Pembrolizumab

Pembrolizumab is a prescription medication indicated for the treatment of:

• unresectable or metastatic melanoma
• non-small cell lung cancer (NSCLC)
• head and neck squamous cell carcinoma (HNSCC)
• classical Hodgkin lymphoma (cHL)
• primary mediastinal large B-Cell lymphoma (PMBCL)
• urothelial carcinoma (UC)
• microsatellite instability-high cancer
• microsatellite instability-high or mismatch repair deficient colorectal cancer
• gastric cancer
• esophageal cancer
• cervical cancer
• hepatocellular carcinoma
• merkel cell carcinoma
• renal cell carcinoma
• endometrial cancer
• tumor mutational burden-high (TMB-H) cancer
• cutaneous squamous cell carcinoma (cSCC)
• triple-negative breast cancer (TNBC) and
• biliary tract cancer

Pembrolizumab is available under the following different brand names: Keytruda.

Common side effects of Pembrolizumab include:

• fatigue
• anemia
• high blood sugar (hyperglycemia)
• hyponatremia
• hypoalbuminemia
• nausea
• cough
• itching
• rash
• decreased appetite
• hypertriglyceridemia
• increased AST
• constipation
• diarrhea
• joint pain
• pain in extremities
• shortness of breath
• swelling of extremities
• vomiting
• headache
• muscle pain
• chills
• insomnia
• abdominal pain
• back pain
• dizziness
• fever
• upper respiratory tract infection
• loss of skin pigmentation (vitiligo)
• sepsis
• hypothyroidism
• pneumonitis
• hyperthyroidism
• colitis

Serious side effects of Pembrolizumab include:

• chest pain, irregular heartbeat, shortness of breath, swelling of ankles 
• confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs 
• double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight 
• persistent or severe muscle pain or weakness, muscle cramps 
• low red blood cells, bruising
• Infusion reactions: symptoms may include chills or shaking, dizziness, itching or rash, feeling like passing out, flushing, fever, shortness of breath or wheezing, and back pain

Rare side effects of Pembrolizumab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms include sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injectable solution

• 100mg/4mL (25mg/mL)

Melanoma

Adult dosage

Unresectable or metastatic melanoma

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression or unacceptable toxicity

Adjuvant treatment

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
• Continue until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence

Non-Small Cell Lung Cancer

Adult dosage

Single-agent for localized disease

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression or unacceptable toxicity, or up to 12 months without disease progression

Single-agent for unresectable or advanced disease

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression or unacceptable toxicity, or up to 24 months without disease progression

Combination therapy for resectable NSCLC

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Administer before chemotherapy if 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 pembrolizumab as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity

Combination therapy for metastatic NSCLC

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Head & Neck Squamous Cell Carcinoma

Adult dosage

Single-agent therapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Combination therapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Classical Hodgkin Lymphoma

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
• Continue until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Primary Mediastinal Large B-Cell Lymphoma

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/day

Urothelial Carcinoma

Adult dosage

Combination with enfortumab

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Administer pembrolizumab approximately 30 minutes after enfortumab vedotin when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Single-agent therapy

Locally advanced or metastatic urothelial carcinoma

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until persistent or recurrent high-risk NMIBC, disease progression, or unacceptable toxicity, or up to 24 months in patients without disease progression

Microsatellite Instability-High Cancer

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
• Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

Adult dosage

• 200 mg IV every 3 weeks or 400 mg IV every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Gastric Cancer

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks PLUS trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy
• Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Esophageal Cancer

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Cervical Cancer

Adult dosage

Single-agent therapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Combination chemotherapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Combination chemoradiotherapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Hepatocellular Carcinoma

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Merkel Cell Carcinoma

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
• Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Renal Cell Carcinoma

Adult dosage

Combination therapy with axitinib

• Pembrolizumab 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
• Axitinib 5 mg orally two times a day (initial dose)
• Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression
• When axitinib is used in combination with pembrolizumab, consider dose escalation of axitinib above the initial 5 mg dose at more than 6 weeks intervals

Combination therapy with lenvatinib

• Pembrolizumab 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
• Lenvatinib 20 mg orally once a day 
• Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression

Adjuvant treatment

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months

Endometrial Cancer

Adult dosage

Combination therapy with lenvatinib

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks, PLUS
• Lenvatinib 20 mg orally once a day 
• Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months

Combination with carboplatin and paclitaxel chemotherapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Continue until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months
• Administer before chemotherapy if given on the same day

Single-agent therapy

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Tumor Mutational Burden-High Cancer

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Pediatric dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose
• Continue until disease progression, unacceptable toxicity, or up to 24 months without disease progression

Cutaneous Squamous Cell Carcinoma

Adult dosage

• 200 mg IV every 3 weeks OR 400 mg every 6 weeks
• Continue until disease progression or unacceptable toxicity, or up to 24 months without disease progression

Breast Cancer

Adult dosage

• High-risk early-stage triple-negative breast cancer (TNBC)

Neoadjuvant treatment

• In combination with chemotherapy: 200 mg IV every 3 weeks for 8 doses or 400 mg IV every 6 weeks for 4 doses or until disease progression or unacceptable toxicity
• Followed by single-agent adjuvant therapy

Adjuvant treatment

• Single-agent therapy: 200 mg IV every 3 weeks for 9 doses or 400 mg IV every 6 weeks for 5 doses or until disease progression or unacceptable toxicity

Locally recurrent unresectable or metastatic TNBC

• 200 mg IV every 3 weeks or 400 mg IV every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months
• Administer before chemotherapy when given on the same day

Biliary Tract Cancer

Adult dosage

• 200 mg IV every 3 weeks or 400 mg IV every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pembrolizumab has no noted severe interactions with any other drugs
• Pembrolizumab has no noted serious interactions with any other drugs
• Pembrolizumab has no noted moderate interactions with any other drugs
• Pembrolizumab has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pembrolizumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pembrolizumab?”

Cautions

• Monitor for signs and symptoms of adrenal insufficiency; administer corticosteroids and hormone replacement as clinically indicated; withhold therapy for moderate (Grade 2) adrenal insufficiency and withhold or discontinue for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency
• Solid organ transplant rejection reported in post-marketing setting; treatment increases risk of rejection in solid organ transplant recipients; consider benefit of treatment versus risk of possible organ rejection
• Infusion-related reactions, including severe and life-threatening reactions, reported; monitor for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever; interrupt or slow rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions; for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue therapy
• Hypophysitis reported; monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency)
• Thyroid disorders can occur; monitor for changes in thyroid function (at the start of treatment, periodically during treatment, and as clinically indicated) and clinical signs and symptoms of thyroid disorders
• Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman (see Pregnancy)
• In two randomized clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analog plus dexamethasone resulted in increased mortality; treatment of patients with multiple myeloma with a PD-1 or PDL1 blocking antibody in combination with a thalidomide analog plus dexamethasone is not recommended outside of controlled clinical trials

Immune-mediated adverse effects

• 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
• For patients with TNBC treated in the neoadjuvant setting, monitor blood cortisol at baseline, before surgery, and as clinically indicated
• 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
• 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
• Clinical trials reported immune-mediated pneumonitis, colitis, hepatitis, nephritis, and other immune-mediated adverse reactions (eg, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, myasthenic syndrome, optic neuritis, and rhabdomyolysis)
• Immune-mediated rashes, including SJS, TEN, exfoliative dermatitis, and bullous pemphigoid, reported; monitor for suspected severe skin reactions and exclude other causes
• Immune-mediated endocrinopathies (eg, adrenal insufficiency, changes in thyroid function, type 1 diabetes mellitus including diabetic ketoacidosis) reported
• Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with pembrolizumab
• Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid- requiring febrile syndrome (without an identified infectious cause); these complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
• Follow patients closely for evidence of transplant-related complications and intervene promptly; consider benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT
• Institute medical management promptly, including specialty consultation as appropriate

Pregnancy and Lactation

• Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman
• No human data available informing the risk of embryo-fetal toxicity

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months following final dose

Lactation

• Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to this drug are unknown
• No studies conducted to assess the impact of pembrolizumab on milk production or its presence in breast milk
• Instruct women to discontinue nursing during treatment and for 4 months after the final dose