Drug & supplement interaction

Comfrey + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium states a food rule worth keeping to.

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Interaction report

Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium

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 Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium and Comfrey? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Diphenhydramine Hydrochloride, Naproxen Sodium

Interactions in our licensed database are recorded against drug classes, not just single drug names. Diphenhydramine Hydrochloride, Naproxen Sodium is filed under 14 classifications — including nonsteroidal anti-inflammatory drugs (nsaids), cytochrome p450 2c9 (cyp2c9) substrates, anticoagulant/antiplatelet 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 Diphenhydramine Hydrochloride, Naproxen Sodium’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 — Diphenhydramine Hydrochloride, Naproxen Sodium 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. Diphenhydramine Hydrochloride, Naproxen Sodium)
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

What Comfrey Itself Has Been Linked To

This is not an interaction — nothing below involves Diphenhydramine Hydrochloride, Naproxen Sodium. It is the side-effect record for Comfrey on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Comfrey, this list is the first place to look. 2 entries are worth acting on rather than waiting out — marked below.

  • Raised blood pressure Worth acting on Additional detail

    “The pyrrolizidine alkaloid constituents of comfrey can damage the lungs, resulting in pulmonary hypertension. A case report involving a 66-year-old female with known arterial hypertension, mild kidney insufficiency, and type 2 diabetes described severe partial respiratory insufficiency and pulmonary hypertension. The patient admitted to using a number of alternative therapies daily, including comfrey.”

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

    4 sources cited
    1. 11987. Stewart MJ, Steenkamp V. Pyrrolizidine poisoning: a neglected area in human toxicology. Ther Drug Monit 2001;23:698-708. PubMed
    2. 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.
    3. 11990. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed
    4. 44911. 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.
  • Liver problems Worth acting on Additional detail

    “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
  • Itching / A skin rash Additional detail

    “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
  • Swelling / Stomach pain / Tiredness / Diarrhea / Vomiting Additional detail

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

Everything above comes from the Natural Medicines adverse-effect record for Comfrey — expand a row for the licensed statement it rests on. We haven’t matched Diphenhydramine Hydrochloride, Naproxen Sodium to its FDA label in our system yet, so we can’t compare its own side-effect list here — the leaflet that comes with your prescription is the authoritative list for Diphenhydramine Hydrochloride, Naproxen Sodium.

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 Diphenhydramine Hydrochloride, Naproxen Sodium Products Have a Food Rule — Comfrey Should Not Break It

At least one FDA label for a product containing Diphenhydramine Hydrochloride, Naproxen Sodium says to take it with food. If you take Comfrey on an empty stomach out of habit, keep them separate — and take Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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.

Directions • do not take more than directed • drink a full glass of water with each dose • adults and children 12 years and over: take 2 caplets at bedtime • do not take more than 2 caplets in 24 hours • if taken with food, this product may take longer to work

From the Dosage and Administration section of the FDA label we read for Diphenhydramine Hydrochloride, Naproxen Sodium — where that label names a specific product, the instruction is that product's.

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 Diphenhydramine Hydrochloride, Naproxen Sodium

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 320 moderate · 45 minor.

From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page

“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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
Steady interest

#1,128 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Steady interest

#1,762 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 13, 2026. The Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium 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
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 Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions

Is it safe to take Comfrey with Diphenhydramine Hydrochloride, Naproxen Sodium?
We do not list a known interaction between Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium. 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.
Should I take Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium at the same time of day?
At least one FDA label for a product containing Diphenhydramine Hydrochloride, Naproxen Sodium says to take it with food. If you take Comfrey on an empty stomach out of habit, keep them separate and take Diphenhydramine Hydrochloride, Naproxen Sodium with a meal where the label says to. Food instructions belong to the product rather than the ingredient — two Diphenhydramine Hydrochloride, Naproxen Sodium products can differ — so check the directions on your own box. This is about absorption, not an interaction.
How was the Comfrey and Diphenhydramine Hydrochloride, Naproxen Sodium combination checked?
Interactions in our licensed database are recorded against drug classes. Diphenhydramine Hydrochloride, Naproxen Sodium is filed under 14 classifications, and Comfrey has documented interactions with 2 drug classes — none of Diphenhydramine Hydrochloride, Naproxen Sodium'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 — Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium interact with any supplements?
Yes. Diphenhydramine Hydrochloride, Naproxen Sodium has documented interactions with 378 supplements in our database — Comfrey is not one of them. The Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium supplement interactions Every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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.