Drug & supplement interaction

Methylene Blue + Chlorpheniramine, Phenylephrine

Chlorpheniramine, Phenylephrine brand names: Histatab Plus, Ed A Hist, Rynatan, Dallergy JR.

Moderate Interaction
The bottom line Moderate

Chlorpheniramine, Phenylephrine 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 Chlorpheniramine, Phenylephrine

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. Chlorpheniramine, Phenylephrine 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 Chlorpheniramine, Phenylephrine

Chlorpheniramine, Phenylephrine 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 short version: one of the two ingredients in your medicine, chlorpheniramine, is an antihistamine with strong anticholinergic (drying) effects. Methylene blue can add to that anticholinergic load, so combining them may push those drying effects further than either would alone.

In real terms, that could mean things like a very dry mouth, blurry vision, dilated pupils, trouble sweating (which can let your body overheat), constipation, urinary trouble, and confusion. Honestly, though, the evidence here is thin. It comes mainly from a single case report in a very sick hospitalized patient, so it isn't a proven everyday risk. Still, since methylene blue as a supplement isn't well supported and carries its own risks, please check with your pharmacist or doctor before pairing these.

Moderate

Serotonergic Drugs

2 of 2

Chlorpheniramine, Phenylephrine 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 deal with this combo. Methylene blue can act like a monoamine oxidase (MAO) inhibitor, which means it blocks an enzyme that helps clear certain brain chemicals like serotonin and norepinephrine. Your medicine has phenylephrine (a decongestant that nudges up norepinephrine-type activity) and chlorpheniramine (an antihistamine with mild serotonin effects), so stacking them with methylene blue could add up.

In theory this raises the chance of things like a spike in blood pressure, jitteriness, fast heartbeat, or, rarely, serotonin syndrome (agitation, sweating, tremor, confusion). Honestly, the scary cases were with injected methylene blue, not the oral supplement, so the real-world risk from a pill is likely low. Still, it's worth a quick chat with your pharmacist or doctor before combining them.

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 Chlorpheniramine, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

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 Chlorpheniramine, Phenylephrine

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 Chlorpheniramine, Phenylephrine, 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 Chlorpheniramine, Phenylephrine

This page covers Methylene Blue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Chlorpheniramine, Phenylephrine page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Henbane (major) and Lithium (major).

By severity: 10 major · 175 moderate · 44 minor.

From our pharmacist’s overview on the Chlorpheniramine, Phenylephrine page

“A medicine that stimulates the heart and dries the body doesn't leave much room for supplements pulling the same way, and that describes chlorpheniramine, phenylephrine (Histatab Plus, Ed A Hist, Rynatan) well. Dozens of stimulant herbs, everyday caffeine sources among them, add to the decongestant's strain on blood pressure and heart…”

Reviewed by 2 · Jul 18, 2026

Open the Chlorpheniramine, Phenylephrine interaction page

How much people look this up

Where Methylene Blue and Chlorpheniramine, Phenylephrine 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

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

29 days ago today
Medication Chlorpheniramine, Phenylephrine
Steady interest

#1,436 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
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
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

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Pharmacist Counseling Corner

Taking Methylene Blue and Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Methylene Blue with Chlorpheniramine, Phenylephrine?
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 Chlorpheniramine, Phenylephrine?
Chlorpheniramine, Phenylephrine 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 Chlorpheniramine, Phenylephrine 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

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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.