Drug & supplement interaction

Black Pepper + Mexiletine

Mexiletine brand name: Mexitil.

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

Mexiletine falls into 2 drug categories that Black Pepper can interact with; the most serious is rated moderate. Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Pepper and Mexiletine

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Mexiletine

Mexiletine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Black Pepper interacts with.

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.
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 for mexiletine. Your liver uses an enzyme called CYP2D6 to clear this medicine from your body. Lab studies hint that piperine, the active compound in black pepper, can slow that same enzyme down. If that happened in real life, mexiletine could build up a bit higher than expected, which might mean more of its usual side effects like nausea, dizziness, lightheadedness, tremor, or, less often, changes in your heart rhythm.

The good news: this is purely theoretical and based on test-tube work, not anything seen in people. Everyday cooking amounts of black pepper are very unlikely to matter. Concentrated piperine supplements are the bigger question mark. Since mexiletine is a heart-rhythm drug where small changes count, just check with your pharmacist before adding one.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  2. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  3. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Mexiletine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.
Severity Minor 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 for mexiletine: your liver relies heavily on an enzyme called CYP1A2 to clear it out. Lab studies (test-tube, not people) hint that piperine, the active part of black pepper, might speed that enzyme up. If that happened in real life, your body could clear mexiletine a little faster, which in theory might leave you with less drug on board and a weaker hold on your heart rhythm.

I want to keep this in perspective. This is theoretical and has never actually been seen in humans, so the food amounts you sprinkle on dinner aren't a worry. Concentrated piperine supplements are a different story. Since mexiletine is a heart-rhythm drug where steady levels matter, just give your pharmacist or doctor a heads-up before starting one.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed

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

Black Pepper Also Interacts With Other Medications

Black Pepper has 975 moderate, 43 minor known drug interactions in our database — the Mexiletine one above is among them. If you take anything else, check it against the full list below.

Moderate 975 Minor 43 No known interaction 1,812 (incl. Mexiletine)
Taking anything else?

Check Another of Your Medications Against Black Pepper

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

From our Q&A

Questions About Black Pepper or Mexiletine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Black Pepper or Mexiletine, 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 Mexiletine

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mexiletine page lists 152 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), 1,3-dmaa (moderate), Acacia Rigidula (moderate), Active Hexose Correlated Compound (ahcc) (moderate) and Adrafinil (moderate).

By severity: 1 major · 107 moderate · 44 minor.

From our pharmacist’s overview on the Mexiletine page

“Mexiletine (Mexitil) steadies the heart's rhythm, and its benefit depends on holding a fairly precise blood level, so the 152 supplements on this list deserve real attention rather than a shrug. Only one entry, activated charcoal, is rated major, because it can soak up the drug in the gut and cut how much actually reaches your bloodstr…”

Reviewed by 2 · Jul 18, 2026

Open the Mexiletine interaction page

One more smart check

Taking Black Pepper as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5,528 real supplement products containing Black Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Pepper. Your product may carry other ingredients that interact with Mexiletine too, on top of Black Pepper — 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 Black Pepper and Mexiletine 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 Black Pepper
Top 5%

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

29 days ago today
Medication Mexiletine
Top half

#803 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 Black Pepper

What is Black Pepper?

Black Pepper
  • Flavoring and culinary use
  • Digestive complaints like bloating and indigestion
  • Boosting absorption of other supplements
  • Antioxidant and anti-inflammatory support
  • Cold and congestion remedies

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (like curcumin from turmeric). Strong human evidence for black pepper treating specific health conditions is limited, so use supplement-strength products with care and check with your pharmacist.

Read the full Black Pepper monograph & all interactions
Medication

About Mexiletine

What Is Mexiletine Used For?

Brand name: Mexitil

Mexiletine Hydrochloride capsules are indicated for the treatment of documented, life-threatening ventricular arrhythmias — for example, sustained ventricular tachycardia (a dangerously fast heart rhythm originating in the lower chambers). Because mexiletine itself can trigger arrhythmias, it is not recommended for minor or symptom-free irregular heartbeats.

Treatment is started in a hospital setting so heart rhythm can be monitored closely. Antiarrhythmic drugs, including mexiletine, have not been shown to improve overall survival in patients with ventricular arrhythmias.

See full Mexiletine drug information
Keep checking

Other Drugs & Black Pepper

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

0Major
975Moderate
43Minor
1,811No known interaction
975 Moderate 43 Minor 1,811 No interaction
Moderate

975 interactions

Showing 60 of 975 moderate interactions — see all 975 on the Black Pepper page.

Minor

43 interactions

No interaction 1,811 drugs checked — show the list

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

Showing the 60 most looked-up of 1,811 medications checked with no known interaction — see the full Black Pepper list.

See the full Black Pepper interactions page
See every supplement checked against Mexiletine, 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
Black Pepper monograph › Uses, safety, and every drug interaction in one place Mexiletine supplement interactions › Every supplement checked against Mexiletine, ranked by severity Mexiletine 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 Black Pepper and Mexiletine Together: Common Questions

Can you take Black Pepper with Mexiletine?
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 Black Pepper and Mexiletine?
Mexiletine belongs to more than one drug category, and Black Pepper 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 Black Pepper and Mexiletine 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 Mexiletine and Black Pepper?

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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.