Drug Interaction Report

Primidone and Levothyroxine: Interaction Details

A pharmacist-reviewed analysis of the Primidone and Levothyroxine interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Primidone

Mysoline
+

Levothyroxine

Ermeza Euthyrox Levo-T Levo-T® Levothroid® Levoxyl Levoxyl® Synthroid
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
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.

Of 204 documented Primidone interactions, 10 are rated moderate — including this one.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Reduced levothyroxine exposure and reduced efficacy of levothyroxine

Interaction Deep Dive

PHENobarbital or primidone (prodrug of PHENobarbital) increases L-thyroxine metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Concomitant use of levothyroxine and PHENobarbital may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements21.

Why it happens (mechanism)

Induction of uridine 5-diphospho-glucuronosyltransferase (UGT)

Common questions

Can I take Primidone and Levothyroxine together?

Reduced levothyroxine exposure and reduced efficacy of levothyroxine Always confirm with your pharmacist or prescriber before making any change.

How serious is the Primidone and Levothyroxine 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Primidone or Levothyroxine 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 (2)

  1. Product Information: LEVO-T® oral tablets, levothyroxine sodium oral tablets. Neolpharma Inc, Caguas, PR, 2026. DailyMed
  2. Product Information: TIROSINT(R)-SOL oral solution, levothyroxine sodium oral solution. IBSA Pharma Inc. (per FDA), Parsippany, NJ, 2023. DailyMed
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Primidone

Keep reading about Primidone

All Primidone interactions (204)
Also serious with: Nifedipine Maraviroc Doravirine Orlistat
Levothyroxine

Keep reading about Levothyroxine

All Levothyroxine interactions (214) Levothyroxine drug information
Also serious with: Furosemide Polystyrene Sulfonate Insulin Glargine, Recombinant Ferrous Sulfate
Beyond drug–drug

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:

Primidone + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Kava L-tryptophan Wine 5-htp + 116 more
Levothyroxine + Activated Charcoal Tiratricol Acetyl-l-carnitine Alpha-lipoic Acid Ascophyllum Nodosum Ashwagandha Bugleweed Calcium + 42 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.