Adverse Side Effects of Keytruda (Pembrolizumab)
Keytruda (pembrolizumab) can cause serious immune-mediated adverse reactions affecting multiple organ systems, with the most common side effects including fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, fever, cough, dyspnea, and constipation.
Common Adverse Effects
Keytruda (pembrolizumab) is an immune checkpoint inhibitor that works by blocking the PD-1 pathway, enhancing the immune system's ability to detect and fight cancer cells. However, this immune activation can lead to various side effects:
Frequently Reported Side Effects
- Fatigue (reported in 30-50% of patients)
- Musculoskeletal pain (20-30%)
- Decreased appetite (20-25%)
- Pruritus/itching (20-30%)
- Diarrhea (20%)
- Nausea (15-20%)
- Rash (15-20%)
- Fever (10-15%)
- Cough (10-15%)
- Dyspnea/shortness of breath (10-15%)
- Constipation (10-15%)
Serious Immune-Mediated Adverse Reactions
Keytruda can cause the immune system to attack normal organs and tissues in any area of the body, potentially resulting in severe and fatal adverse reactions:
Endocrine System
- Thyroid disorders (hypothyroidism or hyperthyroidism) (5-10%)
- Adrenal insufficiency (1%)
- Type 1 diabetes mellitus with diabetic ketoacidosis (1%)
- Hypophysitis/pituitary inflammation (<1%)
Gastrointestinal System
- Colitis/severe diarrhea (1-3%)
- Hepatitis with elevated liver enzymes (1-2%)
- Pancreatitis (rare)
Pulmonary System
- Pneumonitis/lung inflammation (3-5%)
- Can range from mild to life-threatening
Skin Reactions
- Severe dermatitis (1-2%)
- Stevens-Johnson syndrome (rare)
- Toxic epidermal necrolysis (rare)
Renal System
- Nephritis/kidney inflammation (1-2%)
- Acute kidney injury
Neurological System
- Encephalitis (<1%)
- Guillain-Barré syndrome (rare)
- Myasthenic syndrome (rare)
- Myositis (rare)
- Neuropathy (rare)
Cardiovascular System
- Myocarditis (<1%)
- Pericarditis (rare)
- Vasculitis (rare)
Hematologic
- Hemolytic anemia (rare)
- Aplastic anemia (rare)
- Thrombocytopenia (rare)
Ocular
- Uveitis (rare)
- Retinitis (rare)
Infusion-Related Reactions
- Fever, chills, flushing, pruritus, hypotension, dyspnea (2-3%)
- Can range from mild to severe
Monitoring and Management
Baseline Assessment
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Urinalysis
Ongoing Monitoring
- Regular assessment of liver function tests
- Thyroid function monitoring
- Blood glucose monitoring
- Evaluation for new or worsening respiratory symptoms
- Monitoring for signs of colitis, nephritis, or skin reactions
Management Algorithm
- Grade 1 (mild) reactions: Often continue treatment with close monitoring
- Grade 2 (moderate) reactions: Consider holding treatment and initiating corticosteroids
- Grade 3-4 (severe or life-threatening) reactions: Permanently discontinue Keytruda and administer high-dose corticosteroids
Special Considerations
Risk Factors for Increased Toxicity
- History of autoimmune disease
- Prior organ transplantation
- Previous radiation therapy
- Concurrent use of other immunosuppressive medications
Timing of Adverse Events
- Some adverse reactions may occur during treatment
- Others may manifest weeks to months after discontinuation
- Delayed toxicities can occur up to a year after treatment cessation
Patient Education
Patients should be instructed to:
- Report any new or worsening symptoms promptly
- Not self-treat symptoms without consulting healthcare providers
- Understand that side effects may occur even after treatment discontinuation
- Carry information about their treatment for emergency situations
By understanding these potential adverse effects and implementing appropriate monitoring strategies, healthcare providers can optimize the safety profile of Keytruda while maintaining its therapeutic benefits.