Omeprazole and Tacrolimus: 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
Tacrolimus
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. Tacrolimus is a medicine that quiets your immune system, often after a transplant. Your body breaks it down using a liver enzyme called CYP3A4. Omeprazole (Prilosec), a common heartburn medicine, can slow that enzyme down a bit. When that happens, tacrolimus can build up in your blood.
Too much tacrolimus can be hard on your kidneys and can lower your blood cell counts. The good news is this is very manageable. Your care team keeps a close eye on tacrolimus with simple blood tests and can adjust your dose so your levels stay right where they should be. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor.
Effect: Increased tacrolimus whole-blood exposure and increased toxicity risk.
Mechanism: Omeprazole inhibits CYP3A4-mediated tacrolimus metabolism, reducing clearance and raising trough concentrations. Effect is most pronounced when CYP2C19 metabolism of omeprazole is efficient (extensive/rapid metabolizers), shunting more toward CYP3A4. Tacrolimus is a narrow-therapeutic-index substrate, so small changes matter.
- Direction: Increased tacrolimus levels (neither drug is a prodrug requiring activation here).
- Evidence: Probable; onset unspecified.
- Management: Consider avoiding coadministration. If used together, monitor tacrolimus trough levels, individualize dose, and watch for nephrotoxicity and myelosuppression.
What happens
Increased tacrolimus exposure and an increased risk of toxicity
Interaction Deep Dive
CYP3A serves as the main metabolic pathway for tacrolimus, and giving omeprazole, which is a substrate of both CYP3A4 and CYP2C19, at the same time could raise tacrolimus concentrations12. In a patient classified as a CYP2C19 extensive metabolizer, combining tacrolimus with omeprazole led to increased trough tacrolimus levels. When these two drugs are taken together, track tacrolimus levels and adjust dosing as needed, while also watching for signs of tacrolimus toxicity (for example, nephrotoxicity, myelosuppression)1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated tacrolimus metabolism by omeprazole
How to manage this interaction
This can be managed with monitoring and dose tailoring. Because tacrolimus is a narrow-margin drug, your team pays close attention when omeprazole is added.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may check tacrolimus blood levels more closely and adjust your dose so it stays in the right range.
- They may watch for signs of too much tacrolimus, such as kidney changes or lower blood counts.
- Sometimes a different acid-reducing medicine may be considered, so ask if that fits you.
Raise any new symptoms (less urination, swelling, unusual tiredness, easy bruising) with your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) An 18-year-old woman, identified as a CYP2C19 extensive metabolizer (normal), was given tacrolimus 6 mg/day together with lansoprazole 30 mg/day as part of an ongoing maintenance regimen following kidney transplantation. Over a period of 9 months, trough tacrolimus blood concentrations stayed within the target range of 5 to 8 nanograms/milliliter (ng/mL; 6.2 to 9.9 nanomol/L). At 8 months after the transplant, her therapy was changed to esomeprazole 40 mg/day, and 1 month afterward she presented with fatigue, ongoing sinusitis, and a tacrolimus level of 27.4 ng/mL (34.07 nanomol/L). Tacrolimus was withheld for 24 hours and subsequently lowered to 4 mg/day, after which the tacrolimus level fell to 9.6 ng/mL (11.94 nanomol/L). Ten days later she presented with nausea, vomiting, a raised serum creatinine, and a tacrolimus level of 13.7 ng/mL (17.04 nanomol/L). Tacrolimus was stopped and the patient was changed to omeprazole 40 mg/day. Three days afterward, the tacrolimus level was still elevated at 20.1 ng/mL (24.99 nanomol/L). Omeprazole was then substituted with lansoprazole, and the patient became free of symptoms with a normalized tacrolimus level. The tacrolimus target concentration of 5 to 8 ng/mL (6.2 to 9.9 nanomol/L) was reached within 1 week, and the dose was adjusted upward to the original 6 mg/day 1.
Common questions
Can I take Omeprazole and Tacrolimus together?
Omeprazole can raise tacrolimus levels and increase toxicity risk, so your care team may avoid the combination or monitor your tacrolimus levels and adjust the dose. Keep taking both as prescribed and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Tacrolimus 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 Tacrolimus interaction managed?
This can be managed with monitoring and dose tailoring. Because tacrolimus is a narrow-margin drug, your team pays close attention when omeprazole is added. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may check tacrolimus blood levels more closely and adjust your dose so it stays in the right range. They may watch for signs of too much tacrolimus, s… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
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 Tacrolimus 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 (3)
- Maguire M, Franz T, & Hains DS: A clinically significant interaction between tacrolimus and multiple proton pump inhibitors in a kidney transplant recipient. Pediatr Transplant 2012; 16(6):E217-E220. PubMed
- Product Information: PROGRAF(R) oral capsules, oral granules for suspension, intravenous injection, tacrolimus oral capsules, oral granules for suspension, intravenous injection. Astellas Pharma US Inc (per FDA), Northbrook, IL, 2023. DailyMed
- Product Information: PRILOSEC(TM) oral delayed release capsules, omeprazole oral delayed release capsules. AstraZeneca LP (per FDA), Wilmington, DE, 2012. DailyMed
Keep reading about Tacrolimus
Keep reading about Omeprazole
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