Management of Fever After First Pembrolizumab Infusion
This fever 3 hours post-infusion is most likely a Grade 1-2 infusion reaction, and you should continue symptomatic treatment with acetaminophen, monitor vital signs closely for the next 1-2 hours, and watch for any progression to more severe symptoms that would indicate a Grade 3-4 reaction requiring aggressive intervention. 1, 2
Immediate Assessment and Classification
The clinical scenario describes a Grade 1-2 infusion reaction, characterized by:
- Pyrexia (101.3°F) occurring 4 hours after infusion start 1
- Pembrolizumab infusion reactions occur in approximately 3% of patients, with pyrexia and chills being the primary symptoms 1
- The patient has already received appropriate initial management with acetaminophen 1000mg 2
This fever pattern is consistent with a typical infusion reaction rather than infection, given the temporal relationship (within hours of infusion) and the known side effect profile of pembrolizumab. 1, 2
Current Management Steps
Continue Symptomatic Treatment
- The acetaminophen 1000mg already administered is appropriate first-line therapy 2
- Consider adding an antihistamine (diphenhydramine 25-50 mg IV or oral) if not already given 2, 3
- Monitor temperature every 30-60 minutes until fever resolves 2
Vital Sign Monitoring
- Check vital signs every 15 minutes for the next 1-2 hours, including blood pressure, heart rate, respiratory rate, and oxygen saturation 2, 3
- Watch specifically for signs of progression to Grade 3-4 reactions, including bronchospasm, severe respiratory compromise, severe hypotension, or angioedema 1, 4
Observation Period
- Observe the patient for at least 1-2 hours after symptom onset, as infusion reactions can progress 2, 3
- Be aware that delayed reactions can occur up to 24 hours post-infusion 2
Red Flags Requiring Escalation
Immediately escalate care if any of the following develop:
- Bronchospasm, wheezing, or severe dyspnea 1, 4
- Severe hypotension or hemodynamic instability 1, 4
- Angioedema, facial swelling, or severe urticaria 1, 4
- Chest pain, back pain, or feeling like passing out 4
- Any Grade 3-4 reaction requires permanent discontinuation of pembrolizumab 1
Prevention for Next Infusion
For the second pembrolizumab infusion, implement the following premedication protocol:
- Administer acetaminophen 1000 mg orally 30-60 minutes before infusion 1, 2
- Give antihistamine (diphenhydramine 25-50 mg or equivalent) prior to infusion 1, 2
- Consider starting the infusion at a slower rate and gradually increasing if tolerated 2, 3
Patient Education
Educate the patient about:
- Delayed reactions can occur up to 24 hours after infusion 2
- Report immediately: difficulty breathing, chest tightness, severe rash, dizziness, or worsening fever 4
- Continue monitoring temperature at home for 24 hours 2
Important Caveats
Do not confuse this infusion reaction with immune-related adverse events (irAEs):
- Fever occurring weeks to months after pembrolizumab may represent serious irAEs like pneumonitis, colitis, or hemophagocytic lymphohistiocytosis, which require different management 5, 6, 7
- The timing (within hours of infusion) strongly suggests infusion reaction rather than irAE 1, 2
This is NOT an indication to permanently discontinue pembrolizumab unless symptoms progress to Grade 3-4 severity. 1