Management of Fever After Pembrolizumab Infusion
For fever occurring within hours of pembrolizumab infusion, immediately stop or slow the infusion rate, administer symptomatic treatment with acetaminophen 650-1000 mg and diphenhydramine 25-50 mg IV, and restart at 50% of the previous infusion rate once symptoms completely resolve. 1, 2
Immediate Assessment and Intervention
This represents a Grade 1-2 infusion reaction, which occurs in approximately 3% of pembrolizumab patients and typically presents with pyrexia and chills as the primary symptoms without hemodynamic instability. 1, 2
Stop or slow the infusion immediately upon recognition of fever, and switch the IV line to normal saline to maintain venous access. 2
Acute Symptomatic Management
Administer the following medications promptly:
- Antipyretic: Acetaminophen 650-1000 mg orally or IV 2
- Antihistamine: Diphenhydramine 25-50 mg IV or oral equivalent 2
Monitor vital signs continuously for 15 minutes until complete symptom resolution. 2 This monitoring period is critical to ensure the reaction is not progressing to a more severe grade.
Restarting the Infusion
Once symptoms have completely resolved:
- Restart the infusion at 50% of the previous infusion rate 1, 2
- If well tolerated for 15 minutes, gradually increase the rate back to the original infusion speed 2
- Continue vital sign monitoring throughout the remainder of the infusion 2
Critical pitfall to avoid: Never restart at the full infusion rate after a reaction—always resume at 50% of the previous rate. 2
Post-Infusion Monitoring
Observe the patient for 1-2 hours after infusion completion, particularly since this patient has now experienced a reaction. 1, 2 Educate the patient that delayed reactions can occur up to 24 hours post-infusion, including flu-like symptoms, fever, arthralgias, and myalgias. 2
Prevention for Future Infusions
For subsequent pembrolizumab infusions, premedication with antipyretic and antihistamine should be considered given this patient's history of infusion reaction:
- Acetaminophen 1000 mg administered 30-60 minutes before infusion 1, 2
- Antihistamine (diphenhydramine 50 mg or equivalent) prior to infusion 1, 2
When to Permanently Discontinue
Do not rechallenge if the patient develops any of the following Grade 3-4 reactions: 1, 2
- Bronchospasm or severe respiratory compromise
- Severe hypotension requiring vasopressor support
- Angioedema
- Anaphylaxis
- Any Grade 3-4 infusion reaction
Important Differential Considerations
While this presentation is consistent with a typical Grade 1-2 infusion reaction, be vigilant for alternative diagnoses if fever persists beyond the immediate post-infusion period or recurs days later. Pembrolizumab can cause serious immune-related adverse events including pneumonitis, cytokine release syndrome (which can present 4 hours post-infusion with fever and systemic inflammatory response), and other inflammatory conditions. 3, 4 However, these typically present with additional symptoms beyond isolated fever and occur with different timing patterns than the immediate post-infusion fever described in this scenario.