Omeprazole and Methadone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methadone
Omeprazole
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Here's what's going on. Your body uses an enzyme called CYP2C19 to break down methadone. Omeprazole (Prilosec) can slow that enzyme down. When that happens, methadone may build up in your blood a little more than usual, which can increase opioid side effects like heavy drowsiness, slowed breathing, and feeling very sedated.
I want to be honest: this is based mostly on how the drugs work rather than a lot of real-world reports. Still, methadone is a medicine we watch carefully, so it's worth flagging. Please don't stop or change either medicine on your own. Just check in with your pharmacist or doctor so they can keep an eye on you and adjust things if needed.
Effect: Omeprazole (a CYP2C19 inhibitor) may reduce methadone (a CYP2C19 substrate) metabolism, increasing methadone plasma concentrations and the risk of opioid toxicity, including sedation and potentially fatal respiratory depression.
- Direction: Increased methadone exposure (neither drug is a prodrug requiring activation here).
- Onset: Unspecified; highest concern when an inhibitor is added to a stable methadone regimen.
- Evidence: Theoretical; magnitude not quantified.
- Management: Consider methadone dose reduction and monitor closely for respiratory depression and sedation. On omeprazole discontinuation, watch for withdrawal and consider a methadone dose increase.
What happens
Increased methadone exposure and an increased risk of opioid adverse effects
Interaction Deep Dive
Because methadone is metabolized by CYP2C19, taking it together with an agent that inhibits this enzyme can raise methadone plasma levels, extend opioid-related adverse effects, and potentially produce fatal respiratory depression; this risk is especially notable when the inhibitor is introduced after the patient has already reached a stable methadone dose. In patients on methadone who require a concurrent CYP2C19 inhibitor, a reduction in the methadone dose should be considered, and these patients should be monitored closely and frequently for indications of sedation and respiratory depression. If the CYP2C19 inhibitor is later stopped, monitor for evidence of opioid withdrawal and consider raising the methadone dose as needed1234.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism of methadone
How to manage this interaction
The good news is your care team can manage this. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your methadone dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for a while.
- Watch for extra drowsiness, confusion, or slow or shallow breathing, and get help right away if breathing feels difficult.
- If the omeprazole is ever stopped, tell your team, since your methadone dose may need adjusting to avoid withdrawal.
- Ask your pharmacist before adding any new medicine, including over-the-counter heartburn products.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Omeprazole and Methadone together?
Omeprazole may raise methadone levels and increase opioid side effects like sedation and slowed breathing, so keep taking both as prescribed and ask your care team to monitor you and adjust the methadone dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Methadone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Omeprazole and Methadone interaction managed?
The good news is your care team can manage this. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your methadone dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for a while. Watch for extra drowsiness, confusion, or slow or shallow breathing, and get help right away if breathing feels difficult. If… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole or Methadone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: DOLOPHINE(R) oral tablets, methadone HCl oral tablets. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2019. DailyMed
- Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
- Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
- Product Information: Methadone HCl injection, methadone HCl injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2023. DailyMed
Keep reading about Methadone
Keep reading about Omeprazole
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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