Drug & supplement interaction

Indian Long Pepper + Apremilast

Apremilast brand name: Otezla.

Moderate Interaction
The bottom line Moderate

Apremilast falls into 2 drug categories that Indian Long Pepper can interact with; the most serious is rated moderate. Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.

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

Indian Long Pepper and Apremilast

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

Why Are There 2 Interactions?

Indian Long Pepper interacts with whole categories of medication. Apremilast falls into 2 of those categories, so it can interact with Indian Long 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Apremilast

Apremilast falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Indian Long Pepper interacts with.

Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4.
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 on pairing Indian long pepper with Otezla (apremilast). Your body relies on an enzyme called CYP3A4 to break apremilast down and clear it. The piperine in long pepper may slow that enzyme, so in theory apremilast could linger a bit longer and build up in your blood. Apremilast is an active drug (not a prodrug), so more of it means a stronger effect and a higher chance of its usual side effects, things like nausea, loose stools or diarrhea, headache, and sometimes low mood.

Now, the honest part: this is based on lab (in vitro) studies, not real people, so it's theoretical. A pinch of the spice in cooking is unlikely to matter. Concentrated daily supplements are where I'd be more careful. If you take it regularly, just give your pharmacist or doctor a heads-up before changing anything.

References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Apremilast also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, can inhibit P-glycoprotein.
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 with Otezla (apremilast) and Indian long pepper. The piperine in this spice can block a transporter called P-glycoprotein, which acts like a bouncer that helps shuttle certain drugs out of your body. If that bouncer is slowed down, a little more apremilast could theoretically stick around in your bloodstream. Apremilast is not a prodrug, so more of it in your system generally means a stronger effect and a bit more chance of its usual side effects, like nausea, diarrhea, headache, or feeling down.

I want to be honest though: this is a theoretical concern based on lab (test tube) data, not real patient studies. The pinch you'd get in cooking is very unlikely to matter. If you're taking concentrated pippali supplements regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.

References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  2. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. 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

Indian Long Pepper Also Interacts With Other Medications

Indian Long Pepper has 893 moderate, 3 minor known drug interactions in our database — the Apremilast 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 Indian Long Pepper

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

Everything else you take

See Every Supplement That Interacts With Apremilast

This page covers Indian Long Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Apremilast page lists 144 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 94 moderate · 41 minor.

From our pharmacist’s overview on the Apremilast page

“St. John's wort is the first thing I would rule out for anyone taking apremilast (Otezla) for psoriasis, psoriatic arthritis, or Behçet's mouth sores.”

Reviewed by 2 · Jul 18, 2026

Open the Apremilast interaction page

One more smart check

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

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Your product may carry other ingredients that interact with Apremilast too, on top of Indian Long 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 Indian Long Pepper and Apremilast 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 Indian Long Pepper
Top 25%

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

29 days ago today
Medication Apremilast
Steady interest

#1,565 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 Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Read the full Indian Long Pepper monograph & all interactions
Medication

About Apremilast

What Is Apremilast Used For?

Brand name: Otezla

Apremilast treats several inflammatory conditions. In adults, it is used for active psoriatic arthritis, plaque psoriasis in people who are candidates for phototherapy or systemic therapy, and oral ulcers associated with Behçet's Disease.

Children 6 and older can use it for active psoriatic arthritis and moderate to severe plaque psoriasis. Otezla is for children weighing at least 20 kg. Otezla XR is for children weighing at least 50 kg. Neither product is established for Behçet's Disease in children.

See full Apremilast drug information
Keep checking

Other Drugs & Indian Long Pepper

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

0Major
893Moderate
3Minor
1,933No known interaction
Moderate

893 interactions

Showing 60 of 893 moderate interactions — see all 893 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,933 drugs checked — show the list

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

Showing the 60 most looked-up of 1,933 medications checked with no known interaction — see the full Indian Long Pepper 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 Indian Long Pepper and Apremilast Together: Common Questions

Can you take Indian Long Pepper with Apremilast?
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 Indian Long Pepper and Apremilast?
Apremilast belongs to more than one drug category, and Indian Long 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 Indian Long Pepper and Apremilast 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.