Drug & supplement interaction

Black Pepper + Hydrochlorothiazide, Propranolol

Hydrochlorothiazide, Propranolol brand name: Inderide.

Moderate Interaction
The bottom line Moderate

Hydrochlorothiazide, Propranolol falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Pepper and Hydrochlorothiazide, Propranolol

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Black Pepper interacts with whole categories of medication. Hydrochlorothiazide, Propranolol falls into 3 of those categories, so it can interact with Black Pepper in 3 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 3

Why this applies to Hydrochlorothiazide, Propranolol

Hydrochlorothiazide, Propranolol 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

This combination pill pairs a water pill (hydrochlorothiazide) with propranolol, a beta-blocker that helps slow your heart and lower blood pressure. The part that matters here is the propranolol, which your liver partly clears using an enzyme called CYP2D6. In test-tube studies, piperine (the active compound in black pepper) seems to slow that enzyme down a bit. In theory, that could let a little more propranolol linger in your body, which might nudge your heart rate or blood pressure lower than expected, leaving you tired, lightheaded, or with a slow pulse.

Here's the honest part: this has only been seen in lab dishes, never in real people, so I wouldn't lose sleep over it. Pepper on your dinner is a non-issue. Concentrated piperine supplements (often paired with turmeric) are worth a quick mention to your pharmacist or doctor first.

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
Moderate

PROPRANOLOL (Inderal)

2 of 3
Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.
Severity Moderate Likelihood Possible Evidence B

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

Your combo pill (Inderide) pairs propranolol with a water pill, hydrochlorothiazide. The part that interacts here is the propranolol. Concentrated black pepper extracts (the piperine you find in many supplements, often added to boost turmeric absorption) can help your body soak up more propranolol and clear it more slowly. That means more of it may linger in your blood.

In practice, higher propranolol levels could lead to a slower heart rate, lower blood pressure, lightheadedness, or feeling unusually tired. The everyday black pepper you sprinkle on food is very unlikely to cause this. The concern is supplement-strength piperine. If you take or are thinking about a black pepper supplement, check with your pharmacist or doctor first rather than changing anything on your own.

References
  1. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 3

Hydrochlorothiazide, Propranolol 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

Inderide is a combination pill: propranolol (a beta-blocker that lowers blood pressure and slows heart rate) plus hydrochlorothiazide (a water pill). The propranolol part is partly handled by a liver enzyme called CYP1A2. Lab studies hint that piperine, the active compound in black pepper, might speed that enzyme up. If that happened, your body could clear propranolol a little faster, which in theory might slightly weaken its effect on blood pressure or heart rate.

Here's the reassuring part: this is rated minor, and it's only been seen in test-tube research, never in real people. Food-amounts of black pepper are not a concern. If you take concentrated piperine supplements, just mention it to your pharmacist or doctor so they can keep an eye on your readings.

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 Hydrochlorothiazide, Propranolol 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 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 Hydrochlorothiazide, Propranolol

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 Hydrochlorothiazide, Propranolol, 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 Hydrochlorothiazide, Propranolol

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrochlorothiazide, Propranolol page lists 324 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Asarabacca (major) and Dolomite (major).

By severity: 11 major · 273 moderate · 40 minor.

From our pharmacist’s overview on the Hydrochlorothiazide, Propranolol page

“Inderide combines hydrochlorothiazide, a water pill, with propranolol, a beta blocker, so a supplement that also lowers blood pressure or pulls potassium out of the body hits the drug on its own turf. That describes most of this list, and I'd approach it with genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol
Steady interest

#1,698 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
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
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
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 Black Pepper and Hydrochlorothiazide, Propranolol Together: Common Questions

Can you take Black Pepper with Hydrochlorothiazide, Propranolol?
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 3 interactions listed for Black Pepper and Hydrochlorothiazide, Propranolol?
Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol 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.