Drug interactions
Hydrocortisone + Phenytoin
Severity: Major
Hydrocortisone 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
Phenytoin is a strong inducer of CYP3A4 and P-glycoprotein and substantially accelerates corticosteroid clearance, which can reduce hydrocortisone effect. Corticosteroids can also alter phenytoin levels unpredictably.
What this interaction means in plain words
Hydrocortisone 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.
Hydrocortisone belongs to Endocrine; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induction of CYP3A4 and P-glycoprotein increases hydrocortisone clearance.
What to do
Increase the hydrocortisone dose as needed in adrenal insufficiency and monitor clinical response. Check phenytoin concentrations when steroids are started or stopped.
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 Hydrocortisone
- Hydrocortisone + Mifepristone Contraindicated
- Hydrocortisone + Poliovirus vaccine live oral trivalent Contraindicated
- Hydrocortisone + Smallpox vaccine live Contraindicated
- Adenovirus types 4 and 7 live + Hydrocortisone Major
- Aldesleukin + Hydrocortisone Major
- Aspirin + Hydrocortisone Major
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 Hydrocortisone with Phenytoin?
MediHelp rates the interaction as major. Hydrocortisone 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. Phenytoin is a strong inducer of CYP3A4 and P-glycoprotein and substantially accelerates corticosteroid clearance, which can reduce hydrocortisone effect. Corticosteroids can also alter phenytoin levels unpredictably.
How serious is the interaction between Hydrocortisone 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: Increase the hydrocortisone dose as needed in adrenal insufficiency and monitor clinical response. Check phenytoin concentrations when steroids are started or stopped.
What other medicines interact with Hydrocortisone?
MediHelp also lists interactions of Hydrocortisone with, for example, Mifepristone, Poliovirus vaccine live oral trivalent, Smallpox vaccine live. The full list is on the Hydrocortisone page.
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