What Proton Pump Inhibitor (PPI) or Histamine-2 (H2) blocker does not affect the QT interval?

PPI and H2 Blocker Options That Do Not Affect QT Interval

Famotidine (H2 blocker) is the preferred acid-suppressing medication for patients concerned about QT interval prolongation, while pantoprazole is the safest PPI option if an H2 blocker is insufficient.

QT Interval Effects of Acid-Suppressing Medications

H2 Blockers

• Famotidine: The safest option with minimal to no QT interval effects 1
  • The FDA specifically notes that H2 blockers like famotidine do not interfere with antiplatelet activity of clopidogrel, unlike some PPIs
  • No evidence that H2 blockers interfere with QT interval

Proton Pump Inhibitors (PPIs)

• All PPIs carry some risk of QT prolongation, but with varying degrees:
  • Pantoprazole: Lowest risk among PPIs 2, 3
    • Has lower propensity to become activated in slightly acidic body compartments
    • Fewer drug-drug interactions than other PPIs
  • Omeprazole: Moderate risk 4
  • Lansoprazole: Higher risk (OR 1.80,95% CI: 1.18-2.76 compared to omeprazole) 4
  • Pantoprazole: Highest risk among studied PPIs (OR 2.14,95% CI 1.52-3.03 compared to omeprazole) 4

Decision Algorithm for Acid-Suppressing Therapy in Patients with QT Concerns

1. First-line therapy: Famotidine (H2 blocker)

   • Starting dose: 20mg twice daily
   • Safe option with minimal QT effects 1, 5
   • Particularly useful for:
     • Patients on multiple QT-prolonging medications
     • Patients with existing QT prolongation
     • Patients with risk factors for QT prolongation (female sex, age >65, electrolyte abnormalities, heart disease)

2. If H2 blocker is insufficient:

   • Consider pantoprazole as the safest PPI option 2, 3
   • Starting dose: 40mg once daily
   • Lower risk of drug interactions compared to other PPIs
   • Monitor QT interval with ECG at baseline and after 2 weeks of therapy 5

3. Avoid if possible:

   • Lansoprazole and rabeprazole due to higher risk of QT prolongation 4
   • Combinations of multiple PPIs or PPI with other QT-prolonging medications 5, 4

Risk Factors for QT Prolongation to Consider

• Female sex
• Age >65 years
• Electrolyte abnormalities (especially hypokalemia, hypomagnesemia)
• Heart disease or bradyarrhythmias
• Concomitant QT-prolonging medications
• Genetic factors affecting drug metabolism (CYP2C19 polymorphisms) 5, 3

Monitoring Recommendations

• Obtain baseline ECG before starting therapy
• Check electrolytes (potassium, magnesium) before starting therapy
• Follow-up ECG at 2 weeks after initiation
• Additional ECG monitoring when adding any new QT-prolonging medication
• Correct any electrolyte abnormalities promptly 5

Clinical Pearls

• Consider on-demand therapy with famotidine for patients with mild symptoms, which may be effective while minimizing medication exposure 6
• The combination of PPIs with other QT-prolonging drugs should be avoided whenever possible 5, 4
• For patients requiring stress ulcer prophylaxis in critical care settings, famotidine is preferred over PPIs when QT prolongation is a concern 1
• In patients with GERD requiring long-term therapy, famotidine may be less effective than PPIs but offers a safer QT profile 6

Remember that while PPIs are generally more effective for acid suppression, the benefit of using a medication with less QT effect may outweigh the slightly reduced efficacy in patients with significant risk factors for arrhythmias.