Keytruda

/ MSD

Patient Selection for Treatment of NSCLC or Gastric Cancer: Select patients with metastatic NSCLC for treatment based on the presence of positive PD-L1 expression.
For metastatic gastric cancer, select patients for treatment with this agent as monotherapy based on positive PD-L1 expression. If PD-L1 expression is not detected in an archival gastric tumor specimen, evaluate the feasibility of obtaining a new tumor biopsy for PD-L1 testing.
Recommended Dosage for Melanoma: 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
Recommended Dosage for NSCLC:  200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.
Recommended Dosage for MPM: 200 mg administered as an intravenous
infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity or up to 24 months.
Recommended Dosage for HNSCC: 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Recommended Dosage for cHL: In adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Recommended Dosage for Urothelial Carcinoma: 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Recommended Dosage for MSI-H Cancer: In adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
In children is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Recommended Dosage for Gastric Cancer: 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Dose Modifications: Withhold treatment for any of the following:
– Grade 2 pneumonitis
– Grade 2 or 3 colitis
– Grade 3 or 4 endocrinopathies
– Grade 4 hematological toxicity in cHL patients
– Grade 2 nephritis
– Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
– Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 and up to 5 times upper limit of normal (ULN) or total bilirubin greater than 1.5 and up to 3 times ULN.
– Any other Grade 2 or 3 treatment-related adverse reaction, based on the severity and type of reaction.
Resume in patients whose adverse reactions recover to Grade 0-1.
Permanently discontinue for any of the following:
– Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy, or hematological toxicity in patients with cHL)
– Grade 3 or 4 myocarditis, encephalitis, or Guillain-Barré syndrome
– Grade 3 or 4 pneumonitis or recurrent pneumonitis of Grade 2 severity
– Grade 3 or 4 nephritis
– Grade 4 severe skin reactions or confirmed SJS or TEN
– AST or ALT greater than 5 times ULN or total bilirubin greater than 3 times ULN: For patients with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT increases by greater than or equal to 50% relative to baseline and lasts for at least 1 week.
– Grade 3 or 4 infusion-related reactions
– Inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks.
– Persistent Grade 2 or 3 adverse reactions (excluding endocrinopathies controlled with hormone replacement therapy) that do not recover to Grade 0-1 within 12 weeks after last dose.
– Any severe or Grade 3 treatment-related adverse reaction that recurs.
See prescribing information for full details.

Melanoma
Treatment of adult and pediatric (12 years and older) patients with unresectable or metastatic melanoma. Adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
* In combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) negative for EGFR or ALK genomic tumor aberrations.
* In combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
* As a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 [Tumor Proportion Score (TPS) ≥50%)] as determined by a validated test. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on or after platinum-containing chemotherapy and an approved therapy for these aberrations prior to receiving this medical product.
* As a single agent, is indicated for the treatment of patients with advanced NSCLC whose tumors express PD-L1 as determined by a validated test, with disease progression on or after platinum containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on approved therapy for these aberrations prior to receiving this medical product.
* In combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, is indicated for the treatment of resectable NSCLC at high risk of recurrence in adults.
* As a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Malignant Pleural Mesothelioma
In combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adults with unresectable non-epithelioid malignant pleural mesothelioma.
Head and Neck Cancer
* In combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
* As a single agent, is indicated 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 a validated test
* As a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
*Aadult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
* Pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal large B-Cell Lymphoma
Treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
Limitation of Use: is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
* In combination with enfortumab vedotin, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer.
* As a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by a validated test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
* As a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
* As a single agent, is indicated 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.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
Treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
• solid tumors that have progressed following prior systemic treatment and who have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
Limitation of Use: The safety and effectiveness of this medical product in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC)
First-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).
Gastric Cancer
* In combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 with a CPS≥1 as determined by a validated test.
* In combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated 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 with a CPS ≥ 1 as determined by a validated test.
Esophageal Cancer
* Treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (Siewert type I) carcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with platinum- and fluoropyrimidine-based chemotherapy.
* Treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS≥10) as determined by a validated test, with disease progression after one or more prior lines of systemic therapy.
Cervical Cancer
* In combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
* In combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by a validated test.
* As a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by a validated test.
Biliary Tract Cancer
In combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
Treatment of adult and pediatric patients with recurrent locally advanced
or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
* In combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
* In combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.
* Adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
* In combination with carboplatin and paclitaxel, followed as a single agent, for the treatment of adult patients with primary advanced or recurrent pMMR endometrial carcinoma at least 12 months from prior adjuvant chemotherapy, and dMMR endometrial carcinoma regardless of prior adjuvant treatment.
* In combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy and who are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
Treatment of adult and pediatric patients with unresectable or metastatic
tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Limitations of Use: The safety and effectiveness in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
Treatment of patients with recurrent or metastatic cutaneous squamous
cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple Negative Breast Cancer
* Treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
* In combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by a validated test.

Hypersensitivity to the active ingredient or any excipient.

Immune-Mediated Pneumonitis: KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis. Evaluate patients with suspected pneumonitis with radiographic imaging and administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for moderate (Grade 2) pneumonitis, and
permanently discontinue KEYTRUDA for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis.
Immune-Mediated Colitis: KEYTRUDA can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis.
Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater colitis. Withhold KEYTRUDA for moderate (Grade 2) or severe (Grade 3) colitis, and permanently discontinue KEYTRUDA for life-threatening (Grade 4) colitis.
Immune-Mediated Hepatitis: KEYTRUDA can cause immune-mediated hepatitis. Monitor patients for changes in liver function.
Administer corticosteroids (initial dose of 0.5 to 1 mg/kg/day [for Grade 2 hepatitis] and 1 to 2 mg/kg/day [for Grade 3 or greater hepatitis] prednisone or equivalent followed by a taper) and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Immune-Mediated Endocrinopathies:
Hypophysitis: KEYTRUDA can cause hypophysitis. Monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for moderate (Grade 2) hypophysitis and withhold or discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) hypophysitis.
Thyroid Disorders: KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism and thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders.
Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) hyperthyroidism.
Type 1 Diabetes mellitus: KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.
Immune-Mediated Nephritis and Renal Dysfunction: KEYTRUDA can cause immune-mediated nephritis. Monitor patients for changes in renal function.
Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater nephritis. Withhold KEYTRUDA for moderate (Grade 2), and permanently discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) nephritis.
For full details see prescribing information.

Immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions. Other immune-mediated adverse reactions. Infusion-related reactions.
For full details see prescribing information.

No formal pharmacokinetic drug interaction studies have been conducted with this drug.

Pregnancy: Based on its mechanism of action, this drug may cause fetal harm when administered to a pregnant woman.
Lactation: It is not known whether this drug is excreted in human milk. No studies have been conducted to assess the impact of this drug on milk production or its presence in breast milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
See prescribing information for full details.

There is no information on overdose with this drug.

Storage: The product does not contain a preservative.
Store the reconstituted and diluted solution from the KEYTRUDA 50 mg vial either:
– At room temperature for no more than 6 hours from the time of reconstitution. This includes room temperature storage of reconstituted vials, storage of the infusion solution in the IV bag, and the duration of infusion.
– Under refrigeration at 2°C to 8°C for no more than 24 hours from the time of reconstitution. If refrigerated, allow the diluted solution to come to room temperature prior to administration.
Store the diluted solution from the KEYTRUDA 100 mg/4 mL vial either:
– At room temperature for no more than 6 hours from the time of dilution. This includes room temperature storage of the infusion solution in the IV bag, and the duration of infusion.
– Under refrigeration at 2°C to 8°C for no more than 24 hours from the time of dilution. If refrigerated, allow the diluted solution to come to room temperature prior to administration.
Do not freeze.