Levofloxacin and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Levofloxacin
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
Decrease in phenytoin levels
Interaction Deep Dive
In 2 case reports, coadministration of levofloxacin and phenytoin resulted in difficulty achieving therapeutic levels of phenytoin despite repeated increases of phenytoin dosage. High dosages of phenytoin were needed to reach plasma concentrations in the therapeutic range until levofloxacin was discontinued. In one case, the patient was rechallenged with levofloxacin and had a similar decrease in phenytoin levels. The Drug Interaction Probability Scale rated these interactions as probable1.
Why it happens (mechanism)
Unspecified
Literature reports
2 reports — tap to read
a) A 46-year-old man receiving valproic acid and phenytoin for non-convulsive epileptic status following a triple coronary bypass and receiving levofloxacin for suspected ventilator-associated pneumonia, required high dosages of phenytoin to reach plasma concentrations in the therapeutic range. Levofloxacin was discontinued resulting in adequate phenytoin plasma levels. Levofloxacin was subsequently reintroduced and despite high phenytoin doses, once again resulted in a decrease in phenytoin levels. Levofloxacin was discontinued a second time and phenytoin dosage was decreased resulting in an increase in phenytoin levels after 48 hours. The Drug Interaction Probability Scale rated this interaction as probable 1.
b) A 31-year-old man with severe craniocerebral trauma was receiving levofloxacin for ventilator-associated pneumonia and prophylactic phenytoin. Despite the administration of a phenytoin loading dose, levels were subtherapeutic and repeated dosage increases were required. When levofloxacin was discontinued, the free fraction of phenytoin increased to greater than 100%. The Drug Interaction Probability Scale rated this interaction as probable 1.
Common questions
Can I take Levofloxacin and Phenytoin together?
Decrease in phenytoin levels Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levofloxacin and Phenytoin 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.
Questions for your pharmacist
- Does my dose of Levofloxacin or Phenytoin 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 (1)
- Catala Ripoll JV, Domingo Chiva E, & Marco Del Rio J: Interaction between levofloxacin and phenytoin: report of two cases. Med Clin (Barc) 2017; 149(6):278-279. DOI
Keep reading about Phenytoin
Keep reading about Levofloxacin
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