Standard Dose
2 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 ) 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) ]. An FDA-authorized test for the detection of PD-L1 for the selection of patients with PD-L1 (CPS ≥ 1) expression in esophageal carcinoma in combination with platinum- and fluoropyrimidine-based chemotherapy is not available. 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 chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC [see Clinical Studies (14.20) ] . For use of KEYTRUDA in combination with paclitaxel, with or without bevacizumab, select patients based on the presence of positive PD-L1 expression (CPS ≥1) in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma [see Clinical Studies (14.21) ] . 2.2 Recommended Dosage Administer KEYTRUDA as a 30-minute intravenous infusion. The recommended dosages of KEYTRUDA are presented in Table 1. Table 1: Recommended Dosage Indication Recommended Dosage of KEYTRUDA Duration/Timing of Treatment Monotherapy Adult patients with unresectable or metastatic melanoma 200 mg every 3 weeks or 400 mg every 6 weeks Until disease progression or unacceptable toxicity Adjuvant treatment of adult patients with melanoma, NSCLC, or RCC 200 mg every 3 weeks or 400 mg every 6 weeks Until disease recurrence, unacceptable toxicity, or up to 12 months Adult patients with NSCLC, HNSCC, cHL, PMBCL, locally advanced or metastatic Urothelial Carcinoma, MSI-H or dMMR Cancer, MSI-H or dMMR CRC, MSI-H or dMMR Endometrial Carcinoma, Esophageal Cancer, Cervical Cancer, HCC, MCC, TMB-H Cancer, or cSCC 200 mg every 3 weeks or 400 mg every 6 weeks Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with high-risk BCG- unresponsive NMIBC 200 mg every 3 weeks or 400 mg every 6 weeks Until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months Pediatric patients with cHL, PMBCL, MSI-H or dMMR Cancer, MCC, or TMB- H Cancer 2 mg/kg every 3 weeks (up to a maximum of 200 mg) Until disease progression, unacceptable toxicity, or up to 24 months Pediatric patients (12 years and older) for adjuvant treatment of melanoma 2 mg/kg every 3 weeks (up to a maximum of 200 mg) Until disease recurrence, unacceptable toxicity, or up to 12 months Combination Therapy Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate. Adult patients with resectable NSCLC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to chemotherapy when given on the same day. Neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity Adult patients with NSCLC, MPM, HNSCC, HER2-negative Gastric Cancer, Esophageal Cancer, or BTC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to chemotherapy when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with locally advanced or metastatic urothelial cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA after enfortumab vedotin when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with MIBC 200 mg every 3 weeks (neoadjuvant) 200mg every 3 weeks or 400 mg every 6 weeks (adjuvant) Administer KEYTRUDA after enfortumab vedotin when given on the same day. Neoadjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 3 doses in combination with enfortumab vedotin or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity. Adjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 14 doses or 400 mg every 6 weeks for 7 doses in combination with enfortumab vedotin or until disease recurrence or unacceptable toxicity Adult patients with locally advanced HNSCC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to cisplatin when given on the same day. Neoadjuvant: Administer KEYTRUDA for 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity. Adjuvant: Administer KEYTRUDA in combination with RT with or without cisplatin. Continue KEYTRUDA as a single agent. Continue KEYTRUDA until disease recurrence or unacceptable toxicity or up to one year Adult patients with HER2-positive Gastric Cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to trastuzumab and chemotherapy when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with Cervical Cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to chemoradiotherapy or prior to chemotherapy with or without bevacizumab when given on the same day. Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months Adult patients with RCC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA in combination with axitinib 5 mg orally twice daily When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. or Administer KEYTRUDA in combination with lenvatinib 20 mg orally once daily. Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months Adult patients with Endometrial Carcinoma 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to carboplatin and paclitaxel when given on the same day. or Administer KEYTRUDA in combination with lenvatinib 20 mg orally once daily. Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months Adult patients with high-risk early-stage TNBC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to chemotherapy when given on the same day. Neoadjuvant treatment in combination with chemotherapy for 24 weeks (8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks) or until disease progression or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent for up to 27 weeks (9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks) or until disease recurrence or unacceptable toxicity Patients who experience disease progression or unacceptable toxicity related to KEYTRUDA with neoadjuvant treatment in combination with chemotherapy should not receive adjuvant single agent KEYTRUDA. Adult patients with locally recurrent unresectable or metastatic TNBC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to chemotherapy when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with Ovarian Cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to paclitaxel with or without bevacizumab when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months 2.3 Dose Modifications No dose reduction for KEYTRUDA is recommended. In general, withhold KEYTRUDA for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue KEYTRUDA for Life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids. Dosage modifications for KEYTRUDA for adverse reactions that require management different from these general guidelines are summarized in Table 2. Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 Dosage Modification ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grades 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids. Grade 3 or 4 Permanently discontinue Colitis Grade 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold For liver enzyme elevations in patients treated with combination therapy with axitinib, see Table 3 . AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue KEYTRUDA based on recommendations for hepatitis with no liver involvement. Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN Withhold ALT or AST increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grade 3 or 4 Withhold until clinically stable or permanently discontinue depending on severity Nephritis with Renal Dysfunction Grade 2 or 3 increased blood creatinine Withhold Grade 4 increased blood creatinine Permanently discontinue Exfoliative Dermatologic Conditions Suspected SJS, TEN, or DRESS Withhold Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grade 2, 3, or 4 Permanently discontinue Neurological Toxicities Grade 2 Withhold Grade 3 or 4 Permanently discontinue Hematologic toxicity in patients with cHL or PMBCL Grade 4 Withhold until resolution to Grades 0 or 1 Other Adverse Reactions Infusion-related reactions [see Warnings and Precautions (5.2) ] Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Permanently discontinue The following table represents dosage modifications that are different from those described above for KEYTRUDA or in the Full Prescribing Information for the drug administered in combination. Table 3: Recommended Specific Dosage Modifications for Adverse Reactions for KEYTRUDA in Combination with Axitinib Treatment Adverse Reaction Severity Dosage Modification ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal KEYTRUDA in combination with axitinib Liver enzyme elevations Consider corticosteroid therapy ALT or AST increases to at least 3 times but less than 10 times ULN without concurrent total bilirubin at least 2 times ULN Withhold both KEYTRUDA and axitinib until resolution to Grades 0 or 1 Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery. If rechallenging with axitinib, consider dose reduction as per the axitinib Prescribing Information. ALT or AST increases to more than 3 times ULN with concurrent total bilirubin at least 2 times ULN or ALT or AST ≥10 times ULN Permanently discontinue both KEYTRUDA and axitinib Recommended Dose Modifications for Adverse Reactions for KEYTRUDA in Combination with Lenvatinib When administering KEYTRUDA in combination with lenvatinib, modify the dosage of one or both drugs. Withhold or discontinue KEYTRUDA as shown in Table 2. Refer to lenvatinib prescribing information for additional dose modification information. 2.4 Preparation and Administration Preparation for Intravenous Infusion Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to slightly yellow. Discard the vial if visible particles are observed. Dilute KEYTRUDA injection (solution) prior to intravenous administration. Withdraw the required volume from the vial(s) of KEYTRUDA and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake. The final concentration of the diluted solution should be between 1 mg/mL to 10 mg/mL. Discard any unused portion left in the vial. Storage of Diluted Solution The product does not contain a preservative. Store the diluted solution from the KEYTRUDA 100 mg/4 mL vial either: At room temperature (temperatures at or below 25°C) for no more than 6 hours from the time of dilution. This includes room temperature storage of the diluted solution, and the duration of infusion. Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 96 hours from the time of dilution. If refrigerated, allow the diluted solution to come to room temperature prior to administration. Do not shake. Discard after 6 hours at room temperature or after 96 hours under refrigeration. Do not freeze. Administration Administer diluted solution intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Do not co-administer other drugs through the same infusion line.