoid keratosis (includes lichen planus, lichen sclerosus), papule, hair color changes
Rare (0.01% to 0.1%): Stevens-Johnson syndrome, erythema nodosum, toxic epidermal necrolysis
Frequency not reported: Drug rash with eosinophilia and systemic symptoms (DRESS)
Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving this drug, including grade 3 (1%) and grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in 40% (15/38) of patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions led to permanent discontinuation of this drug in 0.1% (2) of patients and withholding of therapy in 0.6% (16) of patients. All patients who were withheld restarted this drug after symptom improvement; of these, 6% had recurrence of immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 79% of the 38 patients.
Severe skin reactions also included grade 3 or greater of the following: bullous dermatitis, exfoliative dermatitis, generalized exfoliative dermatitis, erythema multiforme, lichen planus, oral lichen planus, pemphigoid, pruritus, genital pruritus, rash, erythematous rash, maculopapular rash, pruritic rash, pustular rash, skin necrosis, and toxic skin eruption.
Endocrine
Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving this drug, including grade 4 (less than 0.1%), grade 3 (0.3%), and grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in 77% (17/22) of patients with adrenal insufficiency; of these, most remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of this drug in less than 0.1% (1) of patients and withholding of therapy in 0.3% (8) of patients. All patients who were withheld restarted this drug after symptom improvement.
Hypophysitis occurred in 0.6% (17/2799) of patients receiving this drug, including grade 4 (less than 0.1%), grade 3 (0.3%), and grade 2 (0.2%) adverse reactions. Systemic corticosteroids were required in 94% (16/17) of patients with hypophysitis; of these, most remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of this drug in 0.1% (4) of patients and withholding of therapy in 0.3% (7) of patients. All patients who were withheld restarted this drug after symptom improvement.
Thyroiditis occurred in 0.6% (16/2799) of patients receiving this drug, including grade 2 (0.3%). No patients discontinued this drug due to thyroiditis; this drug was withheld in less than 0.1% (1) of patients.
Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving this drug, including grade 3 (0.1%) and grade 2 (0.8%). Hyperthyroidism led to permanent discontinuation of this drug in less than 0.1% (2) of patients and withholding of therapy in 0.3% (7) of patients. All patients who were withheld restarted this drug after symptom improvement. The incidence of new/worsening hyperthyroidism was higher in 580 patients with resected non-small cell lung cancer (NSCLC), occurring in 11% of patients receiving this drug as a single agent as adjuvant treatment, including grade 3 (0.2%) hyperthyroidism.
Hypothyroidism occurred in 8% (237/2799) of patients receiving this drug, including grade 3 (0.1%) and grade 2 (6.2%). Hypothyroidism led to permanent discontinuation of this drug in less than 0.1% (1) of patients and withholding of therapy in 0.5% (14) of patients. All patients who were withheld restarted this drug after symptom improvement. Most patients with hypothyroidism required long-term thyroid hormone replacement.
The incidence of new/worsening hypothyroidism was higher in 1185 patients with head and neck squamous cell carcinoma, occurring in 16% of patients receiving this drug as a single agent or in combination with platinum and fluorouracil, including grade 3 (0.3%) hypothyroidism. The incidence of new/worsening hypothyroidism was higher in 389 patients with classical Hodgkin lymphoma (cHL) (17%) receiving this drug as a single agent, including grade 1 (6.2%) and grade 2 (10.8%) hypothyroidism. The incidence of new/worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving this drug as a single agent as adjuvant treatment, including grade 3 (0.3%) hypothyroidism.
Type 1 diabetes mellitus occurred in 0.2% (6/2799) of patients receiving this drug. Type 1 diabetes mellitus led to permanent discontinuation in less than 0.1% (1) of patients and withholding of therapy in less than 0.1% (1) of patients. All patients who were withheld restarted this drug after symptom improvement. All patients with type 1 diabetes mellitus required long-term insulin therapy.
Clinically significant immune-mediated endocrine adverse reactions (including hypoparathyroidism) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Very common (10% or more): Hypothyroidism (includes hypothyroidism, increased blood thyroid stimulating hormone, secondary hypothyroidism, thyroiditis, myxedema, immune-mediated hypothyroidism; up to 67%), hyperthyroidism (includes Basedow's disease; up to 12%)
Common (1% to 10%): Thyroiditis (includes autoimmune thyroiditis, thyroid disorder, acute thyroiditis), adrenal insufficiency (includes Addison's disease, acute adrenocortical insufficiency, secondary adrenocortical insufficiency)
Uncommon (0.1% to 1%): Hypophysitis (includes hypopituitarism, lymphocytic hypophysitis)
Rare (0.01% to 0.1%): Hypoparathyroidism
Frequency not reported: Adrenal crisis
Gastrointestinal
Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving this drug, including grade 4 (less than 0.1%), grade 3 (1.1%), and grade 2 (0.4%) adverse reactions. Systemic corticosteroids were required in 69% (33/48) of patients with colitis. Additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of this drug in 0.5% (15) of patients and 0.5% (13) of patients withheld therapy. All patients who withheld therapy restarted this drug after symptom improvement; of these, 23% had recurrence of colitis. Colitis resolved in 85% of the 48 patients.
Clinically significant immune-mediated gastrointestinal adverse reactions (including pancreatitis [to include increases in serum amylase and lipase levels], gastritis, duodenitis) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Very common (10% or more): Nausea (up to 67%), diarrhea (includes diarrhea, colitis, hemorrhagic diarrhea, microscopic colitis, gastroenteritis, enterocolitis, frequent bowel movements, enteritis, hemorrhagic enterocolitis; up to 62%), increased lipase (up to 61%), increased amylase (up to 59%), stomatitis (includes aphthous ulcer, cheilitis, gingival pain, glossitis, glossodynia, lip pain, lip ulceration, mouth ulceration, mucosal inflammation, oral discomfort, oral mucosal blistering, oral mucosal eruption, oral mucosal erythema, oral pain, oropharyngeal pain, pharyngeal inflammation, stomatitis, tongue blistering, tongue ulceration; up to 43%), constipation (up to 42%), vomiting (up to 37%), abdominal pain (includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, pelvic pain, flank pain, tumor pain, bladder pain, hepatic pain, suprapubic pain, abdominal distension, abdominal rigidity, abdominal tenderness, epigastric discomfort, gastrointestinal pain; up to 34%), dysphagia (up to 12%)
Common (1% to 10%): Immune-mediated colitis, colitis (includes microscopic colitis, enterocolitis, hemorrhagic enterocolitis, autoimmune colitis, immune-mediated enterocolitis), ascites, dry mouth, gastritis, pancreatitis (includes autoimmune pancreatitis, acute pancreatitis, immune-mediated pancreatitis)
Uncommon (0.1% to 1%): Gastrointestinal ulceration (includes gastric ulcer, duodenal ulcer)
Rare (0.01% to 0.1%): Small intestinal perforation
Frequency not reported: Duodenitis, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction
Genitourinary
Very common (10% or more): Urinary tract infection (UTI) (includes bacterial pyelonephritis, acute pyelonephritis, UTI, bacterial UTI, pseudomonal UTI, urosepsis, cystitis, pyelonephritis; up to 31%), proteinuria (includes hemoglobinuria, nephrotic syndrome, proteinuria, protein urine present; up to 30%), hematuria (includes blood urine present, hematuria, chromaturia; up to 19%)
Common (1% to 10%): Urosepsis, urinary retention
Uncommon (0.1% to 1%): Noninfective cystitis
Hematologic
Clinically significant immune-mediated hematologic adverse reactions (including hemolytic anemia, aplastic anemia, immune thrombocytopenic purpura) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Very common (10% or more): Anemia (up to 97%), leukopenia (up to 93%), neutropenia (up to 88%), lymphopenia (up to 80%), thrombocytopenia (up to 73%), increased INR (up to 27%), prolonged activated partial thromboplastin time (up to 22%), increased prothrombin INR (up to 21%), febrile neutropenia (up to 15%), decreased platelet count (up to 14%), decreased WBC count (up to 13%)
Uncommon (0.1% to 1%): Immune thrombocytopenia, eosinophilia
Rare (0.01% to 0.1%): Hemolytic anemia, pure red cell aplasia
Frequency not reported: aplastic anemia, immune thrombocytopenic purpura
Postmarketing reports: Autoimmune hemolytic anemia
Hepatic
Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving this drug, including grade 4 (less than 0.1%), grade 3 (0.4%), and grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in 68% (13/19) of patients with hepatitis; 11% of these patients required additional immunosuppressant therapy. Hepatitis led to permanent discontinuation of this drug in 0.2% (6) of patients and withholding of therapy in 0.3% (9) of patients. All patients who were withheld restarted this drug after symptom improvement; of these, none had recurrence of hepatitis. Hepatitis resolved in 79% of the 19 patients.
In combination with axitinib, hepatic toxicity with higher than expected frequencies of grades 3 and 4 ALT and AST elevations occurred compared to this drug alone. With this combination, grades 3 and 4 increased ALT (20%) and increased AST (13%) occurred; 59% of the patients with increased ALT received systemic corticosteroids. In patients with ALT at least 3 times the upper limit of normal (3 x ULN) (grades 2 to 4, n=116), ALT resolved to grades 0 to 1 in 94%. Among the 92 patients who were rechallenged with either this drug (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT at least 3 x ULN was observed in 1 patient receiving this drug, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT at least 3 x ULN subsequently recovered from the event.
Very common (10% or more): Increased AST (up to 73%), increased ALT (up to 71%), hepatotoxicity (includes increased ALT, increased AST, autoimmune hepatitis, increased blood bilirubin, drug-induced liver injury, increased hepatic enzyme, abnormal hepatic function, hepatitis, fulminant hepatitis, hepatocellular injury, hepatotoxicity, hyperbilirubinemia, immune-mediated hepatitis, increased liver function test, liver injury, increased transaminases, hepatic failure, hypertransaminasemia, increased GGT, increased conjugated bilirubin; up to 39%), hypertransaminasemia (includes elevated AST, elevated ALT; up to 34%), increased blood bilirubin (up to 22%), hyperbilirubinemia (up to 16%), elevated liver function tests (includes autoimmune hepatitis, hepatitis, toxic hepatitis, liver injury, increased transaminases, hyperbilirubinemia, increased blood bilirubin, increased ALT, increased AST, increased hepatic enzymes, increased liver function tests; up to 13%)
Common (1% to 10%): Immune-mediated hepatitis, liver enzyme elevation, increased transaminase, hepatitis (includes autoimmune hepatitis, immune-mediated hepatitis, drug induced liver injury, acute hepatitis)
Uncommon (0.1% to 1%): Autoimmune hepatitis
Rare (0.01% to 0.1%): Sclerosing cholangitis (includes immune-mediated cholangitis)
Frequency not reported: Hepatic toxicity
Postmarketing reports: Sclerosing cholangitis
Hypersensitivity
Common (1% to 10%): Hypersensitivity
Uncommon (0.1% to 1%): Allergic reaction
Immunologic
Common (1% to 10%): Immune-mediated adverse reactions, graft versus host disease, anti-drug antibodies
Uncommon (0.1% to 1%): Sarcoidosis, neutralizing antibodies
Rare (0.01% to 0.1%): Hemophagocytic lymphohistiocytosis
Frequency not reported: Solid organ transplant rejection
Postmarketing reports: Hemophagocytic lymphohistiocytosis
Immune-mediated adverse reactions have occurred in various organ systems and tissues and have affected more than 1 body system simultaneously. Severe or fatal cases have been reported for some of these adverse reactions.
Clinically significant immune-mediated immunologic adverse reactions (including hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis], sarcoidosis, solid organ transplant rejection) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Local
Uncommon (0.1% to 1%): Infusion site extravasation
Metabolic
Very common (10% or more): Hypertriglyceridemia (up to 80%), hyperglycemia (up to 74%), hypercholesterolemia (up to 64%), hyponatremia (up to 60%), hypoalbuminemia (up to 60%), hypomagnesemia (up to 53%), hypophosphatemia (up to 51%), increased glucose (up to 48%), decreased appetite (includes decreased appetite, early satiety; up to 44%), hypoglycemia (up to 44%), hypocalcemia (up to 44%), hyperkalemia (up to 44%), hypokalemia (up to 35%), hypercalcemia (up to 27%), hypermagnesemia (up to 23%), decreased bicarbonate (up to 22%)
Common (1% to 10%): Dehydration, diabetic ketoacidosis
Uncommon (0.1% to 1%): Type 1 diabetes mellitus
Musculoskeletal
Very common (10% or more): Musculoskeletal disorders/musculoskeletal pain (includes arthralgia, arthritis, back pain, bone pain, breast pain, musculoskeletal discomfort, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, noncardiac chest pain, pain in extremity, spinal pain, myositis, pain in jaw; up to 58%), arthralgia (up to 30%), increased creatine phosphokinase (up to 24%), myalgia (includes back pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, torticollis; up to 20%), back pain (up to 12%), neck pain (up to 10%), myositis (includes myalgia, myopathy, necrotizing myositis, polymyalgia rheumatica, rhabdomyolysis), pain in extremity
Common (1% to 10%): Joint pain, fistula, arthritis (includes joint swelling, polyarthritis, joint effusion)
Uncommon (0.1% to 1%): Tenosynovitis (includes tendonitis, synovitis, tendon pain)
Rare (0.01% to 0.1%): Sjogren's syndrome
Frequency not reported: Polymyositis, rhabdomyolysis (with associated sequelae [including renal failure]), polymyalgia rheumatica, autoimmune myositis (with respiratory failure), femur fracture (with perioperative pulmonary embolus), Fournier's gangrene, immune-mediated myositis
Postmarketing reports: Arthritis, Sjogren's syndrome
Clinically significant immune-mediated musculoskeletal and connective tissue adverse reactions occurred at an incidence of less than 1% (myositis/polymyositis, rhabdomyolysis [and associated sequelae, including renal failure], polymyalgia rheumatica) or 1.5% (arthritis) in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Nervous system
Clinically significant immune-mediated nervous system adverse reactions (including meningitis, encephalitis, myelitis, demyelination, myasthenic syndrome/myasthenia gravis [including exacerbation], Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Very common (10% or more): Peripheral neuropathy (includes dysesthesia, hypoesthesia, peripheral neuropathy, paresthesia, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, muscular weakness, gait disturbance; up to 65%), dysgeusia (up to 35%), headache (includes headache, migraine, tension headache, sinus headache, migraine with aura; up to 30%), dizziness (up to 23%), peripheral sensory neuropathy (includes peripheral sensory neuropathy, peripheral neuropathy, hypoesthesia, dysesthesia; up to 14%)
Common (1% to 10%): Myasthenia gravis, cerebrovascular accident, lethargy
Uncommon (0.1% to 1%): Polyneuropathy, myelitis (including transverse myelitis), myasthenic syndrome/myasthenia gravis (including exacerbation), subarachnoid hemorrhage, epilepsy, encephalitis (includes autoimmune encephalitis, noninfective encephalitis)
Rare (0.01% to 0.1%): Guillain-Barre syndrome (includes axonal neuropathy, demyelinating polyneuropathy), aseptic meningitis (includes meningitis, noninfective meningitis)
Frequency not reported: Meningitis, demyelination, nerve paresis, autoimmune neuropathy, autoimmune encephalitis
Postmarketing reports: Optic neuritis
Ocular
Very common (10% or more): Dry eye (up to 25%)
Common (1% to 10%): Uveitis (includes chorioretinitis, iritis, iridocyclitis)
Rare (0.01% to 0.1%): Vogt-Koyanagi-Harada syndrome
Frequency not reported: Iritis, other ocular inflammatory toxicities, retinal detachment, visual impairment (various grades, including blindness), Vogt-Koyanagi-Harada-like syndrome
Postmarketing reports: Vogt-Koyanagi-Harada syndrome
Clinically significant immune-mediated ocular adverse reactions (including uveitis, iritis, other ocular inflammatory toxicities) occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD-1/PD-L1 blocking antibodies. Some cases were associated with retinal detachment, and various grades of visual impairment (including blindness) have occurred.
Oncologic
Common (1% to 10%): Tumor flare
Frequency not reported: Histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), plasma cell myeloma, myelodysplastic syndrome
Other
Very common (10% or more): Fatigue (includes asthenia, fatigue, malaise, lethargy; up to 70%), weight loss (up to 48%), increased alkaline phosphatase (up to 42%), decreased sodium (up to 37%), decreased albumin (up to 34%), mucosal inflammation (up to 31%), pyrexia (up to 28%), increased potassium (up to 27%), increased calcium (up to 27%), peripheral edema (includes peripheral edema, peripheral swelling; up to 26%), pain (includes breast pain, cancer pain, dysesthesia, dysuria, ear pain, gingival pain, groin pain, lymph node pain, oropharyngeal pain, pain, pain of skin, pelvic pain, radicular pain, stoma site pain, toothache; up to 22%), asthenia (up to 20%), fever (up to 18%), infections (except UTIs) (includes cellulitis, Clostridioides difficile infection, device-related infection, empyema, erysipelas, herpes virus infection, infected neoplasm, infection, influenza, lower respiratory tract congestion, lung infection, oral candidiasis, oral fungal infection, osteomyelitis, pseudomonas infection, respiratory tract infection, tooth abscess, upper respiratory tract infection, uterine abscess, vulvovaginal candidiasis; up to 16%), influenza-like illness (up to 11%), facial edema (up to 10%), edema (includes peripheral edema, generalized edema, fluid overload, fluid retention, eyelid edema, lip edema, face edema, localized edema, periorbital edema)
Common (1% to 10%): General physical health deterioration, generalized edema, death (due to unknown cause), sepsis, septic shock, herpes virus infection, infusion reactions, herpes zoster, malaise, infusion-related reaction (includes drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction, hypersensitivity, infusion-related hypersensitivity reaction, cytokine release syndrome, serum sickness), chills
Uncommon (0.1% to 1%): Severe/life-threatening infusion-related reactions (including hypersensitivity, anaphylaxis), multiple organ dysfunction syndrome
Frequency not reported: Systemic inflammatory response syndrome, complications after allogeneic hematopoietic stem cell transplant, pelvic infection
Psychiatric
Very common (10% or more): Insomnia (up to 21%)
Common (1% to 10%): Confusional state, altered mental state
Renal
Very common (10% or more): Increased creatinine (up to 69%), acute kidney injury (includes acute kidney injury, azotemia, increased blood creatinine, decreased CrCl, hypercreatininemia, renal failure, renal impairment, oliguria, decreased GFR, toxic nephropathy; up to 21%)
Common (1% to 10%): Nephritis (includes autoimmune nephritis, tubulointerstitial nephritis, renal failure/acute renal failure/acute kidney injury with evidence of nephritis, nephrotic syndrome, glomerulonephritis, membranous glomerulonephritis)
Uncommon (0.1% to 1%): Immune-mediated nephritis
Frequency not reported: Renal failure
Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving this drug, including grade 4 (less than 0.1%), grade 3 (0.1%), and grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in 89% (8/9) of patients with nephritis. Nephritis led to permanent discontinuation of this drug in 0.1% (3) of patients and withholding of therapy in 0.1% (3) of patients. All patients who were withheld restarted this drug after symptom improvement; of these, none had recurrence of nephritis. Nephritis resolved in 56% of the 9 patients.
Respiratory
Very common (10% or more): Upper respiratory tract infection (includes acute sinusitis, nasopharyngitis, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, bacterial sinusitis, tonsillitis, upper respiratory tract infection, viral upper respiratory tract infection, rhinorrhea; up to 41%), dysphonia (up to 30%), cough (includes cough, productive cough, allergic cough, upper-airway cough syndrome; up to 26%), dyspnea (includes dyspnea, exertional dyspnea, wheezing; up to 23%), pneumonia (includes pneumonia, atypical pneumonia, bacterial pneumonia, staphylococcal pneumonia, aspiration pneumonia, lower respiratory tract infection, lung infection, pseudomonal lung infection; up to 19%), pneumonitis (includes pneumonitis, interstitial lung disease, organizing pneumonia, immune-mediated pneumonitis, immune-mediated lung disease; up to 11%), nasopharyngitis (up to 10%)
Common (1% to 10%): Immune-mediated pneumonitis, respiratory failure, pulmonary embolism, pleural effusion, oropharyngeal pain, coronavirus disease 2019 (COVID-19)
Frequency not reported: Interstitial lung disease
Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving this drug, including fatal (0.1%), grade 4 (0.3%), grade 3 (0.9%), and grade 2 (1.3%) adverse reactions; the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Systemic corticosteroids were required in 67% (63/94) of patients with pneumonitis. Pneumonitis led to permanent discontinuation of this drug in 1.3% (36) of patients and withholding of therapy in 0.9% (26) of patients. All patients who were withheld restarted this drug after symptom improvement; of these, 23% had recurrence of pneumonitis. Pneumonitis resolved in 59% of the 94 patients.
In clinical studies enrolling 389 adult patients with cHL who received this drug as a single agent, pneumonitis occurred in 31 (8%) patients, including grades 3 to 4 pneumonitis in 2.3% of patients. Patients received high-dose corticosteroids for 10 days (median duration; range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of this drug in 21 (5.4%) patients. Of the patients who developed pneumonitis, 42% interrupted therapy, 68% discontinued this drug, and 77% had resolution.
In a clinical study enrolling 580 adult patients with resected NSCLC who received this drug as a single agent for adjuvant treatment, pneumonitis occurred in 41 (7%) patients, including fatal (0.2%), grade 4 (0.3%), and grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for 10 days (median duration; range: 1 day to 2.3 months). Pneumonitis led to discontinuation of this drug in 26 (4.5%) patients. Of the patients who developed pneumonitis, 54% interrupted therapy, 63% discontinued this drug, and 71% had resolution.
