Phenytoin and Trimethoprim Sulfamethoxazole: Drug Interaction Guide

Quick answer: This combination requires caution. Phenytoin and Trimethoprim Sulfamethoxazole can be used together with adjustments and monitoring.

Interaction severity: Moderate — caution required

How Phenytoin interacts with Trimethoprim Sulfamethoxazole

Sulfamethoxazole inhibits CYP2C9-mediated metabolism of phenytoin and may displace it from protein binding, increasing free phenytoin levels and risk of toxicity.

What you should do

Monitor phenytoin levels (preferably free phenytoin if available) and watch for nystagmus, ataxia, and confusion; adjust phenytoin dose downward if toxicity occurs.

Key facts

Severity

Moderate — caution required

Mechanism

Sulfamethoxazole inhibits CYP2C9-mediated metabolism of phenytoin and may displace it from protein binding, increasing f...

Action

Monitor phenytoin levels (preferably free phenytoin if available) and watch for nystagmus, ataxia, and confusion; adjust...

Important medical disclaimer: This page provides educational information about drug interactions for general reference. It is not a substitute for professional medical advice, diagnosis, or treatment. Always discuss your specific medications with a qualified healthcare provider before starting, stopping, or changing any treatment. About our editorial team.

Frequently asked questions

Can I take Phenytoin and Trimethoprim Sulfamethoxazole together?

With caution. Monitor phenytoin levels (preferably free phenytoin if available) and watch for nystagmus, ataxia, and confusion; adjust phenytoin dose downward if toxicity occurs.

What is the severity of this interaction?

The interaction between Phenytoin and Trimethoprim Sulfamethoxazole is classified as Moderate — caution required. Sulfamethoxazole inhibits CYP2C9-mediated metabolism of phenytoin and may displace it from protein binding, increasing free phenytoin levels and risk of toxicity.

What should I do if I'm prescribed both?

Monitor phenytoin levels (preferably free phenytoin if available) and watch for nystagmus, ataxia, and confusion; adjust phenytoin dose downward if toxicity occurs. Always consult your prescribing clinician — do not stop or change medications without medical guidance.

Last reviewed: by iMedic Medical Editorial Team. Our editorial process.