Can pantoprazole, gabapentin, metoprolol, apixaban, and digoxin cause leukopenia and eosinophilia?

Can Pantoprazole, Gabapentin, Metoprolol, Apixaban, and Digoxin Cause Leukopenia and Eosinophilia?

Yes, pantoprazole can cause leukopenia and eosinophilia, while digoxin is also associated with eosinophilia. The other medications (gabapentin, metoprolol, and apixaban) are not significantly linked to these specific hematologic abnormalities.

Medication-Specific Evidence

Pantoprazole

• Strong evidence for leukopenia and eosinophilia
  • The FDA label for pantoprazole explicitly lists leukopenia and thrombocytopenia as reported adverse reactions in the hematologic category 1
  • Case reports have documented pantoprazole-induced neutropenia with cross-reactivity with other proton pump inhibitors 2
  • Pantoprazole has been associated with acute interstitial nephritis with eosinophilia 3
  • A case report showed pantoprazole-induced drug fever with leukocytosis 4

Digoxin

• Associated with eosinophilia
  • Digoxin is listed in clinical guidelines as a medication that can cause hypersensitivity reactions including eosinophilia 5
  • Digoxin is mentioned in drug interaction tables as requiring therapeutic drug monitoring due to potential adverse effects 5

Metoprolol

• Limited evidence for leukopenia/eosinophilia
  • While metoprolol is mentioned in drug interaction tables in guidelines 5, there is no specific mention of it causing leukopenia or eosinophilia
  • Pharmacokinetic differences in women may lead to higher concentrations of metoprolol 5, but this does not specifically correlate with increased risk of hematologic abnormalities

Apixaban

• No significant evidence for leukopenia/eosinophilia
  • No specific mentions in the provided evidence linking apixaban to leukopenia or eosinophilia

Gabapentin

• No significant evidence for leukopenia/eosinophilia
  • No specific mentions in the provided evidence linking gabapentin to leukopenia or eosinophilia

Mechanisms and Risk Factors

Immune-Mediated Reactions

• Proton pump inhibitors like pantoprazole can cause immune-mediated neutropenia 2
• Cross-reactivity between different PPIs has been documented, suggesting patients who develop neutropenia with one PPI may experience it with others 2

Patient-Specific Risk Factors

• Age: Older adults may be at higher risk due to:

  • Reduced renal clearance affecting drug levels 5
  • Changes in pharmacodynamics 5
  • Polypharmacy increasing risk of adverse drug reactions 5

• Renal impairment: Can increase risk of adverse drug reactions, particularly with medications that are renally cleared 5

Monitoring Recommendations

For patients on these medications, especially pantoprazole and digoxin:

1. Baseline complete blood count before initiating therapy
2. Periodic monitoring of blood counts, particularly during the first few months of treatment
3. Increased vigilance in patients with:
   • Advanced age
   • Renal impairment
   • History of hematologic disorders
   • Polypharmacy

Management of Hematologic Abnormalities

If leukopenia or eosinophilia develops:

1. Consider drug discontinuation - particularly pantoprazole if leukopenia occurs
2. Evaluate for cross-reactivity - if switching between PPIs, monitor closely as cross-reactivity has been documented 2
3. Alternative medications - consider H2 receptor antagonists instead of PPIs if PPI-induced leukopenia occurs

Key Takeaways

• Pantoprazole has the strongest association with both leukopenia and eosinophilia among the listed medications
• Digoxin has been associated with eosinophilia as part of hypersensitivity reactions
• Metoprolol, apixaban, and gabapentin have limited or no evidence linking them to leukopenia or eosinophilia based on the provided information
• Careful monitoring is warranted, especially in high-risk patients taking pantoprazole or digoxin