Drug Interaction Report

Doravirine and Primidone: Interaction Details

A pharmacist-reviewed analysis of the Doravirine and Primidone 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
+

Doravirine

Pifeltro Pifeltro®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
Interaction severity
Contraindicated
These should generally not be used together.
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 57 documented Doravirine interactions, 16 are rated contraindicated — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Contraindicated

What happens

Reduced doravirine exposure, reduced efficacy of doravirine and an increased risk of doravirine resistance

Interaction Deep Dive

Concomitant use of doravirine and strong CYP3A inducer, such as PHENobarbital is contraindicated. Coadministration may result in reduced doravirine exposure, loss of doravirine efficacy and development of resistance. In a drug interaction study, coadministration of rifAMPin (strong CYP3A inducer) and doravirine decreased the AUC, Cmax, and Cmin of doravirine by 0.12-fold, 0.43-fold. and 0.03-fold, respectively. Before initiating doravirine, it is recommended to wait at least 4 weeks after discontinuing the CYP3A inducer21.

Why it happens (mechanism)

Induction of CYP3A-mediated doravirine metabolism

Literature reports

1 report — tap to read

a) In a drug interaction study, coadministration of rifAMPin (strong CYP3A inducer) and doravirine decreased the AUC, Cmax, and Cmin of doravirine by 0.12-fold, 0.43-fold. and 0.03-fold, respectively 21.

Common questions

Can I take Doravirine and Primidone together?

Reduced doravirine exposure, reduced efficacy of doravirine and an increased risk of doravirine resistance Always confirm with your pharmacist or prescriber before making any change.

How serious is the Doravirine and Primidone interaction?

It is rated contraindicated. These should generally not be used together.

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 Doravirine or Primidone 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 (2)

  1. Product Information: PIFELTRO(TM) oral tablets, doravirine oral tablets. Merck Sharp & Dohme Corp (per FDA), Whitehouse Station, NJ, 2022. DailyMed
  2. Product Information: DELSTRIGO(TM) oral tablets, doravirine, lamivudine, tenofovir disoproxil fumarate oral tablets. Merck Sharp & Dohme Corp (per FDA), Whitehouse Station, NJ, 2022. DailyMed
Was this write-up helpful?
Primidone

Keep reading about Primidone

All Primidone interactions (204)
Also serious with: Nifedipine Maraviroc Nintedanib Felbamate
Doravirine

Keep reading about Doravirine

All Doravirine interactions (57) Doravirine drug information
Also serious with: Carbamazepine Apalutamide Ensitrelvir Encorafenib
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
Doravirine + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 130 more

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

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
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.