Drug & supplement interaction

St. John's Wort + Oxycodone, Naloxone

Oxycodone, Naloxone brand name: Targiniq ER.

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

St. John's Wort has a major interaction with Oxycodone, Naloxone. St. John's wort decreases the levels and clinical effects of oxycodone.

Read the full interaction report
SeverityMajor
LikelihoodProbable
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Oxycodone, Naloxone

Here is the interaction we found between these two, with the evidence behind it.

Major

OXYCODONE (Oxycontin)

St. John's wort decreases the levels and clinical effects of oxycodone.
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity.
Severity Major Likelihood Probable Evidence B

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with Targiniq ER (oxycodone with naloxone): St. John's wort revs up a liver enzyme called CYP3A4, which is one of the main ways your body breaks down oxycodone. When that enzyme works faster, your oxycodone gets cleared out sooner, so blood levels drop and the pain relief can fade.

In real life that often means your medicine just doesn't control pain as well as it should, and if you've been on it a while, your body could even start feeling early withdrawal (restlessness, achiness, sweating, a runny nose). A decent-quality study backs this up, so it's worth taking seriously. Please don't change anything on your own. Loop in your pharmacist or doctor before mixing these two so they can help you stay comfortable and safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M. Clinical risks of St John's Wort (Hypericum perforatum) co-administration. Expert Opin Drug Metab Toxicol. 2017;13(10):1047-62.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 754 major, 388 moderate known drug interactions in our database — the Oxycodone, Naloxone one above is one of them. If you take anything else, check it against the full list below.

Major 754 Moderate 388 No known interaction 1,688 (incl. Oxycodone, Naloxone)
Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Oxycodone, Naloxone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Oxycodone, Naloxone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Oxycodone, Naloxone

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Oxycodone, Naloxone page lists 145 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 8 major · 114 moderate · 23 minor.

From our pharmacist’s overview on the Oxycodone, Naloxone page

“Targiniq ER combines the opioid oxycodone with naloxone for around-the-clock pain, and because opioids can dangerously slow breathing once sedation stacks up, the 145 supplements on file here deserve genuine respect, above all the eight rated major. The largest group, 78 ingredients, layers drowsiness onto the opioid's own, with alcoho…”

Reviewed by 2 · Jul 18, 2026

Open the Oxycodone, Naloxone interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Oxycodone, Naloxone too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where St. John's Wort and Oxycodone, Naloxone Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement St. John's Wort
Top 25%

#156 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Oxycodone, Naloxone
Steady interest

#2,002 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Keep checking

Other Drugs & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

754Major
388Moderate
0Minor
1,687No known interaction
754 Major 388 Moderate 1,687 No interaction
Major

754 interactions

Showing 60 of 754 major interactions — see all 754 on the St. John's Wort page.

Moderate

388 interactions

Showing 60 of 388 moderate interactions — see all 388 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list

We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.

See the full St. John's Wort interactions page
See every supplement checked against Oxycodone, Naloxone, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
St. John's Wort monograph › Uses, safety, and every drug interaction in one place Oxycodone, Naloxone supplement interactions › Every supplement checked against Oxycodone, Naloxone, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking St. John's Wort and Oxycodone, Naloxone Together: Common Questions

Can you take St. John's Wort with Oxycodone, Naloxone?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the St. John's Wort and Oxycodone, Naloxone interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Oxycodone, Naloxone and St. John's Wort?

Our pharmacists answer your medication & supplement questions — free.

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.