Drug Interaction Report

Phenytoin and Doxycycline Injection: Interaction Details

A pharmacist-reviewed analysis of the Phenytoin and Doxycycline Injection 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

Phenytoin

Dilantin Phenytek
+

Doxycycline Injection

Acticlate Adoxa Alodox Avidoxy Doryx Doxy Doxy 100® Doxy 200®
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
Major
Potentially serious — often needs a change or close 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 237 documented Phenytoin interactions, 191 are rated major — 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
delayed
Evidence
theoretical
Severity
Major

What happens

Reduced doxycycline exposure

Interaction Deep Dive

Concurrent administration of phenytoin or fosphenytoin (prodrug of phenytoin) and doxycycline have resulted in reduced doxycycline exposure. Consider doxycycline dose adjustments to achieve optimal clinical response when phenytoin or fosphenytoin is added to or withdrawn from a patient's regimen123. Clinical studies have shown that concurrent use of doxycycline and phenytoin or fosphenytoin (prodrug of phenytoin) has resulted in significantly shorter doxycycline half-life and lower mean serum levels 45.

Why it happens (mechanism)

Induction of hepatic drug-metabolizing enzymes by phenytoin

Literature reports

1 report — tap to read

a) Clinical studies have shown that concurrent use of doxycycline and phenytoin has resulted in significantly shorter doxycycline half-life and lower mean serum levels 45.

Common questions

Can I take Phenytoin and Doxycycline Injection together?

Reduced doxycycline exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Phenytoin and Doxycycline Injection interaction?

It is rated major. Potentially serious — often needs a change or close 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Phenytoin or Doxycycline Injection 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 (5)

  1. Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
  2. Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
  3. Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
  4. Neuvonen PJ, Penttila O, Lehtovaara R, et al: Effect of antiepileptic drugs on the elimination of various tetracycline derivatives. Eur J Clin Pharmacol 1975; 9:147-154. PubMed
  5. Penttila O, Neuvonen PJ, Aho K, et al: Interaction between doxycycline and some antiepileptic drugs. Br Med J 1974; 2:470-472. DOI
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Phenytoin

Keep reading about Phenytoin

All Phenytoin interactions (237)
Also serious with: Doravirine Lurasidone Cabotegravir Fostemsavir
Doxycycline Injection

Keep reading about Doxycycline Injection

All Doxycycline Injection interactions (118) Doxycycline Injection drug information
Also serious with: Acitretin Acenocoumarol Amobarbital Amoxicillin
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:

Phenytoin + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Kava L-tryptophan Siberian Cocklebur St. John's Wort + 216 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.