Drug & supplement interaction

Caffeine + Ephedrine, Phenobarbital, Theophylline

Ephedrine, Phenobarbital, Theophylline brand name: Tedral.

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

Ephedrine, Phenobarbital, Theophylline falls into 4 drug categories that Caffeine can interact with; the most serious is rated major. Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Caffeine and Ephedrine, Phenobarbital, Theophylline

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Caffeine interacts with whole categories of medication. Ephedrine, Phenobarbital, Theophylline falls into 4 of those categories, so it can interact with Caffeine in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

EPHEDRINE

1 of 4
Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.
Severity Major Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing about combining caffeine with this older combo product (Tedral): two of its ingredients, ephedrine and theophylline, are both stimulants. Caffeine is a stimulant too. Stack them all together and the effects can pile up, not cancel out. That can mean a pounding or racing heart, shakiness, anxiety, trouble sleeping, and higher blood pressure. In larger amounts the concern gets more serious, with reports linking ephedrine plus caffeine to events like dangerous spikes in blood pressure, heart problems, and seizures.

I'll be honest: this warning rests mostly on anecdotal reports rather than strong studies, so I don't want to scare you. Still, theophylline is a touchy drug to begin with. Please run your daily coffee or energy drink habit by your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  2. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  3. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
Moderate

STIMULANT DRUGS

2 of 4

Why this applies to Ephedrine, Phenobarbital, Theophylline

Ephedrine, Phenobarbital, Theophylline falls under STIMULANT DRUGS — the group Caffeine interacts with.

Theoretically, concomitant use might increase stimulant adverse effects.
Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects.
Severity Moderate Likelihood Probable Evidence C

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version: Tedral is a combo medicine, and two of its pieces (ephedrine and theophylline) are already stimulants in their own right. Adding caffeine, which is also a stimulant, can pile on top of that. Both caffeine and theophylline are actually close chemical cousins, so they tend to push in the same direction.

What that can feel like is more of the jittery side: a racing or pounding heart, shakiness, trouble sleeping, headache, or feeling wired and anxious. This concern is mostly based on expert reasoning rather than hard studies, so it's not a guarantee. Still, if you regularly drink coffee, tea, or energy drinks while taking Tedral, it's worth a quick chat with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
Moderate

THEOPHYLLINE

3 of 4

Ephedrine, Phenobarbital, Theophylline also falls under THEOPHYLLINE.

Theoretically, caffeine might increase the levels and adverse effects of theophylline.
Large amounts of caffeine might inhibit theophylline metabolism.
Severity Moderate Likelihood Probable Evidence C

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combination pill (Tedral) contains theophylline, and that is the piece caffeine can bump into. Caffeine and theophylline are chemical cousins, and your liver clears them using some of the same pathways. When you take in a lot of caffeine, it may slow down how fast your body breaks theophylline down, letting it build up a bit higher than expected.

Theophylline already has a narrow safe range, so even small increases matter. Higher levels can bring on a fast or pounding heartbeat, jitters, trouble sleeping, nausea, or feeling wired. This is mostly expert opinion rather than hard proof, and an occasional cup of coffee usually is not a big deal, but heavy caffeine (energy drinks, lots of coffee, or caffeine pills) is where I would be cautious. Please check with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
Moderate

PHENOBARBITAL (Luminal)

4 of 4
Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, the exact mechanism of this interaction is unclear.
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

Tedral is an older combo product, and the piece that matters here is the phenobarbital, a seizure and sedative medicine. The concern on file is fairly simple: caffeine is a brain stimulant, while phenobarbital works by calming brain activity. Because they push in opposite directions, a lot of caffeine could, in theory, chip away at how well phenobarbital controls seizures. In animal studies, caffeine lowered phenobarbital's anti-seizure effect, so if you rely on it for that, big caffeine doses might mean less protection.

That said, this is theoretical and based only on animal data, so I would not panic over a normal cup of coffee. Heavy caffeine or energy drinks are the bigger question. Please run your usual caffeine habits by your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  2. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  3. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. 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

Caffeine Also Interacts With Other Medications

Caffeine has 7 major, 483 moderate, 164 minor known drug interactions in our database — the Ephedrine, Phenobarbital, Theophylline one above is among them. If you take anything else, check it against the full list below.

Major 7 Moderate 483 Minor 164 No known interaction 2,176 (incl. Ephedrine, Phenobarbital, Theophylline)
Taking anything else?

Check Another of Your Medications Against Caffeine

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

From our Q&A

Questions About Caffeine or Ephedrine, Phenobarbital, Theophylline

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Caffeine or Ephedrine, Phenobarbital, Theophylline, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Ephedrine, Phenobarbital, Theophylline

This page covers Caffeine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ephedrine, Phenobarbital, Theophylline page lists 184 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), Black Tea (major) and Coffee (major).

By severity: 22 major · 140 moderate · 22 minor.

Open the Ephedrine, Phenobarbital, Theophylline interaction page

One more smart check

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

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Your product may carry other ingredients that interact with Ephedrine, Phenobarbital, Theophylline too, on top of Caffeine — 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 Caffeine and Ephedrine, Phenobarbital, Theophylline 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 Caffeine
Top 5%

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

29 days ago today
Medication Ephedrine, Phenobarbital, Theophylline
Steady interest

#2,001 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 Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Read the full Caffeine monograph & all interactions
Keep checking

Other Drugs & Caffeine

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

7Major
483Moderate
164Minor
2,175No known interaction
7 Major 483 Moderate 164 Minor 2,175 No interaction
Major

7 interactions

Moderate

483 interactions

Showing 60 of 483 moderate interactions — see all 483 on the Caffeine page.

Minor

164 interactions

Showing 60 of 164 minor interactions — see all 164 on the Caffeine page.

No interaction 2,175 drugs checked — show the list

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

Showing the 60 most looked-up of 2,175 medications checked with no known interaction — see the full Caffeine list.

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

Can you take Caffeine with Ephedrine, Phenobarbital, Theophylline?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Caffeine and Ephedrine, Phenobarbital, Theophylline?
Ephedrine, Phenobarbital, Theophylline belongs to more than one drug category, and Caffeine 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 Caffeine and Ephedrine, Phenobarbital, Theophylline interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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.