Levothyroxine and Rabeprazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Levothyroxine
Rabeprazole
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.
What happens
Reduced efficacy of levothyroxine and an increased risk of hypothyroidism
Interaction Deep Dive
Proton pump inhibitors (PPIs) may cause hypochlorhydria (low stomach acid), decrease levothyroxine absorption, and affect intragastric pH3. Some pharmacokinetic studies have shown that concomitant use of levothyroxine and PPIs may cause clinically significant increases in TSH levels in patients with hypothyroidism 45. Monitor closely during coadministration and adjust levothyroxine dose if necessary 2. Consider administering levothyroxine at least 4 hours before PPIs 1.
Why it happens (mechanism)
Binding or preventing absorption of T4; changes in gastric pH
Literature reports
2 reports — tap to read
a) Two small pharmacokinetic studies using young, healthy volunteers found that concomitant use of levothyroxine with pantoprazole 40 mg daily or esomeprazole 40 mg daily for 1 week did not significantly affect TSH or thyroxine (T4) AUCs or T4 peak level 67.
b) One study found that patients receiving lansoprazole in addition to levothyroxine for 2 to 6 months had a significant mean TSH increase of 0.69 +/- 1.9 microinternational Units/mL from baseline, and 19% (7 of 37) required a levothyroxine dose increase (mean dose increase, 20 mcg) 5. In another study, median TSH significantly increased by 0.22 milliunits/L in patients taking levothyroxine and a proton pump inhibitor for 6 months. Of 887 patients who had been on a stable levothyroxine dose for at least 2 years prior to initiation of a proton pump inhibitor, 5.6% had a 5 milliunit/L or greater increase in TSH 4.
Common questions
Can I take Levothyroxine and Rabeprazole together?
Reduced efficacy of levothyroxine and an increased risk of hypothyroidism Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levothyroxine and Rabeprazole interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
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 Levothyroxine or Rabeprazole 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 anything you'd monitor while I'm on both?
References (7)
- Centanni M, Duntas L, Feldt-Rasmussen U, et al: ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism. Eur Thyroid J 2025; 14(4):e250123. PubMed
- Liu H, Lu M, Hu J, et al: Medications and food interfering with the bioavailability of levothyroxine: a systematic review. Ther Clin Risk Manag 2023; 19:503-523. DOI
- Product Information: SYNTHROID(R) oral tablets, levothyroxine sodium oral tablets. AbbVie Inc (per FDA), North Chicago, IL, 2024. DailyMed
- Irving S, Vadiveloo T, & Leese GP: Drugs that interact with levothyroxine; an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf) 2015; 82(1):136-141.
- Sachmechi I, Reich DM, Aninyei M, et al: Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract 2007; 13(4):345-349. PubMed
- Ananthakrishnan S, Braverman LE, Levin RM, et al: The effect of famotidine, esomeprazole, and ezetimibe on levothyroxine absorption. Thyroid 2008; 18(5):493-498. DOI
- Dietrich JW, Gieselbrecht K, Holl RW, et al: Absorption kinetics of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res 2006; 38(1):57-59. PubMed
Keep reading about Levothyroxine
Keep reading about Rabeprazole
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