Drug & supplement interaction

Papain + Regorafenib

Regorafenib brand name: Stivarga.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Papain and Regorafenib in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Papain and Regorafenib

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Regorafenib and Papain in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Papain safety at a glance

Papain overall Use caution Generally tolerated as a food, but supplements may irritate the digestive tract and cause allergic reactions.
Pregnancy Possibly Unsafe When used orally. There is some concern that crude papain is teratogenic and embryotoxic. Read the full pregnancy detail
Breastfeeding Use caution Not enough reliable safety information exists, so it is best to avoid supplemental papain while breastfeeding.

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Regorafenib and Papain? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Regorafenib

Interactions in our licensed database are recorded against drug classes, not just single drug names. Regorafenib is filed under 2 classifications — cytochrome p450 3a4 (cyp3a4) substrates, oral drugs. Papain has documented interactions with 1 drug class — the most serious being warfarin (coumadin) (moderate) — and none of Regorafenib’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Papain Does Interact With Other Medications

Papain has 2 moderate known drug interactions in our database — Regorafenib isn’t one of them. If you take anything else, check it against the full list below.

Moderate 2 No known interaction 2,828 (incl. Regorafenib)
Taking anything else?

Check Another of Your Medications Against Papain

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

What to actually watch for

No Interaction Found — But Data Suggests Papain and Regorafenib May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do.

  • Diarrhea reported in 12.3% of FDA reports for Regorafenib Additional detail

    Papain

    “Orally, papain may cause allergic reactions, including itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea, in individuals sensitive to papain (6,967). Occupational exposure to airborne papain dust may also cause respiratory allergic reactions.”

    Papain · Natural Medicines adverse-effect record, reported in diarrhea.

    6 sources cited
    1. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    2. 967. Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann Allergy 1985;55:541-3.
    3. 95532. Tymoszuk D, Wiszniewska M, Walusiak-Skorupa J. Papain-induced occupational rhinoconjunctivitis and asthma - A case report. Med Pr 2016;67(1):109-12. PubMed
    4. 95533. Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
    5. 95534. Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
    6. 95535. Baur X, König G, Bencze K, Fruhmann G. Clinical symptoms and results of skin test, RAST and bronchial provocation test in thirty-three papain workers: Evidence for strong immunogenic potency and clinically relevant proteolytic e?ects of airborne papain. C

    “Orally, papain has been associated with diarrhea. In a randomized controlled trial assessing the effects of papain, trypsin, and chymotrypsin on adverse effects from radiotherapy, moderate to severe diarrhea was more frequent in the enzyme-treated group than the placebo group. However, it is unclear if this adverse effect is due to papain, other enzymes, or the combination.”

    Papain · Natural Medicines adverse-effect record, reported in diarrhea.

    3 sources cited
    1. 67834. Martin, T., Uhder, K., Kurek, R., Roeddiger, S., Schneider, L., Vogt, H. G., Heyd, R., and Zamboglou, N. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial PubMed
    2. 67848. Walker-Renard, P. Update on the medicinal management of phytobezoars. Am J Gastroenterol. 1993;88(10):1663-1666.
    3. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

    Regorafenib

    Listed in the ADVERSE REACTIONS section of the FDA label for Regorafenib, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Stomach pain Additional detail

    Papain

    Recorded for Papain in the same Natural Medicines adverse-effect record shown under Diarrhea above.

    Regorafenib

    Listed in the ADVERSE REACTIONS section of the FDA label for Regorafenib. Read the label on DailyMed ›

Reported for Papain but not commonly for Regorafenib: an allergic reaction, a stuffy or runny nose, stomach upset and hives.

Effects for Regorafenib come from the ADVERSE REACTIONS section of its FDA label; effects for Papain come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 11,442 voluntary FDA FAERS reports for Regorafenib that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Papain in Pregnancy & Breastfeeding

Pregnancy Possibly Unsafe

When used orally. There is some concern that crude papain is teratogenic and embryotoxic.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Overlapping uses

What Regorafenib Is Prescribed For, and What Papain Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Regorafenib is a prescription medicine with approved uses on its FDA label. Papain is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Regorafenib is prescribed for: 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.

Papain has been studied for:

  • Cancer studied, not established Papain has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Papain for cancer

    Although there has been interest in using oral papain for cancer, there is insufficient reliable information about the clinical effects of papain for this purpose.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Regorafenib on your own; if you are taking Papain for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

Everything else you take

See Every Supplement That Interacts With Regorafenib

This page covers Papain 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 Papain as Part of a Dietary Supplement Product? Check It for Interactions

We hold 3,790 real supplement products containing Papain, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Papain. Even though Papain itself has no known interaction with Regorafenib, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Papain 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 Papain
Top 10%

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

29 days ago today
Medication Regorafenib
Top half

#1,313 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Papain reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Papain and Regorafenib records this page draws on were last updated July 11, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Papain

What is Papain?

Papain
  • Digestive support for protein digestion
  • Wound cleaning (debridement of dead tissue)
  • Sore throat and inflammation
  • Sports injuries such as sprains
  • Skin conditions

Papain is a protein-digesting enzyme from the papaya plant that is used in digestive supplements and some topical products. While it has clear food and laboratory uses, strong human evidence for most health claims is limited, and it can cause allergic reactions or throat irritation. Check with a pharmacist or doctor before using it, especially if you have a latex or papaya allergy.

Carica papaya · Caricaceae · Latex (sap) from the unripe fruit; also derived from leaves · Capsules, tablets, chewable digestive enzyme blends, topical ointments and gels, meat tenderizer powder

An interaction check asks whether these two react with each other — it does not ask whether Papain is a good idea for someone in your situation. Here is what our Papain record says about it on its own.

Papain: dosing

There is no official, standardized dose for papain. The amount in supplements varies widely between products and is often measured in enzyme activity units rather than milligrams.The safest approach is to follow the directions on the product label and not exceed the recommended amount.

From our Papain monograph — the full record covers uses, side effects and every documented interaction.

Read the full Papain 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.

Most-Reported Side Effects for Regorafenib

From FAERS, the FDA’s public side-effect reporting system (11,542 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Fatigue 1,769 reports
Palmar-plantar erythrodysaesthesia syndrome 1,439 reports
Diarrhea 1,418 reports
Decreased appetite 1,091 reports
Asthenia 946 reports
See full Regorafenib drug information
Keep checking

Other Drugs & Papain

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

0Major
2Moderate
0Minor
2,827No known interaction
2 Moderate 2,827 No interaction
Moderate

2 interactions

No interaction 2,827 drugs checked — show the list

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

Showing the 60 most looked-up of 2,827 medications checked with no known interaction — see the full Papain list.

See the full Papain interactions page
See every supplement checked against Regorafenib, ranked by severity
Evidence & sources

Papain References

The 11 references that drive our Papain monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Saf 1997;17:342-56.
  3. Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaesthetic agents. Br J Dermatol 1988;119:535-40.
  4. Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann Allergy 1985;55:541-3.
  5. Martin, T., Uhder, K., Kurek, R., Roeddiger, S., Schneider, L., Vogt, H. G., Heyd, R., and Zamboglou, N. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial PubMed
  6. Walker-Renard, P. Update on the medicinal management of phytobezoars. Am J Gastroenterol. 1993;88(10):1663-1666.
  7. Tymoszuk D, Wiszniewska M, Walusiak-Skorupa J. Papain-induced occupational rhinoconjunctivitis and asthma - A case report. Med Pr 2016;67(1):109-12. PubMed
  8. Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
  9. Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
  10. Baur X, König G, Bencze K, Fruhmann G. Clinical symptoms and results of skin test, RAST and bronchial provocation test in thirty-three papain workers: Evidence for strong immunogenic potency and clinically relevant proteolytic e?ects of airborne papain. C
  11. Novey HS, Keenan WJ, Fairshter RD, Wells ID, Wilson AF, Culver BD. Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies. Clin Allergy 1980;10(6):721-31. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Papain and Regorafenib Together: Common Questions

Is it safe to take Papain with Regorafenib?
We do not list a known interaction between Papain and Regorafenib. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Papain and Regorafenib have any of the same side effects?
Yes — our sources link each of them separately to 2 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Papain and Regorafenib used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Papain in each. That is a conversation for your prescriber, especially if Regorafenib is being adjusted to a target.
How was the Papain and Regorafenib combination checked?
Interactions in our licensed database are recorded against drug classes. Regorafenib is filed under 2 classifications, and Papain has documented interactions with 1 drug class — none of Regorafenib's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Papain interact with any other medications?
Yes. Papain has 2 documented drug interactions in our database — Regorafenib is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Regorafenib interact with any supplements?
Yes. Regorafenib has documented interactions with 138 supplements in our database — Papain is not one of them. The Regorafenib interaction page linked on this page lists every one, ranked by severity.

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

Where next

Keep Exploring

Papain monograph Uses, safety profile, and every drug interaction in one place Regorafenib drug information The full plain-English guide to this medication Regorafenib supplement interactions Every supplement checked against Regorafenib, 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 References The 11 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Regorafenib and Papain?

Our pharmacists answer your medication & supplement questions — free.

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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.