Drug interactions
Glycerol phenylbutyrate + Valproic acid
Severity: Major
Glycerol phenylbutyrate and Valproic acid: 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
Glycerol phenylbutyrate is used to lower ammonia in urea cycle disorders, whereas valproate can cause hyperammonemia, sometimes severe, by interfering with the urea cycle. Valproate can therefore counteract the treatment and may precipitate hyperammonemic crises in these patients.
What this interaction means in plain words
Glycerol 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.
Glycerol phenylbutyrate belongs to Miscellaneous; Valproic acid belongs to Central Nervous System.
Why it happens
Valproate inhibits urea cycle function (carbamoyl phosphate synthetase I via carnitine depletion and metabolite effects), opposing ammonia-lowering therapy.
What to do
Avoid valproate in urea cycle disorders when possible and choose another anticonvulsant. If it must be used, monitor plasma ammonia closely and adjust the nitrogen-scavenger therapy.
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 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
Other interactions of Glycerol phenylbutyrate
- Dexamethasone + Glycerol phenylbutyrate Major
- Glycerol phenylbutyrate + Sodium valproate Major
- Cyclosporin + Glycerol phenylbutyrate Moderate
- Dexamethasone-neomycin-polymyxin + Glycerol phenylbutyrate Moderate
- Dexamethasone-tobramycin + Glycerol phenylbutyrate Moderate
- Fludrocortisone + Glycerol phenylbutyrate Moderate
Frequently asked questions
Can I take Glycerol phenylbutyrate with Valproic acid?
MediHelp rates the interaction as major. Glycerol 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. Glycerol phenylbutyrate is used to lower ammonia in urea cycle disorders, whereas valproate can cause hyperammonemia, sometimes severe, by interfering with the urea cycle. Valproate can therefore counteract the treatment and may precipitate hyperammonemic crises in these patients.
How serious is the interaction between Glycerol 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 when possible and choose another anticonvulsant. If it must be used, monitor plasma ammonia closely and adjust the nitrogen-scavenger therapy.
What other medicines interact with Valproic acid?
MediHelp also lists interactions of Valproic acid with, for example, Ertapenem, Imipenem / cilastatin / relebactam, Imipenem / cilastatin. The full list is on the Valproic acid page.
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