Drug & supplement interaction

Polypodium Leucotomos + Tramadol, Acetaminophen

Tramadol, Acetaminophen brand name: Tramacet.

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

Polypodium Leucotomos has a minor interaction with Tramadol, Acetaminophen. Theoretically, Polypodium leucotomos might increase levels of drugs metabolized by CYP3A4.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
EvidenceB
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Polypodium Leucotomos and Tramadol, Acetaminophen

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

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Tramadol, Acetaminophen

Tramadol, Acetaminophen falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Polypodium Leucotomos interacts with.

Theoretically, Polypodium leucotomos might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggests that Polypodium leucotomos can decrease the metabolism of midazolam by a mechanism possibly related to the inhibition of CYP3A4. However, a small study in humans suggests that taking Polypodium leucotomos with midazolam does not affect the metabolism of midazolam.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the gist with Tramadol/Acetaminophen (Tramacet) and Polypodium leucotomos. The fern extract has been looked at in the lab for possibly slowing down a liver enzyme called CYP3A4, which is one of the enzymes that helps clear tramadol. In theory, if that enzyme is blocked, tramadol could hang around a bit longer and feel slightly stronger, meaning more drowsiness, dizziness, nausea, or constipation.

That said, the human evidence here is reassuring. When researchers tested this fern with another CYP3A4 drug in people, they saw no real effect, so this is mostly a theoretical concern rated as minor and unlikely. I wouldn't lose sleep over it, but since tramadol is an opioid, it's always smart to run your full list past your pharmacist or doctor before adding anything new.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Shinya K, Nishimura Y, Ryu K, et al. Short-term administration of Polypodium leucotomos extract does not inhibit CYP3A4-mediated metabolism of midazolam in healthy subjects: an open-label, two-period, fixed-sequence study. Int J Dermatol 2022.

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

Polypodium Leucotomos Also Interacts With Other Medications

Polypodium Leucotomos has 642 minor known drug interactions in our database — the Tramadol, Acetaminophen one above is one of them. If you take anything else, check it against the full list below.

Minor 642 No known interaction 2,188 (incl. Tramadol, Acetaminophen)
Taking anything else?

Check Another of Your Medications Against Polypodium Leucotomos

Covers the 2,830 medications we’ve checked against Polypodium Leucotomos. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Tramadol, Acetaminophen

This page covers Polypodium Leucotomos only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 12 major · 224 moderate · 44 minor.

From our pharmacist’s overview on the Tramadol, Acetaminophen page

“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol, Acetaminophen interaction page

One more smart check

Taking Polypodium Leucotomos as Part of a Dietary Supplement Product? Check It for Interactions

We hold 26 real supplement products containing Polypodium Leucotomos, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Polypodium Leucotomos. Your product may carry other ingredients that interact with Tramadol, Acetaminophen too, on top of Polypodium Leucotomos — 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 Polypodium Leucotomos and Tramadol, Acetaminophen 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 Polypodium Leucotomos
Steady interest

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

29 days ago today
Medication Tramadol, Acetaminophen
Top 25%

#350 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 Polypodium Leucotomos

What is Polypodium Leucotomos?

  • Sun sensitivity and sunburn protection
  • Skin conditions like vitiligo and melasma
  • Polymorphic light eruption
  • Skin aging and photoaging
  • Atopic dermatitis support

Polypodium leucotomos is a fern extract taken by mouth, mostly studied as an add-on to (not a replacement for) sunscreen and for certain light-triggered skin conditions. Some early research is promising for reducing sun sensitivity, but the evidence is still limited and it should not replace standard sun protection. Talk with your pharmacist or doctor before starting it.

Read the full Polypodium Leucotomos monograph & all interactions
Keep checking

Other Drugs & Polypodium Leucotomos

Browse every other medication we’ve checked against Polypodium Leucotomos — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
0Moderate
642Minor
2,187No known interaction
642 Minor 2,187 No interaction
Minor

642 interactions

Showing 60 of 642 minor interactions — see all 642 on the Polypodium Leucotomos page.

No interaction 2,187 drugs checked — show the list

We also checked Polypodium Leucotomos against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,187 medications checked with no known interaction — see the full Polypodium Leucotomos list.

See the full Polypodium Leucotomos interactions page
See every supplement checked against Tramadol, Acetaminophen, 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
Polypodium Leucotomos monograph › Uses, safety, and every drug interaction in one place Tramadol, Acetaminophen supplement interactions › Every supplement checked against Tramadol, Acetaminophen, 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 Polypodium Leucotomos and Tramadol, Acetaminophen Together: Common Questions

Can you take Polypodium Leucotomos with Tramadol, Acetaminophen?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Polypodium Leucotomos and Tramadol, Acetaminophen interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Tramadol, Acetaminophen and Polypodium Leucotomos?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.