Drug interactions
Phenytoin + Siponimod
Severity: Major
Phenytoin 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
Phenytoin induces CYP3A4 and CYP2C9, the enzymes that clear siponimod, and may lower siponimod exposure and reduce its efficacy. The effect is more important in patients with reduced CYP2C9 function, such as CYP2C9*1/*3 or *2/*3 genotypes.
What this interaction means in plain words
Phenytoin 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.
Phenytoin belongs to Central Nervous System; Siponimod belongs to Central Nervous System.
Why it happens
Induction of CYP3A4 and CYP2C9 by phenytoin increases siponimod metabolism.
What to do
Avoid the combination in patients with CYP2C9*1/*3 or *2/*3 genotypes. In other patients, choose a non-inducing anticonvulsant where possible and monitor for loss of MS disease control.
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 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
Frequently asked questions
Can I take Phenytoin with Siponimod?
MediHelp rates the interaction as major. Phenytoin 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. Phenytoin induces CYP3A4 and CYP2C9, the enzymes that clear siponimod, and may lower siponimod exposure and reduce its efficacy. The effect is more important in patients with reduced CYP2C9 function, such as CYP2C9*1/*3 or *2/*3 genotypes.
How serious is the interaction between Phenytoin 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 in patients with CYP2C9*1/*3 or *2/*3 genotypes. In other patients, choose a non-inducing anticonvulsant where possible and monitor for loss of MS disease control.
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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