Drug & supplement interaction

Ilex Guayusa + Promethazine, Pseudoephedrine

Promethazine, Pseudoephedrine brand name: Phenergan D.

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

Promethazine, Pseudoephedrine falls into 2 drug categories that Ilex Guayusa can interact with; the most serious is rated moderate. Theoretically, concomitant use might increase stimulant adverse effects.

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

Ilex Guayusa and Promethazine, Pseudoephedrine

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

Why Are There 2 Interactions?

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

Moderate

STIMULANT DRUGS

1 of 2

Why this applies to Promethazine, Pseudoephedrine

Promethazine, Pseudoephedrine falls under STIMULANT DRUGS — the group Ilex Guayusa interacts with.

Theoretically, concomitant use might increase stimulant adverse effects.
Ilex guayusa contains caffeine. 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 thing to keep in mind: Phenergan D contains pseudoephedrine, a decongestant that's also a stimulant. Guayusa tea brings caffeine to the table, which is a stimulant too. When you stack two stimulants together, their effects can add up. You might notice a racing or pounding heart, jitteriness, anxiety, trouble sleeping, or a bump in your blood pressure.

This is mostly a theoretical, common-sense concern rather than something proven in studies, so don't panic. A single cup now and then is usually mild. Still, if you have heart issues or high blood pressure, it's worth a quick chat with your pharmacist or doctor before pairing them regularly.

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
Minor

PHENOTHIAZINES

2 of 2

Promethazine, Pseudoephedrine also falls under PHENOTHIAZINES.

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Ilex guayusa contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2).
Severity Minor 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 deal with Phenergan D and a guayusa tea or supplement. The promethazine part can gently slow down a liver enzyme called CYP1A2, which is the same enzyme your body uses to clear caffeine. So the caffeine from guayusa may hang around a bit longer than usual. On top of that, Phenergan D already contains pseudoephedrine, which is its own stimulant. Stacking caffeine on top could leave you feeling more jittery, with a faster or pounding heartbeat, restlessness, or trouble sleeping.

Honestly though, this one is rated minor and is only theoretical, based on lab work rather than real patients. A regular cup of guayusa probably won't cause trouble, but concentrated supplements are a different story. If you notice the jitters or a racing heart, check in with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  2. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.

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

Ilex Guayusa Also Interacts With Other Medications

Ilex Guayusa has 8 major, 469 moderate, 127 minor known drug interactions in our database — the Promethazine, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 469 Minor 127 No known interaction 2,226 (incl. Promethazine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Ilex Guayusa

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

Everything else you take

See Every Supplement That Interacts With Promethazine, Pseudoephedrine

This page covers Ilex Guayusa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Promethazine, Pseudoephedrine page lists 116 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Henbane (major), Peyote (major) and Rauvolfia Vomitoria (major).

By severity: 7 major · 93 moderate · 16 minor.

From our pharmacist’s overview on the Promethazine, Pseudoephedrine page

“Phenergan D combines a sedating antihistamine, promethazine, with the decongestant stimulant pseudoephedrine, and its supplement list pulls hard in both directions, so this is one to treat with genuine care. The biggest cluster, from everyday caffeine sources like coffee and cola nut up to ephedra, stacks extra stimulation on the pseud…”

Reviewed by 2 · Jul 18, 2026

Open the Promethazine, Pseudoephedrine interaction page

How much people look this up

Where Ilex Guayusa and Promethazine, Pseudoephedrine 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 Ilex Guayusa
Steady interest

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

29 days ago today
Medication Promethazine, Pseudoephedrine
Top 25%

#686 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 Ilex Guayusa

What is Ilex Guayusa?

  • Energy and alertness
  • Mental focus
  • Antioxidant support
  • Appetite control
  • Athletic and physical performance

Ilex guayusa is a caffeine-containing holly leaf from the Amazon, traditionally brewed as a tea for energy and alertness, much like yerba mate or green tea. There is limited human research confirming specific health benefits, and its main reliable effect comes from its caffeine content. Because it is a stimulant, use it cautiously and check with your pharmacist or doctor if you have heart concerns or are pregnant.

Read the full Ilex Guayusa monograph & all interactions
Keep checking

Other Drugs & Ilex Guayusa

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

8Major
469Moderate
127Minor
2,225No known interaction
8 Major 469 Moderate 127 Minor 2,225 No interaction
Major

8 interactions

Moderate

469 interactions

Showing 60 of 469 moderate interactions — see all 469 on the Ilex Guayusa page.

Minor

127 interactions

Showing 60 of 127 minor interactions — see all 127 on the Ilex Guayusa page.

No interaction 2,225 drugs checked — show the list

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

Showing the 60 most looked-up of 2,225 medications checked with no known interaction — see the full Ilex Guayusa list.

See the full Ilex Guayusa interactions page
See every supplement checked against Promethazine, Pseudoephedrine, 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
Ilex Guayusa monograph › Uses, safety, and every drug interaction in one place Promethazine, Pseudoephedrine supplement interactions › Every supplement checked against Promethazine, Pseudoephedrine, 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 Ilex Guayusa and Promethazine, Pseudoephedrine Together: Common Questions

Can you take Ilex Guayusa with Promethazine, Pseudoephedrine?
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 Ilex Guayusa and Promethazine, Pseudoephedrine?
Promethazine, Pseudoephedrine belongs to more than one drug category, and Ilex Guayusa 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 Ilex Guayusa and Promethazine, Pseudoephedrine 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.