Levothyroxine and Rifampin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rifampin
Levothyroxine
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
Interaction Deep Dive
Coadministration of levothyroxine and rifAMPin may reduce levothyroxine exposure68. Concomitant use may increase clearance of levothyroxine resulting in increased levothyroxine requirements 21. Increased clearance of levothyroxine induced by rifAMPin may return the patient to a hypothyroid state with a compensatory rise in the TSH level 10. However, in 1 study, thyroxine AUC was increased by 25% with coadministration of oral levothyroxine 1000 mcg and rifAMPin 600 mg. Closer monitoring of thyroid status may be warranted 4.
Why it happens (mechanism)
Induction of levothyroxine metabolism by rifAMPin
Literature reports
4 reports — tap to read
a) RifAMPin has been shown to accelerate the metabolism of levothyroxine, resulting in increased requirement of levothyroxine 5.
b) During a prospective, double-blind, randomized study in healthy adult volunteers (n=8), mean baseline-corrected thyroxine (T4) AUC was significantly increased (25%; p=0.003) with coadministration of rifAMPin and levothyroxine compared with crossover treatment with placebo and levothyroxine (p=0.035). Study doses were levothyroxine 1000 mcg orally and rifAMPin 600 mg orally. The washout period between study days was at least 4 weeks. Total plasma T4 concentrations were measured over a 6-hour period after dosing. This effect of rifAMPin was unexpected and the exact mechanism of the interaction was unknown 4.
c) A 31-year old female with Turner's syndrome was maintained on levothyroxine 0.1 mg daily following a total thyroidectomy. When nafcillin could not eradicate a staphylococcus aureus infection, rifAMPin 300 mg every 12 hours was added to therapy. Although the dose of levothyroxine stayed constant during the course of hospitalization, the serum thyroxine levels and free thyroxine index decreased during rifAMPin therapy and the serum thyrotropin levels increased. The patient did not develop any symptoms of hypothyroidism. These effects were attributed to an increased metabolic clearance of levothyroxine caused by rifAMPin. The administration of rifAMPin in normal-thyroid patients will not induce hypothyroidism because the basal and stimulated serum thyrotropin levels remain unchanged. However, in this patient, the increase in levothyroxine clearance induced by rifAMPin resulted in a marked increased in serum thyrotropin because the patient did not have an intact thyroid 9.
d) A 50-year-old male with a thyroid-stimulating hormone (TSH) level of 8.52 mIU/L was started on levothyroxine 0.025 mg daily. Two and four months later, his TSH level was 3.67 mIU/L and 4.67 mIU/L, respectively. At approximately the same time, the patient experienced a methicillin resistant staphylococcus aureus wound infection following coronary artery bypass surgery. Despite aggressive and long-term treatment with vancomycin, the infection persisted. Oral rifAMPin 600 mg daily was added to the vancomycin regimen for synergy and a total of 14 days of combination therapy was completed. Three days after rifAMPin was discontinued, the TSH was measured at 9.44 mIU/L, although the patient did not show signs of hypothyroidism. The levothyroxine dose was increased to 0.05 mg daily, and the TSH level dropped to 4.34 mIU/L nine days after rifAMPin was stopped 10.
Common questions
Can I take Levothyroxine and Rifampin together?
Reduced efficacy of levothyroxine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levothyroxine and Rifampin interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
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 Rifampin 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 (10)
- Product Information: LEVO-T® oral tablets, levothyroxine sodium oral tablets. Neolpharma Inc, Caguas, PR, 2026. DailyMed
- Product Information: TIROSINT(R)-SOL oral solution, levothyroxine sodium oral solution. IBSA Pharma Inc. (per FDA), Parsippany, NJ, 2023. DailyMed
- Product Information: TIROSINT(R) oral capsule, levothyroxine sodium oral capsule. Provell Pharma Inc (per DailyMed), Parsippany, NJ, 2022. DailyMed
- Goldberg AS, Tirona RG, Asher LJ, et al: Ciprofloxacin and rifampin have opposite effects on levothyroxine absorption. Thyroid 2013; 23(11):1374-1378. PubMed
- Product Information: SYNTHROID(R) oral tablets, levothyroxine sodium oral tablets. AbbVie Inc (per FDA), North Chicago, IL, 2024. DailyMed
- Product Information: RIFADIN(R) IV intravenous injection, rifampin intravenous injection. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFADIN(R) oral capsules, rifampin oral capsules. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Isley WL: Effect of rifampin therapy on thyroid function tests in a hypothyroid patients on replacement L-thyroxine. Ann Intern Med 1987; 107:517-518.
- Nolan SR, Self TH, & Norwood JM: Interaction between rifampin and levothyroxine. South Med J 1999; 92:529-531. PubMed
Keep reading about Rifampin
Keep reading about Levothyroxine
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