The short answer
If you take valproate for epilepsy, avoid St John’s wort: UK regulatory guidance advises against combining it with any antiepileptic medicine. This is a seizure-control precaution, not proof that St John’s wort lowers valproate levels or causes added sedation.
What this answer covers
Oral Hypericum perforatum with valproate. Class-wide regulatory advice specifically addresses epilepsy; other indications require separate clinical review.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- valproate
The strongest advice concerns epilepsy
MHRA extended its warning to all antiepileptic medicines after a report of more frequent and severe seizures with St John’s wort and several other seizure medicines. Those drugs were levetiracetam, lamotrigine and clobazam, not valproate. The recommendation nevertheless explicitly covers the whole antiepileptic group.
A CYP explanation is not enough
St John’s wort is often discussed as an enzyme-inducing herb. Valproate is handled mainly through glucuronidation and beta-oxidation; CYP oxidation is relatively minor. Evidence about a CYP3A interaction with another medicine cannot by itself establish reduced valproate levels or absorption. MHRA considered possible routes beyond recognized CYP pathways.
Sedation is a separate question
The regulatory warning is about possible loss of seizure control. It does not demonstrate additive sedation from St John’s wort and valproate. Valproate can cause drowsiness on its own, but that fact does not verify every herbal sedation warning. The risk and direction of a specific concentration interaction remain uncertain.
Act on the indication and current use
For epilepsy, follow the advice to avoid St John’s wort rather than trying to solve the concern by spacing doses. If you already use it, contact the treating team to review changes safely. If valproate is prescribed for another reason, discuss that indication and all other medicines individually. Do not stop valproate abruptly.
Evidence and practical considerations
Absorption & effectiveness
Narrow to a regulatory class-wide concern about seizure control in epilepsy; no demonstrated valproate absorption or concentration change.
- Exact scope
- Oral Hypericum perforatum with valproate. Class-wide regulatory advice specifically addresses epilepsy; other indications require separate clinical review. with Oral valproate active moiety (RxNorm 40254 IN), with formulation boundaries preserved.
- Medication form and route
- oral valproate; oral supplement
What remains uncertain
- Evidence does not quantify all-product interaction risk; source-specific limits apply.
Factors that may matter: Indication; Exact preparation; Other sedating medicines.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed oral valproic acid; valproate somnolence trial in elderly dementia patients.
Valproate may impair alertness, especially with other CNS depressants. Older adults may have more somnolence. Major metabolic pathways are glucuronidation and beta-oxidation; CYP oxidation is relatively minor. Serious liver injury is an intrinsic risk.
How this applies: Explicit oral active-moiety bridge to RxNorm IN 40254 valproate; no dose conversion or intravenous extrapolation.
No named interaction with the seven supplements. Active-moiety relevance does not establish identical kinetics or dosing for every valproate formulation.
Source 2: regulatory safety communication
gov.uk · Source check Sep 10, 2026
Population: People with epilepsy taking antiepileptic medicines.
Advises people with epilepsy not to use St John’s wort with any antiepileptic medicine. Triggering report involved increased seizures with levetiracetam, lamotrigine and clobazam; warning extended beyond recognized CYP pathways.
How this applies: Regulatory recommendation applies to valproate when used for epilepsy; underlying case and mechanism remain indirect.
Triggering case did not involve valproate. This is an explicit class-wide precaution, not proof of valproate-specific pharmacokinetic loss or sedation.
Research assessment: · Open full citations ↗
Side effects & toxicity
The antiepileptic warning concerns seizure control and does not support the separate sedation statement. No qualifying direct clinical sedation evidence found in targeted sources.
- Exact scope
- Oral Hypericum perforatum with valproate. Class-wide regulatory advice specifically addresses epilepsy; other indications require separate clinical review. with Oral valproate active moiety (RxNorm 40254 IN), with formulation boundaries preserved.
- Medication form and route
- oral valproate; oral supplement
What remains uncertain
- Evidence does not quantify all-product interaction risk; source-specific limits apply.
Factors that may matter: Indication; Exact preparation; Other sedating medicines.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed oral valproic acid; valproate somnolence trial in elderly dementia patients.
Valproate may impair alertness, especially with other CNS depressants. Older adults may have more somnolence. Major metabolic pathways are glucuronidation and beta-oxidation; CYP oxidation is relatively minor. Serious liver injury is an intrinsic risk.
How this applies: Explicit oral active-moiety bridge to RxNorm IN 40254 valproate; no dose conversion or intravenous extrapolation.
No named interaction with the seven supplements. Active-moiety relevance does not establish identical kinetics or dosing for every valproate formulation.
Source 2: regulatory safety communication
gov.uk · Source check Sep 10, 2026
Population: People with epilepsy taking antiepileptic medicines.
Advises people with epilepsy not to use St John’s wort with any antiepileptic medicine. Triggering report involved increased seizures with levetiracetam, lamotrigine and clobazam; warning extended beyond recognized CYP pathways.
How this applies: Regulatory recommendation applies to valproate when used for epilepsy; underlying case and mechanism remain indirect.
Triggering case did not involve valproate. This is an explicit class-wide precaution, not proof of valproate-specific pharmacokinetic loss or sedation.
Research assessment: · Open full citations ↗
Timing & monitoring
Avoidance is supported for people with epilepsy by explicit MHRA class-wide advice. No protective spacing rule and no automatic extension of that guidance to other indications.
- Exact scope
- Oral Hypericum perforatum with valproate. Class-wide regulatory advice specifically addresses epilepsy; other indications require separate clinical review. with Oral valproate active moiety (RxNorm 40254 IN), with formulation boundaries preserved.
- Medication form and route
- oral valproate; oral supplement
What remains uncertain
- Evidence does not quantify all-product interaction risk; source-specific limits apply.
Factors that may matter: Indication; Exact preparation; Other sedating medicines.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed oral valproic acid; valproate somnolence trial in elderly dementia patients.
Valproate may impair alertness, especially with other CNS depressants. Older adults may have more somnolence. Major metabolic pathways are glucuronidation and beta-oxidation; CYP oxidation is relatively minor. Serious liver injury is an intrinsic risk.
How this applies: Explicit oral active-moiety bridge to RxNorm IN 40254 valproate; no dose conversion or intravenous extrapolation.
No named interaction with the seven supplements. Active-moiety relevance does not establish identical kinetics or dosing for every valproate formulation.
Source 2: regulatory safety communication
gov.uk · Source check Sep 10, 2026
Population: People with epilepsy taking antiepileptic medicines.
Advises people with epilepsy not to use St John’s wort with any antiepileptic medicine. Triggering report involved increased seizures with levetiracetam, lamotrigine and clobazam; warning extended beyond recognized CYP pathways.
How this applies: Regulatory recommendation applies to valproate when used for epilepsy; underlying case and mechanism remain indirect.
Triggering case did not involve valproate. This is an explicit class-wide precaution, not proof of valproate-specific pharmacokinetic loss or sedation.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Prepared article with direct-study limits, preparation boundaries and claim-specific conclusions. | |
| Research summary published |
Article revision: 80e9250d6b268a00
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.