Drug & supplement interaction

Dhea + Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate brand name: Fiorinal w/ Codeine.

Moderate Interaction
The bottom line Moderate

Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 2 drug categories that Dhea can interact with; the most serious is rated moderate. Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.

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

Dhea and Aspirin, Butalbital, Caffeine, Codeine Phosphate

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Aspirin, Butalbital, Caffeine, Codeine Phosphate

Aspirin, Butalbital, Caffeine, Codeine Phosphate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Dhea interacts with.

Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
Some preliminary evidence shows that DHEA may inhibit CYP3A4; however, the clinical significance of this potential interaction is not known.
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

This combination pill (Fiorinal with Codeine) is a mix of aspirin, the barbiturate butalbital, caffeine, and codeine. Some of these pieces, especially butalbital, lean on the liver enzyme CYP3A4 to be broken down. There's early, anecdotal hint that DHEA might gently slow that enzyme. If that happened, a bit more of the medicine could linger, which could mean extra drowsiness, dizziness, or slowed breathing.

Honestly, this is a theoretical concern with weak evidence, so I wouldn't lose sleep over it. Codeine is actually a prodrug that depends on a different enzyme (CYP2D6), so DHEA shouldn't change how well it relieves pain. Since butalbital and opioids are already sedating, just mention you take DHEA to your pharmacist or doctor so they can keep an eye on things.

References
  1. Frye RF, Kroboth PD, Folan MM, et al. Effect of DHEA on CYP3A-mediated metabolism of triazolam. Clin Pharmacol Ther 2000;67:109 (abstract PI-82).
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Human and laboratory research show that DHEA and DHEA-S can inhibit platelet aggregation.
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 thing about Fiorinal with Codeine: one of its ingredients is aspirin, which already thins the blood and makes platelets less sticky. DHEA has shown, mostly in lab and test-tube studies, that it can also slow platelets from clumping together. So in theory, taking them together could nudge your bleeding risk a little higher, on top of what aspirin already does.

What that might look like in real life is easier bruising, nosebleeds, bleeding gums, or stomach upset that's slow to stop. To be honest, the evidence here is weak and theoretical, so I don't want you to panic. Still, it's worth a quick chat with your pharmacist or doctor, especially if you bruise easily or take other blood thinners.

References
  1. Jesse, R. L., Loesser, K., Eich, D. M., Qian, Y. Z., Hess, M. L., Nestler, J. E. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N.Y.Acad Sci 1995;774:281-90.
  2. Bertoni, A., Rastoldo, A., Sarasso, C., Di Vito C., Sampietro, S., Nalin, M., Bagarotti, A., Sinigaglia, F. Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation. Steroids 2012;77(3):260-8. 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

Dhea Also Interacts With Other Medications

Dhea has 767 moderate, 8 minor known drug interactions in our database — the Aspirin, Butalbital, Caffeine, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Dhea

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Butalbital, Caffeine, Codeine Phosphate

This page covers Dhea only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine, Codeine Phosphate page lists 398 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: 17 major · 334 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine, Codeine Phosphate page

“Fiorinal with Codeine packs four active drugs into one capsule, and I would treat its supplement list with genuine wariness rather than a quick skim. The aspirin component is why roughly half of the 398 ingredients on file raise bleeding risk, while the codeine and butalbital explain a second large cluster that deepens sedation, someti…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Butalbital, Caffeine, Codeine Phosphate interaction page

One more smart check

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

We hold 945 real supplement products containing Dhea, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Dhea. Your product may carry other ingredients that interact with Aspirin, Butalbital, Caffeine, Codeine Phosphate too, on top of Dhea — 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 Dhea and Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Dhea
Top 25%

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

29 days ago today
Medication Aspirin, Butalbital, Caffeine, Codeine Phosphate
Steady interest

#1,942 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 Dhea

What is Dhea?

Dhea
  • Anti-aging and low DHEA levels
  • Mood and depression
  • Vaginal dryness and sexual health
  • Fertility support
  • Muscle mass and athletic performance
  • Adrenal insufficiency

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed and limited for most uses, and because it acts as a hormone it can cause real side effects. Talk to a pharmacist or doctor before using it, especially if you have a hormone-sensitive condition.

Read the full Dhea monograph & all interactions
Keep checking

Other Drugs & Dhea

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

0Major
767Moderate
8Minor
2,054No known interaction
Moderate

767 interactions

Showing 60 of 767 moderate interactions — see all 767 on the Dhea page.

Minor

8 interactions

No interaction 2,054 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 Dhea and Aspirin, Butalbital, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Dhea with Aspirin, Butalbital, Caffeine, Codeine Phosphate?
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 Dhea and Aspirin, Butalbital, Caffeine, Codeine Phosphate?
Aspirin, Butalbital, Caffeine, Codeine Phosphate belongs to more than one drug category, and Dhea 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 Dhea and Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.