Drug & supplement interaction

Papain + Nintedanib Esylate

Nintedanib Esylate brand name: Ofev.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Oct 4, 2026
The bottom line No known interaction

We found no known interaction between Papain and Nintedanib Esylate 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 label for Nintedanib Esylate states a food rule worth keeping to, and 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 Nintedanib Esylate

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 Nintedanib Esylate 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 Nintedanib Esylate and Papain? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Nintedanib Esylate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Nintedanib Esylate is filed under 5 classifications — including anticoagulant/antiplatelet drugs, p-glycoprotein substrates, cytochrome p450 3a4 (cyp3a4) substrates. Papain has documented interactions with 1 drug class — the most serious being warfarin (coumadin) (moderate) — and none of Nintedanib Esylate’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 — Nintedanib Esylate 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. Nintedanib Esylate)
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 Nintedanib Esylate 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 32.4% of FDA reports for Nintedanib Esylate 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.

    Nintedanib Esylate

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

  • Stomach upset Additional detail

    Papain

    “Orally and topically, papain seems to be well tolerated when used short-term at appropriate doses. Taking high oral doses may be unsafe.

    Most Common Adverse Effects:

    Orally: Allergic reactions in sensitive individuals.

    Topically: Urticaria and pruritus in sensitive individuals.

    Serious Adverse Effects (Rare):

    Orally: Esophageal perforation and severe gastritis with high doses.”

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

    Nintedanib Esylate

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

  • Itching Additional detail

    Papain

    “Topically, papain can cause itching. Urticarial reactions and itching have been reported in people occupationally exposed to papain, with papain confirmed as the causative agent by skin prick tests or radioallergosorbent tests (RAST).”

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

    4 sources cited
    1. 966. 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.
    2. 95533. Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
    3. 95534. Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
    4. 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

    Nintedanib Esylate

    Listed in the ADVERSE REACTIONS section of the FDA label for Nintedanib Esylate. 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.

    Nintedanib Esylate

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

Reported for Papain but not commonly for Nintedanib Esylate: an allergic reaction, a stuffy or runny nose, hives and wheezing.

Effects for Nintedanib Esylate 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 31,339 voluntary FDA FAERS reports for Nintedanib Esylate 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

How to take them

Some Nintedanib Esylate Products Have a Food Rule — Papain Should Not Break It

At least one FDA label for a product containing Nintedanib Esylate says to take it with food. If you take Papain on an empty stomach out of habit, keep them separate — and take Nintedanib Esylate with a meal where the label says to.

This may not be true of your version. Food instructions belong to the product, not the ingredient: two Nintedanib Esylate products can carry different directions, and extended-release forms often differ from immediate-release ones. The label we read is quoted below — check the directions on your own box or bottle, or ask your pharmacist, for how to take the exact product you were given.

2 DOSAGE AND ADMINISTRATION Recommended dosage: 150 mg taken orally twice daily approximately 12 hours apart taken with food.

From the Dosage and Administration section of the FDA label we read for Nintedanib Esylate — where that label names a specific product, the instruction is that product's. Read the label on DailyMed ›

A food rule is not an interaction — it is about how much of the medicine you absorb. The directions that came with your own product, and your pharmacist, outrank anything on this page.

Everything else you take

See Every Supplement That Interacts With Nintedanib Esylate

This page covers Papain only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nintedanib Esylate page lists 285 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Danshen (major), Grapefruit (major), Piracetam (major) and St. John's Wort (major).

By severity: 5 major · 240 moderate · 40 minor.

From our pharmacist’s overview on the Nintedanib Esylate page

“You take Ofev (nintedanib) to slow lung scarring, and this page deserves a careful read before any supplement joins it. Of the 285 ingredients here, the biggest cluster, over 200, can add to bleeding risk, a real concern since nintedanib itself can make you bleed more easily.”

Reviewed by 2 · Jul 18, 2026

Open the Nintedanib Esylate 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 Nintedanib Esylate, 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 Nintedanib Esylate 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 5%

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

29 days ago today
Medication Nintedanib Esylate
Top half

#1,095 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 October 4, 2026. The Papain and Nintedanib Esylate 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 Nintedanib

What Is Nintedanib Used For?

Brand name: Ofev

Nintedanib treats certain scarring lung diseases in adults. All the supported products are indicated for idiopathic pulmonary fibrosis (IPF) and for chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype (scarring lung disease that keeps getting worse).

Ofev, nintedanib capsules (100 mg and 150 mg) and one other nintedanib capsule product are also indicated to slow the decline in lung function in systemic sclerosis-associated interstitial lung disease (SSc-ILD). The nintedanib esylate capsule label lists only IPF and progressive chronic fibrosing ILDs.

See full Nintedanib 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 Nintedanib Esylate, 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 Nintedanib Esylate Together: Common Questions

Is it safe to take Papain with Nintedanib Esylate?
We do not list a known interaction between Papain and Nintedanib Esylate. 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 Nintedanib Esylate have any of the same side effects?
Yes — our sources link each of them separately to 4 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.
Should I take Papain and Nintedanib Esylate at the same time of day?
At least one FDA label for a product containing Nintedanib Esylate says to take it with food. If you take Papain on an empty stomach out of habit, keep them separate and take Nintedanib Esylate with a meal where the label says to. Food instructions belong to the product rather than the ingredient — two Nintedanib Esylate products can differ — so check the directions on your own box. This is about absorption, not an interaction.
How was the Papain and Nintedanib Esylate combination checked?
Interactions in our licensed database are recorded against drug classes. Nintedanib Esylate is filed under 5 classifications, and Papain has documented interactions with 1 drug class — none of Nintedanib Esylate'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 — Nintedanib Esylate 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 Nintedanib Esylate interact with any supplements?
Yes. Nintedanib Esylate has documented interactions with 285 supplements in our database — Papain is not one of them. The Nintedanib Esylate 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 Nintedanib drug information The full plain-English guide to this medication Nintedanib Esylate supplement interactions Every supplement checked against Nintedanib Esylate, 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 Nintedanib Esylate 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.