Keytruda

Pembrolizumab · Injection, Solution · Intravenous

Prescription (Rx) Programmed Death Receptor-1 Blocking Antibody

Uses

1 INDICATIONS AND USAGE KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated: Melanoma for the treatment of patients with unresectable or metastatic melanoma. ( 1.1 ) for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection. ( 1.1 ) Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations. ( 1.2 ) in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of patients with metastatic squamous NSCLC. ( 1.2 ) as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations, and is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic. ( 1.2 , 2.1 ) as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-authorized test, with 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 KEYTRUDA. ( 1.2 , 2.1 ) for the treatment of patients with 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. ( 1.2 ) as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. ( 1.2 ) Malignant Pleural Mesothelioma (MPM) in combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with unresectable advanced or metastatic MPM. ( 1.3 ) Head and Neck Squamous Cell Cancer (HNSCC) for the treatment of adult patients with resectable locally advanced HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent. ( 1.4 ) in combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC. ( 1.4 ) as a single agent for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test. ( 1.4 , 2.1 ) as a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. ( 1.4 ) Classical Hodgkin Lymphoma (cHL) for the treatment of adult patients with relapsed or refractory cHL. ( 1.5 ) for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy. ( 1.5 ) Primary Mediastinal Large B-Cell Lymphoma (PMBCL) for the treatment of adult and pediatric patients with refractory PMBCL, or who have relapsed after 2 or more prior lines of therapy. ( 1.6 ) Limitations of Use : KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy. Urothelial Cancer in combination with enfortumab vedotin-ejfv, for the treatment of adult patients with locally advanced or metastatic urothelial cancer. ( 1.7 ) as a single agent for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. ( 1.7 ) in combination with enfortumab vedotin-ejfv, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment of adult patients with muscle invasive bladder cancer (MIBC). ( 1.7 ) as a single agent for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. ( 1.7 ) Microsatellite Instability-High or Mismatch Repair Deficient Cancer for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. ( 1.8 , 2.1 ) Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC) for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-authorized test. ( 1.9 , 2.1 ) Gastric Cancer in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test. ( 1.10 ) in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test.

Dosage and administration

Melanoma: 200 mg every 3 weeks or 400 mg every 6 weeks; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. ( 2.2 ) NSCLC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) MPM: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) HNSCC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) cHL or PMBCL: 200 mg every 3 weeks or 400 mg every 6 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. ( 2.2 ) Urothelial Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) MSI-H or dMMR Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. ( 2.2 ) MSI-H or dMMR CRC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) Gastric Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) Esophageal Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) Cervical Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) HCC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) BTC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) MCC: 200 mg every 3 weeks or 400 mg every 6 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. ( 2.2 ) RCC: 200 mg every 3 weeks or 400 mg every 6 weeks as a single agent in the adjuvant setting, or in the advanced setting with either: axitinib 5 mg orally twice daily or lenvatinib 20 mg orally once daily. ( 2.2 ) ccRCC: 200 mg every 3 weeks or 400 mg every 6 weeks in combination with belzutifan 120 mg orally once daily in the adjuvant setting. ( 2.2 ) Endometrial Carcinoma: 200 mg every 3 weeks or 400 mg every 6 weeks in combination with carboplatin and paclitaxel regardless of MMR or MSI status, or in combination with lenvatinib 20 mg orally once daily for pMMR or not MSI-H tumors, or as a single agent for MSI-H or dMMR tumors. ( 2.2 ) TMB-H Cancer: 200 mg every 3 weeks or 400 mg every 6 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. ( 2.2 ) cSCC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) TNBC: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) Ovarian cancer: 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.2 ) Administer KEYTRUDA as an intravenous infusion over 30 minutes after dilution. ( 2.4 ) See Full Prescribing Information for dosage modifications for adverse reactions and preparation and administration instructions. ( 2.3 , 2.4 ) 2.1 Patient Selection Information on FDA-authorized tests for patient selection is available at: http://www.fda.gov/CompanionDiagnostics . Patient Selection for Single-Agent Treatment Select patients for treatment with KEYTRUDA as a single agent based on the presence of positive PD-L1 expression in: Stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation [see Clinical Studies (14.2) ] . metastatic NSCLC [see Clinical Studies (14.2) ]. first-line treatment of metastatic or unresectable, recurrent HNSCC [see Clinical Studies (14.4) ] . previously treated recurrent locally advanced or metastatic esophageal cancer [see Clinical Studies (14.11) ] . recurrent or metastatic cervical cancer with disease progression on or after chemotherapy [see Clinical Studies (14.12) ] . For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA as a single agent based on MSI-H/dMMR status in tumor specimens [see Clinical Studies (14.8 , 14.9) ]. For the TMB-H indication, select patients for treatment with KEYTRUDA as a single agent based on TMB-H status in tumor specimens [see Clinical Studies (14.18) ]. Because subclonal dMMR mutations and microsatellite instability may arise in high-grade gliomas during temozolomide therapy, it is recommended to test for TMB-H, MSI-H, and dMMR in the primary tumor specimens obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas. Additional Patient Selection Information for MSI-H or dMMR in Patients with non-CRC Solid Tumors Due to discordance between local tests and FDA-authorized tests, confirmation of MSI-H or dMMR status is recommended by an FDA-authorized test in patients with MSI-H or dMMR solid tumors, if feasible. If unable to perform confirmatory MSI-H/dMMR testing, the presence of TMB ≥10 mut/Mb, as determined by an FDA-authorized test, may be used to select patients for treatment [see Clinical Studies (14.8) ] . Patient Selection for Combination Therapy For use of KEYTRUDA as a single agent as neoadjuvant treatment, then in combination with radiotherapy (RT) with or without chemotherapy then continued as a single agent as adjuvant treatment, select patients based on presence of positive PD-L1 expression (CPS ≥1) in resectable locally advanced HNSCC [see Clinical Studies (14.4) ]. For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression (CPS ≥1) in locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, and esophageal or gastroesophageal junction (GEJ) carcinoma [see Clinical Studies (14.10) , (14.11) ]. For use of KEYTRUDA in combination with chemotherapy, with or without bevacizumab, select patients based on the presence of positive PD-L1 expression in persistent, recurrent, or metastatic cervical cancer [see Clinical Studies (14.12) ]. For the pMMR/not MSI-H advanced endometrial carcinoma indication, select patients for treatment with KEYTRUDA in combination with lenvatinib based on MMR or MSI status in tumor specimens [see Clinical Studies (14.17) ] . For use of KEYTRUDA in combination with sacituzumab govitecan-hziy, select patients based on the presence of positive PD-L1 expression in unresectable locally advanced or metastatic TNBC [see Clinical Studies (14.20) ] . For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC [see Clinical Studies (14.20) ] .

Dosage forms and strengths

Injection: 100 mg/4 mL (25 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial Injection: 100 mg/4 mL (25 mg/mL) solution in a single-dose vial ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Immune-Mediated Adverse Reactions ( 5.1 ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue based on severity and type of reaction. Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue KEYTRUDA based on the severity of reaction. ( 5.2 ) Complications of allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. ( 5.3 ) Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. ( 5.4 ) Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective method of contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated adverse reactions. 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. 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. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. 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. Withhold or permanently discontinue KEYTRUDA depending on severity [see Dosage and Administration (2.3) ] . In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis KEYTRUDA can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) adverse reactions. Systemic corticosteroids were required in 67% (63/94) of patients with pneumonitis. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) of patients and withholding of KEYTRUDA in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence of pneumonitis. Pneumonitis resolved in 59% of the 94 patients. In clinical studies enrolling 389 adult patients with cHL who received KEYTRUDA as a single agent, pneumonitis occurred in 31 (8%) patients, including Grades 3-4 pneumonitis in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 21 (5.4%) patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution. In a clinical study enrolling 580 adult patients with resected NSCLC (KEYNOTE-091) who received KEYTRUDA as a single agent for adjuvant treatment, pneumonitis occurred in 41 (7%) patients, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution. Immune-Mediated Colitis KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling. Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1) ] . Infusion-related reactions [see Warnings and Precautions (5.2) ]. Most common adverse reactions (reported in ≥20% of patients) were: KEYTRUDA as a single agent: fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. ( 6.1 ) KEYTRUDA in combination with chemotherapy or chemoradiotherapy: fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, hypothyroidism, radiation skin injury, dysphagia, dry mouth, and musculoskeletal pain. ( 6.1 ) KEYTRUDA in combination with chemotherapy and bevacizumab: peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, decreased appetite, pyrexia, epistaxis, decreased white blood cell count, and stomatitis. ( 6.1 ) KEYTRUDA in combination with axitinib: diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation. ( 6.1 ) KEYTRUDA in combination with lenvatinib: hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, rash, hepatotoxicity, and acute kidney injury. ( 6.1 ) KEYTRUDA in combination with belzutifan (reported in ≥25% of patients): decreased hemoglobin, increased alanine aminotransferase, fatigue, increased aspartate aminotransferase, decreased lymphocytes, and increased alkaline phosphatase. ( 6.1 ) KEYTRUDA in combination with enfortumab vedotin-ejfv: rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, weight loss, decreased appetite, dry eye, nausea, constipation, dysgeusia, and urinary tract infection. ( 6.1 ) KEYTRUDA in combination with sacituzumab govitecan-hziy: anemia, neutropenia, diarrhea, nausea, fatigue, alopecia, constipation, rash, vomiting, headache and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in the WARNINGS AND PRECAUTIONS reflect exposure to KEYTRUDA as a single agent in 2799 patients in three randomized, open-label, active-controlled trials (KEYNOTE-002, KEYNOTE-006, and KEYNOTE-010), which enrolled 912 patients with melanoma and 682 patients with NSCLC, and one single-arm trial (KEYNOTE-001), which enrolled 655 patients with melanoma and 550 patients with NSCLC. In addition to the 2799 patients, certain subsections in the WARNINGS AND PRECAUTIONS describe adverse reactions observed with exposure to KEYTRUDA as a single agent in a randomized, placebo-controlled trial (KEYNOTE-091), which enrolled 580 patients with resected NSCLC, a non-randomized, open-label, multi-cohort trial (KEYNOTE-012), a non-randomized, open-label, single-cohort trial (KEYNOTE-055), and two randomized, open-label, active-controlled trials (KEYNOTE-040 and KEYNOTE-048 single agent arms), which enrolled 909 patients with HNSCC; in two non-randomized, open-label trials (KEYNOTE-013 and KEYNOTE-087) and one randomized, open-label, active-controlled trial (KEYNOTE-204), which enrolled 389 patients with cHL; in a randomized, open-label, active-controlled trial (KEYNOTE-048 combination arm), which enrolled 276 patients with HNSCC; in combination with axitinib in a randomized, active-controlled trial (KEYNOTE-426), which enrolled 429 patients with RCC; and in post-marketing use. Across all trials, KEYTRUDA was administered at doses of 2 mg/kg intravenously every 3 weeks, 10 mg/kg intravenously every 2 weeks, 10 mg/kg intravenously every 3 weeks, or 200 mg intravenously every 3 weeks. Among the 2799 patients, 41% were exposed for 6 months or more and 21% were exposed for 12 months or more. Melanoma Ipilimumab-Naive Melanoma The safety of KEYTRUDA for the treatment of patients with unresectable or metastatic melanoma who had not received prior ipilimumab and who had received no more than one prior systemic therapy was investigated in KEYNOTE-006. KEYNOTE-006 was a multicenter, open-label, active-controlled trial where patients were randomized (1:1:1) and received KEYTRUDA 10 mg/kg every 2 weeks (n=278) or KEYTRUDA 10 mg/kg every 3 weeks (n=277) until disease progression or unacceptable toxicity or ipilimumab 3 mg/kg every 3 weeks for 4 doses unless discontinued earlier for disease progression or unacceptable toxicity (n=256) [see Clinical Studies (14.1) ] . Patients with autoimmune disease, a medical condition that required systemic corticosteroids or other immunosuppressive medication; a history of interstitial lung disease; or active infection requiring therapy, including HIV or hepatitis B or C, were ineligible. The median duration of exposure was 5.6 months (range: 1 day to 11.0 months) for KEYTRUDA and similar in both treatment arms. Fifty-one and 46% of patients received KEYTRUDA 10 mg/kg every 2 or 3 weeks, respectively, for ≥6 months.

Use in specific populations

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. There are no available human data informing the risk of embryo-fetal toxicity. 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 (see Data ) . Human IgG4 (immunoglobulins) are known to cross the placenta; therefore, pembrolizumab has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with KEYTRUDA to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects of the PD-1 pathway on reproduction demonstrated that a central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering KEYTRUDA during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 knockout mice. Based on its mechanism of action, fetal exposure to pembrolizumab may increase the risk of developing immune-mediated disorders or of altering the normal immune response. 8.2 Lactation Risk Summary There are no data on the presence of pembrolizumab in either animal or human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to KEYTRUDA are unknown. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with KEYTRUDA and for 4 months after the last dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating KEYTRUDA [see Use in Specific Populations (8.1) ]. Contraception KEYTRUDA can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with KEYTRUDA and for 4 months after the last dose. 8.4 Pediatric Use The safety and effectiveness of KEYTRUDA as a single agent have been established in pediatric patients with melanoma, cHL, PMBCL, MCC, MSI-H or dMMR cancer, and TMB-H cancer. Use of KEYTRUDA in pediatric patients for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.1 , 14.5 , 14.6 , 14.8 , 14.15 , 14.18) ] . In KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to younger than 12 years and 108 pediatric patients aged 12 to 17 years) with advanced melanoma, lymphoma, or PD-L1 positive or MSI-H solid tumors received KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months). Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults included pyrexia (33%), vomiting (29%), headache (25%), abdominal pain (23%), decreased lymphocyte count (13%), and decreased white blood cell count (11%). Laboratory abnormalities that occurred at a ≥10% higher rate in pediatric patients when compared to adults were leukopenia (30%), neutropenia (28%), thrombocytopenia (22%), and Grade 3 anemia (17%). The safety and effectiveness of KEYTRUDA in pediatric patients have not been established in the other approved indications [see Indications and Usage (1) ] . 8.5 Geriatric Use Of 3781 patients with melanoma, NSCLC, HNSCC, or urothelial carcinoma who were treated with KEYTRUDA in clinical studies, 48% were 65 years and over and 17% were 75 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 389 adult patients with cHL who were treated with KEYTRUDA in clinical studies, 46 (12%) were 65 years and over. Patients aged 65 years and over had a higher incidence of serious adverse reactions (50%) than patients aged younger than 65 years (24%). Clinical studies of KEYTRUDA in cHL did not include sufficient numbers of patients aged 65 years and over to determine whether effectiveness differs from that in younger patients. Of 506 adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC following complete resection and platinum-based chemotherapy who were treated with KEYTRUDA in KEYNOTE-091, 242 (48%) were 65 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 596 adult patients with TNBC who were treated with KEYTRUDA in combination with paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin in KEYNOTE-355, 137 (23%) were 65 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 221 adult patients with TNBC who were treated with KEYTRUDA in combination with sacituzumab govitecan-hziy in KEYNOTE-D19, 26% of patients were 65 years and over and 5% were 75 years and older.

Pregnancy

8.1 Pregnancy Risk Summary Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. There are no available human data informing the risk of embryo-fetal toxicity. 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 (see Data ) . Human IgG4 (immunoglobulins) are known to cross the placenta; therefore, pembrolizumab has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with KEYTRUDA to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects of the PD-1 pathway on reproduction demonstrated that a central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering KEYTRUDA during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 knockout mice. Based on its mechanism of action, fetal exposure to pembrolizumab may increase the risk of developing immune-mediated disorders or of altering the normal immune response.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of KEYTRUDA as a single agent have been established in pediatric patients with melanoma, cHL, PMBCL, MCC, MSI-H or dMMR cancer, and TMB-H cancer. Use of KEYTRUDA in pediatric patients for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.1 , 14.5 , 14.6 , 14.8 , 14.15 , 14.18) ] . In KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to younger than 12 years and 108 pediatric patients aged 12 to 17 years) with advanced melanoma, lymphoma, or PD-L1 positive or MSI-H solid tumors received KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months). Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults included pyrexia (33%), vomiting (29%), headache (25%), abdominal pain (23%), decreased lymphocyte count (13%), and decreased white blood cell count (11%). Laboratory abnormalities that occurred at a ≥10% higher rate in pediatric patients when compared to adults were leukopenia (30%), neutropenia (28%), thrombocytopenia (22%), and Grade 3 anemia (17%). The safety and effectiveness of KEYTRUDA in pediatric patients have not been established in the other approved indications [see Indications and Usage (1) ] .

Geriatric use

8.5 Geriatric Use Of 3781 patients with melanoma, NSCLC, HNSCC, or urothelial carcinoma who were treated with KEYTRUDA in clinical studies, 48% were 65 years and over and 17% were 75 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 389 adult patients with cHL who were treated with KEYTRUDA in clinical studies, 46 (12%) were 65 years and over. Patients aged 65 years and over had a higher incidence of serious adverse reactions (50%) than patients aged younger than 65 years (24%). Clinical studies of KEYTRUDA in cHL did not include sufficient numbers of patients aged 65 years and over to determine whether effectiveness differs from that in younger patients. Of 506 adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC following complete resection and platinum-based chemotherapy who were treated with KEYTRUDA in KEYNOTE-091, 242 (48%) were 65 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 596 adult patients with TNBC who were treated with KEYTRUDA in combination with paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin in KEYNOTE-355, 137 (23%) were 65 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of 221 adult patients with TNBC who were treated with KEYTRUDA in combination with sacituzumab govitecan-hziy in KEYNOTE-D19, 26% of patients were 65 years and over and 5% were 75 years and older. No overall differences in effectiveness were observed between elderly patients and younger patients. There was a higher rate of serious adverse reactions in patients aged 65 years or older (48%) compared with younger adult patients (34%). Of 406 adult patients with endometrial carcinoma who were treated with KEYTRUDA in combination with lenvatinib in KEYNOTE-775, 201 (50%) were 65 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Of the 564 patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin-ejfv, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients. Patients 75 years of age or older treated with KEYTRUDA in combination with enfortumab vedotin-ejfv experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older. Of the 570 patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin-ejfv, 45% (n=259) were 65-74 years and 22% (n=125) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients. Patients 75 years of age or older treated with KEYTRUDA in combination with enfortumab vedotin-ejfv experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 3.6% in patients younger than 75 and 11% in patients 75 years or older. Of the 432 patients randomized to KEYTRUDA in combination with axitinib in the KEYNOTE-426 trial, 40% were 65 years or older. No overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. Of 294 adult patients with FIGO 2014 Stage III-IVA cervical cancer who were treated with KEYTRUDA in combination with CRT in KEYNOTE-A18, 42 (14%) were 65 years and over. No overall difference in safety was observed between patients ≥65 years of age and younger patients. Of 643 adult patients with ovarian cancer who were treated with KEYTRUDA in combination with paclitaxel with or without bevacizumab in KEYNOTE-B96, 236 (37%) were 65 years and over and 58 (9%) were 75 years and over. No overall differences in safety or effectiveness were observed between patients ≥65 years of age and younger patients.

Description

Pembrolizumab is a programmed death receptor-1 (PD 1)-blocking antibody. Pembrolizumab is a humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in recombinant Chinese hamster ovary (CHO) cells. KEYTRUDA (pembrolizumab) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for intravenous use. Each vial contains 100 mg of pembrolizumab in 4 mL of solution. Each 1 mL of solution contains 25 mg of pembrolizumab and is formulated in: L-histidine (1.55 mg), polysorbate 80 (0.2 mg), sucrose (70 mg), and Water for Injection, USP.

Mechanism of action

12.1 Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. In syngeneic mouse tumor models, combination treatment of a PD-1 blocking antibody and kinase inhibitor lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and reduced tumor growth compared to either treatment alone.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING KEYTRUDA injection (clear to slightly opalescent, colorless to slightly yellow solution): Carton containing one 100 mg/4 mL (25 mg/mL), single-dose vial (NDC 0006-3026-02) Carton containing two 100 mg/4 mL (25 mg/mL), single-dose vials (NDC 0006-3026-04) Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

Storage

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune-Mediated Adverse Reactions Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of KEYTRUDA. These reactions may include: Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1) ] . Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1) ] . Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding [see Warnings and Precautions (5.1) ] . Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, or Type 1 diabetes mellitus [see Warnings and Precautions (5.1) ] . Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis [see Warnings and Precautions (5.1) ] . Severe skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS or TEN [see Warnings and Precautions (5.1) ] . Other immune-mediated adverse reactions: Advise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new or worsening signs or symptoms [see Warnings and Precautions (5.1) ] . Advise patients of the risk of solid organ transplant rejection and other transplant (including corneal graft) rejection. Advise patients to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection and other transplant (including corneal graft) rejection [see Warnings and Precautions (5.1) ] . Infusion-Related Reactions Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2) ] . Complications of Allogeneic HSCT Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3) ]. Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1 , 8.3) ]. Advise females of reproductive potential to use effective contraception during treatment with KEYTRUDA and for 4 months after the last dose [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1 , 8.3) ] . Lactation Advise women not to breastfeed during treatment with KEYTRUDA and for 4 months after the last dose [see Use in Specific Populations (8.2) ] . Laboratory Tests Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests [see Warnings and Precautions (5.1) ] .

Label text from the FDA structured product label by Merck Sharp & Dohme LLC (revised Jul 10, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Pembrolizumab in 1 product

Keytruda NDC products (1)

NDC	Strength & form	Labeler	Type
0006-3026	Pembrolizumab 25 mg/mL Injection, Solution	Merck Sharp & Dohme LLC	BLA

Frequently asked questions

What is Keytruda used for?

What are the side effects of Keytruda?

Who makes Keytruda?

Keytruda is listed by 1 labeler in the FDA NDC directory, including Merck Sharp & Dohme LLC.