Drug interactions
Fosphenytoin + Siponimod
Severity: Major
Fosphenytoin and Siponimod: 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
Fosphenytoin is converted to phenytoin, which induces CYP3A4 and CYP2C9 and can substantially reduce siponimod concentrations. This may lead to loss of efficacy in multiple sclerosis. The effect is greater in patients with impaired CYP2C9 function who rely on CYP3A4.
What this interaction means in plain words
Fosphenytoin and Siponimod 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 belongs to Central Nervous System; Siponimod belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4 and CYP2C9, increasing siponimod clearance and lowering exposure.
What to do
Avoid the combination and choose a non-inducing anticonvulsant where feasible. Siponimod labeling advises against use with combined moderate CYP2C9 and CYP3A4 inducers, and with CYP3A4 inducers alone in CYP2C9*1/*3 or *2/*3 patients.
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 Siponimod
- Cladribine + Siponimod Contraindicated
- Fingolimod + Siponimod Contraindicated
- Fluconazole + Siponimod Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Siponimod Contraindicated
- Ponesimod + Siponimod Contraindicated
- Siponimod + Thioridazine 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 Fosphenytoin with Siponimod?
MediHelp rates the interaction as major. Fosphenytoin and Siponimod 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 induces CYP3A4 and CYP2C9 and can substantially reduce siponimod concentrations. This may lead to loss of efficacy in multiple sclerosis. The effect is greater in patients with impaired CYP2C9 function who rely on CYP3A4.
How serious is the interaction between Fosphenytoin and Siponimod?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination and choose a non-inducing anticonvulsant where feasible. Siponimod labeling advises against use with combined moderate CYP2C9 and CYP3A4 inducers, and with CYP3A4 inducers alone in CYP2C9*1/*3 or *2/*3 patients.
What other medicines interact with Siponimod?
MediHelp also lists interactions of Siponimod with, for example, Cladribine, Fingolimod, Fluconazole. The full list is on the Siponimod page.
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