The short answer
Do not add St John’s wort to clorazepate without prescriber review. An original case series reports withdrawal-type problems with this exact medication, although the mechanism and frequency remain uncertain.
What this answer covers
Oral Hypericum perforatum products; case-series extracts and doses were not characterized.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- clorazepate
What was actually reported
Two reports described withdrawal symptoms, seizures and worsening anxiety during clorazepate and St John’s wort use. The report gives little individual dosing or timing detail and cannot show how commonly this happens.
What the reports do not prove
The authors describe an interaction signal, but the table does not establish intestinal absorption failure or a specific enzyme mechanism. Do not treat a case report as a prediction of your exact drug level.
Extract composition changes interpretation
In healthy volunteers, one St John’s wort extract substantially lowered alprazolam exposure; a low-hyperforin product had little effect. These are studies of another medicine, and retail extracts should not be assumed equivalent.
Make changes with the treating clinician
Tell the prescriber if you already take the herb, especially if anxiety, sleep or seizures change. Do not compensate with extra clorazepate or stop it abruptly. A dosing gap has not been shown to remove this concern.
Evidence and practical considerations
Absorption & effectiveness
Exact-drug adverse-event signal supports a conditional avoid/review precaution and possible loss-of-effect concern, not proven reduced intestinal absorption.
- Exact scope
- Oral Hypericum perforatum products; case-series extracts and doses were not characterized. with Exact oral clorazepate dipotassium tablets. Rapid oral decarboxylation forms nordiazepam, with essentially no circulating parent; nordiazepam half-life about 40-50 hours. Human-serum-albumin binding of the swallowed parent is not an in vivo metabolite study. RxNorm IN 2353 relates to PIN 2607 dipotassium, matching the label.
- Medication form and route
- oral
- Timing or duration
- Source-specific single-dose, repeated-dose and observational exposures distinguished.
What remains uncertain
- Selected case reports have no denominator, pair-specific concentration measurements or adequate extract/dose details. Low-hyperforin results with alprazolam do not establish safety here.
Factors that may matter: preparation and plant part; clinical indication; dose; other medicines; baseline alertness.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: Patients prescribed oral clorazepate.
Can impair alertness and coordination; other CNS depressants can increase impairment. Opioid combinations have a specific respiratory-depression warning. Dependence and withdrawal require supervised changes. Rapid oral decarboxylation forms nordiazepam, with essentially no circulating parent; nordiazepam half-life about 40-50 hours. Human-serum-albumin binding of the swallowed parent is not an in vivo metabolite study. RxNorm IN 2353 relates to PIN 2607 dipotassium, matching the label.
How this applies: Exact IN and labeled oral formulation; route, salt and metabolite distinctions retained.
No quantified risk for every herb or universal protective spacing interval. Opioid-specific evidence does not prove equal botanical respiratory risk.
Source 2: original adverse-event case series
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 147 selected adverse-event referrals in Poland, September 2016-July 2017.
Clinical picture described as withdrawal syndrome, seizures and aggravation of anxiety.
How this applies: Exact exposures and preparation limitations apply; no untested dose or route equivalence.
Uncontrolled selected referrals; no exposed-population denominator, pair-specific dose, extract assay, drug concentration or detailed time course. Overall 132 dechallenge responses cannot be assigned to these specific two cases.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Twelve healthy volunteers in an open-label fixed-order crossover.
Alprazolam exposure fell about one-half and clearance increased; elimination half-life shortened.
How this applies: Original named medication and preparation only; indirect evidence for clorazepate. Comparator arms are not coadministration.
Single extract and short exposure, healthy volunteers; no anxiety-treatment failure endpoint. Does not imply reduced gut absorption or transfer to predominantly conjugated benzodiazepines.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy participants in randomized placebo-controlled studies.
Changes in probe exposures were small and judged clinically irrelevant; hyperforin levels were below quantification.
How this applies: Original named medication and preparation only; indirect evidence for clorazepate. Comparator arms are not coadministration.
Preparation-specific result, not permission to assume all retail products are low-hyperforin or all doses safe.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Current exact available claims adjudicated using original captures and explicit identity and comparator limits. | |
| Research summary published |
Article revision: 65aefc7c15d90b48
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.