Drug interactions
Phenytoin + Tolbutamide
Severity: Moderate
Phenytoin and Tolbutamide: moderate 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
Tolbutamide may increase free phenytoin concentrations, and phenytoin can reduce the glucose-lowering effect of tolbutamide. Phenytoin can also inhibit insulin release and induce metabolism of the sulfonylurea.
What this interaction means in plain words
Phenytoin and Tolbutamide can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Phenytoin belongs to Central Nervous System; Tolbutamide belongs to Endocrine.
Why it happens
Protein-binding displacement and metabolic inhibition affect phenytoin, while phenytoin induces tolbutamide metabolism and impairs insulin secretion.
What to do
Monitor blood glucose closely and adjust tolbutamide dose as needed. Watch for phenytoin toxicity and check free phenytoin levels if it is suspected.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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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
Other interactions of Tolbutamide
- Glyburide-metformin + Tolbutamide Major
- Insulin degludec-liraglutide + Tolbutamide Major
- Aceclofenac + Tolbutamide Moderate
- Acemetacin + Tolbutamide Moderate
- Acetylsalicylic acid + Tolbutamide Moderate
- Albiglutide + Tolbutamide Moderate
Frequently asked questions
Can I take Phenytoin with Tolbutamide?
MediHelp rates the interaction as moderate. Phenytoin and Tolbutamide can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Tolbutamide may increase free phenytoin concentrations, and phenytoin can reduce the glucose-lowering effect of tolbutamide. Phenytoin can also inhibit insulin release and induce metabolism of the sulfonylurea.
How serious is the interaction between Phenytoin and Tolbutamide?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor blood glucose closely and adjust tolbutamide dose as needed. Watch for phenytoin toxicity and check free phenytoin levels if it is suspected.
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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