Drug & supplement interaction

Comfrey + Fosphenytoin Sodium

Fosphenytoin Sodium brand name: Sesquient.

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

Fosphenytoin Sodium falls into 2 drug categories that Comfrey can interact with; the most serious is rated moderate. Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Comfrey and Fosphenytoin Sodium

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Comfrey interacts with whole categories of medication. Fosphenytoin Sodium falls into 2 of those categories, so it can interact with Comfrey in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Fosphenytoin Sodium

Fosphenytoin Sodium 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 short version: this isn't about comfrey changing how your fosphenytoin works. Fosphenytoin is a prodrug that your body converts into phenytoin to control seizures, and phenytoin itself can be hard on the liver in some people. The concern is that comfrey, when taken by mouth, contains pyrrolizidine alkaloids that are genuinely toxic to the liver. Stack two liver stressors together and you may raise the risk of liver injury.

I'll be honest, this is a theoretical concern based on how each one behaves, not proven cases of the two combined. Still, oral comfrey is risky on its own and best avoided entirely. Short-term use on intact skin is far less of a worry. Please run your specific situation by your doctor or pharmacist before changing anything.

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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

2 of 2

Fosphenytoin Sodium also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might increase the risk of adverse effects from the pyrrolizidine alkaloid constituents in comfrey.
CYP3A4 enzymes convert pyrrolizidine alkaloids, constituents of comfrey, to toxic metabolites. Some case reports show that enzyme inducers, such as phenobarbital, seem to enhance the toxicity of comfrey.
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 twist with this pairing: it's not your seizure medicine that gets thrown off. Fosphenytoin (Sesquient) is converted to phenytoin in your body, and phenytoin is a known inducer of the liver enzyme CYP3A4, meaning it speeds that enzyme up. Comfrey contains compounds called pyrrolizidine alkaloids, and that same enzyme turns them into toxic byproducts that can harm the liver.

So the theory is that being on fosphenytoin could make comfrey more dangerous to your liver, not less. This is based on pharmacology and a few older case reports, so the evidence is limited. Still, comfrey already shouldn't be taken by mouth, and only used briefly on intact skin. Please check with your pharmacist or doctor before using any comfrey product while on this medication.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed
  2. Chojkier M. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol 2003;39:437-46. PubMed
  3. 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

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 Fosphenytoin Sodium one above is among them. If you take anything else, check it against the full list below.

Moderate 437 No known interaction 2,393 (incl. Fosphenytoin 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.

Everything else you take

See Every Supplement That Interacts With Fosphenytoin Sodium

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin Sodium page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 179 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin Sodium page

“Fosphenytoin sodium (Sesquient) converts to phenytoin in the body, and phenytoin is unforgiving about blood levels. A little too low invites seizures, a little too high brings toxicity.”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin 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. Your product may carry other ingredients that interact with Fosphenytoin Sodium 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 Fosphenytoin 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

#1,005 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Fosphenytoin Sodium
Steady interest

#2,231 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 Fosphenytoin Sodium, 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 Fosphenytoin Sodium supplement interactions › Every supplement checked against Fosphenytoin 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 Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Comfrey and Fosphenytoin Sodium Together: Common Questions

Can you take Comfrey with Fosphenytoin Sodium?
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.
Why are there 2 interactions listed for Comfrey and Fosphenytoin Sodium?
Fosphenytoin Sodium belongs to more than one drug category, and Comfrey interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Comfrey and Fosphenytoin Sodium 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

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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.