Premedication Prior to Pembrolizumab
Routine Premedication Is Not Required
Premedication with antipyretic and antihistamine is optional for pembrolizumab and should only be considered in patients who have experienced a prior infusion reaction. 1
Standard First-Dose Approach
No routine premedication is recommended for patients receiving their first pembrolizumab infusion, as the incidence of infusion reactions is only approximately 3%, with most being Grade 1-2 reactions presenting as pyrexia and chills. 1, 2
Administer pembrolizumab over 30 minutes without premedication in treatment-naïve patients. 1
Observe patients during and for a short period after the infusion to monitor for signs of infusion reactions (fever, chills, facial flushing). 1
Premedication Strategy for Patients With Prior Reactions
For patients who have experienced a previous infusion reaction to pembrolizumab, implement the following premedication protocol:
Acetaminophen 1000 mg orally administered 30-60 minutes before infusion. 2
Antihistamine (diphenhydramine 25-50 mg IV or oral equivalent, or cetirizine 10 mg orally) given 30-60 minutes before infusion. 1, 2
Consider extending post-infusion observation to 1-2 hours, particularly after a patient has experienced a reaction. 2
Management of Hypersensitivity History
Prior Reaction to Pembrolizumab
Grade 1-2 prior reactions: Use premedication protocol above (acetaminophen + antihistamine) for all subsequent infusions. 1, 2
Grade 3-4 prior reactions: Permanently discontinue pembrolizumab; do not rechallenge even with premedication. 1, 2
Prior Reaction to Another PD-1 Inhibitor (e.g., Nivolumab)
Pembrolizumab may be safely administered to patients who experienced infusion reactions to nivolumab, as cross-reactivity is not universal. 3
Implement premedication with acetaminophen and antihistamine for the first pembrolizumab dose in these patients, given their demonstrated hypersensitivity to the drug class. 3
Monitor closely during the first infusion; if tolerated without reaction, premedication may be discontinued for subsequent doses. 3
Key Distinctions From Other Immunotherapies
Unlike rituximab (which requires mandatory premedication for all patients due to a 77% reaction rate) or certain chemotherapy agents, pembrolizumab's low 3% infusion reaction rate does not justify routine premedication. 1, 4
This approach differs from the conditional premedication strategy used for ipilimumab (another checkpoint inhibitor), where premedication "may be considered" but is similarly not mandated. 1
Critical Safety Points
Never delay epinephrine if anaphylaxis occurs; premedication does not substitute for emergency preparedness. 1
Severe reactions (bronchospasm, severe hypotension, angioedema, anaphylaxis) mandate permanent discontinuation regardless of premedication strategy. 1, 2
Educate patients that delayed reactions can occur up to 24 hours post-infusion, even with premedication. 2