Drug Interaction Between Omeprazole and Tramadol
Omeprazole and tramadol can be used together safely without dose adjustments, as there is no clinically significant pharmacokinetic or pharmacodynamic interaction between these two medications. 1, 2
Metabolic Pathways and Lack of Interaction
Tramadol is primarily metabolized by CYP2D6 (for O-demethylation to its active metabolite M1) and by CYP2B6 and CYP3A4 (for N-demethylation to M2), with minimal involvement of CYP2C19. 1
Omeprazole is predominantly metabolized by CYP2C19 and to a lesser extent by CYP3A4, with no significant involvement of CYP2D6 or CYP2B6. 2, 3
Because these medications utilize different primary metabolic pathways, there is no meaningful pharmacokinetic interaction when they are co-administered. 1, 2
Omeprazole can inhibit hepatic cytochrome P450 enzymes (particularly CYP2C19), but this does not affect tramadol metabolism since tramadol does not rely significantly on this pathway. 2, 3
Clinical Implications
No dose adjustments are required when prescribing these medications together. 1, 2
No special timing or separation of doses is necessary for concurrent administration. 1, 2
Standard monitoring for each medication's individual adverse effects is sufficient; no additional monitoring is needed specifically for this combination. 1, 2
Important Distinctions to Avoid Confusion
Do not confuse this interaction profile with the omeprazole-clopidogrel interaction, which is clinically significant due to shared CYP2C19 metabolism, though even that interaction has been shown not to increase ischemic events in randomized trials. 4
The case report describing trazodone-omeprazole interaction causing AV block 5 is not relevant to tramadol, as trazodone has entirely different pharmacologic properties and cardiac effects compared to tramadol.
Relevant Tramadol Interactions to Monitor
While omeprazole is safe with tramadol, be aware of tramadol's actual clinically significant interactions:
Avoid concurrent use with MAO inhibitors due to risk of hypertensive crisis and serotonin syndrome. 4
Use caution with serotonergic antidepressants (SSRIs, SNRIs), particularly in elderly patients, higher tramadol doses, or with potent CYP2D6 inhibitors, though this combination is not contraindicated. 6
Avoid concurrent use with benzodiazepines due to increased risk of respiratory depression and CNS depression. 4, 7
Monitor for hyponatremia/SIADH, as tramadol was added to the 2019 Beers Criteria list of drugs associated with this adverse effect in older adults. 4