Drug & supplement interaction

Sassafras + Acetaminophen, Dichloralphenazone, Isometheptene

Acetaminophen, Dichloralphenazone, Isometheptene brand name: Midrin.

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

Sassafras has a moderate interaction with Acetaminophen, Dichloralphenazone, Isometheptene. Theoretically, concomitant use of sassafras with drugs with sedative properties may cause additive sedative effects.

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

Sassafras and Acetaminophen, Dichloralphenazone, Isometheptene

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

Moderate

CNS DEPRESSANTS

Why this applies to Acetaminophen, Dichloralphenazone, Isometheptene

Acetaminophen, Dichloralphenazone, Isometheptene falls under CNS DEPRESSANTS — the group Sassafras interacts with.

Theoretically, concomitant use of sassafras with drugs with sedative properties may cause additive sedative effects.
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 situation with Midrin (a combo of acetaminophen, dichloralphenazone, and isometheptene). One of its ingredients, dichloralphenazone, is a mild sedative, so this medication can already make you a bit drowsy or relaxed when you take it for a migraine. Sassafras has been reported to have its own calming, sedative-like properties, so the concern is that pairing the two could leave you more tired, foggy, or lightheaded than usual.

I'll be straight with you though: this is a theoretical interaction based on how these substances behave, not something proven in people taking them together. The bigger issue is sassafras itself, since its safrole content is linked to liver damage and cancer and the FDA banned it in foods. I'd skip internal sassafras entirely, but please run any combination by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

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

Sassafras Also Interacts With Other Medications

Sassafras has 274 moderate known drug interactions in our database — the Acetaminophen, Dichloralphenazone, Isometheptene one above is one of them. If you take anything else, check it against the full list below.

Moderate 274 No known interaction 2,556 (incl. Acetaminophen, Dichloralphenazone, Isometheptene)
Taking anything else?

Check Another of Your Medications Against Sassafras

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Dichloralphenazone, Isometheptene

This page covers Sassafras only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dichloralphenazone, Isometheptene page lists 250 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 Ephedra (major).

By severity: 13 major · 196 moderate · 41 minor.

From our pharmacist’s overview on the Acetaminophen, Dichloralphenazone, Isometheptene page

“Midrin pairs acetaminophen with a sedative (dichloralphenazone) and a stimulant-like blood vessel constrictor (isometheptene), so it can be pushed off course from several directions, and I would approach this list with real vigilance. Thirteen of the 250 ingredients listed are rated major, and most of those either deepen the sedation,…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Dichloralphenazone, Isometheptene interaction page

One more smart check

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

We hold 11 real supplement products containing Sassafras, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sassafras. Your product may carry other ingredients that interact with Acetaminophen, Dichloralphenazone, Isometheptene too, on top of Sassafras — 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 Sassafras and Acetaminophen, Dichloralphenazone, Isometheptene 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 Sassafras
Steady interest

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

29 days ago today
Medication Acetaminophen, Dichloralphenazone, Isometheptene
Top 5%

#88 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 Sassafras

What is Sassafras?

  • Digestive complaints
  • Cold and flu symptoms
  • Joint and muscle aches
  • Skin conditions (topical folk use)
  • As a flavoring agent (traditional root beer)

Sassafras is an aromatic North American tree whose root bark and oil were once popular in teas and as a flavoring, but it contains safrole, a compound the FDA has banned in foods because it can cause cancer and liver damage. There is no good evidence it safely treats any health condition, and most experts recommend avoiding internal use. If you want the flavor, choose products that are labeled safrole-free.

Read the full Sassafras monograph & all interactions
Keep checking

Other Drugs & Sassafras

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

0Major
274Moderate
0Minor
2,555No known interaction
274 Moderate 2,555 No interaction
Moderate

274 interactions

Showing 60 of 274 moderate interactions — see all 274 on the Sassafras page.

No interaction 2,555 drugs checked — show the list

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

Showing the 60 most looked-up of 2,555 medications checked with no known interaction — see the full Sassafras list.

See the full Sassafras interactions page
See every supplement checked against Acetaminophen, Dichloralphenazone, Isometheptene, 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
Sassafras monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Dichloralphenazone, Isometheptene supplement interactions › Every supplement checked against Acetaminophen, Dichloralphenazone, Isometheptene, 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 Sassafras and Acetaminophen, Dichloralphenazone, Isometheptene Together: Common Questions

Can you take Sassafras with Acetaminophen, Dichloralphenazone, Isometheptene?
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 Sassafras and Acetaminophen, Dichloralphenazone, Isometheptene 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 Acetaminophen, Dichloralphenazone, Isometheptene and Sassafras?

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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.