Drug interactions
Clozapine + Fosphenytoin
Severity: Major
Clozapine 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
Phenytoin, the active form of fosphenytoin, induces hepatic enzymes including CYP3A4 and CYP1A2, which can lower clozapine concentrations and risk loss of antipsychotic efficacy. Both drugs can also cause bone marrow suppression, and clozapine lowers the seizure threshold, opposing anticonvulsant therapy.
What this interaction means in plain words
Clozapine 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.
Clozapine belongs to Central Nervous System; Fosphenytoin belongs to Central Nervous System.
Why it happens
Enzyme induction by phenytoin increases clozapine clearance; additive hematologic toxicity is also possible.
What to do
Monitor psychiatric response and clozapine levels, and expect to increase the clozapine dose; reduce it again if the inducer is withdrawn. Monitor the neutrophil count closely and consider alternative anticonvulsants.
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 Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
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 Clozapine with Fosphenytoin?
MediHelp rates the interaction as major. Clozapine 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. Phenytoin, the active form of fosphenytoin, induces hepatic enzymes including CYP3A4 and CYP1A2, which can lower clozapine concentrations and risk loss of antipsychotic efficacy. Both drugs can also cause bone marrow suppression, and clozapine lowers the seizure threshold, opposing anticonvulsant therapy.
How serious is the interaction between Clozapine 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 psychiatric response and clozapine levels, and expect to increase the clozapine dose; reduce it again if the inducer is withdrawn. Monitor the neutrophil count closely and consider alternative anticonvulsants.
What other medicines interact with Clozapine?
MediHelp also lists interactions of Clozapine with, for example, Deferiprone, Irinotecan, Pimozide. The full list is on the Clozapine page.
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