Drug interactions
Sodium phenylbutyrate + Valproic acid
Severity: Major
Sodium phenylbutyrate and Valproic acid: major interaction.
Last updated Sources: UK SmPC
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
Valproate can cause hyperammonemia and may counteract the ammonia-lowering effect of phenylbutyrate in urea cycle disorders. This can precipitate hyperammonemic encephalopathy.
What this interaction means in plain words
Sodium phenylbutyrate and Valproic acid 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.
Sodium phenylbutyrate belongs to Miscellaneous; Valproic acid belongs to Central Nervous System.
Why it happens
Valproate inhibits urea cycle function and depletes carnitine, which raises ammonia.
What to do
Avoid valproate in urea cycle disorders if possible and choose another anticonvulsant. If unavoidable, monitor plasma ammonia closely.
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
- Ammonaps 500 mg tablets - SmPC sections 4.3/4.5 (names the partner; "There have been published reports of hyperammonaemia being induced by haloperidol and by valproate.") — electronic medicines compendium (UK SmPC)
Other interactions of Sodium phenylbutyrate
- Haloperidol + Sodium phenylbutyrate Moderate
- Probenecid + Sodium phenylbutyrate Moderate
Other interactions of Valproic acid
- Ertapenem + Valproic acid Contraindicated
- Imipenem / cilastatin / relebactam + Valproic acid Contraindicated
- Imipenem / cilastatin + Valproic acid Contraindicated
- Meropenem / vaborbactam + Valproic acid Contraindicated
- Meropenem + Valproic acid Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Valproic acid Major
Frequently asked questions
Can I take Sodium phenylbutyrate with Valproic acid?
MediHelp rates the interaction as major. Sodium phenylbutyrate and Valproic acid 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. Valproate can cause hyperammonemia and may counteract the ammonia-lowering effect of phenylbutyrate in urea cycle disorders. This can precipitate hyperammonemic encephalopathy.
How serious is the interaction between Sodium phenylbutyrate and Valproic acid?
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 valproate in urea cycle disorders if possible and choose another anticonvulsant. If unavoidable, monitor plasma ammonia closely.
What other medicines interact with Sodium phenylbutyrate?
MediHelp also lists interactions of Sodium phenylbutyrate with, for example, Haloperidol, Probenecid. The full list is on the Sodium phenylbutyrate page.
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