Drug & supplement interaction

Lime + Regorafenib

Regorafenib brand name: Stivarga.

Moderate Interaction
The bottom line Moderate

Lime has a moderate interaction with Regorafenib. Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4.

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

Lime and Regorafenib

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Regorafenib

Regorafenib falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Lime interacts with.

Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4. This has been demonstrated in rats treated with sildenafil, a CYP3A4 substrate, and high doses of lime juice.
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: your body relies on a liver enzyme called CYP3A4 to break down regorafenib (Stivarga). Lab and animal research suggests certain plant compounds in lime juice can slow that enzyme down a bit. If that happens, regorafenib could clear more slowly and build up in your system, which may mean stronger side effects like high blood pressure, hand-foot skin reactions, fatigue, diarrhea, or liver strain.

The honest part: this concern comes only from animal and test-tube studies using high doses of lime juice, not from people taking regorafenib. A squeeze of lime in your food or water is very unlikely to be a problem. Concentrated lime extracts or large daily amounts are where I'd be cautious. Since regorafenib is a serious cancer medicine, run any lime supplement past your oncology team or pharmacist first.

References
  1. Bailey DG, Dresser GK, Bend JR. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice. Clin Pharmacol Ther 2003;73:529-37. PubMed
  2. Ademosun AO, Mohammed A, Oboh G, Ajeigbe OF. Influence of lemon (Citrus limon) and lime (Citrus aurantifolia) juices on the erectogenic properties of sildenafil in rats with L-NAME-induced erectile dysfunction. J Food Biochem 2022;46(2):e14074.

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

Lime Also Interacts With Other Medications

Lime has 885 moderate known drug interactions in our database — the Regorafenib one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Lime

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

Everything else you take

See Every Supplement That Interacts With Regorafenib

This page covers Lime only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Regorafenib page lists 138 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 Regorafenib page

“Regorafenib (Stivarga) is a targeted oral cancer therapy, and with a drug like this the goal is keeping its blood level inside a fairly tight window, so the 138 supplements and herbs on this page deserve real respect. Nearly all of them, 121 in total, can shift how the liver enzyme CYP3A4 processes the drug, nudging its level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Regorafenib interaction page

One more smart check

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

We hold 322 real supplement products containing Lime, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lime. Your product may carry other ingredients that interact with Regorafenib too, on top of Lime — 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 Lime and Regorafenib 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 Lime
Top 25%

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

29 days ago today
Medication Regorafenib
Steady interest

#2,243 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 Lime

What is Lime?

Lime
  • Source of vitamin C
  • Digestive upset
  • Skin care
  • Mood and aromatherapy
  • Flavoring and food preservation

Lime is a common citrus fruit and a good natural source of vitamin C and plant antioxidants. As a food it is generally safe and enjoyed by most people, but evidence that lime treats any specific health condition is limited. Use the essential oil with care, and check with your pharmacist or doctor before using concentrated lime products for health reasons.

Read the full Lime monograph & all interactions
Medication

About Regorafenib

What Is Regorafenib Used For?

Brand name: Stivarga

Stivarga is approved to treat three types of advanced cancer in adults. It is used for metastatic colorectal cancer (cancer that has spread) after prior chemotherapy and targeted therapy; for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) after two previous treatments; and for hepatocellular carcinoma (liver cancer) after treatment with sorafenib.

All three uses are specific to Stivarga tablets taken by mouth. It is intended for patients whose cancer has progressed despite earlier lines of therapy.

See full Regorafenib drug information
Keep checking

Other Drugs & Lime

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

0Major
885Moderate
0Minor
1,944No known interaction
Moderate

885 interactions

Showing 60 of 885 moderate interactions — see all 885 on the Lime page.

No interaction 1,944 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 Lime and Regorafenib Together: Common Questions

Can you take Lime with Regorafenib?
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.
How serious is the Lime and Regorafenib 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 Regorafenib and Lime?

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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.