St John's Wort and Lenacapavir Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
St John's Wort
No brand names on recordLenacapavir Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir
Interaction Deep Dive
Coadministration of lenacapavir (SUNLENCA®), a CYP3A substrate, together with St John's wort (a strong CYP3A inducer) is contraindicated due to significantly reduced lenacapavir exposure, which may result in the loss of therapeutic effect and development of resistance to lenacapavir2, however lenacapavir (YEZTUGO®) and St John's wort can be used concomitantly with dosage adjustments. For individuals receiving YEZTUGO® and initiating therapy with a strong CYP3A inducer, continue to administer YEZTUGO® 927 mg SUBQ once every 6 months, plus administer the following supplemental YEZTUGO® doses. On the day strong CYP3A inducer is initiated (which should be at least 2 days after YEZTUGO® is first initiated) administer YEZTUGO® 927 mg SUBQ and 600 mg orally. On the day after the strong CYP3A inducer is initiated, administer YEZTUGO® 600 mg orally. If a strong CYP3A inducer is coadministered for longer than 6 months, continue to administer scheduled continuation dosing (YEZTUGO® 927 mg SUBQ once every 6 months) plus supplemental doses of YEZTUGO® every 6 months from CYP3A inducer initiation as previously stated. After stopping strong CYP3A inducer, continue the once every 6 months scheduled continuation injection dosing of YEZTUGO® 1.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of lenacapavir
Literature reports
2 reports — tap to read
a) In a drug interaction study, coadministration of lenacapavir and rifAMPin (strong CYP3A inducer) (fasted) 600 mg once daily resulted in reduced Cmax and AUC by 0.45-fold and 0.16-fold, respectively 21.
b) No clinically significantly drug interactions have been reported with low hyperforin (1 mg or less/day) St John's wort products and exceptions to drug interactions (including contraindications) may be considered in this case. Induction of CYP3A4 by high hyperforin (greater than 1 mg/day) products is reversible generally within 1 week after discontinuation 3.
Common questions
Can I take St John's Wort and Lenacapavir Injection together?
Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir Always confirm with your pharmacist or prescriber before making any change.
How serious is the St John's Wort and Lenacapavir Injection interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of St John's Wort or Lenacapavir Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: YEZTUGO(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2025. DailyMed
- Product Information: SUNLENCA(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per FDA), Foster City, CA, 2024. DailyMed
- European Medicines Agency (EMA): Assessment report on Hypericum perforatum L. herba: final – revision 1. European Medicines Agency (EMA). Amsterdam, Netherlands. 2022.
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