pembrolizumab

Pembrolizumab is a medication used to treat many cancers, often in an advanced or metastatic state, either as a first-line single agent or in combination with other chemotherapy medications. Pembrolizumab is a type of targeted therapy that alters a specific cell mechanism promoting cancer growth and spread. It works by stimulating the body’s immune system to fight against cancer cells.

Pembrolizumab is a highly selective immunoglobulin G4 (IgG4) kappa monoclonal antibody designed to act against a specific protein expressed in T-cells, enhancing the activity of T-cells against cancer cells. T-cells are immune cells that induce programmed death (apoptosis) in damaged and mutated cells. In many cancers, cancer cells develop mechanisms to escape apoptosis. Pembrolizumab blocks a specific protein interaction and cell-signaling with T-cells that cancer cells use to evade death.

Pembrolizumab belongs to a class of medications known as PD-1/PD-L1 inhibitors, which bind to programmed death-1 (PD-1) molecules and inhibit their interactions with PD-L1 and PD-L2 molecules. These proteins are normally expressed in T-cells and their interaction inhibits the activation of T-cells. Cancer cells avoid apoptosis by secreting PD-L1 or inducing the production of PD-L1 in the tumor microenvironment. Inhibition of PD-1 increases T-cell activity against cancer cells.

What types of cancer does pembrolizumab treat?

Pembrolizumab is administered as an intravenous infusion for over 30 minutes. Its uses include:

Adult and pediatric:

• Melanoma
• Classical Hodgkin lymphoma
• Primary mediastinal large B-cell lymphoma
• Microsatellite instability-high cancer (MSI-H)
• Merkel cell carcinoma
• Tumor mutational burden-high cancer
• Non-small cell lung cancer (NSCLC)
• Head and neck squamous cell cancer
• Urothelial carcinoma
• Gastric cancer
• Esophageal cancer
• Cervical cancer
• Endometrial cancer
• Triple-negative breast cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Microsatellite instability-high or mismatch repair deficient colorectal cancer
• Cutaneous squamous cell carcinoma
• PD-L1 positive relapsed or refractory malignant pleural mesothelioma
• Relapsed or refractory mycosis fungoides/Sezary syndrome
• Multiple myeloma
• Nasopharyngeal carcinoma
• Follicular lymphoma
• Biliary tract carcinoma

Warnings

• Use of pembrolizumab may cause severe infusion reactions. Monitor patients for symptoms, interrupt or slow infusion rate in patients with mild or moderate infusion reactions, and discontinue for severe and life-threatening infusion reactions.
• Pembrolizumab can cause immune-mediated severe or fatal inflammatory reactions. In case of moderate reactions, monitor the patient, treat with corticosteroids, and withhold pembrolizumab. Discontinue the drug permanently for severe or life-threatening reactions. Immune-mediated adverse reactions may include:
• Pneumonitis
• Colitis
• Hepatitis
• Endocrinopathies including:
• Hypophysitis
• Thyroid disorders
• Type I diabetes mellitus
• Bullous pemphigoid
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Exfoliative dermatitis

Side effects of pembrolizumab

Common side effects include:

• Fatigue
• Fever
• Pain
• Headache
• Peripheral neuropathy
• Musculoskeletal pain
• Joint pain
• Muscle pain
• Back pain
• Weakness
• Neck pain
• Myositis
• Arthritis
• Decreased appetite
• Diarrhea
• Constipation
• Abdominal pain
• Nausea
• Vomiting
• Dysphagia
• Colitis
• Stomatitis
• Hyperglycemia
• Hypertriglyceridemia
• Hypercholesterolemia
• Hyperkalemia
• Hypercalcemia
• Hyperthyroidism
• Decreased serum bicarbonate
• Hypoalbuminemia
• Hypoglycemia
• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Hyponatremia
• Hypophosphatemia
• Hypothyroidism
• Thyroiditis
• Adrenocortical insufficiency
• Diabetic ketoacidosis
• Weight loss
• Cardiac arrhythmia
• Ischemic heart disease
• Myocarditis
• Myocardial infarction
• Pericarditis
• Pericardial effusion
• Cardiac tamponade
• Peripheral edema
• Facial edema
• Pulmonary embolism
• Upper respiratory tract infection
• Cough
• Dyspnea
• Pneumonia
• Pneumonitis
• Flu-like symptoms
• Oropharyngeal pain
• Nasopharyngitis
• Pleural effusion
• Respiratory failure
• Acute kidney injury
• Increase in serum creatinine
• Hematuria
• Urinary tract infection
• Hyperbilirubinemia
• Increase in liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
• Increase in alkaline phosphatase levels (ALK)
• Hepatitis
• Ascites
• Skin rash
• Pruritus
• Vitiligo
• Infection
• Herpes virus infection
• Herpes zoster infection
• Sepsis
• Infusion-related reactions
• Fistula in the infusion region
• Blood disorders including:
• Anemia
• Leukopenia
• Lymphocytopenia
• Neutropenia
• Febrile neutropenia
• Thrombocytopenia
• Increase in blood clotting time
• Hemorrhage

Less common side effects include:

• Cardiac failure
• Edema
• Vasculitis
• Septic shock
• Gastritis
• Duodenitis
• Pancreatitis
• Increase in serum amylase
• Increase in serum lipase
• Rectal hemorrhage
• Clostridium difficile-associated diarrhea
• Nephritis
• Urinary tract infection with sepsis
• Uterine hemorrhage
• Candidiasis
• Hepatic sinusoidal obstruction syndrome
• Hypoparathyroidism
• Hypophysitis
• Type I diabetes mellitus
• Blood disorders including:
• Aplastic anemia
• Hemolytic anemia
• Immune thrombocytopenia
• Polymyalgia rheumatica
• Polymyositis

Rare side effects include:

• Severe skin reactions:
• Bullous pemphigoid
• Pyoderma gangrenosum
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome

If you experience any of the following symptoms or serious side effects, call your doctor immediately:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.