Drug interactions
Fluoxetine + Fosphenytoin
Severity: Major
Fluoxetine and Fosphenytoin: major interaction.
Last updated Sources: US FDA label
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
Fosphenytoin is converted to phenytoin, which is metabolised by CYP2C9 and CYP2C19. Fluoxetine inhibits these enzymes and has been associated with increased phenytoin concentrations and toxicity. Because phenytoin has a narrow therapeutic index and saturable kinetics, the rise can be substantial.
What this interaction means in plain words
Fluoxetine and Fosphenytoin 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.
Fluoxetine belongs to Central Nervous System; Fosphenytoin belongs to Central Nervous System.
Why it happens
Fluoxetine and norfluoxetine inhibit CYP2C9 and CYP2C19, decreasing phenytoin clearance.
What to do
Monitor phenytoin levels and signs of toxicity (nystagmus, ataxia, confusion) when starting or stopping fluoxetine, and reduce the dose if 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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References
Other interactions of Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Other interactions of Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Fluoxetine with Fosphenytoin?
MediHelp rates the interaction as major. Fluoxetine and Fosphenytoin 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. Fosphenytoin is converted to phenytoin, which is metabolised by CYP2C9 and CYP2C19. Fluoxetine inhibits these enzymes and has been associated with increased phenytoin concentrations and toxicity. Because phenytoin has a narrow therapeutic index and saturable kinetics, the rise can be substantial.
How serious is the interaction between Fluoxetine and Fosphenytoin?
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 phenytoin levels and signs of toxicity (nystagmus, ataxia, confusion) when starting or stopping fluoxetine, and reduce the dose if needed.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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