The short answer
St. John’s wort may lower adagrasib levels and reduce treatment effectiveness. Tell your oncology team before starting it or changing existing use; a few hours of separation is not an established solution.
What this answer covers
Oral Hypericum perforatum products with oral adagrasib. Hyperforin content and repeated use affect enzyme induction; low-hyperforin products and teas are not assumed safe substitutes.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- adagrasib
The label names this herb
The European Krazati patient leaflet specifically lists St. John’s wort as a product that can reduce the amount of adagrasib in blood and how well it works. The U.S. label advises avoiding strong CYP3A inducers. Tell your cancer team promptly if you take St. John’s wort and discuss an alternative.
The concern is increased drug breakdown
Repeated St. John’s wort use can increase the activity of drug-metabolizing enzymes. A human probe study found larger effects with higher-hyperforin preparations. This supports concern about reduced drug exposure, but does not give an exact percentage reduction for adagrasib or prove that less medicine crosses the intestine.
The effect is not limited to the first eight days
Krazati’s early-treatment qualification concerns strong enzyme inhibitors. Its warning about strong inducers is separate. Adagrasib modeling predicts that strong induction can still reduce exposure at steady state, so the inhibitor timing rule should not be used to justify starting St. John’s wort later.
Coordinate any change with the oncology team
Show the team the exact preparation, daily dose and when you started it. Product differences do not establish a safe substitute, and taking doses a few hours apart has not been shown to prevent induction. Arrange a supervised plan for starting or stopping the herb and do not change your cancer-medicine dose yourself.
Evidence and practical considerations
Absorption & effectiveness
St. John’s wort may lower adagrasib exposure and reduce treatment effectiveness through enzyme induction; oncology review and avoidance of interacting preparations are appropriate.
- Exact scope
- Oral Hypericum perforatum products with oral adagrasib. Hyperforin content and repeated use affect enzyme induction; low-hyperforin products and teas are not assumed safe substitutes. with Exact adagrasib RxCUI 2625882 IN, confirmed by current RxNorm properties. Oral Krazati tablets; the August 2026 U.S. label covers single-agent treatment of specified previously treated KRAS G12C-mutated NSCLC. Older cetuximab combination cohorts and regional label instructions are not interchangeable.
- Medication form and route
- Oral
What remains uncertain
- Exact named-herb regulatory warning and indirect human induction evidence, not a direct combination trial. Supports lower blood exposure and possible effectiveness loss, not a measured reduction in intestinal absorption or a quantified cancer outcome.
Factors that may matter: Exact preparation and dose; Treatment phase and duration; Liver function; Electrolyte results and GI symptoms; Other medicines.
Read the supporting source summaries
Source 1: Current U.S. prescribing information
bms.com · Source check Sep 10, 2026
Population: Adults with specified previously treated KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer.
Warns about GI toxicity, QT prolongation and hepatotoxicity. Monitor/correct electrolytes, particularly potassium and magnesium, and monitor liver tests. Strong CYP3A inducers lower exposure. Avoid strong CYP3A inhibitors until steady state, approximately eight days. High-fat meal did not meaningfully change exposure; tablets may be taken with or without food.
How this applies: Exact current U.S. guidance; newer than the retained March 2026 DailyMed version. Exact adagrasib RxCUI 2625882 IN, confirmed by current RxNorm properties. Oral Krazati tablets; the August 2026 U.S. label covers single-agent treatment of specified previously treated KRAS G12C-mutated NSCLC. Older cetuximab combination cohorts and regional label instructions are not interchangeable.
Not direct evidence of each botanical combination. Strong-inhibitor effects after a single dose differ from steady-state model predictions. Effects of adagrasib on other CYP substrates are a separate direction. No universal supplement prescription.
Source 2: Current EU product information
ema.europa.eu · Source check Sep 10, 2026
Population: European patients prescribed Krazati.
Patient leaflet specifically names Hypericum perforatum as potentially reducing the amount of Krazati in blood and its effectiveness. SmPC advises avoiding strong CYP3A inducers.
How this applies: Exact named-herb regulatory bridge for St. John’s wort.
No measured Hypericum-adagrasib trial. Regional strong-inhibitor guidance is more restrictive than the U.S. early-treatment qualification and is not silently substituted for it.
Source 3: Original clinical research
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 42 healthy male volunteers randomized to six St. John’s wort preparation groups.
Midazolam exposure reductions varied with hyperforin dose: approximately 79% with high-hyperforin LI 160 versus 21% with a nearly hyperforin-free powder preparation.
How this applies: Supports the named regulatory warning and preparation-dependent induction, not a numeric adagrasib exposure prediction.
Abstract-only, small groups and no adagrasib. Hyperforin content, duration and formulation matter; low-hyperforin findings do not establish an oncology-safe product.
Source 4: Original clinical and pharmacokinetic modeling research
ebi.ac.uk · Source check Sep 10, 2026
Population: Healthy-volunteer clinical interaction studies and pharmacokinetic data from patients with KRAS G12C tumors, used to develop and verify a model.
Itraconazole increased single-dose exposure approximately fourfold; rifampin reduced it about 95%. Adagrasib inhibits its own CYP3A metabolism. At steady state, inhibitor effects were predicted to be small, whereas strong induction still reduced exposure.
How this applies: Exact medication evidence establishes time and direction boundaries for CYP3A extrapolation.
Steady-state untested scenarios are model predictions, not observed herb interactions. No goldenseal or Hypericum trial, no measured cancer outcome from those supplements. Single-dose and repeated-dose values cannot be pooled.
Source 5: Authoritative medication terminology
rxnav.nlm.nih.gov · Source check Sep 10, 2026
Population: Medication terminology.
Identifies adagrasib as IN.
How this applies: Exact identity confirmation.
Not clinical interaction evidence.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Sources checked and article drafted. | |
| Research summary published |
Article revision: 4487f77e4f126ddb
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.