Drug & supplement interaction

Comfrey + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

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 Comfrey and Penicillamine 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 Penicillamine 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

Comfrey and Penicillamine

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 Penicillamine and Comfrey 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.

Comfrey safety at a glance

Comfrey overall Use caution Topical use on unbroken skin for short periods may be acceptable, but oral use is unsafe due to liver toxicity.
Pregnancy Likely Unsafe When used orally or topically. In addition to hepatotoxicity and possible carcinogenicity, the pyrrolizidine alkaloids (PAs) in comfrey might be teratogenic. PA... Read the full pregnancy detail
Breastfeeding Likely Unsafe When used orally or topically. In addition to hepatotoxicity and possible carcinogenicity, the pyrrolizidine alkaloids (PAs) in comfrey might be teratogenic. PA... Read the full breastfeeding detail

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 Penicillamine and Comfrey? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Penicillamine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Penicillamine is filed under 3 classifications — including nephrotoxic drugs, oral drugs. Comfrey has documented interactions with 2 drug classes — the most serious being cytochrome p450 3a4 (cyp3a4) inducers (moderate) and hepatotoxic drugs (moderate) — and none of Penicillamine’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

Comfrey Does Interact With Other Medications

Comfrey has 438 moderate known drug interactions in our database — Penicillamine isn’t one of them. If you take anything else, check it against the full list below.

Moderate 438 No known interaction 2,392 (incl. Penicillamine)
Taking anything else?

Check Another of Your Medications Against Comfrey

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

What to actually watch for

No Interaction Found — But Data Suggests Comfrey and Penicillamine 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. One of them is worth acting on rather than waiting out — marked below.

  • Liver problems Worth acting on Additional detail

    Comfrey

    “The pyrrolizidine alkaloid constituents of comfrey can cause acute sinusoidal obstruction syndrome characterized by sudden abdominal pain, vomiting, ascites, and hepatomegaly. In subacute disease, comfrey can cause ascites, hepatomegaly, abdominal pain, diarrhea, vomiting, and abdominal swelling. Chronic toxicity appears as asthenia and progressive ascites.”

    Comfrey · Natural Medicines adverse-effect record, reported in cirrhosis.

    2 sources cited
    1. 11988. Food and Drug Administration. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products From the Market. July 6, 2001. Available at: http://www.cfsan.fda.gov/~dms/dspltr06.html.
    2. 11990. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed

    Penicillamine

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

  • Diarrhea / Vomiting reported in 9.6% of FDA reports for Penicillamine Additional detail

    Comfrey

    Recorded for Comfrey in the same Natural Medicines adverse-effect record shown under Liver problems above.

    Penicillamine

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

  • Itching / A skin rash Additional detail

    Comfrey

    “Topically, comfrey-containing creams and ointments may cause skin redness, irritation, itching, rash, and eczema.”

    Comfrey · Natural Medicines adverse-effect record, reported in eczema.

    6 sources cited
    1. 44902. Predel, H. G., Giannetti, B., Koll, R., Bulitta, M., and Staiger, C. Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytome
    2. 44912. Giannetti, B. M., Staiger, C., Bulitta, M., and Predel, H. G. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial. Br.J Spor PubMed
    3. 44917. Tanret, I. and Duh, D. [Pharmaceutical sheet. Symphytum officinale L., dermal use (Flexagile cream)]. J Pharm.Belg. 2012;(1):41-42.
    4. 44919. Laslett, L. L., Quinn, S. J., Darian-Smith, E., Kwok, M., Fedorova, T., Korner, H., Steels, E., March, L., and Jones, G. Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised contr
    5. 92566. Frost R, Macpherson H, O'meara S. A critical scoping review of external uses of comfrey (Symphytum spp.). Complement Ther Med. 2013;21(6):724-45. PubMed
    6. 92570. Pabst H, Schaefer A, Staiger C, Junker-samek M, Predel HG. Combination of comfrey root extract plus methyl nicotinate in patients with conditions of acute upper or low back pain: a multicentre randomised controlled trial. Phytother Res. 2013;27(6):811-7. PubMed

    Penicillamine

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

Reported for Comfrey but not commonly for Penicillamine: stomach pain, raised blood pressure, swelling and tiredness.

Effects for Penicillamine come from the ADVERSE REACTIONS section of its FDA label; effects for Comfrey come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 917 voluntary FDA FAERS reports for Penicillamine 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

Comfrey in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Unsafe

When used orally or topically. In addition to hepatotoxicity and possible carcinogenicity, the pyrrolizidine alkaloids (PAs) in comfrey might be teratogenic. PAs are absorbed through the skin.

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 Penicillamine Products Have a Food Rule — Comfrey Should Not Break It

At least one FDA label for a product containing Penicillamine says to take it on an empty stomach. Most supplements — Comfrey included — are taken with a meal, so the easy mistake is swallowing both together at breakfast. Where that rule applies, keep Penicillamine on its own and move Comfrey to a meal later in the day.

This may not be true of your version. Food instructions belong to the product, not the ingredient: two Penicillamine 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.

DOSAGE AND ADMINISTRATION In all patients receiving penicillamine, it is important that CUPRIMINE be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk.

From the Dosage and Administration section of the FDA label we read for Penicillamine — 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 Penicillamine

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Penicillamine page lists 26 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Siberian Cocklebur (major), Aristolochia (moderate) and Coffee Charcoal (moderate).

By severity: 3 major · 13 moderate · 10 minor.

From our pharmacist’s overview on the Penicillamine page

“People take penicillamine (Cuprimine, Depen) for demanding conditions, Wilson's disease, rheumatoid arthritis, cystinuria, and its 26 supplement interactions are not a list to skim, three of them rated major. Seventeen ingredients can keep an oral dose from being fully absorbed, activated charcoal chief among them, and six more can str…”

Reviewed by 2 · Jul 18, 2026

Open the Penicillamine interaction page

One more smart check

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

We hold 29 real supplement products containing Comfrey, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Comfrey. Even though Comfrey itself has no known interaction with Penicillamine, 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 Comfrey and Penicillamine 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 Comfrey
Top half

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

29 days ago today
Medication Penicillamine
Steady interest

#2,326 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 Comfrey reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Comfrey and Penicillamine records this page draws on were last updated July 10, 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 Comfrey

What is Comfrey?

Comfrey
  • Bruises and sprains
  • Muscle and joint pain
  • Minor wounds and skin irritation
  • Back pain
  • Inflammation

Comfrey is a traditional herb used mainly on the skin for bruises, sprains, and joint pain, and some topical products show modest benefit for these uses. However, comfrey contains compounds that can seriously damage the liver, so it should never be taken by mouth and should only be used on unbroken skin for short periods. Pregnant or breastfeeding people should avoid it entirely.

Symphytum officinale · Boraginaceae · Leaves and roots · Topical ointments, creams, salves, poultices, and (less safely) teas

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

Comfrey: dosing

There is no well-established, standardized dose for comfrey, and oral use is not recommended at any dose because of liver toxicity.For topical products, follow the directions on the product label and do not use more than directed or for longer than recommended (usually a few weeks at most).

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

Read the full Comfrey monograph & all interactions
Medication

About Penicillamine

What Is Penicillamine Used For?

Brand names: Cuprimine, Depen Titratable

Penicillamine is used for three distinct conditions. It treats Wilson's disease — a rare genetic disorder in which the body accumulates dangerous levels of copper — by binding to the excess copper and helping the body remove it. It also treats cystinuria, a condition where the amino acid cystine builds up and forms painful kidney stones, by converting cystine into a more soluble form that the body can excrete more easily.

For patients with severe, active rheumatoid arthritis who have not responded adequately to conventional therapies, penicillamine (available as Aagylur, Cuprimine, Depen, and other products) may be used to help suppress disease activity and reduce joint pain, tenderness, and swelling.

See full Penicillamine drug information
Keep checking

Other Drugs & Comfrey

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

0Major
438Moderate
0Minor
2,391No known interaction
438 Moderate 2,391 No interaction
Moderate

438 interactions

Showing 60 of 438 moderate interactions — see all 438 on the Comfrey page.

No interaction 2,391 drugs checked — show the list

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

Showing the 60 most looked-up of 2,391 medications checked with no known interaction — see the full Comfrey list.

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

Comfrey References

The 13 references that drive our Comfrey 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. Stewart MJ, Steenkamp V. Pyrrolizidine poisoning: a neglected area in human toxicology. Ther Drug Monit 2001;23:698-708. PubMed
  2. Food and Drug Administration. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products From the Market. July 6, 2001. Available at: http://www.cfsan.fda.gov/~dms/dspltr06.html.
  3. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed
  4. Chojkier M. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol 2003;39:437-46. PubMed
  5. Wang YP, Yan J, Fu PP, Chou MW. Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol Lett 2005;155:411-20. PubMed
  6. Predel, H. G., Giannetti, B., Koll, R., Bulitta, M., and Staiger, C. Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytome
  7. Gyorik, S. and Stricker, H. Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy. Swiss.Med.Wkly. 4-4-2009;139(13-14):210-211.
  8. Giannetti, B. M., Staiger, C., Bulitta, M., and Predel, H. G. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial. Br.J Spor PubMed
  9. Tanret, I. and Duh, D. [Pharmaceutical sheet. Symphytum officinale L., dermal use (Flexagile cream)]. J Pharm.Belg. 2012;(1):41-42.
  10. Laslett, L. L., Quinn, S. J., Darian-Smith, E., Kwok, M., Fedorova, T., Korner, H., Steels, E., March, L., and Jones, G. Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised contr
  11. Frost R, Macpherson H, O'meara S. A critical scoping review of external uses of comfrey (Symphytum spp.). Complement Ther Med. 2013;21(6):724-45. PubMed
  12. Pabst H, Schaefer A, Staiger C, Junker-samek M, Predel HG. Combination of comfrey root extract plus methyl nicotinate in patients with conditions of acute upper or low back pain: a multicentre randomised controlled trial. Phytother Res. 2013;27(6):811-7. PubMed
  13. Smith DB, Jacobson BH. Effect of a blend of comfrey root extract (Symphytum officinale L.) and tannic acid creams in the treatment of osteoarthritis of the knee: randomized, placebo-controlled, double-blind, multiclinical trials. J Chiropr Med. 2011;10(3) 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 Comfrey and Penicillamine Together: Common Questions

Is it safe to take Comfrey with Penicillamine?
We do not list a known interaction between Comfrey and Penicillamine. 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 Comfrey and Penicillamine have any of the same side effects?
Yes — our sources link each of them separately to 5 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 Comfrey and Penicillamine at the same time of day?
At least one FDA label for a product containing Penicillamine says to take it on an empty stomach, and supplements are usually taken with a meal — so taking them together at breakfast is the easy mistake. Where that applies, keep Penicillamine on its own and move Comfrey to a meal later in the day. Food instructions belong to the product rather than the ingredient, so check the directions on your own box. This is about absorption, not an interaction.
How was the Comfrey and Penicillamine combination checked?
Interactions in our licensed database are recorded against drug classes. Penicillamine is filed under 3 classifications, and Comfrey has documented interactions with 2 drug classes — none of Penicillamine'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 Comfrey interact with any other medications?
Yes. Comfrey has 438 documented drug interactions in our database — Penicillamine 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 Penicillamine interact with any supplements?
Yes. Penicillamine has documented interactions with 26 supplements in our database — Comfrey is not one of them. The Penicillamine 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

Comfrey monograph Uses, safety profile, and every drug interaction in one place Penicillamine drug information The full plain-English guide to this medication Penicillamine supplement interactions Every supplement checked against Penicillamine, 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 13 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Penicillamine and Comfrey?

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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.