Drug & supplement interaction

Comfrey + Nafcillin Sodium

Nafcillin Sodium brand name: Unipen.

Moderate Interaction
The bottom line Moderate

Comfrey has a moderate interaction with Nafcillin Sodium. Theoretically, CYP3A4 inducers might increase the risk of adverse effects from the pyrrolizidine alkaloid constituents in comfrey.

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

Comfrey and Nafcillin Sodium

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

Why this applies to Nafcillin Sodium

Nafcillin Sodium falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS — the group Comfrey interacts with.

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 concern with pairing comfrey and nafcillin. Comfrey naturally contains pyrrolizidine alkaloids, plant compounds that are already known to be hard on the liver. Your body's CYP3A4 enzyme can turn those alkaloids into even more toxic byproducts. Nafcillin happens to speed up (induce) that same enzyme, so in theory it could ramp up production of those harmful liver-damaging metabolites.

I want to be honest about the evidence here: this is theoretical, based on how these substances behave rather than solid studies with nafcillin itself. Still, comfrey should never be swallowed because of its liver risk, and adding an enzyme booster only stacks the odds higher. The safest move is keeping comfrey to short-term use on unbroken skin only. Please check with your pharmacist or doctor before combining the two.

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

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 Nafcillin Sodium

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nafcillin Sodium page lists 75 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), Alkanna (moderate) and Alpine Ragwort (moderate).

By severity: 3 major · 61 moderate · 11 minor.

From our pharmacist’s overview on the Nafcillin Sodium page

“Nafcillin sodium (Unipen) is a penicillin antibiotic for serious staph infections, often given by IV, so anything that weakens it or piles strain on the kidneys carries real weight. Three of the 75 supplements on this page rate major, and those come first: Siberian cocklebur and asarabacca can each damage the kidneys, and activated cha…”

Reviewed by 2 · Jul 18, 2026

Open the Nafcillin 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 Nafcillin 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 Nafcillin 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

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

29 days ago today
Medication Nafcillin Sodium
Steady interest

#2,097 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
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
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

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Pharmacist Counseling Corner

Taking Comfrey and Nafcillin Sodium Together: Common Questions

Can you take Comfrey with Nafcillin 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.
How serious is the Comfrey and Nafcillin 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.