What are the side effects of Keytruda (pembrolizumab)?

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From the Guidelines

Keytruda (pembrolizumab) can cause various side effects, including common ones like fatigue, diarrhea, nausea, and rash, as well as more serious immune-related adverse reactions such as pneumonitis, colitis, and hepatitis, as reported in the 2024 study 1.

Common Side Effects

  • Fatigue
  • Diarrhea
  • Nausea
  • Rash
  • Pruritus
  • Maculopapular rash
  • Vitiligo
  • Fatigue
  • Pyrexia
  • Arthralgia
  • Myalgia
  • Asthenia
  • Headache
  • Dyspnea
  • Cough
  • Abdominal pain
  • Chills
  • Elevated ALT
  • Elevated AST
  • Hypophysitis
  • Hypothyroidism
  • Hyperthyroidism
  • Elevated lipase
  • Elevated amylase
  • Pneumonitis
  • Creatinine increased

Serious Immune-Related Adverse Reactions

  • Pneumonitis (lung inflammation)
  • Colitis (intestinal inflammation)
  • Hepatitis (liver inflammation)
  • Nephritis (kidney inflammation)
  • Endocrinopathies (hormone gland problems)
  • Skin reactions
  • Thyroid disorders
  • Diabetes
  • Adrenal insufficiency
  • Hypophysitis
  • Infusion reactions can also occur during administration, as noted in the 2019 study 1.

Management of Side Effects

It's essential to report any new or worsening symptoms to your healthcare provider immediately, as early management of side effects is crucial. Some side effects may require corticosteroids or hormone replacement therapy, while severe reactions might necessitate discontinuing Keytruda. Side effect risk varies based on individual factors, cancer type, and treatment duration, as discussed in the 2024 study 1.

From the FDA Drug Label

KEYTRUDA can cause serious side effects. Common side effects of KEYTRUDA when used alone include: feeling tired, pain, including pain in muscles, rash, diarrhea, fever, cough, decreased appetite, itching, shortness of breath, constipation, bones or joints and stomach-area (abdominal) pain, nausea, and low levels of thyroid hormone Side effects of KEYTRUDA when used alone that are more common in children than in adults include: fever, vomiting, headache, stomach area (abdominal) pain, and low levels of white blood cells Common side effects of KEYTRUDA when given with certain chemotherapy or chemotherapy with radiation therapy medicines include: feeling tired or weak, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, trouble breathing, fever, hair loss, inflammation of the nerves that may cause pain, weakness, and paralysis in the arms and legs, swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, mouth sores, headache, weight loss, stomach-area (abdominal) pain, joint and muscle pain, trouble sleeping, bleeding, blisters, or rash on the palms of your hands and soles of your feet, urinary tract infection, and low levels of thyroid hormone Common side effects of KEYTRUDA when given with chemotherapy and bevacizumab include: tingling or numbness of the arms or legs, hair loss, low red blood cell count, feeling tired or weak, nausea, low white blood cell count, diarrhea, high blood pressure, decreased platelet count, constipation, joint aches, vomiting, urinary tract infection, rash, low levels of thyroid hormone, and decreased appetite Common side effects of KEYTRUDA when given with axitinib include: diarrhea, feeling tired or weak, high blood pressure, liver problems, low levels of thyroid hormone, decreased appetite, blisters or rash on the palms of your hands and soles of your feet, nausea, mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, hoarseness, rash, cough, and constipation Common side effects of KEYTRUDA when given with lenvatinib include: low levels of thyroid hormone, high blood pressure, feeling tired, diarrhea, joint and muscle pain, nausea, decreased appetite, vomiting, mouth sores, weight loss, stomach-area (abdominal) pain, urinary tract infection, protein in your urine, constipation, headache, bleeding, blisters or rash on the palms of your hands and soles of your feet, hoarseness, rash, liver problems, and kidney problems. Common side effects of KEYTRUDA when given with enfortumab vedotin include: rash, tingling or numbness of the arms or legs, feeling tired, itching, diarrhea, hair loss, weight loss, decreased appetite, dry eye, nausea, constipation, changes in sense of taste, and urinary tract infection

The side effects of Keytruda (pembrolizumab) include:

  • Feeling tired or weak
  • Pain, including pain in muscles
  • Rash
  • Diarrhea
  • Fever
  • Cough
  • Decreased appetite
  • Itching
  • Shortness of breath
  • Constipation
  • Bones or joints and stomach-area (abdominal) pain
  • Nausea
  • Low levels of thyroid hormone
  • Other side effects may occur when Keytruda is given with other medicines, such as chemotherapy, bevacizumab, axitinib, lenvatinib, or enfortumab vedotin. 2

From the Research

Side Effects of Keytruda (Pembrolizumab)

The side effects of Keytruda (pembrolizumab) can be severe and varied. Some of the reported side effects include:

  • Immune-related hepatitis, which can be lethal 3
  • Pneumonitis, a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials 4
  • Multiple autoimmune side effects, including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica 5
  • Oral mucositis, a rare adverse effect associated with immunotherapy 6
  • Knee inflammatory synovitis, a rare immune-related adverse event 7
  • Other reported side effects include:
    • Colitis
    • Hepatitis
    • Nephritis
    • Hypophysitis
    • Thyroiditis
    • Hyperthyroidism
    • Hypothyroidism
    • Nephritis
    • Type 1 diabetes
    • Xerostomia
    • Dysgeusia
    • Lichenoid reactions

Management of Side Effects

The management of side effects of Keytruda (pembrolizumab) typically involves:

  • Discontinuation of the drug
  • Use of steroids to treat immune-related adverse events
  • Topical or systemic steroids to manage oral mucositis
  • Thyroid replacement therapy to manage thyroid dysfunction
  • Insulin to manage type 1 diabetes
  • Regular monitoring via computed tomography scans and pulmonary consultation to manage pneumonitis
  • Multidisciplinary team approach to prevent further morbidity and mortality 4, 5, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis.

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2023

Research

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab.

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2021

Research

Oral mucositis-case series of a rare adverse effect associated with immunotherapy.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2021

Research

Could knee inflammatory synovitis be induced by pembrolizumab?

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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