Drug interactions
Benzhydrocodone / acetaminophen + Phenytoin
Severity: Major
Benzhydrocodone / acetaminophen and Phenytoin: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Benzhydrocodone is a prodrug of hydrocodone, which is cleared by CYP3A4. Phenytoin induction lowers hydrocodone levels and may cause loss of analgesia or withdrawal. Stopping phenytoin later may allow hydrocodone to rise, with a risk of fatal respiratory depression.
What this interaction means in plain words
Benzhydrocodone / acetaminophen and Phenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Phenytoin induces CYP3A4, accelerating hydrocodone metabolism; this effect reverses when phenytoin is stopped.
What to do
Monitor pain control and for opioid withdrawal during co-administration. If phenytoin is stopped or its dose reduced, monitor for respiratory depression and sedation and reduce the opioid dose as needed.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Benzhydrocodone / acetaminophen with Phenytoin?
MediHelp rates the interaction as major. Benzhydrocodone / acetaminophen and Phenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Benzhydrocodone is a prodrug of hydrocodone, which is cleared by CYP3A4. Phenytoin induction lowers hydrocodone levels and may cause loss of analgesia or withdrawal. Stopping phenytoin later may allow hydrocodone to rise, with a risk of fatal respiratory depression.
How serious is the interaction between Benzhydrocodone / acetaminophen and Phenytoin?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor pain control and for opioid withdrawal during co-administration. If phenytoin is stopped or its dose reduced, monitor for respiratory depression and sedation and reduce the opioid dose as needed.
What other medicines interact with Phenytoin?
MediHelp also lists interactions of Phenytoin with, for example, Artemether / lumefantrine, Bictegravir, Cabotegravir. The full list is on the Phenytoin page.
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