Drug & supplement interaction

Caffeine + Chlorpheniramine, Phenylephrine, Phenylpropanolamine

Chlorpheniramine, Phenylephrine, Phenylpropanolamine brand name: Rutuss.

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

Chlorpheniramine, Phenylephrine, Phenylpropanolamine falls into 2 drug categories that Caffeine 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

Caffeine and Chlorpheniramine, Phenylephrine, Phenylpropanolamine

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

Why Are There 2 Interactions?

Caffeine interacts with whole categories of medication. Chlorpheniramine, Phenylephrine, Phenylpropanolamine falls into 2 of those categories, so it can interact with Caffeine 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine

Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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

This combination product (Rutuss) contains phenylephrine and phenylpropanolamine, which are decongestants that mildly stimulate your system to shrink swollen nasal passages. Adding caffeine on top of that can stack stimulant effects, so you may notice a faster or pounding heartbeat, jitteriness, trouble sleeping, or a bump in blood pressure. The chlorpheniramine part is actually a sedating antihistamine, so caffeine won't really cancel that drowsiness out, it just adds extra stimulation alongside it.

To be clear, this is based on expert reasoning rather than hard studies, and a normal cup of coffee usually isn't a big deal. But if you're loading up on energy drinks or high doses, or you have heart issues or anxiety, check with your pharmacist or doctor first.

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

PHENYLPROPANOLAMINE

2 of 2

Chlorpheniramine, Phenylephrine, Phenylpropanolamine also falls under PHENYLPROPANOLAMINE.

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.
Severity Moderate Likelihood Probable Evidence B

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 watch with a combo product like Rutuss. It contains phenylpropanolamine, a decongestant that tightens blood vessels and can nudge your blood pressure and heart rate up on its own. Caffeine is a stimulant that pushes in the same direction, so taking them together can stack those effects. You may notice a faster or pounding heartbeat, jitteriness, restlessness, or trouble sleeping more than usual.

There's also a second piece: phenylpropanolamine seems to slow how your body clears caffeine, so caffeine can climb higher than expected and feel stronger. This is rated moderate and likely, but the evidence is limited. If you have high blood pressure or heart trouble, go easy on coffee and energy drinks and check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  2. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. 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 8 major, 482 moderate, 164 minor known drug interactions in our database — the Chlorpheniramine, Phenylephrine, Phenylpropanolamine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 482 Minor 164 No known interaction 2,176 (incl. Chlorpheniramine, Phenylephrine, Phenylpropanolamine)
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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine

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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine, 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine

This page covers Caffeine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Chlorpheniramine, Phenylephrine, Phenylpropanolamine page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Henbane (major) and Lithium (major).

By severity: 10 major · 175 moderate · 44 minor.

From our pharmacist’s overview on the Chlorpheniramine, Phenylephrine, Phenylpropanolamine page

“Rutuss combines an antihistamine, chlorpheniramine, with two decongestants, phenylephrine and phenylpropanolamine, and its supplement interactions call for real care. Ten of the 229 ingredients on file carry a major rating.”

Reviewed by 2 · Jul 18, 2026

Open the Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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%

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

29 days ago today
Medication Chlorpheniramine, Phenylephrine, Phenylpropanolamine
Steady interest

#2,578 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.

8Major
482Moderate
164Minor
2,175No known interaction
8 Major 482 Moderate 164 Minor 2,175 No interaction
Major

8 interactions

Moderate

482 interactions

Showing 60 of 482 moderate interactions — see all 482 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine, 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine supplement interactions › Every supplement checked against Chlorpheniramine, Phenylephrine, Phenylpropanolamine, 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine Together: Common Questions

Can you take Caffeine with Chlorpheniramine, Phenylephrine, Phenylpropanolamine?
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 Caffeine and Chlorpheniramine, Phenylephrine, Phenylpropanolamine?
Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine 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 Chlorpheniramine, Phenylephrine, Phenylpropanolamine and Caffeine?

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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.