Drug interactions
Fluconazole + Fosphenytoin
Severity: Major
Fluconazole 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
Fluconazole inhibits the metabolism of phenytoin, the active form of fosphenytoin, which can substantially raise serum phenytoin concentrations. Toxicity such as nystagmus, ataxia, confusion, and sedation may occur, and phenytoin has a narrow therapeutic range with nonlinear kinetics.
What this interaction means in plain words
Fluconazole 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.
Fluconazole belongs to Anti Fungals; Fosphenytoin belongs to Central Nervous System.
Why it happens
Fluconazole inhibits CYP2C9 and CYP2C19, the main enzymes that metabolize phenytoin.
What to do
Monitor phenytoin levels (free levels if albumin is low) and clinical signs of toxicity when starting or stopping fluconazole. Reduce the fosphenytoin dose as guided by levels.
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 Fluconazole
- Dihydroergotamine intranasal + Fluconazole Contraindicated
- Dihydroergotamine + Fluconazole Contraindicated
- Dofetilide + Fluconazole Contraindicated
- Dronedarone + Fluconazole Contraindicated
- Erythromycin + Fluconazole Contraindicated
- Flibanserin + Fluconazole 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 Fluconazole with Fosphenytoin?
MediHelp rates the interaction as major. Fluconazole 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. Fluconazole inhibits the metabolism of phenytoin, the active form of fosphenytoin, which can substantially raise serum phenytoin concentrations. Toxicity such as nystagmus, ataxia, confusion, and sedation may occur, and phenytoin has a narrow therapeutic range with nonlinear kinetics.
How serious is the interaction between Fluconazole 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 (free levels if albumin is low) and clinical signs of toxicity when starting or stopping fluconazole. Reduce the fosphenytoin dose as guided by levels.
What other medicines interact with Fluconazole?
MediHelp also lists interactions of Fluconazole with, for example, Dihydroergotamine intranasal, Dihydroergotamine, Dofetilide. The full list is on the Fluconazole page.
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