Drug & supplement interaction

Methylene Blue + Nortriptyline

Nortriptyline brand names: Pamelor, Nortriptyline, Aventyl, Allegron.

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

Nortriptyline 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 Nortriptyline

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. Nortriptyline 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 Nortriptyline

Nortriptyline 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 gist: nortriptyline (Pamelor) already carries what we call anticholinergic effects, things like dry mouth, blurry vision, constipation, trouble urinating, and a faster heartbeat. Methylene blue can add its own anticholinergic-type burden on top, so combining the two may make those side effects stronger or more noticeable.

I want to be honest about how solid this is: the concern mostly comes from a single case report in a very sick, hospitalized patient who also had kidney failure and other medications on board, so it's anecdotal, not proven for everyday use. There's also a separate, more serious worry worth knowing about: methylene blue acts like an MAO inhibitor and can raise serotonin, which doesn't mix well with antidepressants. Please don't stop or change anything on your own. Loop in your pharmacist or doctor before using methylene blue with nortriptyline.

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

Serotonergic Drugs

2 of 2

Nortriptyline 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 pairing these two. Nortriptyline (Pamelor) raises serotonin levels in your brain, which is part of how it helps with depression. Methylene blue is a strong blocker of an enzyme called monoamine oxidase A, which normally clears serotonin. Put them together and serotonin can pile up too much, which may lead to serotonin syndrome: agitation, a racing heart, sweating, shaking, muscle twitching, or confusion.

The scary cases (some fatal) happened mostly with methylene blue given by IV, not the oral supplement kind, so the real-world risk from an oral product is likely lower. Still, this is a serious combination worth avoiding. Please don't start or stop either one on your own, just check with your pharmacist or doctor first.

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 Nortriptyline 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. Nortriptyline)
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 Nortriptyline

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 Nortriptyline, 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 Nortriptyline

This page covers Methylene Blue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nortriptyline page lists 198 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Lithium (major), Scopolia (major) and 1,3-dmaa (moderate).

By severity: 4 major · 150 moderate · 44 minor.

Open the Nortriptyline interaction page

How much people look this up

Where Methylene Blue and Nortriptyline 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

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

29 days ago today
Medication Nortriptyline
Top 10%

#201 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 Nortriptyline

What Is Nortriptyline Used For?

Brand names: Pamelor, Nortriptyline, Aventyl, Allegron

Nortriptyline is approved to relieve symptoms of depression. This applies to nortriptyline hydrochloride capsules, nortriptyline hydrochloride oral solution, and Pamelor capsules — all used for the same core indication.

The label notes that depression arising from within the body (endogenous depression) may respond better than other types of depression, though all of these products are indicated for the broader relief of depressive symptoms.

See full Nortriptyline 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 Nortriptyline, 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 Nortriptyline supplement interactions › Every supplement checked against Nortriptyline, ranked by severity Nortriptyline 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 Nortriptyline Together: Common Questions

Can you take Methylene Blue with Nortriptyline?
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 Nortriptyline?
Nortriptyline 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 Nortriptyline 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 Nortriptyline 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.