Drug & supplement interaction

St. John's Wort + Orphenadrine

Orphenadrine brand names: Norflex, Disipal, Banflex, Flexoject, Flexon, and others.

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

St. John's Wort has a moderate interaction with Orphenadrine. St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.

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

St. John's Wort and Orphenadrine

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

Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Why this applies to Orphenadrine

Orphenadrine falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES — the group St. John's Wort interacts with.

St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%.
Severity Moderate Likelihood Possible Evidence B

Interaction 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.

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

Here's the gist for orphenadrine (Norflex): St. John's wort tends to rev up a liver enzyme called CYP2B6, which helps clear orphenadrine from your body. Speeding up that cleanup can mean less of the medicine sticking around, so your muscle relaxer may simply not work as well for that strain or sprain. Orphenadrine is an active drug, not a prodrug, so this points toward a weaker effect, not a stronger one.

To be honest, this is based mostly on a study with a different CYP2B6 drug (bupropion), where the drop was modest, around 14%. So it's a reasonable concern but not a dramatic one. If your relief seems off while using both, check with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed

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 755 major, 387 moderate known drug interactions in our database — the Orphenadrine one above is one of them. If you take anything else, check it against the full list below.

Major 755 Moderate 387 No known interaction 1,688 (incl. Orphenadrine)
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 Orphenadrine

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 Orphenadrine, 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 Orphenadrine

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Orphenadrine page lists 35 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Procaine (major), Adrafinil (moderate), African Wild Potato (moderate) and Artichoke (moderate).

By severity: 2 major · 22 moderate · 11 minor.

Open the Orphenadrine 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 Orphenadrine 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 Orphenadrine 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%

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

29 days ago today
Medication Orphenadrine
Top half

#1,160 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
Medication

About Orphenadrine

What Is Orphenadrine Used For?

Brand names: Norflex, Disipal, Banflex, Flexoject, Flexon, Norflex Injection

Orphenadrine citrate is used to ease discomfort from acute, painful musculoskeletal conditions — things like muscle pain and stiffness. It is always used as part of a broader treatment plan that includes rest and physical therapy, not as a stand-alone cure.

Both the extended-release tablet and the injection form are approved for this use. Neither form directly relaxes tight muscles — the relief it provides is thought to be related to its pain-relieving (analgesic) properties.

See full Orphenadrine drug information
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.

755Major
387Moderate
0Minor
1,687No known interaction
755 Major 387 Moderate 1,687 No interaction
Major

755 interactions

Showing 60 of 755 major interactions — see all 755 on the St. John's Wort page.

Moderate

387 interactions

Showing 60 of 387 moderate interactions — see all 387 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 Orphenadrine, 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 Orphenadrine supplement interactions › Every supplement checked against Orphenadrine, ranked by severity Orphenadrine drug information › The full plain-English guide to this medication 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 Orphenadrine Together: Common Questions

Can you take St. John's Wort with Orphenadrine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the St. John's Wort and Orphenadrine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Orphenadrine and St. John's Wort?

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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.