Drug & supplement interaction

Methylene Blue + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

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

Benzhydrocodone, Acetaminophen 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?
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Interaction report

Methylene Blue and Benzhydrocodone, Acetaminophen

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. Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen 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 situation if you're using methylene blue alongside Apadaz (benzhydrocodone with acetaminophen). Benzhydrocodone is a prodrug, meaning your body converts it into hydrocodone to relieve pain. The concern here isn't really about that conversion, though. It's that both methylene blue and opioids can add to so-called anticholinergic-type effects in the body, and together they may nudge those effects higher.

What might that look like? Think dry mouth, flushed skin, less sweating, a faster heartbeat, dilated pupils, and in serious cases confusion or overheating. Honestly, this is based on a single case report in a very sick patient, so the evidence is weak. But because opioids also slow breathing, I'd want your doctor or pharmacist to weigh in before you combine them.

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

Serotonergic Drugs

2 of 2

Benzhydrocodone, Acetaminophen 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

Here's the concern with mixing methylene blue and Apadaz (benzhydrocodone with acetaminophen). Methylene blue blocks an enzyme called monoamine oxidase A, which normally helps clear the brain chemical serotonin. Opioid pain relievers like the benzhydrocodone part of Apadaz can also nudge serotonin levels up. Stack the two together and you may get too much serotonin activity, a reaction called serotonin syndrome.

That could look like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion. Serious cases have mostly been tied to intravenous methylene blue, not oral doses, so the risk from a swallowed supplement is less clear. Still, this combo is worth avoiding. Please check with your pharmacist or doctor before pairing these two.

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 Benzhydrocodone, Acetaminophen 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. Benzhydrocodone, Acetaminophen)
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 Benzhydrocodone, Acetaminophen

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 Benzhydrocodone, Acetaminophen, 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 Benzhydrocodone, Acetaminophen

This page covers Methylene Blue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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: 14 major · 239 moderate · 46 minor.

Open the Benzhydrocodone, Acetaminophen interaction page

How much people look this up

Where Methylene Blue and Benzhydrocodone, 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 Methylene Blue
Top half

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,282 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
Medication

About Benzhydrocodone and Acetaminophen

What Is Benzhydrocodone and Acetaminophen Used For?

Brand name: Apadaz

Apadaz is indicated for the short-term management of acute pain — specifically pain severe enough to require an opioid analgesic and for which other treatments are inadequate. It is approved for use for no more than 14 days.

Apadaz is reserved for patients who have not been able to tolerate non-opioid pain relievers, or for whom those options have not provided adequate pain relief. It should not be used long-term unless pain remains severe and alternative treatments continue to be insufficient.

See full Benzhydrocodone and Acetaminophen drug information
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 Benzhydrocodone, 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
Methylene Blue monograph › Uses, safety, and every drug interaction in one place Benzhydrocodone, Acetaminophen supplement interactions › Every supplement checked against Benzhydrocodone, Acetaminophen, ranked by severity Benzhydrocodone and Acetaminophen 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 Methylene Blue and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Methylene Blue with Benzhydrocodone, Acetaminophen?
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 Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen and Methylene Blue?

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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.