Drug & supplement interaction

Grapefruit + Loperamide, Simethicone

Loperamide, Simethicone brand name: Imodium Advanced.

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

Grapefruit has a minor interaction with Loperamide, Simethicone. Grapefruit juice does not seem to affect renal P-glycoprotein (P-gp).

Read the full interaction report
SeverityMinor
LikelihoodPossible
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Loperamide, Simethicone

Here is the interaction we found between these two, with the evidence behind it.

Minor

P-GLYCOPROTEIN SUBSTRATES

Why this applies to Loperamide, Simethicone

Loperamide, Simethicone falls under P-GLYCOPROTEIN SUBSTRATES — the group Grapefruit interacts with.

Grapefruit juice does not seem to affect renal P-glycoprotein (P-gp). Theoretically, it might inhibit intestinal P-gp, but evidence is conflicting.
While most in vitro research shows that grapefruit products inhibit P-gp,, research in humans is less clear. Two small clinical studies in healthy adults using digoxin as a probe substrate show that grapefruit juice does not inhibit P-gp in the kidneys. It is unclear whether this applies to intestinal P-gp, for which digoxin is not considered to be a sensitive probe. Grapefruit juice has been shown to reduce levels of fexofenadine, and increase levels of quinidine. However, as both of these drugs are also substrates of other enzymes and transporters, it is unclear what role, if any, intestinal P-gp has in these findings.
Severity Minor 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

Imodium Advanced combines loperamide (which slows down your gut) and simethicone (a simple anti-gas ingredient). Loperamide is handled in part by a transporter called P-glycoprotein, which acts like a bouncer keeping some of the drug out of your bloodstream and inside your gut, where it does its job. Grapefruit may slow that bouncer down a little, which could let slightly more loperamide get absorbed.

In theory, that might mean a touch more constipation, drowsiness, or dizziness. But honestly, the human evidence here is weak and conflicting, and grapefruit's effect on gut P-glycoprotein is not well proven. For most people taking occasional Imodium, this isn't a big concern. If you eat grapefruit often or use this medicine regularly, just run it by your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Soldner A, Christians U, Susanto M, et al. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res 1999;16:478-85. PubMed
  2. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999;48:829-38. PubMed
  3. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  4. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  5. Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2001;70:311-6. DOI
  6. Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 2002;71:11-20. PubMed
  7. Parker RB, Yates CR, Soberman JE, Laizure SC. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 2003;23:979-87. PubMed
  8. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  9. Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005;77:170-7. PubMed
  10. Min, D. I., Ku, Y. M., Geraets, D. R., and Lee, H. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol 1996;36(5):469-476. PubMed
  11. Jia Y, Liu J, Xu J. Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide. Xenobiotica. 2017 Apr 16:1-5. PubMed
  12. Guideline on the investigation of drug interactions. CPMP/EWP/560/95/Rev. 1 Corr. 2. European Medicines Agency, 2015. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions-revision-1_en.pdf (As
  13. Piscitelli J, Nikanjam M, Capparelli EV, et al. Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach. Ther Drug Monit 2023;45(4):539-545. 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 776 major, 151 moderate, 62 minor known drug interactions in our database — the Loperamide, Simethicone one above is one of them. If you take anything else, check it against the full list below.

Major 776 Moderate 151 Minor 62 No known interaction 1,841 (incl. Loperamide, Simethicone)
Taking anything else?

Check Another of Your Medications Against Grapefruit

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

From our Q&A

Questions About Grapefruit or Loperamide, Simethicone

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

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Loperamide, Simethicone page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Scopolia (major), St. John's Wort (major) and Angel's Trumpet (moderate).

By severity: 4 major · 59 moderate · 19 minor.

From our pharmacist’s overview on the Loperamide, Simethicone page

“Imodium Advanced combines loperamide, an anti-diarrheal opioid that normally stays out of the brain thanks to a transporter called P-glycoprotein, with simethicone for gas, and I treat its interaction list with more respect than most over-the-counter medicines warrant. Thirty-seven of the 82 interacting ingredients on file affect that…”

Reviewed by 2 · Jul 18, 2026

Open the Loperamide, Simethicone interaction page

One more smart check

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

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Loperamide, Simethicone too, on top of Grapefruit — 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 Grapefruit and Loperamide, Simethicone 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 Grapefruit
Top 10%

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

29 days ago today
Medication Loperamide, Simethicone
Top 25%

#478 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

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

776Major
151Moderate
62Minor
1,840No known interaction
776 Major 151 Moderate 62 Minor 1,840 No interaction
Major

776 interactions

Showing 60 of 776 major interactions — see all 776 on the Grapefruit page.

Moderate

151 interactions

Showing 60 of 151 moderate interactions — see all 151 on the Grapefruit page.

Minor

62 interactions

Showing 60 of 62 minor interactions — see all 62 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

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

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

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

Can you take Grapefruit with Loperamide, Simethicone?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Grapefruit and Loperamide, Simethicone interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Loperamide, Simethicone and Grapefruit?

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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.