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Selected Safety Information (SSI)

KEYTRUDA® (pembrolizumab) injection, for intravenous use
KEYTRUDA® is a programmed death receptor-1 (PD-1)-blocking antibody indicated:

Melanoma
  • For the treatment of patients with unresectable or metastatic melanoma.
  • For the 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 (NSCLC)
  • In combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations.
  • In combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of patients with metastatic squamous NSCLC.
  • As a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS ≥ 1%)] as determined by a validated 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.
  • As a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥ 1%) 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 FDA-approved therapy for these aberrations prior to receiving KEYTRUDA®.
  • 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.
  • 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.
Malignant Pleural Mesothelioma (MPM)
  • In combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with unresectable advanced or metastatic MPM.
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 a validated 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.
  • In combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC.
  • 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 a validated test.
  • As a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma (cHL)
  • For the treatment of adult patients with relapsed or refractory cHL.
  • For the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Urothelial Cancer
  • In combination with enfortumab vedotin, for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
  • 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.
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 a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
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 a validated test.
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 a validated test.1
  • 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 a validated test.1
Esophageal Cancer
  • In combination with platinum- and fluoropyrimidine-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to @ centimeters above the GEJ) carcinoma that express PD-L1 (CPS ≥ 1) and is not amenable to surgical resection or definitive chemoradiation.
Cervical Cancer
  • In combination with chemoradiotherapy, for the treatment of patients with locally advanced cervical cancer involving the lower third of the vagina, with or without extension to pelvic sidewall, or hydronephrosis/non-functioning kidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA).
  • ln combination with chemotherapy, with or without bevacizumab, 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.
Hepatocellular Carcinoma (HCC)
  • For the treatment of patients with HCC secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer (BTC)
  • In combination with gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer.
Merkel Cell Carcinoma (MCC)
  • For the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma.
Renal Cell Carcinoma (RCC)
  • In combination with axitinib, for the first-line treatment of adult patients with advanced RCC.
  • In combination with lenvatinib, for the first-line treatment of adult patients with advanced RCC.
  • For the 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 by KEYTRUDA® as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.
  • In combination with lenvatinib, for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by a validated test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Triple-Negative Breast Cancer (TNBC)
  • For the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
  • In combination with chemotherapy, 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.
Adult Classical Hodgkin Lymphoma:
Additional Dosing Regimen of 400 mg Every 6 Weeks
  • For use at an additional recommended dosage of 400 mg every 6 weeks for Classical Hodgkin Lymphoma.2
    1This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
    2This indication is approved under accelerated approval based on pharmacokinetic data, the relationship of exposure to efficacy, and the relationship of exposure to safety. Continued approval for this dosing may be contingent upon verification and description of clinical benefit in the confirmatory trials.
DOSAGE FORMS AND STRENGTHS
  • Injection: 100 mg/4 ml (25 mg/ml) solution in a single-dose vial.
CONTRAINDICATIONS
  • None.
WARNINGS AND PRECAUTIONS
  • Immune-mediated Adverse Reactions

o 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.

o Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.

o 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.
  • 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.
  • 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.
  • 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.
ADVERSE REACTIONS

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, nausea, and hypothyroidism.
  • 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.
  • 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, and decreased appetite.
  • 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.
  • 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.
  • KEYTRUDA® in combination with enfortumab vedotin: rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, weight loss, decreased appetite, dry eye, nausea, constipation, dysgeusia, and urinary tract infection.
COMMON SIDE EFFECTS

Common side effects of KEYTRUDA® when used alone include:

  • Feeling tired, pain in muscles, rash, diarrhea, fever, cough, decreased appetite, itching, shortness of breath, constipation, bones or joints pain, nausea, and low levels of thyroid hormone.
  • Side effects of KEYTRUDA® when used alone that are more common in children than in adults include: fever, vomiting, headache, stomach area (abdominal) pain, and low levels of white blood cells.

Common side effects of KEYTRUDA® when given with certain chemotherapy or chemotherapy with radiation therapy medicines include:

  • feeling tired or weak, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, trouble breathing, fever, hair loss, inflammation of the nerves that may cause pain, weakness, and paralysis in the arms and legs, swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, mouth sores, headache, weight loss, stomach-area (abdominal) pain, joint and muscle pain, trouble sleeping, blisters or rash on the palms of your hands and soles of your feet, urinary tract infection, low levels of thyroid hormone, skin irritation in the radiation area, trouble swallowing and dry mouth.

Common side effects of KEYTRUDA® when given with chemotherapy and bevacizumab include:

  • Tingling or numbness of the arms or legs, hair loss, low red blood cell count, feeling tired or weak, nausea, low white blood cell count, diarrhea, high blood pressure, decreased plateletcount, constipation, joint aches, vomiting, urinary tract infection, rash, low levels of thyroid hormone, and decreased appetite.

Common side effects of KEYTRUDA® when given with axitinib include:

  • Diarrhea, feeling tired or weak, high blood pressure, liver problems, low levels of thyroid hormone, decreased appetite, blisters or rash on the palms of your hands and soles of your feet, nausea, mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, hoarseness, rash, cough, and constipation.

Common side effects of KEYTRUDA® when given with lenvatinib include:

  • Diarrhea, feeling tired or weak, high blood pressure, liver problems, low levels of thyroid hormone, decreased appetite, blisters or rash on the palms of your hands and soles of your feet, nausea, mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, hoarseness, rash, cough, and constipation.

Common side effects of KEYTRUDA® when given with enfortumab vedotin include:

  • Rash, tingling or numbness of the arms or legs, feeling tired, itching, diarrhea, hair loss, weight loss, decreased appetite, dry eye, nausea, constipation, changes in sense of taste, and urinary tract infection.
USE IN SPECIFIC POPULATIONS

Lactation:

  • Advise women not to breastfeed during treatment with KEYTRUDA® and for 4 months after the final dose.

Pregnancy:

  • Pembrolizumab has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women of the potential risk to a fetus.

Fertility:

  • Fertility studies have not been conducted with pembrolizumab.

Pediatric Use:

  • The safety and effectiveness of KEYTRUDA® as a single agent have been established in pediatric patients with melanoma, cHL, MCC and MSI-H or dMMR cancer. Use of KEYTRUDA® in pediatric patients for these indications. The safety and effectiveness of KEYTRUDA® in pediatric patients have not been established in the other approved indications.

  • Egyptian Drug Authority KEYTRUDA® leaflet approval date 27/11/2024
  • Always read the full prescribing information.
  • Healthcare professionals are asked to report any suspected adverse reactions to Egyptian Pharmacovigilance Centre e-mail: pv.followup@edaegypt.gov.eg or Egyptian Drug Authority (EDA) website: https://www.edaegypt.gov.eg or (EPVC) [hotline 15301].