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Pembrolizumab

Medically reviewed by Drugs.com. Last updated on May 22, 2020.

Pronunciation

(pem broe LIZ ue mab)

Index Terms

  • Anti-PD-1 Monoclonal Antibody MK-3475
  • Lambrolizumab
  • MK-3475
  • SCH 90045

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Keytruda: 100 mg/4 mL (4 mL) [contains polysorbate 80]

Brand Names: U.S.

  • Keytruda

Pharmacologic Category

  • Antineoplastic Agent, Anti-PD-1 Monoclonal Antibody
  • Antineoplastic Agent, Immune Checkpoint Inhibitor
  • Antineoplastic Agent, Monoclonal Antibody

Pharmacology

Pembrolizumab is a highly selective anti-PD-1 humanized monoclonal antibody which inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor on T-cells to block PD-1 ligands (PD-L1 and PD-L2) from binding. Blocking the PD-1 pathway inhibits the negative immune regulation caused by PD-1 receptor signaling (Hamid 2013). Anti-PD-1 antibodies (including pembrolizumab) reverse T-cell suppression and induce antitumor responses (Robert 2014).

Distribution

Vdss: 6 L.

Excretion

Clearance: First dose: 252 mL/day; steady state: 195 mL/day.

Half-Life Elimination

22 days.

Use: Labeled Indications

Cervical cancer (recurrent or metastatic): Treatment of recurrent or metastatic cervical cancer in patients whose tumors express PD-L1 (combined positive score [CPS] ≥1), as determined by an approved test, and with disease progression on or after chemotherapy.

Cutaneous squamous cell carcinoma (recurrent or metastatic): Treatment of recurrent or metastatic cutaneous squamous cell carcinoma not curable by surgery or radiation.

Endometrial carcinoma (advanced): Treatment of advanced endometrial carcinoma (in combination with lenvatinib) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) in patients who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.

Esophageal cancer (recurrent locally advanced or metastatic): Treatment of recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in patients whose tumors express PD-L1 (CPS ≥10) as determined by an approved test, with disease progression after one or more prior lines of systemic therapy.

Gastric cancer (recurrent locally advanced or metastatic): Treatment of recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy, and if appropriate, HER2/neu-targeted therapy.

Head and neck cancer, squamous cell (recurrent or metastatic):

First-line treatment (in combination with platinum and fluorouracil) of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

First-line, single-agent treatment of metastatic or unresectable recurrent HNSCC in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test.

Single-agent treatment of recurrent or metastatic HNSCC in patients with disease progression on or after platinum-containing chemotherapy.

Hepatocellular carcinoma (advanced): Treatment of hepatocellular carcinoma in patients who have been previously treated with sorafenib.

Hodgkin lymphoma, classical (relapsed or refractory): Treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma or patients who have relapsed after 3 or more prior lines of therapy.

Melanoma:

Adjuvant treatment of melanoma with lymph node(s) involvement following complete resection.

Treatment of unresectable or metastatic melanoma.

Merkel cell carcinoma (recurrent or metastatic): Treatment of recurrent locally advanced or metastatic Merkel cell carcinoma in adult and pediatric patients.

Microsatellite instability-high or mismatch repair-deficient cancer (unresectable or metastatic):

Solid tumors: Treatment of unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors in adult and pediatric patients that have progressed following prior treatment and have no satisfactory alternate treatment options.

Limitation of use: Safety and efficacy in pediatric patients with MSI-H central nervous system cancers have not been established.

Colorectal cancer: First-line treatment of unresectable or metastatic MSI-H of dMMR colorectal cancer; treatment of unresectable or metastatic, MSI-H or mismatch repair deficient colorectal cancer in adult and pediatric patients that have progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

Non-small cell lung cancer:

First-line, single-agent treatment of non-small cell lung cancer (NSCLC) in patients with stage III NSCLC (who are not candidates for surgical resection or definitive chemoradiation) or in patients with metastatic NSCLC, and with tumors with PD-L1 expression (tumor proportion score [TPS] ≥1%), as determined by an approved test, and with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

First-line treatment (in combination with pemetrexed and platinum chemotherapy) of metastatic nonsquamous NSCLC in patients with no EGFR or ALK genomic tumor aberrations.

First-line treatment (in combination with carboplatin and either paclitaxel or paclitaxel [protein bound]) of metastatic squamous NSCLC.

Single-agent treatment of metastatic NSCLC in patients with tumors with PD-L1 expression (TPS ≥1%), as determined by an approved test, and with disease progression on or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression (on approved EGFR- or ALK-directed therapy) prior to receiving pembrolizumab.

Primary mediastinal large B-cell lymphoma (relapsed or refractory): Treatment of primary mediastinal large B-cell lymphoma (PMBCL) in adult and pediatric patients with refractory disease or who have relapsed after 2 or more prior lines of therapy.

Limitation of use: Not recommended for treatment of PMBCL in patients who require urgent cytoreductive therapy.

Renal cell carcinoma (advanced): First-line treatment of advanced renal cell carcinoma (in combination with axitinib).

Small cell lung cancer (metastatic): Treatment of metastatic small cell lung cancer in patients with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy.

Tumor mutational burden-high cancer (unresectable or metastatic): Treatment of unresectable or metastatic, tumor mutational burden-high solid tumors (TMB-H; ≥10 mutations/megabase [mut/Mb]; as determined by an approved test) in adult and pediatric patients who have progressed following prior treatment and have no satisfactory alternative treatment options.

Limitation of use: Safety and efficacy in pediatric patients with TMB-H CNS cancers have not been established.

Urothelial carcinoma:

Treatment of Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors in patients who are ineligible for or have elected not to undergo cystectomy.

Treatment of locally advanced or metastatic urothelial cancer in patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by an approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

Treatment of locally advanced or metastatic urothelial cancer in patients with disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Off Label Uses

Breast cancer, triple-negative, early stage

Data from a phase 3 trial support the use of pembrolizumab as a component of neoadjuvant therapy (followed by definitive surgery) and adjuvant therapy for the treatment of previously untreated stage II or stage III triple-negative breast cancer. The percentage of patients with a pathological complete response (defined as ypT0/Tis ypN0 at the time of definitive surgery) was significantly higher in the pembrolizumab plus neoadjuvant chemotherapy arm compared to the placebo plus neoadjuvant chemotherapy arm. However, the follow-up period was not long enough to show longer event-free survival in the pembrolizumab plus neoadjuvant chemotherapy arm versus the placebo/chemotherapy arm [Schmid 2020].

Malignant pleural mesothelioma, relapsed/refractory, PD-L1+

Data from a small, phase 1b, open-label trial in previously treated patients with PD-L1-positive malignant pleural mesothelioma as well as data from a retrospective analysis suggest that pembrolizumab is well tolerated and may be a subsequent treatment option in patients with relapsed/refractory disease [Alley 2017], [Metaxas 2018].

Mycosis fungoides/Sézary syndrome, relapsed/refractory

Data from a small, single-arm, multicenter, phase 2 study support the use of pembrolizumab in the management of multiply relapsed/refractory advanced (stage IIB or higher) mycosis fungoides/Sézary syndrome (MF/SS). Single-agent pembrolizumab treatment showed significant activity in heavily pretreated (median of 4 prior systemic therapies) relapsed/refractory MF/SS, with durable responses [Khodadoust 2020].

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to pembrolizumab or any component of the formulation.

Dosing: Adult

Breast cancer, triple negative, early stage (off-label use): IV:

Neoadjuvant therapy: 200 mg once every 3 weeks (in combination with paclitaxel and carboplatin) for 4 cycles (first neoadjuvant treatment), followed by 200 mg once every 3 weeks (in combination with cyclophosphamide and either doxorubicin or epirubicin) for 4 cycles (second neoadjuvant treatment). Patients underwent definitive surgery 3 to 6 weeks after the last cycle of the neoadjuvant phase (Schmid 2020).

Adjuvant therapy: 200 mg once every 3 weeks (in combination with radiation therapy) for up to 9 cycles (Schmid 2020).

Cervical cancer (recurrent or metastatic): IV: 200 mg once every 3 weeks (Chung 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Colorectal cancer, microsatellite instability high or mismatch repair deficient (unresectable or metastatic; first-line therapy or therapy for progressive disease): IV: 200 mg once every 3 weeks (Andre 2020; Le 2020) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Cutaneous squamous cell carcinoma (recurrent or metastatic): IV: 200 mg once every 3 weeks or 400 mg once every 6 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Endometrial carcinoma (advanced): IV: 200 mg once every 3 weeks (Makker 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (in combination with lenvatinib).

Esophageal cancer (recurrent locally advanced or metastatic): IV: 200 mg once every 3 weeks (Shah 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Gastric cancer (recurrent locally advanced or metastatic): IV: 200 mg once every 3 weeks (Fuchs 2018) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Head and neck cancer, squamous cell, (unresectable/recurrent or metastatic), single-agent therapy: IV: 200 mg once every 3 weeks (Mehra 2018) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Head and neck cancer, squamous cell, (unresectable/recurrent or metastatic), combination therapy: IV: 200 mg once every 3 weeks (Burtness 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (initially in combination with 6 cycles of fluorouracil and either carboplatin or cisplatin).

Hepatocellular carcinoma (advanced): IV: 200 mg once every 3 weeks (Zhu 2018) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Hodgkin lymphoma, classical (relapsed or refractory): IV: 200 mg once every 3 weeks (Chen 2017; Chen 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Malignant pleural mesothelioma, relapsed/refractory, PD-L1+ (off-label use): IV: 200 mg once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (Alley 2017; Metaxas 2018).

Melanoma (adjuvant treatment): IV: 200 mg once every 3 weeks (Eggermont 2018) or 400 mg once every 6 weeks; continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence.

Melanoma (unresectable or metastatic): IV: 200 mg once every 3 weeks or 400 mg once every 6 weeks until disease progression or unacceptable toxicity.

Off-label dosing: 2 mg/kg once every 3 weeks until disease progression or unacceptable toxicity (Ribas 2015).

Merkel cell carcinoma, recurrent or metastatic: IV: 200 mg once every 3 weeks or 400 mg once every 6 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Off-label dosing: 2 mg/kg once every 3 weeks for up to 2 years or until complete response, or until disease progression or unacceptable toxicity (Nghiem 2016).

Microsatellite instability-high or mismatch repair-deficient cancer (unresectable or metastatic): IV: 200 mg once every 3 weeks (Marabelle 2020) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Mycosis fungoides/Sézary syndrome, relapsed/refractory (off-label use): IV: 2 mg/kg once every 3 weeks until disease progression or unacceptable toxicity, for up to 24 months (Khodadoust 2020).

Non-small cell lung cancer (stage III or metastatic), single-agent therapy: IV: 200 mg once every 3 weeks (Mok 2019; Reck 2016) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Off-label dosing (in patients with metastatic non-small cell lung cancer (NSCLC) with disease progression following platinum-containing chemotherapy): 2 mg/kg once every 3 weeks for 24 months or until disease progression or unacceptable toxicity (Herbst 2016).

Non-small cell lung cancer (metastatic, nonsquamous), combination therapy: IV: 200 mg once every 3 weeks (in combination with pemetrexed and either cisplatin or carboplatin) for 4 cycles, followed by pembrolizumab monotherapy of 200 mg once every 3 weeks (with or without optional indefinite pemetrexed maintenance therapy) until disease progression, unacceptable toxicity, or (in patients without disease progression) for a total duration of pembrolizumab therapy of up to 35 cycles or 24 months (Gandhi 2018; Langer 2016). Pembrolizumab 400 mg once every 6 weeks has been approved as an additional dosing option.

Non-small cell lung cancer (metastatic, squamous), combination therapy: IV: 200 mg once every 3 weeks (in combination with carboplatin and either paclitaxel or paclitaxel [protein bound]) for 4 cycles, followed by pembrolizumab monotherapy of 200 mg once every 3 weeks until radiographic disease progression, unacceptable toxicity, or (in patients without disease progression) for a total duration of pembrolizumab therapy of up to 35 cycles (Paz-Ares 2018). Pembrolizumab 400 mg once every 6 weeks has been approved as an additional dosing option.

Primary mediastinal large B-cell lymphoma (relapsed or refractory): IV: 200 mg once every 3 weeks (Armand 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Renal cell carcinoma (advanced): IV: 200 mg once every 3 weeks (Rini 2019) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (in combination with axitinib).

Small cell lung cancer (metastatic): IV: 200 mg once every 3 weeks (Chung 2020) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Tumor mutational burden-high cancer (unresectable or metastatic): IV: 200 mg once every 3 weeks or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Urothelial carcinoma, non-muscle invasive (high-risk, Bacillus Calmette-Guerin–unresponsive): IV: 200 mg once every 3 weeks or 400 mg once every 6 weeks until persistent or recurrent non-muscle invasive bladder cancer, disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Urothelial carcinoma (locally advanced or metastatic): IV: 200 mg once every 3 weeks (Bellmunt 2017) or 400 mg once every 6 weeks; continue until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: FDA approval through an accelerated process; well-controlled trials in pediatric patients are scant and dosing based on adult efficacy and safety trials and pediatric pharmacokinetic and safety data.

Hodgkin lymphoma, classical (relapsed or refractory): Children ≥2 years and Adolescents: IV: 2 mg/kg/dose; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 24 months.

Merkel cell carcinoma (recurrent locally advanced or metastatic): Children ≥2 years and Adolescents: IV: 2 mg/kg/dose; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 24 months.

Microsatellite instability-high cancer (MSI-H) (unresectable or metastatic); non-CNS solid tumors that have progressed following prior treatment without satisfactory alternative treatment options: Children ≥2 years and Adolescents: IV: 2 mg/kg/dose; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 24 months.

Primary mediastinal large B-cell lymphoma (PMBCL) (relapsed or refractory): Children ≥2 years and Adolescents: IV: 2 mg/kg/dose; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 24 months.

Tumor mutational burden-high (TMB-H) (unresectable or metastatic); non-CNS solid tumors that have progressed following prior treatment without satisfactory alternative treatment options: Children ≥2 years and Adolescents: IV: 2 mg/kg/dose; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 24 months. Note: TMB-H defined as ≥10 mutations/megabase (Mut/Mb) and determined by an FDA-approved test.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: Children ≥2 years and Adolescents: In general, no dosage reductions of pembrolizumab are recommended; pembrolizumab therapy is withheld or discontinued to manage toxicities. Concomitant medications may also require treatment interruption, dosage reduction, and/or discontinuation.

Colitis (immune-mediated):

Grade 2 or 3: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.

Grade 4: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

Dermatologic toxicity (immune-mediated):

Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): Withhold pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids (based on the severity).

Grade 4 severe skin reactions or confirmed SJS or TEN: Permanently discontinue pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids (based on the severity).

Endocrinopathies (immune-mediated):

Grade 3 or 4: Withhold pembrolizumab until clinically stable.

Adrenal insufficiency (primary and secondary): Withhold pembrolizumab for grade 2 adrenal insufficiency and withhold or discontinue pembrolizumab for grade 3 or 4 adrenal insufficiency. Administer corticosteroids and hormone replacement as clinically indicated.

Hyperglycemia, severe: Also administer antihyperglycemics.

Hyperthyroidism, severe (grade 3) or life-threatening (grade 4): Manage with thionamides and beta blockers as appropriate; may resume upon recovery to grade 0 or 1 toxicity or discontinue.

Hypophysitis, grade 2 (symptomatic): Also administer corticosteroids (followed by a taper) and hormone-replacement therapy if appropriate; may resume upon recovery to grade 0 or 1 toxicity or discontinue.

Hypophysitis, grade 3 or 4: Withhold or discontinue pembrolizumab (based on severity); also administer corticosteroids (followed by a taper) and hormone-replacement therapy as clinically indicated.

Hematologic toxicity (in patients with classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma), grade 4: Withhold pembrolizumab until resolution to grade 0 or 1.

Pneumonitis (immune-mediated):

Grade 2: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.

Grade 3 or 4 or recurrent grade 2: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

Other immune-mediated toxicities:

Grade 2 or grade 3 (based on the severity and type of reaction): Withhold pembrolizumab; may require corticosteroids (based on severity). Upon improvement to grade 0 or 1, initiate corticosteroid taper and continue to taper over at least 1 month. Restart pembrolizumab if the adverse reaction remains at grade 0 or 1 following corticosteroid taper. May consider other systemic immunosuppressants if not controlled by corticosteroids (based on limited data).

Grade 3 (based on the severity and type of reaction) or grade 4: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Recurrent immune-mediated adverse reactions, grades 3 or 4: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Inability to taper corticosteroids: Permanently discontinue pembrolizumab if unable to reduce corticosteroid dose within 12 weeks after last pembrolizumab dose (ie, in adults, prednisone <10 mg/day [or equivalent]); may consider other systemic immunosuppressants if not controlled by corticosteroids (based on limited data).

Persistent grade 2 or 3 adverse reaction (excluding endocrinopathy) that does not recover to grade 0 or 1 within 12 weeks after the last pembrolizumab dose: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Infusion-related reaction: See "Administration: Pediatric."

Dosing: Adjustment for Toxicity

No dosage reductions of pembrolizumab are recommended; treatment is withheld or discontinued to manage toxicities. Concomitant medications may also require treatment interruption, dosage reduction, and/or discontinuation.

Colitis (immune mediated):

Grade 2 or 3: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.

Grade 4: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

Dermatologic toxicity (immune mediated):

Grade 3 skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): Withhold pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids (based on the severity).

Grade 4 skin reactions or confirmed SJS or TEN: Permanently discontinue pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids (based on the severity).

Endocrinopathies (immune mediated):

Grade 3 or 4: Withhold pembrolizumab until clinically stable.

Adrenal insufficiency (primary and secondary): Withhold pembrolizumab for grade 2 adrenal insufficiency and withhold or discontinue pembrolizumab for grade 3 or 4 adrenal insufficiency. Administer corticosteroids and hormone replacement as clinically indicated.

Hyperglycemia, severe: Also administer antihyperglycemics.

Hyperthyroidism, severe (grade 3) or life-threatening (grade 4): Manage with thionamides and beta blockers as appropriate; may resume upon recovery to grade 0 or 1 toxicity or discontinue.

Hypophysitis, grade 2 (symptomatic): Also administer corticosteroids (followed by a taper) and hormone-replacement therapy if appropriate; may resume upon recovery to grade 0 or 1 toxicity or discontinue.

Hypophysitis, grade 3 or 4: Withhold or discontinue pembrolizumab (based on severity); also administer corticosteroids (followed by a taper) and hormone-replacement therapy as clinically indicated.

Hematologic toxicity (in patients with classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma), grade 4: Withhold pembrolizumab until resolution to grade 0 or 1.

Pneumonitis (immune mediated):

Grade 2: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.

Grade 3 or 4 or recurrent grade 2: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

Other immune-mediated toxicities:

Grade 2 or grade 3 (based on the severity and type of reaction): Withhold pembrolizumab; may require corticosteroids (based on severity). Upon improvement to grade 0 or 1, initiate corticosteroid taper and continue to taper over at least 1 month. Restart pembrolizumab if the adverse reaction remains at grade 0 or 1 following corticosteroid taper. May consider other systemic immunosuppressants if not controlled by corticosteroids (based on limited data).

Grade 3 (based on the severity and type of reaction) or grade 4: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Recurrent immune-mediated adverse reactions, grades 3 or 4: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Inability to taper corticosteroids: Permanently discontinue pembrolizumab if unable to reduce corticosteroid dose to prednisone <10 mg/day (or equivalent) within 12 weeks after last pembrolizumab dose (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Persistent grade 2 or 3 adverse reaction (excluding endocrinopathy) that does not recover to grade 0 or 1 within 12 weeks after the last pembrolizumab dose: Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

Infusion-related reaction:

Grade 1 or 2: Interrupt infusion or slow the infusion rate.

Grade 3 or 4: Permanently discontinue pembrolizumab.

Reconstitution

Withdraw appropriate volume from vial and transfer to IV bag containing NS or D5W; final concentration should be between 1 to 10 mg/mL. Mix by gently inverting bag; do not shake. Discard unused portion of the vial.

Administration

IV: Infuse over 30 minutes through a 0.2 to 5 micron sterile, nonpyrogenic, low-protein binding inline or add-on filter. Do not infuse other medications through the same infusion line.

Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions; permanently discontinue for grade 3 or 4 infusion-related reactions.

Head and neck squamous cell carcinoma (unresectable/recurrent, metastatic) and non-small cell lung cancer (metastatic): When administered in combination with chemotherapy, administer pembrolizumab prior to chemotherapy when administered on the same day.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Protect from light. Solutions diluted for infusion in NS or D5W may be stored at room temperature for up to 6 hours (infusion must be completed within 6 hours of dilution) or refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 96 hours from the time of dilution (discard after 6 hours at room temperature or 96 hours refrigerated). Do not freeze. If refrigerated, allow to reach room temperature prior to administration. Do not shake.

Drug Interactions

Axitinib: May enhance the hepatotoxic effect of Pembrolizumab. Monitor therapy

Thalidomide Analogues: Pembrolizumab may enhance the adverse/toxic effect of Thalidomide Analogues. Specifically, mortality may be increased when this combination is used for treatment of refractory multiple myeloma. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Incidence of adverse reactions include unapproved dosing regimens.

>10%:

Cardiovascular: Peripheral edema (11% to 15%), cardiac arrhythmia (11%)

Dermatologic: Pruritus (11% to 28%), skin rash (13% to 24%), vitiligo (13%)

Endocrine & metabolic: Hyperglycemia (19% to 59%), hyponatremia (10% to 46%), hypoalbuminemia (24% to 44%), hypertriglyceridemia (33% to 43%), hypophosphatemia (19% to 29%), hypocalcemia (15% to 27%), hyperkalemia (13% to 23%), decreased serum bicarbonate (22%), hypercalcemia (14% to 22%), hypercholesterolemia (20%), hypokalemia (15% to 20%), hypoglycemia (13% to 19%), hypothyroidism (9% to 18%), hypomagnesemia (16%), weight loss (10% to 15%)

Gastrointestinal: Diarrhea (12% to 28%), decreased appetite (15% to 25%), constipation (12% to 22%), abdominal pain (13% to 22%), nausea (11% to 22%), vomiting (11% to 19%)

Genitourinary: Hematuria (12% to 19%), urinary tract infection (12% to 19%)

Hematologic & oncologic: Lymphocytopenia (24% to 54%; grades 3/4: 1% to 25%), anemia (17% to 54%; grades 3/4: 1% to 24%), leukopenia (35%; grades 3/4: 9%), neutropenia (7% to 30%; grades 3/4: 1% to 11%), thrombocytopenia (12% to 27%; grades 3/4: 4%), increased INR (19% to 21%), hemorrhage (19%; grades 3/4: 5%), prolonged partial thromboplastin time (14%)

Hepatic: Increased serum alkaline phosphatase (17% to 42%), increased serum transaminases (27% to 34%), increased serum aspartate aminotransferase (20% to 34%), increased serum alanine aminotransferase (9% to 33%), increased liver enzymes (13%)

Immunologic: Graft versus host disease (followed by allogeneic hematopoietic stem cell transplantation: 26%)

Infection: Infection (16%)

Nervous system: Fatigue (23% to 43%), pain (22%), headache (11% to 14%)

Neuromuscular & skeletal: Musculoskeletal pain (19% to 32%), arthralgia (10% to 18%), myalgia (12%), back pain (11% to 12%), asthenia (10% to 11%)

Renal: Increased serum creatinine (11% to 35%)

Respiratory: Upper respiratory tract infection (13% to 28%), cough (14% to 26%), dyspnea (10% to 23%), pneumonia (12%), flu-like symptoms (11%)

Miscellaneous: Fever (10% to 28%)

1% to 10%:

Cardiovascular: Facial edema (10%), pericarditis (4%), pericardial effusion (2%)

Endocrine & metabolic: Hyperthyroidism (3% to 10%), thyroiditis (≤2%)

Gastrointestinal: Dysphagia (8%), stomatitis (3% to 4%; grades 3/4: 1%), colitis (2%)

Hepatic: Hyperbilirubinemia (10%), hepatic sinusoidal obstruction syndrome (followed by allogeneic hematopoietic stem cell transplantation: 9%), ascites (grades 3/4: 8%), hepatitis (≤3%)

Immunologic: Antibody development (2%; neutralizing: <1%)

Nervous system: Peripheral neuropathy (2% to 10%), insomnia (7%), dizziness (5%), peripheral sensory neuropathy (1%)

Neuromuscular & skeletal: Neck pain (6%), arthritis (2%), myositis (≤1%)

Ophthalmic: Uveitis (≤1%)

Renal: Acute renal failure (2%)

Respiratory: Nasopharyngitis (10%), pneumonitis (2% to 8%)

Miscellaneous: Infusion related reaction (≤9%)

Frequency not defined:

Cardiovascular: Acute myocardial infarction, cardiac failure, cardiac tamponade, edema, pulmonary embolism, septic shock

Dermatologic: Cellulitis, dermatitis, erythematous rash, follicular rash, maculopapular rash

Genitourinary: Uterine hemorrhage

Hematologic & oncologic: Rectal hemorrhage

Infection: Candidiasis, Clostridioides difficile associated diarrhea, herpes zoster infection, sepsis

Nervous system: Confusion, polyneuropathy

Neuromuscular & skeletal: Osteomyelitis

Respiratory: Epistaxis, hemoptysis, pleural effusion, respiratory failure

Miscellaneous: Fistula, physical health deterioration

<1%, postmarketing, and/or case reports: Adrenocortical insufficiency, anaphylaxis, chronic inflammatory demyelinating polyneuropathy (Maleissye 2016), diabetic ketoacidosis, encephalitis, Guillain-Barré syndrome, hemolytic anemia, hypersensitivity reaction, hypophysitis, myasthenia gravis, myelitis, myocarditis, nephritis, organ transplant rejection (solid), pancreatitis, sarcoidosis, subacute cutaneous lupus erythematosus (Blakeway 2019), type 1 diabetes mellitus, vasculitis

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal insufficiency: Primary and secondary adrenal insufficiency have occurred, including cases of grade 2 to 4 adrenal insufficiency. The median time to onset of adrenal insufficiency was 5.3 months (range: 26 days to over 16 months) and the median duration was not reached (range: 4 days to close to 2 years). Over 75% of cases were managed with systemic corticosteroids, with a median duration of 4 days (range 1 to 6 days), followed by a taper. Nearly one quarter of patients with adrenal insufficiency experienced resolution. Monitor for signs/symptoms of adrenal insufficiency. May require treatment interruption, systemic corticosteroids and hormone replacement therapy (as clinically indicated), and/or permanent discontinuation.

• Dermatologic toxicity: Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN, some fatal), exfoliative dermatitis, and bullous pemphigoid may occur with pembrolizumab. Monitor for suspected severe skin reactions and exclude other causes. Based on the severity of the dermatologic toxicity, withhold or permanently discontinue pembrolizumab and administer corticosteroids. Withhold pembrolizumab for signs/symptoms of SJS or TEN and refer for specialized care for assessment and management. Permanently discontinue pembrolizumab if SJS or TEN is confirmed.

• Diabetes mellitus: Type 1 diabetes mellitus has occurred (including diabetic ketoacidosis). Monitor closely for hyperglycemia and other signs/symptoms of diabetes. Insulin therapy may be required; if severe hyperglycemia is observed, administer antihyperglycemics and withhold pembrolizumab treatment until glucose control has been accomplished.

• Gastrointestinal toxicity: Immune-mediated colitis has occurred, including cases of grade 2 to 4 colitis. The median time to onset of colitis was 3.5 months (range: 10 days to 16.2 months) and the median duration was 1.3 months (range: 1 day to over 8 months). In many patients, colitis was managed with high-dose systemic corticosteroids for a median duration of 7 days (range: 1 day to 5.3 months), followed by a corticosteroid taper. Most patients with colitis experienced resolution. May require treatment interruption, systemic corticosteroid therapy, and/or permanent discontinuation. Monitor for signs and symptoms of colitis; administer systemic corticosteroids for ≥ grade 2 colitis.

• Hepatotoxicity: Immune-mediated hepatitis occurred (grades 2 to 4 hepatitis). The median onset for hepatitis was 1.3 months (range: 8 days to 21.4 months); the median duration was 1.8 months (range: 8 days to over 20 months). Hepatitis resolved in most patients. Administer corticosteroids (prednisone 0.5 to 1 mg/kg/day [or equivalent] for grade 2 hepatitis, and prednisone 1 to 2 mg/kg/day [or equivalent] for ≥ grade 3, each followed by a taper), and withhold or discontinue therapy based on the severity of liver enzyme elevations. Systemic corticosteroids were used to manage immune-mediated hepatitis in many patients; the median duration of high-dose corticosteroid therapy was 5 days (range: 1 to 26 days), followed by a taper. Monitor for liver function changes. May require treatment interruption, systemic corticosteroids (for grade 2 or higher toxicity), and/or permanent discontinuation. Pembrolizumab/axitinib combination therapy may result in higher frequencies of grades 3 and 4 ALT and AST elevations (compared to single-agent therapy). The median time to onset of ALT elevation was 2.3 months (range: 7 days to ~20 months) for pembrolizumab/axitinib combination therapy, and over half of patients with ALT elevation required systemic corticosteroids; resolution of grades 2 to 4 ALT elevation occurred in most patients. When rechallenged with either pembrolizumab, axitinib, or both, over half of patients did not experience recurrence of ALT elevation to >3 times ULN. Monitor liver enzymes at baseline and then periodically during treatment; consider more frequent liver enzyme monitoring than for pembrolizumab (or axitinib) monotherapy. If liver enzymes are elevated, withhold pembrolizumab and axitinib, and consider corticosteroids as needed.

• Hypersensitivity: Hypersensitivity and anaphylaxis have been observed (rare).

• Hypophysitis: Immune-mediated hypophysitis occurred (grades 2, 3, and 4). The median time to onset was 3.7 months (range: 1 day to 12 months) and the median duration was 4.7 months (range: 8 days to over 12 months). Most cases were managed with systemic corticosteroids. Nearly half of patients with hypophysitis experienced resolution. Monitor for signs/symptoms of hypophysitis, including hypopituitarism. May require treatment interruption, systemic corticosteroids and hormone replacement therapy (as clinically indicated), and/or permanent discontinuation.

• Infusion-related reactions: Infusion-related reactions (including severe and life-threatening cases) have occurred. Monitor for signs/symptoms of a reaction (eg, rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever). Interrupt infusion and permanently discontinue for severe (grade 3) or life-threatening (grade 4) infusion-related reactions.

• Nephrotoxicity: Immune-mediated nephritis has occurred. The onset for autoimmune nephritis was 3.2 to 5.1 months (range: 12 days to 12.8 months) and the median duration was 3.3 months (range: 12 days to over 16 months). Grade 2 or higher nephritis should be managed with systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg/day [or equivalent], followed by a taper). Most patients required systemic corticosteroids. The median duration of corticosteroid use was 3 to 15 days (range: 1 day to 4 months), followed by a taper. Nephritis resolved in approximately one-third to one-half of affected patients. Monitor for renal function changes. May require treatment interruption, systemic corticosteroids (for ≥ grade 2 toxicity), and/or permanent discontinuation.

• Pulmonary toxicity: Immune-mediated pneumonitis has been observed, including grade 3, grade 4, and fatal cases. In patients with non-small cell lung cancer (NSCLC), a higher incidence of pneumonitis was reported in patients who had received prior thoracic radiation. The median time to development was 3.3 months (range: 2 days to ~19 months) and the median duration was 1.5 months (range: 1 day to over 17 months). Many patients required initial management with high-dose systemic corticosteroids; the median duration of initial corticosteroid therapy was 5 to 16 days (range: 1 day to ~10 months) followed by a corticosteroid taper. Pneumonitis resolved in over half of the affected patients. May require treatment interruption, corticosteroid therapy (prednisone 1 to 2 mg/kg /day [or equivalent] followed by a taper, for ≥ grade 2 pneumonitis), and/or permanent discontinuation. Monitor for signs and symptoms of pneumonitis; if pneumonitis is suspected, evaluate with radiographic imaging and administer systemic corticosteroids for ≥ grade 2 pneumonitis. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation.

• Thyroid disorders: Immune-mediated hyperthyroidism, hypothyroidism, and thyroiditis have occurred. The median onset for hyperthyroidism was 1.4 months (range: 1 day to ~22 months) and the median duration was 2.1 months (range: 3 days to over 15 months). Hyperthyroidism resolved in nearly three-fourths of affected patients. Hypothyroidism occurred with a median onset of 3.5 months (range: 1 day to 19 months) and median duration was not reached (range: 2 days to over 27 months). Hypothyroidism resolved in one-fifth of affected patients. The incidence of new or worsening hypothyroidism was higher in patients with squamous cell cancer of the head and neck (as a single agent or in combination with chemotherapy). Monitor for changes in thyroid function (at baseline, periodically during treatment, and as clinically indicated) and for signs/symptoms of thyroid disorders. Administer thionamides and beta-blockers for hyperthyroidism as appropriate; may require treatment interruption and/or permanent discontinuation. Isolated hypothyroidism may be managed with replacement therapy. Thyroiditis occurred with a median onset of 1.2 months (range 0.5 to 3.5 months).

• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed (may involve any organ system or tissue, and may be severe or fatal), including rash, exfoliative dermatitis, bullous pemphigoid, uveitis, arthritis, vasculitis, myositis, Guillain-Barré syndrome, pancreatitis, hemolytic anemia, sarcoidosis, serum sickness, myasthenia gravis, myelitis, myocarditis, and encephalitis. While immune-mediated toxicity generally occurs during treatment with pembrolizumab, adverse reactions may also develop after therapy discontinuation. If an immune-mediated adverse event is suspected, evaluate appropriately to confirm or exclude other causes; withhold treatment and administer systemic corticosteroids based on severity of reaction. Upon resolution to grade 0 or 1, initiate corticosteroid taper (continue tapering over at least 1 month). When reaction remains at ≤ grade 1 during taper may reinitiate pembrolizumab. Immune-mediated adverse reactions that do not resolve with systemic corticosteroids may be managed with other systemic immunosuppressants (based on limited data). Discontinue permanently for severe or grade 3 immune-mediated adverse event that is recurrent or life-threatening.

Disease-related concerns:

• Autoimmune disorders: Anti-PD-1 monoclonal antibodies generate an immune response that may aggravate underlying autoimmune disorders or prior immune-related adverse events. A retrospective study analyzed the safety and efficacy of treatment with anti-PD-1 monoclonal antibodies (eg, pembrolizumab, nivolumab) in melanoma patients with preexisting autoimmune disease or prior significant ipilimumab-mediated adverse immune events. Results showed that while immune toxicities associated with this class of therapy did occur, most reactions were mild and easily manageable and did not require permanent drug therapy discontinuation. A significant percentage of patients achieved clinical response with anti-PD-1 monoclonal antibody therapy, despite baseline autoimmunity or prior ipilimumab-related adverse events (Menzies 2017).

• Hematopoietic stem cell transplant: Patients who received allogeneic hematopoietic stem cell transplant (HSCT) after being treated with pembrolizumab experienced immune-mediated complications (some fatal) including graft versus host disease (GVHD) and severe sinusoidal obstructive syndrome (SOS; formerly called veno-occlusive disease) following reduced-intensity conditioning. Fatal hyperacute GVHD post HSCT has also been reported in lymphoma patients who received an anti PD-1 antibody prior to transplant. These complications may occur despite intervening therapy between pembrolizumab and HSCT. Monitor closely for early signs/symptoms of transplant-related complications (eg, hyperacute GVHD, severe [grade 3 to 4] acute GVHD, steroid-requiring febrile syndrome, SOS, and other immune-mediated adverse reactions) and manage promptly. In patients who received allogeneic HSCT prior to receiving pembrolizumab, acute GVHD (including fatal GVHD) has been reported after pembrolizumab treatment. Patients who experienced GVHD following transplant may be at increased risk for GVHD following pembrolizumab; assess the GVHD risks versus pembrolizumab treatment benefits in patients with a history of allogeneic HSCT.

• Multiple myeloma: An increase in mortality was noted in 2 clinical studies in patients with multiple myeloma who received pembrolizumab in combination with a thalidomide analogue and dexamethasone. Causes of death in the experimental arm (containing pembrolizumab, dexamethasone, and a thalidomide analogue [pomalidomide or lenalidomide]) included myocarditis, Stevens-Johnson syndrome, MI, pericardial hemorrhage, cardiac failure, respiratory tract infection, neutropenic sepsis, sepsis, multiple organ dysfunction, respiratory failure, intestinal ischemia, cardiopulmonary arrest, suicide, pulmonary embolism, cardiac arrest, pneumonia, sudden death, and large intestine perforation. Multiple myeloma is not an approved indication for PD-1 or PD-L1 blocking antibodies; pembrolizumab should not be used to treat multiple myeloma in combination with a thalidomide analogue and dexamethasone unless as part of a clinical trial.

• Solid organ transplant: Solid organ transplant rejection has been reported in postmarketing surveillance. Pembrolizumab may increase the risk of rejection; consider benefit versus risk of pembrolizumab treatment in solid organ transplant patients.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Select patients for recurrent or metastatic cervical cancer, metastatic esophageal cancer, metastatic gastric cancer, metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC; first-line single agent treatment), metastatic or stage III (unresectable) non-small cell lung cancer (NSCLC; single-agent treatment), or cisplatin-ineligible locally advanced or metastatic urothelial cancer based on PD-L1 expression. If PD-L1 expression is not detected in a gastric cancer archived specimen, evaluate feasibility of obtaining a tumor biopsy to test for PD-L1 expression. Select patients for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) cancers (including colorectal cancer), or tumor mutational burden-high (TMB-H) cancer based on MSI-H/dMMR or TMB-H status, respectively, in tumor specimens. The effect of prior chemotherapy on test results for TMB-H, MSI-H, or dMMR in patients with high-grade gliomas is unclear; it is recommended to test for these markers in the primary tumor specimens obtained prior to temozolomide initiation (in patients with high-grade gliomas). Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.

Monitoring Parameters

PD-L1 expression status in patients with cervical cancer, esophageal cancer, gastric cancer, first-line (single agent) treatment of head and neck squamous cell carcinoma, metastatic or stage III (unresectable) non-small cell lung cancer (when used as single-agent therapy), or cisplatin-ineligible urothelial cancer; microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) status in MSI-H/dMMR cancers (including colorectal cancer); tumor mutational burden-high (TMB-H) status in TMB-H cancer; LFTs (AST, ALT, and total bilirubin; in patients receiving pembrolizumab/axitinib, monitor liver enzymes at baseline and periodically during treatment; consider monitoring more frequently); renal function; thyroid function (at baseline, periodically during treatment and as clinically indicated); glucose; CBC with differential (in patients with Hodgkin lymphoma or primary mediastinal large B-cell lymphoma); pregnancy test (prior to initiation of pembrolizumab treatment in females of reproductive potential); signs/symptoms of adrenal insufficiency, colitis, dermatologic toxicity, hypophysitis, thyroid disorders, pneumonitis, infusion reactions.

Reproductive Considerations

Verify pregnancy status prior to initiation of pembrolizumab treatment in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for at least 4 months after treatment is complete.

Pregnancy Considerations

Pembrolizumab is a humanized monoclonal antibody (IgG4). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action, pembrolizumab may cause fetal harm if administered during pregnancy; an alteration in the immune response or immune mediated disorders may develop following in utero exposure.

Patient Education

What is this drug used for?

• It is used to treat cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Back, bone, joint, or muscle pain

• Constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry

• Flu-like signs

• Headache

• Weight loss

• Hair loss

• Change in taste

• Trouble sleeping

• Signs of a common cold

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Kidney problems like not able to pass urine; change in how much urine is passed; bloody, brown, or foamy urine; shortness of breath or cough; or puffy or swollen face, feet, or hands

• Urinary tract infection like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain

• Thyroid, pituitary, or adrenal gland problems like change in mood or the way you act, change in weight, constipation, deeper voice, dizziness, fainting, feeling cold, feeling very tired, hair loss, headache that lasts or is very bad, or lowered interest in sex

• Bowel problems like black, tarry, or bloody stools; fever; mucus in the stools; throwing up blood or throw up that looks like coffee grounds; or very bad stomach pain, constipation, or diarrhea

• Brain problem like change in balance, feeling confused, fever, memory problems, muscle weakness, seizures, stiff neck, or very upset stomach or throwing up

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Infusion reaction

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up

• Lung or breathing problems like shortness of breath or other trouble breathing, cough, or fever

• Spinal cord problem (myelitis) like pain, numbness, tingling, or weakness in the arms or legs; bladder problems like passing urine more often, leaking of urine, or trouble passing urine; or bowel problems like severe constipation

• Chest pain or pressure

• Fast or abnormal heartbeat

• Change in eyesight, eye pain, or very bad eye irritation

• Swollen gland

• Dizziness or passing out

• Fever, chills, or sore throat; any unexplained bruising or bleeding; or feeling very tired or weak

• Flushing

• Sweating a lot

• Burning, numbness, or tingling feeling that is not normal

• Not able to move

• White patches on skin

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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

Frequently Asked Questions