Drug & supplement interaction

Adrafinil + Ergotamine, Belladonna, Phenobarbital

Ergotamine, Belladonna, Phenobarbital brand names: Bellaspas, Bellamine, Eperbel-S.

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

Ergotamine, Belladonna, Phenobarbital falls into 2 drug categories that Adrafinil can interact with; the most serious is rated moderate. Theoretically, adrafanil might reduce levels and clinical effects of CYP3A4 substrates.

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

Adrafinil and Ergotamine, Belladonna, Phenobarbital

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

Why Are There 2 Interactions?

Adrafinil interacts with whole categories of medication. Ergotamine, Belladonna, Phenobarbital falls into 2 of those categories, so it can interact with Adrafinil 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 Ergotamine, Belladonna, Phenobarbital

Ergotamine, Belladonna, Phenobarbital falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Adrafinil interacts with.

Theoretically, adrafanil might reduce levels and clinical effects of CYP3A4 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP3A4 activity.
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: once your body turns adrafinil into modafinil, that modafinil can mildly speed up a liver enzyme called CYP3A4. Your combo product contains ergotamine, which leans on that same enzyme to be broken down. So in theory, adrafinil could nudge your body to clear the ergotamine a little faster, which might make it less effective at stopping a migraine.

I want to be honest about how soft this is. This concern is purely theoretical, based on how the drugs work on paper, not on real patient cases, and modafinil is only a weak inducer. On top of that, the phenobarbital piece can cause its own grogginess, which somewhat opposes adrafinil's wake-promoting effect. Before mixing these, please check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

2 of 2

Ergotamine, Belladonna, Phenobarbital also falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES.

Theoretically, adrafinil might reduce the levels and clinical effects of CYP2B6 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP2B6 activity in vitro.
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 for this combo product, which mixes ergotamine (for migraines), belladonna (an anticholinergic), and phenobarbital (a sedative barbiturate). The piece that matters most here is the phenobarbital, since it's partly handled by a liver enzyme called CYP2B6. In a test tube, modafinil (the compound your body makes from adrafinil) seems to gently speed up that enzyme. The worry, in theory, is that this could nudge phenobarbital levels a bit lower over time, possibly making it slightly less effective for whatever it was prescribed to do.

I want to be honest with you: this is theoretical, based only on lab data, not real patient reports, so I wouldn't lose sleep over it. Still, adrafinil itself is unregulated and hard on the liver, and stimulating effects don't mix well with a sedative like phenobarbital. Please run this past your doctor or pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
  3. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.

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

Adrafinil Also Interacts With Other Medications

Adrafinil has 1 major, 1,057 moderate known drug interactions in our database — the Ergotamine, Belladonna, Phenobarbital one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,057 No known interaction 1,772 (incl. Ergotamine, Belladonna, Phenobarbital)
Taking anything else?

Check Another of Your Medications Against Adrafinil

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

Everything else you take

See Every Supplement That Interacts With Ergotamine, Belladonna, Phenobarbital

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ergotamine, Belladonna, Phenobarbital 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 11 major · 200 moderate · 39 minor.

From our pharmacist’s overview on the Ergotamine, Belladonna, Phenobarbital page

“Sedation stacking is the risk I would put first with ergotamine, belladonna, and phenobarbital (Bellamine, Bellaspas). Phenobarbital is a barbiturate, sedating on its own, and 78 of the ingredients on this page deepen that drowsiness, alcohol most seriously of all.”

Reviewed by 2 · Jul 18, 2026

Open the Ergotamine, Belladonna, Phenobarbital interaction page

One more smart check

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

We hold 7 real supplement products containing Adrafinil, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adrafinil. Your product may carry other ingredients that interact with Ergotamine, Belladonna, Phenobarbital too, on top of Adrafinil — 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 Adrafinil and Ergotamine, Belladonna, Phenobarbital 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 Adrafinil
Top half

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

29 days ago today
Medication Ergotamine, Belladonna, Phenobarbital
Top 10%

#211 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 Adrafinil

What is Adrafinil?

Adrafinil
  • Wakefulness and alertness
  • Fatigue
  • Focus and concentration
  • Cognitive enhancement (nootropic)
  • Daytime sleepiness

Adrafinil is a synthetic compound that the body converts into modafinil, a prescription wakefulness-promoting drug. It is sometimes sold as a nootropic supplement, but it is unregulated, carries real risks (especially to the liver), and is banned in some sports and countries. Talk with a doctor or pharmacist before using it.

Read the full Adrafinil monograph & all interactions
Keep checking

Other Drugs & Adrafinil

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

1Major
1,057Moderate
0Minor
1,771No known interaction
1 Major 1,057 Moderate 1,771 No interaction
Major

1 interaction

Moderate

1,057 interactions

Showing 60 of 1,057 moderate interactions — see all 1,057 on the Adrafinil page.

No interaction 1,771 drugs checked — show the list

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

Showing the 60 most looked-up of 1,771 medications checked with no known interaction — see the full Adrafinil list.

See the full Adrafinil interactions page
See every supplement checked against Ergotamine, Belladonna, Phenobarbital, 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
Adrafinil monograph › Uses, safety, and every drug interaction in one place Ergotamine, Belladonna, Phenobarbital supplement interactions › Every supplement checked against Ergotamine, Belladonna, Phenobarbital, 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 Adrafinil and Ergotamine, Belladonna, Phenobarbital Together: Common Questions

Can you take Adrafinil with Ergotamine, Belladonna, Phenobarbital?
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 Adrafinil and Ergotamine, Belladonna, Phenobarbital?
Ergotamine, Belladonna, Phenobarbital belongs to more than one drug category, and Adrafinil 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 Adrafinil and Ergotamine, Belladonna, Phenobarbital 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.