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Pembrolizumab Side Effects

Medically reviewed by Drugs.com. Last updated on Jan 22, 2022.

For the Consumer

Applies to pembrolizumab: intravenous solution

Side effects requiring immediate medical attention

Along with its needed effects, pembrolizumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking pembrolizumab:

More common

  • Black, tarry stools
  • bladder pain
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • bloody or cloudy urine
  • blurred vision
  • body aches or pain
  • burning, numbness, tingling, or painful sensations
  • chills
  • clay-colored stools
  • confusion
  • constipation
  • cough
  • dark urine
  • decreased appetite
  • depressed mood
  • difficult, burning, or painful urination
  • difficulty with breathing
  • difficulty with moving
  • dizziness
  • dry mouth
  • dry skin and hair
  • ear congestion
  • feeling cold
  • fever
  • flushing
  • frequent urge to urinate
  • fruit-like breath odor
  • hair loss
  • headache
  • hoarseness or husky voice
  • increased hunger
  • increased thirst
  • increased urination
  • itching, skin rash
  • joint or bone pain
  • loss of voice
  • lower back or side pain
  • mood or mental changes
  • muscle cramps, pain, and stiffness
  • nausea
  • neck pain
  • nervousness
  • numbness and tingling around the mouth, fingertips, or feet
  • painful or difficult urination
  • pale skin
  • pounding in the ears
  • rapid weight gain
  • redness, swelling, or pain of the skin
  • runny or stuffy nose
  • scaling of the skin on the hands and feet
  • slow or fast heartbeat
  • sneezing
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stomach cramps, pain or tenderness
  • swelling of the face, ankles, or hands
  • tingling of the hands or feet
  • ulceration of the skin
  • unsteadiness or awkwardness
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
  • weakness in the arms, hands, legs, or feet
  • yellow eyes or skin

Less common

  • Blue lips, fingernails, or skin
  • chest pain or discomfort
  • decrease in urine output or decrease in urine-concentrating ability
  • difficulty with chewing, swallowing, or talking
  • double vision
  • drooping eyelids
  • general feeling of discomfort or illness
  • inability to speak
  • irregular, fast or slow, or shallow breathing
  • muscle weakness
  • pain and swelling in the genitals or anal area
  • seizures
  • sensitivity to heat
  • severe or sudden headache
  • slurred speech
  • sweating
  • temporary blindness
  • tenderness
  • thickening of bronchial secretions
  • trouble sleeping
  • watery or bloody diarrhea
  • weakness in the arm or leg on one side of the body, sudden and severe

Rare

  • Back or leg pain
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • cracks in the skin
  • drowsiness
  • eye pain
  • general body swelling
  • indigestion
  • joint redness or swelling
  • joint or muscle pain
  • light-colored stools
  • loss of heat from the body
  • nosebleeds
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • red, swollen skin
  • red irritated eyes
  • red skin lesions, often with a purple center
  • redness of the eye
  • scaly skin
  • sensitivity of the eye to light
  • swollen glands
  • tearing
  • upper right abdominal or stomach pain

Side effects not requiring immediate medical attention

Some side effects of pembrolizumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Cracked lips
  • hair loss or thinning
  • lack or loss of strength
  • sores, ulcers, or white spots on the lips, tongue, or inside the mouth
  • swelling or inflammation of the mouth

For Healthcare Professionals

Applies to pembrolizumab: intravenous powder for injection, intravenous solution

General

The most commonly reported adverse reactions with this drug as a single agent have included fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.

Respiratory

Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2

(1.3%) adverse reactions. Systemic corticosteroids were required in 67% (63/94) of patients with pneumonitis. Pneumonitis led to permanent discontinuation in 1.3% (36) of patients and interruption of therapy in 0.9% (26) of patients. For patients who restarted therapy, 23% had recurrence of pneumonitis. Pneumonitis resolved in 59% of the 94 patients.[Ref]

Very common (10% or more): Cough (up to 30%), dyspnea (up to 18%), upper respiratory tract infection (up to 11%)

Common (1% to 10%): Pneumonitis[Ref]

Endocrine

Adrenal insufficiency occurred in 0.8% (22/2799) of patients, 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, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation in less than 0.1% (1) of patients and interrupting therapy in 0.3% (8) of patients.

Hypophysitis occurred in 0.6% (17/2799) of patients receiving including Grade 4 (less than 0/1%), Grade 3 (0.3%), and Grade 2 (0.2%) adverse reactions. Systemic corticosteroids were required in (16/17) of patients with hypophysitis; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation in 0.1% (4) of patients and interrupting therapy in 0.3% (7) of patients.

Thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). No patients discontinued due to thyroiditis; less than 0.1% of patient interrupted therapy. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 3 (0.1%) and Grade 2 (0.8%). Hyperthyroidism led to permanent discontinuation in less than 0.1% (2) patients and therapy was interrupted in 0.3% (7) patients. Hypothyroidism occurred in 8% (237/2799) of patients, including Grade 3 (0.1%) and Grade 2 (6.2%). Hypothyroidism led to permanent discontinuation in less than 0.1% (1) of patients and therapy interruption in 0.5% (14) of patients. Most patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC (head and neck squamous cell cancer), 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 or worsening hypothyroidism was higher in patients with classic Hodgkin's lymphoma (17%) receiving this drug as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 diabetes mellitus occurred in 0.2% (6/2799) of patients. Type 1 diabetes mellitus led to permanent discontinuation in less than 0.1% (1) of patients. All patients with Type 1 diabetes mellitus required long-term insulin therapy.

Clinically significant immune-mediated adverse reactions of the endocrine system including hypoparathyroidism have occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Very common (10% or more): Hyperglycemia (up to 40%), hypertriglyceridemia (up to 25%)

Common (1% to 10%): Hypothyroidism, hyperthyroidism

Uncommon (0.1% to 1%): Hypophysitis, adrenal insufficiency, thyroiditis, type 1 diabetes mellitus

Frequency not reported: Hypoparathyroidism[Ref]

Local

Common (1% to 10%): Infusion reactions

Rare (0.01% to 0.1%): Anaphylaxis

Severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported in 0.2% of 2799 patients.

Hypersensitivity

Rare (0.01% to 0.1%): Anaphylaxis

Frequency not reported: Hypersensitivity reactions

Hepatic

Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients 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 and 11% required additional immunosuppressant therapy. Hepatitis led to permanent discontinuation in 0.2% (6) of patients and interruption of therapy occurred in 0.3% (9) of patients. Of the patients who reinitiated therapy after symptom improvement, none had recurrence of hepatitis. Hepatitis resolved in 79% of the 19 patients.

In combination with axitinib, higher than expected frequencies of Grades 3 and 4 ALT and AST elevations occurred compared to this drug alone. With the combination, Grades 3 and 4 increased ALT (20%) and AST (13%) occurred; 59% of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 x ULN or greater (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), axitinib (n=34), or both (n=55), recurrence of ALT to 3 x ULN was observed in 1 patient with this drug, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT to 3 x ULN or greater subsequently recovered.[Ref]

Very common (10% or more): Hypoalbuminemia (up to 34%), increased aspartate aminotransferase (up to 24%)

Uncommon (0.1% to 1%): Hepatitis

Postmarketing reports: Sclerosing cholangitis[Ref]

Dermatologic

Very common (10% or more): Pruritus (up to 30%), rash (up to 29%), vitiligo (up to 11%)

Uncommon (0.1% to 1%): Exfoliative dermatitis[Ref]

Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients, including Grade 3 (1%) and Grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in 40% (15/38) of patients. Permanent discontinuation occurred in 0.1% (2) of patients and interruption of therapy occurred in 0.6% (16) of patients. For patients who interrupted therapy, 6% had recurrence of their immune-mediated dermatologic adverse reaction when restarting therapy. Immune-mediated dermatologic adverse reactions resolved in 79% of the 38 patients who experienced reactions.[Ref]

Gastrointestinal

Immune-mediated colitis occurred in 1.7% (48/2799) of patients, 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 in 0.5% (15) of patients, 0.5% (13) of patients interrupted therapy. Of the patients who restarted therapy, 23% had recurrence of colitis. Colitis resolved in 85% of the 48 patients. Clinically significant immune-mediated adverse reactions of the gastrointestinal system including pancreatitis, gastritis, duodenitis have occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Very common (10% or more): Nausea (up to 30%), constipation (up to 21%), diarrhea (up to 20%), vomiting (up to 16%), abdominal pain (up to 12%)

Common (1% to 10%): Colitis

Uncommon (0.1% to 1%): Pancreatitis

Frequency not reported: Cytomegalovirus (CMV) infection/reactivation, gastritis, duodenitis[Ref]

Renal

Uncommon (0.1% to 1%): Nephritis, renal failure[Ref]

Immune-mediated nephritis occurred in 0.3% (9/2799) of patients 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 in 0.1% (3) of patients and interruption of therapy in 0.1% (3) of patients. Nephritis resolved in 56% of the 9 patients.[Ref]

Cardiovascular

Very common (10% or more): Peripheral edema (up to 17%)

Frequency not reported: Myocarditis, pericarditis, vasculitis[Ref]

Clinically significant immune-mediated adverse reactions of the cardiovascular system including myocarditis, pericarditis, vasculitis have occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Hematologic

Clinically significant immune-mediated adverse reactions of the hematologic system including Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic

inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis),

sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection have occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Very common (10% or more): Anemia (up to 55%), immune-mediated hemolytic anemia[Ref]

Metabolic

Very common (10% or more): Hyponatremia (up to 35%), decreased appetite (up to 26%), hypocalcemia (up to 24%)[Ref]

Musculoskeletal

For patients who received this drug or with use of other PD1/PD-L1 blocking antibodies, clinically significant immune-mediated adverse reactions of the musculoskeletal system occurred at less than 1% (myositis/polymyositis, rhabdomyolysis [and associated sequelae, including renal failure], polymyalgia rheumatica) or at 1.5% (arthritis). For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Very common (10% or more): Arthralgia (up to 20%), pain in extremity (up to 18%), myalgia (up to 14%), back pain (up to 12%)

Uncommon (0.1% to 1%): Arthritis, myositis, myasthenic syndrome, rhabdomyolysis

Frequency not reported: Polymyositis, polymyalgia rheumatica[Ref]

Nervous system

Clinically significant immune-mediated adverse reactions of the nervous system have occurred including meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Very common (10% or more): Headache (up to 16%), dizziness (up to 11%)

Uncommon (0.1% to 1%): Partial seizures

Frequency not reported: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy[Ref]

Ocular

Uncommon (0.1% to 1%): Uveitis, optic neuritis[Ref]

Clinically significant ocular immune-mediated adverse reactions including uveitis, iritis and other ocular inflammatory toxicities have occurred at an incidence of less than 1% in patients who received this drug or were reported with the use of other PD1/PD-L1 blocking antibodies. For some of these reactions, severe or fatal cases have been reported. Immune-mediated adverse reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.[Ref]

Other

Very common (10% or more): Fatigue (up to 47%), chills (up to 14%), pyrexia (up to 11%), sepsis (up to 10%)[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 14%)[Ref]

Frequently asked questions

References

1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. http://www.appco.com.au/appguide/default.asp." (2006):

3. "Product Information. Keytruda (pembrolizumab)." Merck & Company Inc (2014):

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.