Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 100mg/4mL (25mg/mL)
Melanoma
Unresectable or metastatic melanoma
- Indicated for treatment of unresectable or metastatic melanoma
- 200 mg IV q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks
- Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence
Non-Small Cell Lung Cancer
Single-agent for localized disease
- Indicated as adjuvant treatment following resection and platinum-based chemotherapy for Stage IB (T2a ≥4 cm), II, or IIIA NSCLC
- 200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression or unacceptable toxicity, or up to 12 months without disease progression
Single-agent for unresectable or advanced disease
- 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%)], with no EGFR or ALK genomic tumor aberrations
- Metastatic NSCLC whose tumors with PD-L1 expression (TPS ≥1%) 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 q3Weeks OR 400 mg q6Weeks until disease progression or unacceptable toxicity, or up to 24 months without disease progression
Combination therapy for resectable NSCLC
- Indicated for resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery
- 200 mg IV q3Weeks OR 400 mg q6Weeks
- Administer before chemotherapy if given on the same day
- Neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by pembrolizumab as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity
Combination therapy for metastatic NSCLC
- 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 q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
- See prescribing information for chemotherapy agents doses administered in combination with pembrolizumab
Head & 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]
- Indicated for treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy
- 200 mg IV q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 prior lines of therapy
200 mg IV q3Weeks OR 400 mg q6Weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression
Urothelial Carcinoma
Combination with enfortumab
- Indicated for locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy
- 200 mg IV q3Weeks OR 400 mg q6Weeks
- Administer pembrolizumab ~30 minutes after enfortumab vedotin when given on the same day
- Continue until disease progression, unacceptable toxicity, or up to 24 months
Single-agent therapy
-
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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks or 400 mg IV q6Weeks
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
Also, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma
200 mg IV q3Weeks OR 400 mg q6Weeks 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 prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10)
- 200 mg IV q3Weeks OR 400 mg q6Weeks 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)
- 200 mg IV q3Weeks OR 400 mg q6Weeks 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)
- 200 mg IV q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks, PLUS
- Axitinib 5 mg PO BID (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 intervals
- Refer also prescribing information for axitinib dosing information
Combination therapy with lenvatinib
- Indicated in combination with lenvatinib, for first-line treatment of patients with advanced RCC
- Pembrolizumab 200 mg IV q3Weeks OR 400 mg q6Weeks, PLUS
- Lenvatinib 20 mg PO qDay
- 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 q3Weeks OR 400 mg q6Weeks 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 q3Weeks OR 400 mg q6Weeks, PLUS
- Lenvatinib 20 mg PO qDay
- Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months
- Refer to the lenvatinib prescribing information for recommended dosing information
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 q3Weeks OR 400 mg q6Week
- 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 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 q3Weeks OR 400 mg q6Weeks
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 q3Weeks OR 400 mg q6Weeks
Continue until disease progression or unacceptable toxicity, or up to 24 months without disease progression
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 q3Weeks for 8 doses or 400 mg IV q6Weeks for 4 doses or until disease progression or unacceptable toxicity
- Followed by single agent adjuvant therapy
-
Adjuvant treatment
- Single-agent therapy: 200 mg IV q3Weeks for 9 doses or 400 mg IV q6Weeks 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) who tumors express PD-L1 (CPS ≥10)
- 200 mg IV q3Weeks or 400 mg IV q6Weeks
- Continue until disease progression, unacceptable toxicity, or up to 24 months
- Administer prior to chemotherapy when given on the same day
Biliary Tract Cancer
Indicated for locally advanced, unresectable, or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin
200 mg IV q3Weeks or 400 mg IV q6Weeks
Administer before chemotherapy when given on same day
Continue until disease progression, unacceptable toxicity, or up to 24 months
Dosage Modifications
Renal impairment (eGFR ≥15 mL/min/1.73 m²): 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 <1)
- Grade 3 or 4 endocrinopathies (eg, 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>3 and up to 5x upper limit of normal (ULN) or total bilirubin >1.5 and up to 3x ULN
Withhold (resume when recover to Grade <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 ≥5x ULN if baseline <2x ULN
- AST/ALT >3x baseline if baseline ≥2x ULN
- Total bilirubin >2 mg/dL if baseline <1.5 mg/dL
- Total bilirubin >3 mg/dL, regardless of baseline levels
RCC treated with pembrolizumab with axitinib
- ALT or AST ≥3x ULN but <10x ULN with concurrent total bilirubin ≥2x 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 ≥10x ULN or ≥3x ULN with concurrent total bilirubin ≥2x 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 week 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
- ALT/AST >10x ULN; or Child-Pugh score ≥9 points
- Gastrointestinal bleeding suggestive of portal hypertension
- New onset of ascites or encephalopathy
-
Immune-mediated hepatitis in patients without HCC
- Patients without liver metastases: AST/ALT >5x ULN or total bilirubin >3x ULN
- Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT ≥50% relative to baseline that persists for ≥1 week
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
- Locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma
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
Orphan Designations
Multiple myeloma
Nasopharyngeal carcinoma
Follicular lymphoma
Sponsor
- Merck, Sharp & Dohme a subsidiary of Merck & Co, Inc; One Merck Drive, Whitehouse Station, NJ 08889
Dosage Forms & Strengths
injectable solution
- 100mg/4mL (25mg/mL)
Classical Hodgkin Lymphoma
Indicated for refractory classical Hodgkin lymphoma (cHL) or relapse after ≥2 prior lines of therapy
2 mg/kg IV q3Weeks; 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 q3Weeks; 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 prior lines of therapy
2 mg/kg IV q3Weeks; 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 q3Weeks; 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 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 q3Weeks; 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 with Stage IIB, IIC, or III melanoma following complete resection
2 mg/kg IV q3Weeks; 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 (eg, 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>3 and up to 5x upper limit of normal (ULN) or total bilirubin >1.5 and up to 3x ULN
Withhold (resume when recover to Grade <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 week 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 >5x ULN or total bilirubin >3x ULN
- Patients with liver metastasis and Grade 2 AST/ALT at baseline: With an increase in AST/ALT ≥50% relative to baseline that persists for ≥1 week
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, obtain 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
Adverse Effects
All grades of severity are listed unless indicated otherwise
>10% (Melanoma)
Hyperglycemia (45%)
Hypertriglyceridemia (43%)
Anemia (3%)
Lymphopenia (33%)
Hyponatremia (28%)
Fatigue (28%)
Increased AST (27%)
Hypoalbuminemia (27%)
Rash (24%)
Increased ALT (23%)
Increased alkaline phosphatase (21%)
Hypercholesterolemia (20%)
Arthralgia (18%)
Cough (17%)
Decreased appetite (16%)
Headache (14%)
Vitiligo (13%)
Back pain (12%)
Dyspnea (11%)
>10% (HNSCC)
HNSCC
Fatigue (33%)
Constipation (20%)
Rash (20%)
Cough (18%)
Hypothyroidism (18%)
Nausea (17%)
Diarrhea (16%)
Decreased appetite/weight (15%)
Dyspnea (14%)
Pyrexia (13%)
Pneumonia (12%)
Headache (12%)
Myalgia (12%)
Vomiting (11%)
Pruritus (11%)
>10% (NSCLC)
Decreased appetite (25%)
Nausea (20%)
Thrombocytopenia (20%)
Constipation (15%)
Vomiting (13%)
Dyspnea (23%)
Cough (19%)
Rash (17%)
Arthralgia (11%)
Back pain (11%)
Pruritus (11%)
Neutropenia (11%)
>10% (Urothelial Cancer)
Glucose increased (52%)
Hemoglobin decreased (52%)
Lymphocytes decreased (45%)
Albumin decreased (43%)
Sodium decreased (37%)
Alkaline phosphatase increased (37%)
Creatinine increased (35%)
Phosphate decreased (29%)
AST increased (28%)
Potassium increased (28%)
Calcium decreased (26%)
Nausea (21%)
Constipation (19%)
Diarrhea (18%)
Vomiting (15%)
Lymphocytes decreased, Grade 3 or 4 (15%)
Hemoglobin decreased, Grade 3 or 4 (13%)
Abdominal pain (13%)
>10% (Cervical Cancer)
Anemia (54%)
Lymphocyte count decreased (47%)
Hypoalbuminemia (44%)
Fatigue (43%)
Alkaline phosphatase increased (42%)
Hyponatremia (38%)
Hyperglycemia (38%)
AST increased (34%)
Increased creatinine (32%)
Musculoskeletal pain (27%)
Hypocalcemia (27%)
Anemia, Grade 3 or 4 (24%)
Diarrhea (23%)
Abdominal pain (22%)
Pain (22%)
ALT increased (21%)
Decreased appetite (21%)
Hypokalemia (20%)
Hemorrhage (19%)
Pain (19%)
Nausea (19%)
Vomiting (19%)
Urinary tract infection (UTI) (18%)
Rash (17%)
Infection (16%)
Peripheral edema (15%)
Constipation (14%)
Hyponatremia, Grade 3 or 4 (13%)
Hypothyroidism (11%)
>10% (Endometrial Cancer)
Combination therapy with lenvatinib
- Fatigue (65%)
- Musculoskeletal pain (65%)
- Hypertension (65%)
- Diarrhea (64%)
- Decreased appetite (52%)
- Hypothyroidism (51%)
- Nausea (48%)
- Stomatitis (43%)
- Vomiting (39%)
- Decreased weight (36%)
- Abdominal pain (33%)
- Headache (33%)
- Constipation (32%)
- Urinary tract infection (31%)
- Dysphoria (29%)
- Hemorrhagic events (28%)
- Hypomagnesemia (27%)
- Palmar-plantar erythrodysesthesia syndrome (26%)
- Dyspnea (24%)
- Cough (21%)
- Rash (21%)
1-10% (HNSCC)
Dysphagia (8%)
Insomnia (7%)
Pneumonia, Grade 3 or 4 (7%)
Neck pain (6%)
Dizziness (5%)
Mucosal inflammation (4.3%)
Fatigue, Grade 3 or 4 (4%)
Stomatitis (3%)
Dysphagia, Grade 3 or 4 (2.3%)
Dyspnea, Grade 3 or 4 (2%)
Weight loss, Grade 3 or 4 (2%)
Mucosal inflammation, Grade 3 or 4 (1.3%)
1-10% (Cervical Cancer)
Lymphocyte count decreased, Grade 3 or 4 (9%)
Hypokalemia, Grade 3 or 4 (6%)
UTI, Grade 3 or 4 (5%)
Hypoalbuminemia, Grade 3 or 4 (5%)
Increased creatinine, Grade 3 or 4 (5%)
Musculoskeletal pain, Grade 3 or 4 (5%)
Fatigue, Grade 3 or 4 (5%)
Hemorrhage, Grade 3 or 4 (5%)
Infection, Grade 3 or 4 (4.1%)
AST increased, Grade 3 or 4 (3.9%)
ALT increased, Grade 3 or 4 (3.9%)
Abdominal pain, Grade 3 or 4 (3.1%)
Peripheral edema, Grade 3 or 4 (3%)
Alkaline phosphatase increased, Grade 3 or 4 (2.6%)
Pain, Grade 3 or 4 (2%)
Rash, Grade 3 or 4 (2%)
Diarrhea, Grade 3 or 4 (2%)
Hyperglycemia, Grade 3 or 4 (1.3%)
Hypokalemia, Grade 3 or 4 (1%)
Vomiting, Grade 3 or 4 (1%)
1-10% (Urothelial Carcinoma)
Sodium decreased, Grade 3 or 4 (9%)
Glucose increased, Grade 3 or 4 (8%)
Phosphate decreased, Grade 3 or 4 (8%)
Alkaline phosphatase increased, Grade 3 or 4 (7%)
Urinary tract infection, Grade 3 or 4 (4.9%)
Fatigue, Grade 3 or 4 (4.5%)
Creatinine increased, Grade 3 or 4 (4.4%)
AST increased, Grade 3 or 4 (4.1%)
Decreased appetite, Grade 3 or 4 (3.8%)
Musculoskeletal pain, Grade 3 or 4 (3%)
Hematuria, Grade 3 or 4 (2.3%)
Dyspnea, Grade 3 or 4 (1.9%)
Albumin decreased, Grade 3 or 4 (1.7%)
Calcium decreased, Grade 3 or 4 (1.6%)
Nausea, Grade 3 or 4 (1.1%)
Constipation, Grade 3 or 4 (1.1%)
Abdominal pain, Grade 3 or 4 (1.1%)
1-10% (NSCLC)
Anemia (6%)
Pneumonia (6%)
Dyspnea, Grade 3 or 4 (3.7%)
Urinary tract infection (3%)
Asthenia (2%)
Diarrhea (2%)
Decreased appetite< Grade 3 or 4 (1.5%)
Back pain, Grade 3 or 4 (1.5%)
Nausea, Grade 3 or 4 (1.3%)
Arthralgia, Grade 3 or 4 (1%)
1-10% (Endometrial Cancer)
Combination therapy with lenvatinib
- Hypertension (9%)
- Abdominal pain (6%)
- Musculoskeletal pain (5%)
- Hemorrhage (4%)
- Fatigue (4%)
- Nausea (4%)
- Confusional state (4%)
- Pleural effusion (4%)
- Adrenal insufficiency (3%)
- Colitis (3%)
- Dyspnea (3%)
- Pyrexia (3%)
<1%
Urothelial cancer
- Vomiting, Grade 3 or 4
- Potassium increased, Grade 3 or 4
NSCLC
- Rash, Grade 3 or 4
- Cough, Grade 3 or 4
- Constipation, Grade 3 or 4
- Vomiting, Grade 3 or 4
HNSCC
- Constipation
- Pyrexia
- Diarrhea
- Vomiting
- Cough
- Headache
- Dizziness
- Neck pain
- Insomnia
Postmarketing reports
Infusion-related reactions
Exfoliative dermatitis
Bullous pemphigoid
Asthenia
Lymphopenia
Sclerosing cholangitis
Warnings
Contraindications
None
Cautions
Monitor for signs and symptoms of adrenal insufficiency; administer corticosteroids and hormone replacement as clinically indicated; withhold therapy for moderate (Grade 2) adrenal insufficiency and withhold or discontinue for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency
Solid organ transplant rejection reported in postmarketing setting; treatment increases risk of rejection in solid organ transplant recipients; consider benefit of treatment versus risk of possible organ rejection
Infusion-related reactions, including severe and life-threatening reactions, reported; monitor for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever; interrupt or slow rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions; for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue therapy
Hypophysitis reported; monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency)
Thyroid disorders can occur; monitor for changes in thyroid function (at the start of treatment, periodically during treatment, and as clinically indicated) and for clinical signs and symptoms of thyroid disorders
Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman (see Pregnancy)
In two randomized clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality; treatment of patients with multiple myeloma with a PD-1 or PDL1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials
Immune-mediated adverse effects
- Also see Dosage Modifications
- Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously;
- Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody
- While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies
- For patients with TNBC treated in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated
- Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies
- Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions
- Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
- In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection; institute medical management promptly, including specialty consultation as appropriate
- Clinical trials reported immune-mediated pneumonitis, colitis, hepatitis, nephritis and other immune-mediated adverse reactions (eg, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, myasthenic syndrome, optic neuritis, and rhabdomyolysis)
- Immune-mediated rashes, including SJS, TEN, exfoliative dermatitis, and bullous pemphigoid, reported; monitor for suspected severe skin reactions and exclude other causes
- Immune-mediated endocrinopathies (eg, adrenal insufficiency, changes in thyroid function, type 1 diabetes mellitus including diabetic ketoacidosis) reported
- Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with pembrolizumab
- Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid- requiring febrile syndrome (without an identified infectious cause); these complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
- Follow patients closely for evidence of transplant-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT
- Institute medical management promptly, including specialty consultation as appropriate
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman
No human data available informing the risk of embryo-fetal toxicity
Animal data
- In animal models, the PD-1/PD-L1 signaling pathway is important in the maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue
- Human IgG4 (immunoglobulins) are known to cross the placenta; therefore, pembrolizumab can potentially be transmitted from the mother to the developing fetus
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months following final dose
Lactation
Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to this drug are unknown
No studies conducted to assess impact of pembrolizumab on milk production or its presence in breast milk
Instruct women to discontinue nursing during treatment and for 4 months after final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks interaction between PD-1 and its ligands, PD-L1 and PD-L2
PD-1 and PD-L1
- PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions; PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound
- This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
- Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells
Absorption
Steady-state concentrations were reached by 16 weeks of repeated every 3-week regimen
Systemic accumulation: 2.1-fold
Distribution
Vd: 6 L
Excretion
Half-life: 22 days
Clearance: 193 mL/day (steady-state); 252 mL/day (first-dose)
Administration
IV Compatibilities
0.9% NaCl
Dextrose 5%
IV Preparation
IV infusion preparation
- Withdraw required volume from vial(s) and transfer into IV bag containing 0.9% NaCl or Dextrose 5%; mix diluted solution by gentle inversion
- Final concentration of diluted solution: 1-10 mg/mL
- Discard any unused portion left in vial
IV Administration
Infuse over 30 minutes through an IV line containing a sterile, nonpyrogenic, low-protein binding 0.2-5 micron in-line or add-on filter
NSCLC, esophageal cancer, TNBC, or HNSCC (combination therapy): Administer pembrolizumab prior to chemotherapy when given on the same day
Gastric cancer (combination therapy): Administer pembrolizumab before chemotherapy and trastuzumab when given on the same day
Do not coadminister other drugs through the same infusion line
Storage
Unopened vials
- Refrigerate between 2-8ºC (36-46ºF)
- Does not contain preservatives
- Do not freeze
Diluted solution
- Room temperature: Not to exceed 6 hr from time of dilution including duration of infusion
- Refrigerate at 2-8ºC (36-46ºF): Not to exceed 24 hr from time of dilution
- If refrigerated, allow diluted solution to come to room temperature before administration
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Keytruda intravenous - | 25 mg/mL vial |  | |
| Keytruda intravenous - | 25 mg/mL vial |  |
Copyright © 2010 First DataBank, Inc.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
