Drug & supplement interaction

Comfrey + Mestranol, Norethynodrel

Mestranol, Norethynodrel brand name: Enovid-E.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Comfrey has a moderate interaction with Mestranol, Norethynodrel. Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Comfrey and Mestranol, Norethynodrel

Here is the interaction we found between these two, with the evidence behind it.

Moderate

HEPATOTOXIC DRUGS

Why this applies to Mestranol, Norethynodrel

Mestranol, Norethynodrel falls under HEPATOTOXIC DRUGS — the group Comfrey interacts with.

Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.
Due to its pyrrolizidine alkaloid constituents, comfrey can cause hepatotoxic effects, including ascites, cirrhosis, hepatic fibrosis, hepatomegaly, and sinusoidal obstruction syndrome.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with this pairing: comfrey is the real troublemaker for your liver. Taken by mouth, it contains pyrrolizidine alkaloids that can genuinely harm liver tissue. Your birth control pill (the mestranol and norethynodrel combo in Enovid-E) is also processed by your liver and, on its own, can occasionally stress it. Stacking the two could theoretically add up to more liver strain than either alone.

I'll be honest, this concern is based on how these things work, not on strong studies, so I'm not trying to alarm you. Still, since comfrey should never really be swallowed anyway, the simplest move is to avoid oral comfrey entirely. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Comfrey Also Interacts With Other Medications

Comfrey has 437 moderate known drug interactions in our database — the Mestranol, Norethynodrel one above is one of them. If you take anything else, check it against the full list below.

Moderate 437 No known interaction 2,393 (incl. Mestranol, Norethynodrel)
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.

Everything else you take

See Every Supplement That Interacts With Mestranol, Norethynodrel

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mestranol, Norethynodrel page lists 188 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 6 major · 140 moderate · 42 minor.

From our pharmacist’s overview on the Mestranol, Norethynodrel page

“The list for Mestranol and Norethynodrel (Enovid-E, a combined birth control pill) deserves genuine care, because several entries can quietly undo the pill itself. St.”

Reviewed by 2 · Jul 18, 2026

Open the Mestranol, Norethynodrel 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. Your product may carry other ingredients that interact with Mestranol, Norethynodrel too, on top of Comfrey — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Comfrey and Mestranol, Norethynodrel 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

#1,142 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Mestranol, Norethynodrel
Steady interest

#1,949 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.

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.

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
437Moderate
0Minor
2,392No known interaction
437 Moderate 2,392 No interaction
Moderate

437 interactions

Showing 60 of 437 moderate interactions — see all 437 on the Comfrey page.

No interaction 2,392 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 2,392 medications checked with no known interaction — see the full Comfrey list.

See the full Comfrey interactions page
See every supplement checked against Mestranol, Norethynodrel, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Comfrey monograph › Uses, safety, and every drug interaction in one place Mestranol, Norethynodrel supplement interactions › Every supplement checked against Mestranol, Norethynodrel, 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 Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Comfrey and Mestranol, Norethynodrel Together: Common Questions

Can you take Comfrey with Mestranol, Norethynodrel?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Comfrey and Mestranol, Norethynodrel interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Mestranol, Norethynodrel and Comfrey?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.