Levofloxacin Absorption with Proton Pump Inhibitors
Proton pump inhibitors reduce levofloxacin absorption minimally, with studies showing approximately 20-40% reduction in bioavailability, but this decrease is not considered clinically significant and does not warrant dose adjustment.
Magnitude of Absorption Reduction
The interaction between PPIs and levofloxacin has been specifically studied with pantoprazole, which provides the clearest quantitative data:
- Peak concentration (Cmax) reduction: Approximately 40% decrease when levofloxacin 150 mg was co-administered with pantoprazole 40 mg twice daily for 48 hours 1
- Overall bioavailability (AUC) reduction: Approximately 20-32% decrease in steady-state area under the curve 2, 1
- Mechanism: PPIs raise gastric pH from approximately 2.2 to 5.9, and levofloxacin has pH-dependent solubility that decreases with higher pH 2
Clinical Significance
Despite these measurable reductions in absorption, the clinical impact is minimal:
- No dose adjustment required: The magnitude of reduction in drug exposure does not necessitate changing levofloxacin dosing when PPIs are co-prescribed 2
- Therapeutic efficacy maintained: Small corresponding changes in pharmacodynamic markers (ECT, aPTT) were not believed to have clinical importance 2
- Time to peak delayed: Cmax occurs at the same time point regardless of PPI co-administration, unlike food which delays absorption 1
Comparison to Other Interactions
This interaction is substantially less severe than with divalent/trivalent cations:
- Antacids containing aluminum, magnesium, calcium, or iron: These agents cause marked decreases in levofloxacin absorption and require separation of administration by at least 2 hours 3, 1, 4
- Ferrous sulfate: Significantly impairs absorption, requiring temporal separation 1
- Sucralfate: Reduces absorption when given concurrently, but effect is eliminated with 2-hour separation 1
Practical Implications
When prescribing levofloxacin with PPIs:
- Continue both medications without timing adjustments: Unlike antacids, PPIs and levofloxacin can be administered together 2
- Standard levofloxacin dosing applies: Use 500-750 mg once daily for most infections, or 750-1,000 mg daily for drug-resistant tuberculosis, regardless of PPI use 3, 5
- Monitor clinical response: The 20-40% reduction in bioavailability falls within the therapeutic window for most indications 2, 1
Special Considerations
The PPI-levofloxacin interaction differs from other drug classes:
- Dabigatran comparison: PPIs similarly reduce dabigatran peak concentrations, but dose adjustment is also not warranted for that medication 2
- H2-receptor antagonists: Cimetidine and ranitidine have minimal effects on levofloxacin pharmacokinetics through different mechanisms (reduced renal clearance rather than absorption) 1