Drug Interaction Report

Fosphenytoin and Linezolid Injection: Interaction Details

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

Fosphenytoin

Cerebyx
+

Linezolid Injection

Zyvox Zyvox®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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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 267 documented Fosphenytoin interactions, 31 are rated moderate — including this one.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Decreased linezolid serum concentrations

Interaction Deep Dive

Concomitant administration of linezolid and rifampin has resulted in decreased linezolid Cmax and AUC concentrations in studies in healthy males. Other strong inducers of hepatic enzymes, such as phenytoin, may cause a similar or smaller decrease in linezolid exposure1. Caution is advised if these agents are coadministered and monitor patients closely for loss of linezolid efficacy.

Why it happens (mechanism)

Altered linezolid metabolism due to hepatic enzyme induction

Literature reports

1 report — tap to read

a) In a pharmacokinetic study, concomitant administration of linezolid and rifampin, a strong CYP450 inducer, resulted in decreased linezolid concentrations. Healthy adult males (n=16) were administered oral linezolid 600 mg twice daily for 5 doses with and without rifampin 600 mg once daily for 8 days. Concomitant administration led to a 21% decrease in linezolid Cmax (90% CI 15% to 27%) and a 32% decrease in linezolid AUC (90% CI 27% to 37%). The exact mechanism for this is not known but other strong inducers of hepatic enzymes, such as phenytoin, may cause a similar or smaller decrease in linezolid exposure 1.

Common questions

Can I take Fosphenytoin and Linezolid Injection together?

Decreased linezolid serum concentrations Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fosphenytoin and Linezolid Injection 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 Fosphenytoin or Linezolid 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 anything you'd monitor while I'm on both?

References (1)

  1. Product Information: ZYVOX(R) oral suspension, oral tablets, solution for IV injection, linezolid oral suspension, oral tablets, solution for IV injection. Pharmacia & Upjohn Company, New York, NY, 2009. DailyMed
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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.