No Clinically Significant Interaction Between Omeprazole and Co-Amoxiclav
Omeprazole and co-amoxiclav (amoxicillin-clavulanic acid) can be safely prescribed together without dose adjustments, as there is no clinically significant pharmacokinetic or pharmacodynamic interaction between these medications.
Mechanism Analysis
The evidence provided focuses primarily on omeprazole's interactions with other drug classes, particularly:
Clopidogrel interactions: The guidelines extensively discuss omeprazole's effect on clopidogrel metabolism through CYP2C19 inhibition, but this is irrelevant to amoxicillin-clavulanic acid, which does not undergo CYP450 metabolism 1
CYP450-mediated interactions: Omeprazole inhibits CYP2C19 and CYP3A4 enzymes, affecting drugs metabolized through these pathways 2, 3
Amoxicillin-clavulanic acid metabolism: Neither amoxicillin nor clavulanic acid requires hepatic CYP450 metabolism for activation or elimination—both are primarily renally excreted unchanged 4, 5
Why No Interaction Occurs
The fundamental reason these drugs don't interact is their completely different metabolic pathways:
Omeprazole's drug interactions occur through CYP450 enzyme inhibition (particularly CYP2C19 and CYP3A4) or through gastric pH elevation affecting drug absorption 2, 3
Amoxicillin-clavulanic acid absorption and elimination are independent of CYP450 enzymes, occurring primarily through renal excretion 4, 5
The elevated gastric pH from omeprazole does not impair amoxicillin absorption—in fact, one guideline suggests PPIs may enhance amoxicillin stability by preventing acid degradation 6
Clinical Practice Implications
When prescribing these medications together:
Use standard dosing for both medications without adjustment 1, 7
For adults with respiratory infections: amoxicillin-clavulanic acid 500/125 mg three times daily or 875/125 mg twice daily 7
For omeprazole: standard 20-40 mg daily dosing as clinically indicated 6
No timing separation between doses is necessary, unlike with some omeprazole-drug combinations 1
Common Clinical Scenarios
This combination is frequently used when patients require:
Treatment of respiratory infections (sinusitis, pneumonia, bronchitis) while managing gastroesophageal reflux disease 1, 7
Antibiotic therapy in patients with peptic ulcer disease or those at risk for NSAID-induced gastropathy 1
Co-administration in elderly patients with polypharmacy, where both medications may be independently indicated 2
Important Caveat
While omeprazole doesn't interact with amoxicillin-clavulanic acid, be aware that omeprazole has significant interactions with other commonly prescribed medications including clopidogrel, warfarin, diazepam, and certain antiretrovirals 2, 3. Always review the complete medication list for other potential interactions when prescribing omeprazole.