Generic Name: pembrolizumab

Brand Name: Keytruda

Drug Class: Antineoplastics, Monoclonal Antibody; PD-1/PD-L1 Inhibitors

What is pembrolizumab, and what is it used for?

Does pembrolizumab cure cancer?

Pembrolizumab is a medication used to treat many cancers, often in an advanced or metastatic state, either as a first-line single agent or in combination with other chemotherapy medications. Pembrolizumab is a type of targeted therapy that does not directly kill cancer cells but alters a specific cell mechanism that promotes cancer growth and spread. Pembrolizumab works by stimulating the body’s own immune system to fight against cancer cells.

Pembrolizumab is a highly selective immunoglobulin G4 (IgG4) kappa monoclonal antibody designed to act against a specific protein expressed in T-cells, which enhances the activity of T-cells against cancer cells. T-cells are immune cells that normally induce programmed death (apoptosis) in damaged and mutated (cancer) cells. In many cancers, cancer cells develop certain cell mechanisms to escape apoptosis. Pembrolizumab blocks a specific protein interaction and cell-signaling with T-cells that cancer cells use to evade death.

Pembrolizumab belongs to a class of medications known as PD-1/PD-L1 inhibitors, which bind to protein molecules known as programmed death-1 (PD-1) and inhibits their interactions with PD-L1 and PD-L2 molecules. These proteins are normally expressed in T-cells and the interaction of PD-1 with PD-L1 and PD-L2 inhibits the activation of T-cells. Cancer cells avoid apoptosis by secreting PD-L1 themselves or inducing the T-cells in the tumor microenvironment to produce PD-L1. Inhibition of PD-1 results in increased T-cell activity against cancer cells.

What types of cancer does pembrolizumab treat?

Pembrolizumab is administered as an intravenous infusion for over 30 minutes. The uses of Pembrolizumab include the following:

FDA-approved:

Adult and pediatric:

Adult:

Off-label uses:

  • PD-L1 positive relapsed or refractory malignant pleural mesothelioma
  • Relapsed or refractory mycosis fungoides/Sezary syndrome

Orphan designations:

  • Multiple myeloma
  • Nasopharyngeal carcinoma
  • Follicular lymphoma
  • Biliary tract carcinoma

Warnings

  • Pembrolizumab may cause severe infusion reactions. Monitor patients for symptoms, Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions, and discontinue for severe and life-threatening infusion reactions.
  • Pembrolizumab can cause immune-mediated severe or even fatal inflammatory reactions. In case of moderate reactions, monitor the patient, treat with corticosteroids, and withhold pembrolizumab. Discontinue the drug permanently in case of severe or life-threatening reactions. Immune-mediated adverse reactions may include:
  • In patients who receive donor (allogeneic) hematopoietic stem cell transplantation (HSCT) before or after pembrolizumab therapy, serious and fatal complications can occur, including graft-versus-host disease (GVHD), veno-occlusive disease and steroid-requiring febrile syndrome. Monitor patients closely and treat them promptly.
  • Increased mortality was observed in patients with multiple myeloma when pembrolizumab was added to thalidomide analog and dexamethasone therapy. This combination is not recommended outside of controlled clinical trials.
  • Pembrolizumab can cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and at least for 4 months following the last dose.

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow

What are the side effects of pembrolizumab?

Common side effects of pembrolizumab include:

Less common side effects of pembrolizumab include:

  • Cardiac failure
  • Edema
  • Blood vessel inflammation (vasculitis)
  • Septic shock
  • Gastritis
  • Inflammation of the duodenum (duodenitis)
  • Inflammation of the pancreas (pancreatitis)
  • Increase in serum amylase, the enzyme that helps digest carbohydrate
  • Increase in serum lipase, the enzyme that digests fats
  • Rectal hemorrhage
  • Clostridium difficile-associated diarrhea
  • Kidney inflammation (nephritis)
  • Urinary tract infection with sepsis
  • Uterine hemorrhage
  • Yeast infection (candidiasis)
  • Hepatic sinusoidal obstruction syndrome, a liver condition that impairs hepatic blood flow
  • Underactive parathyroid (hypoparathyroidism)
  • Inflammation of the pituitary gland (hypophysitis)
  • Type I diabetes mellitus 
  • Blood disorders including:
    • Anemia from lack of red blood cell production (aplastic anemia)
    • Anemia from rapid destruction of red blood cells (hemolytic anemia)
    • Immune thrombocytopenia
  • Lymph node enlargement (lymphadenitis)
  • Excessive, life-threatening immune response (hemophagocytic lymphohistiocytosis)
  • Solid organ transplant rejection
  • Graft-versus-host disease (GVHD), a condition in which donor cells attack hose tissue
  • Severe allergic reaction (anaphylaxis)
  • Damage to myelin sheath that protects nerve fibers (demyelinating disease)
  • Brain inflammation (encephalitis)
  • Spinal cord inflammation (myelitis)
  • Inflammation of meninges, membranes around the brain (meningitis)
  • Guillain-Barre syndrome, an immune-mediated neuromuscular disorder
  • Muscle weakness (myasthenia)
  • Myasthenia gravis, an autoimmune neuromuscular disease 
  • Nerve disease (neuropathy)
  • Inflammatory muscle diseases such as:
  • Breakdown of muscles (rhabdomyolysis)
  • Bone infection and inflammation (osteomyelitis)
  • Inflammation of the iris in the eye (iritis)
  • Nasal bleeding (epistaxis)
  • Coughing up blood (hemoptysis)
  • Cellulitis
  • Dermatitis

Rare side effects of pembrolizumab include:

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

  • Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
  • Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
  • Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
  • Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of pembrolizumab?

Injectable Solution

  • 100 mg/4 mL (25 mg/mL)

Adult:

Melanoma

Unresectable or metastatic melanoma

  • Indicated for treatment of unresectable or metastatic melanoma
  • 200 mg intravenous (IV) every 3 weeks OR 400 mg every 6 weeks until disease progression or unacceptable toxicity

Adjuvant treatment

  • Indicated for adjuvant treatment of adults with Stage IIB, IIC, or III melanoma following complete resection
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence

Non-Small Cell Lung Cancer

Single-agent

  • First-line treatment of patients with stage III non-small cell lung cancer (NSCLC), who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [Tumor Proportion Score (TPS) 1% or higher)], with no EGFR or ALK genomic tumor aberrations
  • Metastatic NSCLC whose tumors with PD-L1 expression (TPS 1% or higher) and disease progression on or after platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression or unacceptable toxicity, or up to 24 months without disease progression

Combination therapy

  • Metastatic nonsquamous NSCLC: First-line treatment in combination with pemetrexed and platinum chemotherapy with no EGFR or ALK genomic tumor aberrations
  • Metastatic squamous NSCLC: First-line treatment in combination with carboplatin and either paclitaxel or paclitaxel protein bound
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Head and Neck Squamous Cell Carcinoma

Single-agent therapy

  • Indicated for first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) 1 or higher]
  • Indicated for treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Combination therapy

  • Indicated in combination with platinum and fluorouracil (FU) for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Classical Hodgkin Lymphoma

  • Indicated for relapsed or refractory classical Hodgkin lymphoma (cHL)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Primary Mediastinal Large B-Cell Lymphoma

  • Indicated for refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Urothelial Carcinoma

Locally advanced or metastatic urothelial carcinoma

  • Indicated for locally advanced or metastatic urothelial carcinoma in patients who are ineligible for any platinum-containing chemotherapy or have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer

  • Indicated for treatment of BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors in patients who are ineligible for, or have elected not to undergo cystectomy
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Microsatellite Instability-High Cancer

  • Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have solid tumors that have progressed following prior treatment and in patients who have no satisfactory alternative treatment options
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

  • Indicated for unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or up to 24 months

Gastric Cancer

  • Indicated in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks PLUS trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy
  • Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Esophageal Cancer

  • Indicated for recurrent locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1-5 cm above GEJ) carcinoma in patients who are not candidates for surgical resection or definitive chemoradiation

Specifically used either

  • In combination with platinum- and fluoropyrimidine-based chemotherapy, or
  • As a single agent after 1 or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS 10 or higher)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Cervical Cancer

Single-agent therapy

  • Indicated for recurrent or metastatic cervical cancer in adults with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1 or higher)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Combination therapy

  • Indicated in combination with chemotherapy, with or without bevacizumab, for persistent, recurrent, or metastatic cervical cancer in adults whose tumors express PD-L1 (CPS 1 or higher)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
  • Refer to prescribing information for agents used in combination

Hepatocellular Carcinoma

  • Indicated for treatment of patients with hepatocellular carcinoma (HCC) who have been previously-treated with sorafenib
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Merkel Cell Carcinoma

  • Indicated for treatment of recurrent, locally advanced, or metastatic Merkel cell carcinoma (MCC)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Renal Cell Carcinoma

Combination therapy with axitinib

  • Indicated in combination with axitinib, for first-line treatment of patients with advanced renal cell carcinoma (RCC)
  • Pembrolizumab 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
  • Axitinib 5 mg orally twice daily (initial dose)
  • Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression
  • When axitinib is used in combination with pembrolizumab, consider dose escalation of axitinib above the initial 5 mg dose at 6 weeks or longer intervals

Combination therapy with lenvatinib

  • Indicated in combination with lenvatinib, for first-line treatment of patients with advanced RCC
  • Pembrolizumab 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
  • Lenvatinib 20 mg orally once daily
  • Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression

Adjuvant treatment

  • Indicated for adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months

Endometrial Cancer

Combination therapy

  • Indicated in combination with lenvatinib for patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
  • Lenvatinib 20 mg orally once daily
  • Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months

Single-agent therapy

  • Indicated for advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, in patients who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or up to 24 months

Tumor Mutational Burden-High Cancer

  • Indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) (10 or more mutations/megabase [mut/Mb]) solid tumors in adult and pediatric patients that have progressed following prior treatment and who have no satisfactory alternative treatment options
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Cutaneous Squamous Cell Carcinoma

  • Indicated for treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not incurable by surgery or radiation
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease progression or unacceptable toxicity, or up to 24 months without disease progression

Triple-Negative Breast Cancer

High-risk early-stage triple-negative breast cancer (TNBC)

  • Indicated for the treatment of patients with high-risk, early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery
  • Neoadjuvant treatment
    • In combination with chemotherapy: 200 mg IV every 3 weeks OR 400 mg every 6 weeks for 4 doses or until disease progression or unacceptable toxicity
    • Followed by single agent adjuvant therapy
  • Adjuvant treatment
    • Single-agent therapy: 200 mg IV every 3 weeks OR 400 mg every 6 weeks for 5 doses or until disease progression or unacceptable toxicity

Locally recurrent unresectable or metastatic TNBC

  • Indicated, in combination with chemotherapy, for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10 or higher)
  • 200 mg IV every 3 weeks OR 400 mg every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or up to 24 months
  • Administer prior to chemotherapy when given on the same day

Dosage Modifications

Renal impairment (eGFR 15 mL/min/1.73 m² or higher)

  • No dosage adjustment required

Hepatic impairment

  • Mild: No dosage adjustment required
  • Moderate or severe: Pharmacokinetics of pembrolizumab is unknown

Interrupt or slow infusion rate

  • Grades 1 or 2 infusion-related reactions

Withhold dose (resume when recover to Grade below 1)

  • Grade 3 or 4 endocrinopathies (e.g., hypophysitis, hypo- or hyperthyroidism)
  • Grade 4 hematological toxicity in cHL or PMBCL
  • Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
  • Immune-mediated hepatitis in patients without HCC: AST/ALT above 3 and up to 5 times upper limit of normal (ULN) or total bilirubin above 1.5 and up to 3 times ULN

Withhold (resume when recover to Grade below 1 after corticosteroid taper)

  • Grade 2 immune-mediated pneumonitis
  • Grades 2 or 3 immune-mediated colitis
  • Grade 2 immune-mediated nephritis
  • Any other Grade 2 or 3 immune-mediated adverse reaction, based on the severity and type of reaction

Withhold dose (resume when AST/ALT and total bilirubin recover to Grades <1 or to baseline)

  • Immune-mediated hepatitis in patients with HCC
    • AST/ALT 5 times or more above ULN if baseline below 2 times ULN
    • AST/ALT above 3 times baseline if baseline 2 times or less below ULN
    • Total bilirubin above 2 mg/dL if baseline below 1.5 mg/dL
    • Total bilirubin above 3 mg/dL, regardless of baseline levels

RCC treated with pembrolizumab with axitinib

  • ALT or AST 3 times or more above ULN but below 10 times ULN with concurrent total bilirubin 2 times or more above ULN: Withhold both drugs and consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery; if rechallenging with axitinib, consider dose reduction as per axitinib prescribing information
  • ALT or AST 10 times or more above ULN or 3 times or more above ULN with concurrent total bilirubin 2 times or more above ULN: Permanently discontinue both drugs and consider corticosteroid therapy

Permanently discontinue for any of the following

  • Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
  • Grades 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
  • Grades 3 or 4 nephritis
  • Grades 4 severe skin reactions or confirmed SJS or TEN
  • Grades 3 or 4 infusion-related reactions
  • Grades 2 or 3 adverse reaction (excluding endocrinopathy) lasting 12 weeks or longer after last dose
  • Grade 3 (based on severity) or Grade 4 other immune-mediated adverse reactions
  • Grade 4 immune-mediated colitis
  • Immune-mediated hepatitis in patients with HCC
  • Immune-mediated hepatitis in patients without HCC
    • Patients without liver metastases: AST/ALT above 5 times ULN or total bilirubin above 3 times ULN
    • Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT 50% or higher relative to baseline that persists for 1 week or longer

Dosing Considerations

Limitation of use

  • Not recommended for PMBCL in patients who require urgent cytoreductive therapy

Select based on presence of a positive PD-L1 expression

  • Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
  • Single-agent therapy
    • Stage III NSCLC or metastatic NSCLC
    • Metastatic or unresectable, recurrent HNSCC
    • Metastatic gastric cancer; if not detected in an archival gastric cancer specimen, consider obtaining a tumor biopsy for PD-L1 testing
    • Locally advanced or metastatic esophageal cancer
    • Recurrent or metastatic cervical cancer
  • Combination therapy
    • Locally recurrent unresectable or metastatic TNBC
    • Persistent, recurrent, or metastatic cervical cancer

Select based on presence of MSI-H/dMMR status in tumor specimens

  • FDA-approved test for the detection of MSI-H, dMMR, or not MSI-H or dMMR is not currently available
  • Single-agent therapy
    • Owing to effect of prior chemotherapy on test results for tumor mutation burden (TMB-H), MSI-H, or dMMR in patients with high-grade gliomas is unclear, obtain test for these markers in the primary tumor specimens prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas
  • Combination therapy
    • Advanced endometrial carcinoma that is not MSI-H or dMMR

Pediatric:

Classical Hodgkin Lymphoma

  • Indicated for refractory classical Hodgkin lymphoma (cHL) or relapse after 2 or more prior lines of therapy
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
  • Continue until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Microsatellite Instability-High Cancer

  • Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have:
    • Solid tumors that have progressed following prior treatment and in patients who have no satisfactory alternative treatment options, OR
    • Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
  • Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Primary Mediastinal Large B-Cell Lymphoma

  • Indicated for refractory primary mediastinal large B-cell lymphoma (PMBCL), or relapse after 2 or more prior lines of therapy
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/day

Merkel Cell Carcinoma

  • Indicated for treatment of recurrent, locally advanced, or metastatic Merkel cell carcinoma (MCC)
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
  • Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Tumor Mutational Burden-High Cancer

  • Indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) (10 or more mutations/megabase [mut/Mb]) solid tumors in adult and pediatric patients that have progressed following prior treatment and who have no satisfactory alternative treatment options
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
  • Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Melanoma

  • Indicated for adjuvant treatment of adult and pediatric patients aged 12 years or above with Stage IIB, IIC, or III melanoma following complete resection
  • 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
  • Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence

Dosage Modifications

Renal impairment

  • No dosage adjustment required

Hepatic impairment

  • Mild: No dosage adjustment required
  • Moderate or severe: Not studied

Interrupt or slow infusion rate

  • Grades 1 or 2 infusion-related reactions

Withhold dose (resume when recover to Grade <1)

  • Grade 3 or 4 endocrinopathies (e.g., hypophysitis, hypo- or hyperthyroidism)
  • Grade 4 hematological toxicity in cHL or PMBCL
  • Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
  • Immune-mediated hepatitis in patients without HCC: AST/ALT above 3 and up to 5 times upper limit of normal (ULN) or total bilirubin above 1.5 and up to 3 times ULN

Withhold (resume when recover to Grade below 1 after corticosteroid taper)

  • Grade 2 immune-mediated pneumonitis
  • Grades 2 or 3 immune-mediated colitis
  • Grade 2 immune-mediated nephritis
  • Any other Grade 2 or 3 immune-mediated adverse reaction, based on the severity and type of reaction

Permanently discontinue for any of the following

  • Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
  • Grades 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
  • Grades 3 or 4 nephritis
  • Grades 4 severe skin reactions or confirmed SJS or TEN
  • Grades 3 or 4 infusion-related reactions
  • Grades 2 or 3 adverse reaction (excluding endocrinopathy) lasting 12 weeks or longer after last dose
  • Grade 3 (based on severity) or Grade 4 other immune-mediated adverse reactions
  • Grade 4 immune-mediated colitis
  • Immune-mediated hepatitis in patients without HCC
    • Patients without liver metastases: AST/ALT above 5 times ULN or total bilirubin above 3 times ULN
    • Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT 50% or higher relative to baseline that persists for 1 week or longer

Dosing Considerations

Limitations of use

  • Safety and effectiveness in pediatric patients with MSI-H or TMB-H central nervous system cancers have not been established
  • Not recommended for treatment of PMBCL who require urgent cytoreductive therapy

Patient selection

  • TMB-H indication: Select for treatment based on TMB-H status in tumor specimens
  • MSI-H/dMMR indication: Select for treatment based MSI-H/dMMR status in tumor specimens
  • Owing to the effect of prior chemotherapy on test results for tumor mutation burden (TMB-H), MSI-H, or dMMR in patients with high-grade gliomas is unclear, obtaining test for these markers in the primary tumor specimens prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas
  • Information on FDA-approved tests for the detection of TMB status is available at: http://www.fda.gov/CompanionDiagnostics

Overdose

Pembrolizumab is administered in clinical settings and overdose is unlikely. In the event of overdose, pembrolizumab should be discontinued and appropriate symptomatic and supportive treatment instituted.

What drugs interact with pembrolizumab?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Severe interactions of pembrolizumab include:
    • thalidomide analogues
  • Pembrolizumab has no known serious interactions with other drugs.
  • Moderate interactions of pembrolizumab include:
  • Pembrolizumab has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

  • Pembrolizumab can cause fetal harm. Women of pregnancy potential should use effective contraception during therapy and for at least 4 months following the last dose of pembrolizumab.
  • There are no human data available on drug-associated fetal risk, but based on animal reproduction studies and pembrolizumab’s mechanism of action, administration of pembrolizumab during pregnancy can:
    • Increase the risk of pregnancy loss and stillbirth
    • Increase the risk of the development of immune-mediated disorders or altering of the normal immune response in the offspring
  • It is not known if pembrolizumab is present in breast milk, however, immunoglobulins are excreted in breast milk and pembrolizumab may also be expected to be present in breast milk. Nursing mothers should discontinue breastfeeding while on treatment with pembrolizumab, and for 4 months after the final dose because of the potential for serious adverse reactions in the breastfed infant.

What else should I know about pembrolizumab?

  • You are likely to need periodic blood and other tests while on pembrolizumab treatment. Do not miss your scheduled appointments.
  • While on pembrolizumab treatment, contact your healthcare provider immediately if you:
    • Develop any symptoms of immune-related inflammatory reactions, which can affect any organ in the body.
    • Experience infusion reactions with symptoms such as rigors, chills, wheezing, itching, flushing, rash, fever, low blood pressure or low tissue oxygen saturation.
  • Inform your healthcare provider immediately or contact Poison Control if you suspect an overdose of pembrolizumab.

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Summary

Pembrolizumab is a medication used to treat many cancers as a targeted therapy that does not directly kill cancer cells but alters a specific cell mechanism that promotes cancer growth and spread. Common side effects of pembrolizumab include fatigue, fever, pain, headache, peripheral nerve damage (neuropathy), musculoskeletal pain, joint pain (arthralgia), muscle pain (myalgia), back pain, weakness (asthenia), neck pain, muscle inflammation (myositis), joint inflammation (arthritis), decreased appetite, diarrhea, constipation, abdominal pain, nausea, vomiting, swallowing difficulties (dysphagia), colon inflammation (colitis), and others. Do not take if pregnant or breastfeeding.

Treatment & Diagnosis

Medications & Supplements

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Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 11/17/2022
References
https://www.rxlist.com/consumer_pembrolizumab_keytruda/drugs-condition.htm

https://reference.medscape.com/drug/keytruda-pembrolizumab-999962

https://www.uptodate.com/contents/pembrolizumab-drug-information

https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125514s040lbl.pdf

https://go.drugbank.com/drugs/DB09037

https://www.ncbi.nlm.nih.gov/books/NBK546616/

https://clinicaltrials.gov/ProvidedDocs/02/NCT02316002/Prot_SAP_000.pdf