Drug & supplement interaction

Methylene Blue + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

Amitriptyline, Perphenazine falls into 2 drug categories that Methylene Blue can interact with; the most serious is rated moderate. Concomitant use may increase anticholinergic effects and adverse effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Methylene Blue and Amitriptyline, Perphenazine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Methylene Blue interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 2 of those categories, so it can interact with Methylene Blue in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

Anticholinergic Drugs

1 of 2

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under Anticholinergic Drugs — the group Methylene Blue interacts with.

Concomitant use may increase anticholinergic effects and adverse effects. In a case report, a critically-ill male in his mid-60s developed a toxicological process attributed to anticholinergic syndrome following treatment with methylene blue for vasoplegia. Symptoms included anhidrosis, fever, lactic acidosis, mucosal dryness, and pupil dilation. Potential exacerbating factors included renal failure and use of fentanyl intra-operatively.
Severity Moderate Likelihood Possible Evidence D

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 thing to know about Triavil (which combines amitriptyline and perphenazine): both ingredients already carry strong anticholinergic activity, meaning they can dry you out and slow certain body functions. Methylene blue seems to add to that same effect. Stacking them could push those side effects higher, things like a very dry mouth, blurred vision, constipation, trouble urinating, a fast heartbeat, confusion, and reduced sweating that can make it harder to cool off.

I want to be honest about how strong the proof is: this comes mostly from a single hospital case report in a very sick patient, so it's more of a caution than a certainty. Still, since the two drugs already lean this way, it's worth a quick chat with your pharmacist or doctor before combining them. Don't change anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
Moderate

Serotonergic Drugs

2 of 2

Amitriptyline, Perphenazine also falls under Serotonergic Drugs.

Combining serotonergic drugs with methylene blue can cause additive serotonergic effects, including serotonin syndrome. Methylene blue inhibits monoamine oxidase A. Intravenous or intrapulmonary use has resulted in serotonin syndrome, including reported fatalities, in patients taking some serotonergic drugs. This effect has not been reported with oral methylene blue. However, tell patients to avoid taking methylene blue with serotonergic drugs.
Severity Moderate Likelihood Possible Evidence C

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

The medicine you're asking about combines amitriptyline (an antidepressant) with perphenazine. Amitriptyline raises serotonin levels in the brain, and that's exactly where methylene blue causes concern. Methylene blue acts like a monoamine oxidase inhibitor, meaning it blocks the enzyme that normally clears serotonin. Put the two together and serotonin can climb too high, which can trigger serotonin syndrome. Warning signs include agitation, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, and confusion.

Here's the honest context: the dangerous cases were reported with injected methylene blue, not the oral supplement form, so the real-world risk from a pill is less clear. Still, this combination is best avoided. Please check with your pharmacist or doctor before mixing them, and don't stop your prescribed medicine on your own.

Contact Dr. Brian directly if you have additional questions on this interaction

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

Methylene Blue Also Interacts With Other Medications

Methylene Blue has 314 moderate known drug interactions in our database — the Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Moderate 314 No known interaction 2,516 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Methylene Blue

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

From our Q&A

Questions About Methylene Blue or Amitriptyline, Perphenazine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Methylene Blue or Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine

This page covers Methylene Blue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine interaction page

How much people look this up

Where Methylene Blue and Amitriptyline, Perphenazine 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 Methylene Blue
Top half

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

29 days ago today
Medication Amitriptyline, Perphenazine
Steady interest

#2,060 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 Methylene Blue

What is Methylene Blue?

Methylene Blue
  • Methemoglobinemia (a blood disorder)
  • Claimed energy or mental focus support
  • Anti-aging or longevity claims
  • Antimicrobial or antimalarial uses (historical)
  • Dye for medical and lab procedures

Methylene blue is a synthetic dye that is an FDA-approved prescription medicine for a rare blood disorder called methemoglobinemia, and it is also used as a diagnostic dye. Its popular use as a supplement for energy, brain health, or anti-aging is not well supported by solid human evidence, and it can cause serious side effects. Talk to a pharmacist or doctor before using it, and never take non-pharmaceutical or industrial-grade products.

Read the full Methylene Blue monograph & all interactions
Keep checking

Other Drugs & Methylene Blue

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

0Major
314Moderate
0Minor
2,515No known interaction
314 Moderate 2,515 No interaction
Moderate

314 interactions

Showing 60 of 314 moderate interactions — see all 314 on the Methylene Blue page.

No interaction 2,515 drugs checked — show the list

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

Showing the 60 most looked-up of 2,515 medications checked with no known interaction — see the full Methylene Blue list.

See the full Methylene Blue interactions page
See every supplement checked against Amitriptyline, Perphenazine, 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
Methylene Blue monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, 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 Methylene Blue and Amitriptyline, Perphenazine Together: Common Questions

Can you take Methylene Blue with Amitriptyline, Perphenazine?
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.
Why are there 2 interactions listed for Methylene Blue and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Methylene Blue interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Methylene Blue and Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine and Methylene Blue?

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.