Brand name: Keytruda
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Introduction

Antineoplastic agent; humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody.^{1 7 8}

Uses for Pembrolizumab

Melanoma

Treatment of unresectable or metastatic melanoma^{1 9 10 11 12 43} (designated an orphan drug by FDA for this use).⁴

Adjuvant therapy of stage IIB, IIC, or III melanoma following complete resection in adult and pediatric patients ≥12 years of age^{1 39 44 45 46 47} (designated an orphan drug by FDA for this use).⁴

Non-small Cell Lung Cancer (NSCLC)

Used in combination with pemetrexed and platinum chemotherapy for the first-line treatment of metastatic nonsquamous NSCLC without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.^{1 38 48 49}

Used in combination with carboplatin and paclitaxel (conventional or protein-bound) for the first-line treatment of metastatic squamous NSCLC.^{1 37 50 51}

Used as a single agent for the first-line treatment of stage III NSCLC, where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, expressing programmed-death ligand-1 (PD-L1; defined as tumor proportion score ≥1% [as determined by an FDA-approved test]) and without EGFR or ALK genomic aberrations.^{1 13 52 53 54}

Used as a single agent for the treatment of PD-L1-positive (i.e., tumor proportion score ≥1% as determined by an FDA-approved test) metastatic NSCLC that has progressed during or following platinum-based chemotherapy and, if the tumor is EGFR mutation- or ALK-positive, during or following therapy with an FDA-labeled EGFR or ALK inhibitor.^{1 15 55}

Used in combination with platinum-containing chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery, for the treatment of patients with resectable (i.e., tumors ≥4 cm or node positive) NSCLC.^{1 56}

Used as a single agent for adjuvant treatment following resection and platinum-based chemotherapy for adults with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.^{1 57}

Malignant Pleural Mesothelioma

Used in combination with pemetrexed and platinum chemotherapy for first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM) in adults.^{1 58}

Head and Neck Squamous Cell Cancer

Used in combination with platinum and fluorouracil for first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).^{1 59}

Used as a single agent for first-line treatment of metastatic or unresectable, recurrent HNSCC expressing PD-L1 (i.e., combined positive score ≥1% as determined by an FDA-approved test).^{1 59}

Used as single agent for treatment of recurrent or metastatic HNSCC that has progressed during or following platinum-containing therapy.^{1 16 17}

Classical Hodgkin Lymphoma

Treatment of relapsed or refractory classical Hodgkin lymphoma (cHL) in adults^{1 18 60 61} (designated an orphan drug by FDA for treatment of this cancer).⁴

Treatment of refractory cHL or cHL that has relapsed after ≥2 prior therapies in pediatric patients^{1 62} (designated an orphan drug by FDA for treatment of this cancer).⁴

Treatment of cHL in adults at an additional dosing regimen of 400 mg every 6 weeks.¹ Accelerated approval based on pharmacokinetic data, relationship of exposure to efficacy, and relationship of exposure to safety.¹ Continued approval for this dosing may be contingent on verification and description of clinical benefit in confirmatory studies.¹

Primary Mediastinal Large B-cell Lymphoma (PMBCL)

Treatment of refractory primary mediastinal large B-cell lymphoma (PMBCL) and PMBCL that has relapsed following ≥2 prior therapies in adults and pediatric patients^{1 63 64} (designated an orphan drug by FDA for this use).¹⁰

Not recommended in patients with PMBCL who require urgent cytoreduction.¹

Treatment of PMBCL in adults at an additional dosing regimen of 400 mg every 6 weeks.¹ Accelerated approval based on pharmacokinetic data, relationship of exposure to efficacy, and relationship of exposure to safety.¹ Continued approval for this dosing may be contingent on verification and description of clinical benefit in confirmatory studies.¹

Urothelial Cancer

Used in combination with enfortumab vedotin for treatment of adults with locally advanced or metastatic urothelial cancer.^{1 200 201 202}

Used as a single agent for treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy or who have disease progression during or following platinum-containing therapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.^{1 19 20 203}

Used as a single agent for treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.^{1 204}

Microsatellite Instability-high or Mismatch Repair Deficient Cancer

Treatment of unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors (as determined by an FDA-approved test) that have progressed following prior therapy in adult and pediatric patients who are not candidates for other satisfactory treatment options.^{1 206 207 208}

Microsatellite Instability-high or Mismatch Repair Deficient Colorectal Cancer

Treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer (as determined by an FDA-approved test).^{1 209 210 211}

Gastric Cancer

Used in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy for first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor type 2 (HER2)-positive gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (combined positive score ≥1) as determined by an FDA-approved test.^{1 212 213} Accelerated approval based on tumor response rate and durability of response.¹ Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.¹

Used in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.^{1 214}

Designated an orphan drug by FDA for the treatment of gastric cancer, including gastroesophageal junction adenocarcinoma.⁴

Esophageal Cancer

Treatment of locally advanced or metastatic esophageal carcinoma or gastroesophageal junction carcinoma (tumors with epicenter 1–5 cm above the gastroesophageal junction) that is not amenable to surgical resection or definitive chemoradiation.¹ May be used in combination with platinum- and fluoropyrimidine-based chemotherapy or as a single agent after 1 or more prior lines of systemic therapy in patients with tumors of squamous cell histology that express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test.^{1 215 216 217}

Designated an orphan drug by FDA for treatment of this cancer.⁴

Cervical Cancer

Used in combination with chemoradiotherapy for treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage III–IVA cervical cancer.^{1 218 219}

Used in combination with chemotherapy (with or without bevacizumab) for treatment of persistent, recurrent, or metastatic cervical cancer in patients whose tumors express PD-L1 (combined positive score ≥1) as determined by an FDA-approved test.^{1 220 221}

Used as a single agent for treatment of recurrent or metastatic cervical cancer that has progressed during or following chemotherapy in patients whose tumors express PD-L1 (combined positive score ≥1) as determined by an FDA-approved test.^{1 222}

Hepatocellular Carcinoma

Treatment of hepatocellular carcinoma secondary to hepatitis B in patients who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen^{1 223} (designated an orphan drug by FDA for treatment of this cancer).⁴

Biliary Tract Cancer

Used in combination with gemcitabine and cisplatin for treatment of locally advanced unresectable or metastatic biliary tract cancer^{1 67} (designated an orphan drug by FDA for treatment of this cancer).⁴

Merkel Cell Carcinoma

Treatment of recurrent locally advanced or metastatic Merkel cell carcinoma^{1 41 65 66} (designated an orphan drug by FDA for treatment of this cancer).⁴

Renal Cell Carcinoma

Used in combination with axitinib or lenvatinib for first-line treatment of adults with advanced renal cell carcinoma.^{1 68 69 70 71 72}

Used as adjuvant treatment for patients with renal cell carcinoma who are at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.^{1 73 74}

Endometrial Carcinoma

Used, first in combination with carboplatin and paclitaxel, then as a single agent for the treatment of adults with primary advanced or recurrent endometrial carcinoma.^{1 75}

Used in combination with lenvatinib for the treatment of adults with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not MSI-H, who have progressed following prior therapy and who are not candidates for curative surgery or radiation.^{1 76 77}

Used as a single agent for the treatment of adults with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have progressed following prior therapy and who are not candidates for curative surgery or radiation.^{1 78}

Tumor Mutational Burden-high Cancer

Used for treatment of unresectable or metastatic tumor mutational burden-high (TMB-H; defined as ≥10 mutations per megabase) solid tumors, as determined by an FDA-approved test, that have progressed following prior therapy in adult and pediatric patients who are not candidates for other satisfactory treatment options.^{1 79}

Accelerated approval based on tumor response rate and durability of response.¹ Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.¹

Safety and efficacy not established in pediatric patients with TMB-H CNS cancers.¹

Cutaneous Squamous Cell Carcinoma

Used for treatment of recurrent or metastatic squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma that cannot be cured by surgery or radiation.^{1 80}

Breast Cancer

Used first as neoadjuvant treatment in combination with chemotherapy and then as a single agent as adjuvant treatment after surgery, for treatment of high-risk, early-stage triple-negative breast cancer.^{1 81 82}

Used in combination with chemotherapy for treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test.^{1 83 84}

Pembrolizumab Dosage and Administration

General

Pretreatment Screening

• Verify pregnancy status in women of reproductive potential.¹

• Assess liver enzymes, serum creatinine, and thyroid function at baseline in patients initiating pembrolizumab.¹

• Patients with triple-negative breast cancer (TNBC) receiving pembrolizumab in the neoadjuvant setting should have blood cortisol assessed at baseline.¹

Patient Monitoring

• Monitor for signs and symptoms of infusion-related reactions (e.g., rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, fever).¹

• Perform periodic assessment of liver enzymes, serum creatinine, and thyroid function during therapy.¹

• Periodic monitoring of liver enzymes is recommended in patients receiving combination therapy with pembrolizumab and axitinib; consider frequent monitoring when these agents are used in combination due to more frequent grade 3 and 4 ALT and AST elevations than with single-agent pembrolizumab.¹

• Patients with TNBC receiving pembrolizumab in the neoadjuvant setting should have blood cortisol monitored at baseline, prior to surgical procedures, and as clinically indicated.¹

• Monitor closely for signs and symptoms of potential clinical manifestations of underlying immune-mediated adverse effects.¹

• Monitor for manifestations of hypophysitis (including hypopituitarism and adrenal insufficiency) during pembrolizumab therapy.¹

• Monitor for manifestations of diabetes mellitus (e.g., hyperglycemia).¹

• Monitor patients closely for manifestations of allogeneic hematopoietic stem cell transplantation-related complications.¹

Administration

IV Administration

Administer by IV infusion.¹

Commercially available as injection concentrate; must be diluted prior to IV administration.¹

Do not infuse simultaneously through the same IV line with other drugs.¹

Administer using a sterile, nonpyrogenic, low-protein-binding, 0.2- to 5-μm inline or add-on filter.¹

Dilution

Dilute appropriate dose of commercially available injection concentrate in a sufficient volume of 0.9% sodium chloride injection or 5% dextrose injection to yield a final concentration of 1–10 mg/mL.¹ Mix the diluted solution by gentle inversion; do not shake.¹ Discard any partially used vials.¹

Rate of Administration

Administer by IV infusion over 30 minutes.¹

Dosage

Pediatric Patients

Classical Hodgkin Lymphoma

IV

2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Primary Mediastinal Large B-cell Lymphoma (PMBCL)

IV

2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Not recommended for PMBCL in patients requiring urgent cytoreduction.¹

Solid Tumors with Microsatellite Instability-high or Mismatch Repair Deficiency

IV

2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status in solid tumors based on FDA-approved test.¹ Because of discordance between local and FDA-approved tests for MSI-H or dMMR, confirmation of status recommended.¹ If confirmatory testing cannot be performed, the presence of TMB ≥10 mut/Mb (as determined by an FDA-approved test) may be used for selection.¹

Merkel Cell Carcinoma

IV

2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Tumor Mutational Burden-high Cancer

IV

2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on tumor mutational burden-high (TMB-H; ≥10 mutations/megabase [mut/Mb]) status in tumor specimens.¹ Safety and efficacy not established in TMB-H CNS cancers.¹

Adjuvant Therapy, Locally Advanced Melanoma

IV

Pediatric patients ≥12 years of age: 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.¹ Continue therapy for up to 12 months or until disease progression or unacceptable toxicity occurs.¹

Adults

Melanoma

Unresectable or Metastatic Melanoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy until disease progression or unacceptable toxicity occurs.¹

Adjuvant Therapy, Completely Resected Advanced Melanoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 12 months or until disease recurrence or unacceptable toxicity occurs.¹

NSCLC

Adjuvant Therapy, NSCLC

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 12 months or until disease progression or unacceptable toxicity occurs.¹

Neoadjuvant Therapy, Resectable NSCLC

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with platinum-containing chemotherapy).¹ Continue neoadjuvant therapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity occurs.¹ Then initiate single-agent adjuvant pembrolizumab therapy after surgery and continue for 39 weeks or until disease recurrence or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to platinum-containing chemotherapy when given on the same day.¹

Initial Monotherapy for Metastatic or Stage III NSCLC

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Patient selection based on presence of PD-L1 expression.¹

Monotherapy for Metastatic NSCLC Progressed on Prior Therapy

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Patient selection based on presence of PD-L1 expression.¹

Combination Therapy for Metastatic Nonsquamous NSCLC

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (use in combination with pemetrexed and a platinum-containing chemotherapy agent).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to pemetrexed and platinum-containing chemotherapy agent when given on the same day.¹

Combination Therapy for Metastatic Squamous NSCLC

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (use in combination with carboplatin and conventional or albumin-bound paclitaxel).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to carboplatin and paclitaxel when given on the same day.¹

Malignant Pleural Mesothelioma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (use in combination with pemetrexed and a platinum-containing chemotherapy agent).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to pemetrexed and platinum-containing chemotherapy agent when given on the same day.¹

Head and Neck Squamous Cell Cancer

Monotherapy for Initial Treatment of Metastatic Head and Neck Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Patient selection based on presence of PD-L1 expression.¹

Monotherapy for Metastatic Head or Neck Cancer Progressed on Prior Therapy

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Combination Therapy for Metastatic Head and Neck Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (use in combination with a platinum-containing chemotherapy agent and fluorouracil).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to platinum-containing chemotherapy agent and fluorouracil when given on the same day.¹

Classical Hodgkin Lymphoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

PMBCL

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Not recommended for patients requiring urgent cytoreduction.¹

Urothelial Cancer

Monotherapy for Urothelial Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Monotherapy for Bacillus Calmette-Guerin (BCG)-Unresponsive Urothelial Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until persistent or recurrent high-risk non-muscle invasive bladder cancer (NMIBC) or disease progression or unacceptable toxicity occurs.¹

Combination Therapy for Urothelial Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with enfortumab vedotin).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer enfortumab vedotin prior to pembrolizumab when given on the same day.¹

Solid Tumors with Microsatellite Instability-high or Mismatch Repair Deficiency

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on MSI-H or dMMR status in solid tumors based on FDA-approved test.¹ Because of discordance between local and FDA-approved tests for MSI-H or dMMR, confirmation of status recommended.¹ If confirmatory testing cannot be performed, the presence of TMB ≥10 mut/Mb (as determined by an FDA-approved test) may be used for selection.¹

Colorectal Cancer with Microsatellite Instability-high or Mismatch Repair Deficiency

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on MSI-H/dMMR status in tumor specimens.¹

Gastric Cancer

HER2-positive Gastric Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to trastuzumab and other chemotherapy agents when given on the same day.¹

Patient selection based on presence of PD-L1 expression.¹

HER2-negative Gastric Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with fluoropyrimidine- and platinum-containing chemotherapy).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to chemotherapy agents when given on same day.¹

Esophageal Cancer

Monotherapy for Esophageal Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on presence of PD-L1 expression.¹

Combination Therapy for Esophageal Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with platinum- and fluoropyrimidine-containing chemotherapy).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to chemotherapy agents when given on same day.¹

Cervical Cancer

Monotherapy for Cervical Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on presence of PD-L1 expression.¹

Combination Therapy for FIGO Stage III-IVA Cervical Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with chemoradiotherapy).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to chemoradiotherapy.¹

Combination Therapy for Metastatic Cervical Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with chemotherapy with or without bevacizumab).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to chemotherapy with or without bevacizumab when given on same day.¹

Selection based on presence of PD-L1 expression.¹

Hepatocellular Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Biliary Tract Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with gemcitabine and cisplatin).¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to gemcitabine and cisplatin therapy when given on same day.¹

Merkel Cell Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Renal Cell Carcinoma

Adjuvant Therapy, Renal Cell Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 12 months or until disease recurrence or unacceptable toxicity occurs.¹

Combination Therapy with Axitinib, Renal Cell Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with axitinib 5 mg orally twice daily).¹ When used in combination with axitinib, escalation of axitinib to doses >5 mg may be considered at intervals of ≥6 weeks.¹ Continue therapy for up to 24 months with pembrolizumab or until disease progression or unacceptable toxicity occurs.¹

Combination Therapy with Lenvatinib, Renal Cell Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with lenvatinib 20 mg orally once daily).¹ Continue therapy for up to 24 months with pembrolizumab or until disease progression or unacceptable toxicity occurs.¹

Endometrial Carcinoma

Monotherapy for Endometrial Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on MSI-H/dMMR status in tumor specimens.¹ Because of discordance between local and FDA-approved tests for MSI-H or dMMR, confirmation of status recommended.¹ If confirmatory testing cannot be performed, the presence of TMB ≥10 mut/Mb (as determined by an FDA-approved test) may be used for selection.¹

Combination Therapy for Endometrial Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with carboplatin and paclitaxel), followed by treatment with single-agent pembrolizumab.¹ Continue therapy for up to 24 months with pembrolizumab or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to carboplatin and paclitaxel.¹

Combination Therapy for Mismatch Repair Proficient (pMMR) Endometrial Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with lenvatinib 20 mg once daily).¹ Continue therapy for up to 24 months with pembrolizumab or until disease progression or unacceptable toxicity occurs.¹

Selection based on pMMR/not MSI-H status in tumor specimens.¹ FDA-approved test for detection of not MSI-H not currently available.¹

Tumor Mutational Burden-high Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Selection based on TMB-H (≥10 mut/Mb) status in tumor specimens.¹

Cutaneous Squamous Cell Carcinoma

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks.¹ Continue therapy for up to 24 months or until disease progression or unacceptable toxicity occurs.¹

Triple-negative Breast Cancer

Neoadjuvant Therapy, Triple-negative Breast Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with chemotherapy and continued as single-agent adjuvant therapy after surgery).¹ Administer neoadjuvant therapy for 24 weeks (8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks), or until disease progression or unacceptable toxicity occurs.¹ Follow with single-agent adjuvant therapy for up to 27 weeks (9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks) or until disease recurrence or unacceptable toxicity occurs.¹

In the neoadjuvant setting, administer pembrolizumab prior to chemotherapy when given on the same day.¹ Patients who experience disease progression or unacceptable toxicity on neoadjuvant pembrolizumab should not receive single-agent adjuvant therapy with pembrolizumab.¹

Combination Therapy for Triple-negative Breast Cancer

IV

200 mg every 3 weeks, or alternatively, 400 mg every 6 weeks (in combination with chemotherapy).¹ Continue therapy for up to 24 months with pembrolizumab or until disease progression or unacceptable toxicity occurs.¹

Administer pembrolizumab prior to chemotherapy when given on same day.¹

Selection based on presence of PD-L1 expression.¹

Dosage Modifications for Toxicity

Dosage reduction of pembrolizumab is not recommended based on adverse reactions; however, temporary or permanent discontinuance of pembrolizumab may be required based on severity of the immune-mediated reaction.¹

In general, temporarily withhold pembrolizumab in patients with severe (grade 3) immune-mediated adverse reactions, and permanently discontinue the drug in patients experiencing life-threatening (grade 4) immune-mediated adverse reactions or recurrent severe (grade 3) immune-mediated adverse reactions that require systemic immunosuppressive therapy.¹ Therapy should also be permanently discontinued in patients unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

When adverse effects occur during concomitant use of pembrolizumab with lenvatinib, modification of the dosage of one or both agents is recommended.¹ Temporary or permanent discontinuance of pembrolizumab may be required based on the severity of the reaction.¹ Refer to lenvatinib prescribing information for additional dosage modifications.¹

Hematologic Toxicity: If grade 4 hematologic toxicity occurs in patients with cHL or PMBCL, interrupt therapy until toxicity resolves to grade 0 or 1.¹

Immune-mediated Pneumonitis: If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

If grade 3 or 4 immune-mediated pneumonitis occurs, permanently discontinue therapy.¹

Immune-mediated GI Effects: If grade 2 or 3 immune-mediated colitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.

If grade 4 immune-mediated colitis occurs, permanently discontinue therapy.¹

Immune-mediated Hepatotoxicity (Except When Used in Combination with Axitinib): For serum aminotransferase (ALT or AST) elevations exceeding 3 times and up to 8 times the upper limit of normal (ULN) or total bilirubin concentrations exceeding 1.5 times and up to 3 times the ULN in patients without liver tumor involvement experiencing hepatotoxicity, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

For ALT or AST elevations exceeding 8 times the ULN or total bilirubin concentrations exceeding 3 times the ULN in patients without liver tumor involvement experiencing hepatotoxicity, permanently discontinue therapy.¹

When AST and ALT concentrations are ≤ULN at baseline in patients with liver tumor involvement experiencing hepatotoxicity, temporary or permanent discontinuance of pembrolizumab may be based on recommendations for hepatotoxicity in patients without liver tumor involvement.¹

For ALT or AST elevations that are exceeding 5 times and are up to 10 times the ULN in patients with liver tumor involvement and baseline ALT and AST concentrations exceeding 1 time and up to 3 times the ULN, interrupt therapy until hepatotoxicity resolves to grade 0 or 1 or the AST and ALT concentrations return to baseline.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

For ALT or AST elevations that are exceeding 8 times and are up to 10 times the ULN in patients with liver tumor involvement and baseline ALT and AST concentrations exceeding 3 times and up to 5 times the ULN, interrupt therapy until hepatotoxicity resolves to grade 0 or 1 or the AST and ALT concentrations return to baseline.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

For ALT or AST concentrations exceeding 10 times the ULN in patients with liver tumor involvement, permanently discontinue therapy.¹

For total bilirubin concentrations exceeding 3 times the ULN in patients with liver tumor involvement, permanently discontinue therapy.¹

Hepatotoxicity When Used in Combination with Axitinib for RCC: For treatment of liver enzyme elevations in patients experiencing adverse hepatotoxic effects from pembrolizumab therapy in combination with axitinib, consider corticosteroid therapy.¹

For ALT or AST concentrations that are ≥3 times but less than 10 times ULN in patients receiving pembrolizumab with concomitant axitinib and without concurrent total bilirubin concentrations of at least 2 times the ULN, interrupt pembrolizumab and axitinib therapy until the toxicity resolves to grade 0 or 1.¹ Consider a single-agent rechallenge or sequential rechallenge with both drugs after resolution of toxicity.¹ If therapy with axitinib is rechallenged, consider dosage reduction according to the axitinib prescribing information.¹

For ALT or AST concentrations exceeding 3 times the ULN with concurrent total bilirubin concentrations ≥2 times the ULN, permanently discontinue both pembrolizumab and axitinib therapy.¹

For ALT or AST concentrations ≥10 times the ULN, permanently discontinue both pembrolizumab and axitinib therapy.¹

Immune-mediated Endocrine Effects: If grade 3 or 4 immune-mediated endocrinopathies occur, interrupt therapy until patient is clinically stable or permanently discontinue the drug.¹

Immune-mediated Renal Effects: If grade 2 or 3 immune-mediated nephritis occurs with increased serum creatinine concentrations, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

If grade 4 immune-mediated nephritis occurs with increased serum creatinine concentrations permanently discontinue therapy.¹

Immune-mediated Dermatologic Effects: If Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) is suspected, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

If SJS, TEN, or DRESS is confirmed, permanently discontinue therapy.¹

Immune-mediated Cardiac Effects: If grade 2—4 immune-mediated myocarditis occurs, permanently discontinue therapy.¹

Immune-mediated Neurologic Effects: If grade 2 immune-mediated neurologic toxicity occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and corticosteroid dosage has been tapered.¹ Permanently discontinue therapy in patients who do not recover to grade 0 or 1 within 12 weeks of initiating corticosteroids or who are unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroids.¹

If grade 3 or 4 immune-mediated neurologic toxicity occurs, permanently discontinue therapy.¹

Infusion-related Reactions: If grade 1 or 2 infusion-related reactions occur, interrupt infusion or slow infusion rate.¹

If grade 3 or 4 infusion-related reactions occur, permanently discontinue therapy.¹

Special Populations

Hepatic Impairment

No special dosage recommendations at this time.¹

Renal Impairment

No special dosage recommendations at this time.¹

Geriatric Patients

No special dosage recommendations at this time.¹

Cautions for Pembrolizumab

Contraindications

• None.¹

Warnings/Precautions

Severe and Fatal Immune-mediated Adverse Reactions

Severe and potentially fatal immune-mediated adverse reactions can occur in any organ system or tissue.¹ Can occur in ≥1 organ system or tissue simultaneously; generally occur during therapy, but can manifest after discontinuation.¹

Early identification and management are essential.¹ Closely monitor for signs and symptoms of clinical manifestations of immune-mediated adverse reactions.¹ Manufacturer recommends baseline assessment of liver enzymes, serum creatinine, and thyroid function, and periodic monitoring thereafter in patients receiving pembrolizumab.¹ In patients with TNBC receiving neoadjuvant therapy, also monitor blood cortisol at baseline, prior to surgical procedures, and as clinically indicated.¹ Initiate appropriate workup to exclude alternative etiologies, including infection, if immune-mediated reaction suspected; initiate prompt medical management with specialty consultation as appropriate for presumed cases.¹

Depending on reaction severity, temporarily withhold or permanently discontinue pembrolizumab.¹ If temporary interruption or discontinuance of pembrolizumab is necessary, systemic corticosteroid therapy (1—2 mg/kg daily of prednisone [or equivalent]) generally recommended until toxicity improvement (unless endocrinopathy or dermatologic reaction) to grade 0 or 1.¹ Upon resolution to grade 0 or 1, may initiate corticosteroid taper and continue over at least 1 month.¹ Consider other systemic immunosuppressive therapies in patients whose immune-mediated adverse reactions are not controlled with systemic corticosteroids.¹

Immune-mediated Pneumonitis

Immune-mediated pneumonitis reported; incidence higher in patients with a history of thoracic radiation.¹

If grade 2 or greater pneumonitis occurs, temporarily withhold or permanently discontinue pembrolizumab.¹

Immune-mediated GI Effects

Immune-mediated colitis reported; may present as diarrhea.¹

If immune-mediated colitis refractory to corticosteroids occurs, consider repeating infectious workup to exclude alternative causes.¹

If grade 2 or greater colitis occurs, temporarily withhold or permanently discontinue pembrolizumab.¹

Hepatotoxicity and Immune-mediated Hepatitis

Immune-mediated hepatitis reported.¹

Monitor patients for changes in liver function.¹

Monitor liver enzymes prior to initiating axitinib and pembrolizumab and periodically thereafter.¹ Consider more frequent monitoring of liver enzymes during combination therapy.¹ If liver enzyme elevations occur during axitinib and pembrolizumab combination therapy, temporarily withhold treatment and consider systemic corticosteroids if needed.¹

If elevations in AST, ALT, or bilirubin concentrations occur, temporarily withhold or permanently discontinue pembrolizumab.¹

Immune-mediated Endocrine Effects

Immune-mediated endocrinopathies, including primary or secondary adrenal insufficiency, hypophysitis, thyroid dysfunction (i.e., hyperthyroidism, hypothyroidism, thyroiditis), and diabetes mellitus, reported.¹

Adrenal Insufficiency

For grade 2 or greater adrenal insufficiency, initiate symptomatic treatment (including hormone replacement therapy) as clinically indicated.¹ If immune-mediated adrenal insufficiency occurs, temporarily withhold pembrolizumab.¹

Hypophysitis

Acute presentation may include symptoms associated with mass effect (e.g., headache, photophobia, visual field defects).¹ If hypophysitis develops, hypopituitarism can occur.¹ Initiate hormone replacement therapy as clinically indicated.¹

If immune-mediated hypophysitis occurs, temporarily withhold or discontinue pembrolizumab.¹

Thyroid Disorders

Immune-mediated thyroid disorders (i.e., hyperthyroidism, hypothyroidism, thyroiditis) can occur.¹

If immune-mediated hypothyroidism occurs, initiate thyroid hormone replacement therapy or institute medical management as clinically indicated.¹

If immune-mediated thyroid disorders occur, temporarily withhold or discontinue pembrolizumab.¹

Diabetes Mellitus and Diabetic Ketoacidosis

Monitor for manifestations of diabetes mellitus (e.g., hyperglycemia).¹

Initiate insulin therapy as clinically indicated.¹ Temporarily withhold pembrolizumab based on severity.¹

Immune-mediated Renal Effects

Immune-mediated nephritis reported.¹

If grade 2 or greater nephritis occurs, temporarily withhold or discontinue pembrolizumab.¹

Immune-mediated Dermatologic Adverse Reactions

Immune-mediated rash or dermatitis can occur.¹ Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), reported.¹ Application of topical emollients and/or topical corticosteroids may be sufficient to treat mild to moderate non-exfoliative rashes.¹

If SJS, TEN, or DRESS is suspected, temporarily withhold pembrolizumab.¹ If SJS, TEN, or DRESS is confirmed, permanently discontinue pembrolizumab.¹

Other Immune-mediated Adverse Reactions

Other clinically significant cardiovascular/vascular, nervous system, ocular, GI, musculoskeletal or connective tissue, endocrine, and hematologic/immune adverse reactions reported.¹ Some cases were severe or fatal.¹

Solid organ transplant rejection and rejection of other transplants (including corneal graft rejection) also reported.¹ Weigh risk of possible organ rejection against potential benefits of the drug.¹

If an immune-mediated adverse reaction is suspected, ensure adequate evaluation to exclude other causes.¹

Depending on type and severity of immune-mediated adverse reaction, temporarily withhold or discontinue pembrolizumab.¹

Infusion-related Reactions

Severe or life-threatening infusion-related reactions, including hypersensitivity reactions and anaphylaxis, reported.¹

Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.¹

For grade 1 or 2 infusion-related reactions, interrupt or slow rate of infusion.¹ If grade 3 or 4 infusion-related reaction occurs, stop infusion and permanently discontinue pembrolizumab.¹

Allogeneic Stem Cell Transplantation-related Complications

Transplant-related complications (sometimes serious or fatal), including hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and corticosteroid-requiring febrile syndrome (without an identified infectious cause), reported in patients who underwent allogeneic stem cell transplantation prior to or following pembrolizumab therapy.¹ Such complications may occur despite other intervening therapy between pembrolizumab administration and transplantation.¹

Prior to or following allogeneic stem cell transplantation, weigh potential benefit of pembrolizumab versus risks of developing complications.¹

Closely monitor patients for evidence of stem cell transplantation-related complications and manage promptly if they occur.¹

Treatment-related Mortality

Increased mortality reported in patients with multiple myeloma receiving pembrolizumab in combination with an immunomodulatory agent (i.e., lenalidomide, pomalidomide); pembrolizumab is not currently FDA-labeled for use in patients with multiple myeloma.^{1 21}

In clinical trials, risk of death was increased by 61 or 106% in patients with multiple myeloma receiving pembrolizumab in combination with pomalidomide or lenalidomide, respectively, and low-dose dexamethasone compared with those receiving the immunomodulatory agent and low-dose dexamethasone.²¹ These trials were terminated at FDA's request.²¹

Patients with multiple myeloma should not receive an anti-PD-1 or anti-PD-L1 antibody in combination with an immunomodulatory agent (i.e., lenalidomide, pomalidomide) and dexamethasone outside of a controlled clinical trial.¹ FDA recommends that ongoing clinical trials evaluating anti-PD-1 or anti-PD-L1 agents given in combination with an immunomodulatory agent or in combination with other drugs for use in hematologic malignancies be evaluated for permanent discontinuance or protocol amendments.²¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.¹ May disrupt maternal immune tolerance to the fetus and increase risk of fetal loss (e.g., abortion, stillbirth); also may increase risk of immune-mediated disorders or alter normal immune response of the developing fetus.¹

Avoid pregnancy during therapy.¹ Women of childbearing potential should use a highly effective contraceptive method while receiving pembrolizumab and for 4 months after the last dose; verify pregnancy status prior to initiation of therapy.¹ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹

Immunogenicity

Development of binding antibodies and neutralizing antibodies to pembrolizumab reported.¹ Effects on pharmacokinetics or safety (i.e., infusion-related reactions) of the drug not observed.¹ Effects on efficacy not known.¹

Specific Populations

Pregnancy

May cause fetal harm.¹ Has potential to cross placenta; advise pregnant women of potential risk to fetus.¹ Verify pregnancy status in women of reproductive potential prior to initiation.¹

Lactation

Not known whether pembrolizumab is distributed into human milk, affects nursing infants, or affects milk production.¹ Maternal immunoglobulin G (IgG) present in human milk.¹ Impact of local GI exposure and minimal systemic exposure on breastfed infant not known.¹ Discontinue nursing during therapy and for 4 months after the last dose.¹

Females and Males of Reproductive Potential

Verify pregnancy status in women of reproductive potential prior to initiating pembrolizumab.¹ Pembrolizumab may cause fetal harm.¹ Advise women of reproductive potential to use effective contraception during treatment with pembrolizumab and for 4 months following the last dose.¹

Pediatric Use

Safety and efficacy established in pediatric patients with melanoma, classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), Merkel cell carcinoma (MCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancer, and tumor mutational burden-high (TMB-H) cancer.¹ Safety and efficacy of these indications are supported by extrapolation of data from clinical studies of pembrolizumab in adults, safety data in pediatric patients, and pharmacokinetic data indicating that age (range: 15–94 years) does not have clinically important effects on clearance of the drug.¹

Safety and efficacy in pediatric patients not established for other approved indications to date.¹

In KEYNOTE-051, some adverse effects occurred at ≥10% higher incidence in pediatric patients versus adults (e.g., pyrexia [33%], vomiting [29%], headache [25%], abdominal pain [23%], decreased lymphocyte count [13%], decreased white blood cell count [11%]).¹ Laboratory abnormalities that occurred at a ≥10% higher incidence were leukopenia (30%), neutropenia (28%), thrombocytopenia (22%), and grade 3 anemia (17%).¹

Geriatric Use

In clinical trials evaluating pembrolizumab in patients with melanoma, NSCLC, squamous cell carcinoma of the head and neck, cHL, and urothelial carcinoma, 48% of patients were ≥65 years of age and 17% were ≥75 years of age; no overall differences in safety or efficacy relative to younger adults.¹

In clinical trials evaluating pembrolizumab in patients with cHL, higher incidence of severe adverse reactions (50%) in patients ≥65 years of age compared to younger adults (24%).¹ In clinical trials evaluating pembrolizumab in combination with enfortumab vedotin in patients with urothelial cancer, patients ≥75 years of age experienced a higher incidence of fatal adverse effects compared to younger adults.¹ Incidence of fatal adverse effects was 4% in patients <75 years of age compared to 7% in patients ≥75 years of age.¹

No overall differences in safety or efficacy observed in geriatric patients relative to younger adults for other indications.¹

Hepatic Impairment

Clearance not significantly affected by mild to moderate hepatic impairment (total bilirubin concentration ≤3 times ULN with any AST concentration).¹ Insufficient data in patients with severe hepatic impairment (total bilirubin concentration >3 times ULN with any AST concentration).¹

Renal Impairment

Clearance not significantly affected by renal impairment (estimated GFR ≥15 mL/minute per 1.73 m²).¹

Common Adverse Effects

Single-agent pembrolizumab (≥20% of patients): Fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.¹

Pembrolizumab in combination with chemotherapy or chemoradiotherapy (≥20% of patients): 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, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, and hypothyroidism.¹

Pembrolizumab in combination with chemotherapy plus bevacizumab (≥20% of patients): Peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.

Pembrolizumab in combination with axitinib (≥20% of patients): Diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.¹

Pembrolizumab in combination with lenvatinib (≥20% of patients): 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.¹

Pembrolizumab in combination with enfortumab vedotin (≥20% of patients): Rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, weight loss, decreased appetite, dry eyes, nausea, constipation, dysgeusia, and urinary tract infection.¹

Drug Interactions

No formal drug interaction studies to date.¹

Pembrolizumab Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved within 16 weeks.¹

AUC, peak plasma concentration, and trough concentration are dose proportional over the dosage range of 2–10 mg/kg every 3 weeks; systemic accumulation is 2.1-fold when administered every 3 weeks.¹

Based on exposure-response relationships for efficacy and safety, no clinically important differences between 200 mg every 3 weeks and 2 mg/kg every 3 weeks regardless of cancer type.¹

Based on exposure-response relationships for efficacy and safety in adults with melanoma, no clinically important differences between 200 mg every 3 weeks or 2 mg/kg every 3 weeks and 400 mg every 6 weeks in patients with solid tumors.¹

Exposure-response relationships for efficacy and safety not fully characterized at pembrolizumab dosages of 400 mg every 6 weeks in patients with classical Hodgkin lymphoma (cHL) or primary mediastinal large B-cell lymphoma (PMBCL).¹

Special Populations

Exposure in pediatric patients 10 months—17 years of age similar to that in adults.¹

Distribution

Extent

Not known whether pembrolizumab is distributed into human milk.¹ Maternal IgG excreted into human milk.¹

Elimination

Half-life

22 days.¹

Clearance is approximately 23% lower at steady state than following initial dose; difference not clinically important.¹

Special Populations

Mild to moderate hepatic impairment (total bilirubin concentration ≤3 times ULN with any AST concentration) does not significantly affect clearance.¹ Effect of severe hepatic impairment (total bilirubin concentration >3 times ULN with any AST concentration) on pharmacokinetics not known.¹

Renal impairment (estimated GFR ≥15 mL/minute per 1.73 m²) does not significantly affect clearance.¹

Age, gender, race, and tumor burden do not have clinically important effects on pharmacokinetics of pembrolizumab.¹

Stability

Storage

Parenteral

Injection Concentrate

2–8°C in original package to protect from light.¹ Do not freeze.¹

Diluted infusion solution: Room temperature for up to 6 hours after dilution (including infusion time) or 2–8°C for up to 96 hours after dilution.¹ Do not freeze.¹

Actions

• An IgG₄ kappa immunoglobulin that is highly selective for PD-1, an immune-checkpoint receptor expressed on activated T-cells, monocytes, B-cells, natural killer (NK) T-cells, and dendritic cells.^{1 3 5 8}

• Overexpression of PD-1 ligands on surface of tumor cells results in activation of PD-1 activity and suppression of cytotoxic T-cell activity.^{1 8}

• Blocks interaction between PD-1 and its ligands, resulting in enhanced immune response, including enhanced antitumor immune response.^{1 8} In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.¹

Advice to Patients

• Advise patients to read the manufacturer's medication guide before beginning treatment and each time the drug is administered.¹

• Inform patients of the risk of immune-mediated pneumonitis and to inform their clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.¹

• Inform patients of the risk of immune-mediated colitis and to inform their clinician immediately if diarrhea, more frequent bowel movements, or severe abdominal pain occurs.¹

• Inform patients of the risk of immune-mediated hepatitis and to inform their clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, dark urine [tea colored], abdominal pain [particularly on the right side], easy bruising or bleeding) occur.¹

• Inform patients of the risk of immune-mediated endocrinopathies and to inform their clinician immediately if signs or symptoms of adrenal insufficiency, hypophysitis, hypothyroidism or hyperthyroidism, or type 1 diabetes mellitus occur.¹

• Inform patients of the risk of immune-mediated nephritis and to inform their clinician immediately if signs or symptoms of nephritis (e.g., decreased urine output, blood in urine, ankle swelling, loss of appetite) occur.¹

• Inform patients of the risk of severe immune-mediated skin reactions and to inform their clinician immediately if any sign or symptoms of severe skin reactions, Stevens-Johnson syndrome, or toxic epidermal necrolysis develop.¹

• Inform patients of the risk of other immune-mediated adverse reactions involving any organ system and to inform their clinician immediately if new or worsening signs or symptoms of potential immune-mediated adverse reactions occur.¹

• Inform patients of the risk of infusion-related reactions and to inform their clinician immediately if signs and symptoms of such reactions (e.g., dizziness, chills or shaking, fever, difficulty breathing, pruritus, back pain, rash, flushing, feeling of faintness) occur.¹

• Inform patients of the risk of immune-mediated rejection of a solid organ transplant or other transplant (including corneal graft) rejection and to inform their clinician immediately if signs or symptoms of solid organ transplant or other transplant (including corneal graft) rejection occur.¹

• Advise patients of the risk of complications following allogeneic stem cell transplantation.¹

• Stress the importance of laboratory monitoring during pembrolizumab therapy.¹

• Advise patients of the risk of fetal harm.¹ Advise patients of childbearing potential that they should use a highly effective method of contraception while receiving pembrolizumab and for 4 months after the last dose.¹ Stress importance of patients informing clinicians if they are or plan to become pregnant.¹ If pregnancy occurs, advise patients of potential risk to the fetus.¹

• Advise patients to avoid breast-feeding while receiving pembrolizumab therapy and for 4 months after the last dose.¹

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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