Drug & supplement interaction

Papain + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

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 Cyclobenzaprine 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 Cyclobenzaprine

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

Why No Interaction Is Listed for Cyclobenzaprine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Cyclobenzaprine is filed under 8 classifications — including skeletal muscle relaxants, serotonergic drugs, serotonergic drugs. Papain has documented interactions with 1 drug class — the most serious being warfarin (coumadin) (moderate) — and none of Cyclobenzaprine’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 — Cyclobenzaprine 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. Cyclobenzaprine)
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 Cyclobenzaprine May Share a Side Effect

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.

  • Stomach upset Additional detail

    Papain

    “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.

    Cyclobenzaprine

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

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

Effects for Cyclobenzaprine come from the ADVERSE REACTIONS section of its FDA label; effects for Papain come from the Natural Medicines adverse-effect record, quoted above. 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

From our Q&A

Questions About Papain or Cyclobenzaprine

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

This page covers Papain only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine 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 Cyclobenzaprine, 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 Cyclobenzaprine 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 Cyclobenzaprine
Top half

#1,105 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 Cyclobenzaprine 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 Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules are used alongside rest and physical therapy to relieve muscle spasm caused by acute, painful musculoskeletal conditions — easing pain, tenderness, and limited movement. This use is intended for short-term treatment only (up to 2–3 weeks).

Tonmya, the sublingual (under-the-tongue) form of cyclobenzaprine, is separately indicated for the treatment of fibromyalgia in adults. It is not the same as the oral tablet or capsule formulations.

See full Cyclobenzaprine 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 Cyclobenzaprine, 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 Cyclobenzaprine Together: Common Questions

Is it safe to take Papain with Cyclobenzaprine?
We do not list a known interaction between Papain and Cyclobenzaprine. 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 Cyclobenzaprine have any of the same side effects?
Yes — our sources link each of them separately to one 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.
How was the Papain and Cyclobenzaprine combination checked?
Interactions in our licensed database are recorded against drug classes. Cyclobenzaprine is filed under 8 classifications, and Papain has documented interactions with 1 drug class — none of Cyclobenzaprine'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 — Cyclobenzaprine 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 Cyclobenzaprine interact with any supplements?
Yes. Cyclobenzaprine has documented interactions with 197 supplements in our database — Papain is not one of them. The Cyclobenzaprine 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 Cyclobenzaprine drug information The full plain-English guide to this medication Cyclobenzaprine supplement interactions Every supplement checked against Cyclobenzaprine, 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 Cyclobenzaprine and Papain?

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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.