What is the recommended use of Proton Pump Inhibitors (PPIs) or Histamine-2 (H2) blockers, such as omeprazole (PPI) or Pepcid (famotidine), in patients undergoing immunotherapy?

Use of PPIs or H2 Blockers with Immunotherapy

For patients on immunotherapy, proton pump inhibitors (PPIs) are recommended over H2 blockers (such as famotidine) for gastric protection when immunosuppressive therapy is needed to manage immune-related adverse events.

Rationale for Acid-Suppressing Medications During Immunotherapy

When Acid Suppression Is Indicated

• PPIs are specifically recommended in immunotherapy guidelines for patients receiving systemic corticosteroids for immune-related adverse events (irAEs) 1
• The NCCN guidelines recommend PPI prophylaxis for patients receiving:
  • Prednisone equivalent ≥20 mg/day for management of moderate (grade 2) to severe (grade 3-4) immune-related adverse events 1
  • Any systemic corticosteroid therapy for irAEs to prevent gastritis 1

PPI vs. H2 Blocker Efficacy

• PPIs provide superior acid suppression compared to H2 blockers:
  • PPIs reduce upper GI bleeding to a greater degree than H2RAs 1
  • PPIs irreversibly inhibit the proton pump (H+/K+ ATPase) and are the most potent gastric acid-suppressing agents in clinical use 2
  • Standard doses of H2 blockers may be insufficient for gastric protection, particularly when corticosteroids are used 1

Specific Recommendations for Immunotherapy Patients

For Patients Requiring Corticosteroids for irAEs

• Grade 2 irAEs: Start PPI prophylaxis when initiating prednisone 0.5-1 mg/kg/day 1
• Grade 3-4 irAEs: PPI prophylaxis is mandatory when starting prednisone 1-2 mg/kg/day 1

Choice of Agent

1. First choice: Pantoprazole (40mg daily)

   • Lowest potential for drug interactions 3
   • Minimal effect on CYP2C19 enzyme system 3, 4

2. Alternative options:

   • Rabeprazole (20mg daily) - lower risk of drug interactions 4
   • Lansoprazole (30mg daily) - intermediate risk of interactions 4

3. Avoid if possible:

   • Omeprazole and esomeprazole - highest risk for drug interactions 3, 4

H2 Blockers as Alternative

• Consider famotidine (Pepcid) only if:
  • Patient has history of PPI intolerance
  • Short-term therapy is needed (less than 2 weeks)
  • Lower risk of GI bleeding exists
• Note: H2 blockers are less effective than PPIs for gastric protection 1

Important Clinical Considerations

Drug Interactions

• PPIs may have varying levels of drug interactions through the CYP450 system:
  • Omeprazole has the highest risk for interactions 4
  • Rabeprazole and pantoprazole have the lowest risk 3, 4
• This is particularly important when patients are on multiple medications during immunotherapy

Duration of Therapy

• Continue PPI prophylaxis for the duration of corticosteroid therapy
• Consider tapering PPI 1-2 weeks after corticosteroid discontinuation
• Regular reassessment of the need for continued PPI therapy is recommended 3

Monitoring

• Monitor for PPI-associated side effects:
  • Headaches, diarrhea, constipation (up to 14% of patients) 3
  • Long-term use: potential vitamin B12 deficiency in elderly patients 3

Special Situations

For Patients with History of GI Bleeding

• PPI prophylaxis is strongly indicated regardless of corticosteroid dose 1
• Higher doses or twice-daily dosing may be considered 3

For Patients with Dyspepsia Despite Standard PPI

• Consider twice-daily PPI dosing 3
• Add an antacid for breakthrough symptoms 3

By following these recommendations, clinicians can provide appropriate gastric protection for patients on immunotherapy while minimizing potential drug interactions and adverse effects.