Drug & supplement interaction

Coffee + Aspirin, Diphenhydramine, Phenylpropanolamine

Aspirin, Diphenhydramine, Phenylpropanolamine brand name: Alka Seltzer Plus Night Time Effervescent.

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

Aspirin, Diphenhydramine, Phenylpropanolamine falls into 3 drug categories that Coffee can interact with; the most serious is rated moderate. Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full interaction report
SeverityModerate
LikelihoodUnlikely
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Coffee and Aspirin, Diphenhydramine, Phenylpropanolamine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Coffee interacts with whole categories of medication. Aspirin, Diphenhydramine, Phenylpropanolamine falls into 3 of those categories, so it can interact with Coffee in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 3

Why this applies to Aspirin, Diphenhydramine, Phenylpropanolamine

Aspirin, Diphenhydramine, Phenylpropanolamine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Coffee interacts with.

Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Coffee contains caffeine. Caffeine is reported to have antiplatelet activity. Theoretically, the caffeine in coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood.
Severity Moderate Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

This combination product (Alka-Seltzer Plus Night Time) contains aspirin, which already thins the blood a little by blocking platelets from sticking together. The thought here is that the caffeine in coffee may have its own mild blood-thinning effect, so in theory drinking coffee on top of the aspirin could add slightly to your bleeding risk (think easier bruising, a cut that takes longer to stop, or stomach upset).

Honestly, I wouldn't lose sleep over this one. It's based only on lab studies, not on real people, and it's rated as unlikely. A normal cup or two of coffee is very different from a concentrated caffeine supplement. Still, if you take aspirin regularly or notice unusual bruising or bleeding, check in with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  2. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  3. Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. PubMed
Moderate

STIMULANT DRUGS

2 of 3

Aspirin, Diphenhydramine, Phenylpropanolamine also falls under STIMULANT DRUGS.

Theoretically, concomitant use might increase stimulant adverse effects.
Coffee 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

This combo product is a bit of a mixed bag. It has aspirin (a pain reliever), diphenhydramine (a sedating antihistamine, the sleepy part), and phenylpropanolamine, which is a decongestant and a mild stimulant. The interaction here is really about that decongestant teaming up with the caffeine in your coffee.

Caffeine and phenylpropanolamine are both stimulants, so stacking them can add up. You might notice a faster or pounding heartbeat, jitteriness, anxiety, or higher blood pressure. Keep in mind this is largely theoretical, based on expert opinion rather than strong studies, and a single normal cup is unlikely to cause trouble for most people. Just be mindful if you tend to drink several cups, and check with your pharmacist if you have heart or blood pressure concerns.

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

3 of 3

Aspirin, Diphenhydramine, Phenylpropanolamine also falls under PHENYLPROPANOLAMINE.

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Coffee contains 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

This product contains phenylpropanolamine, a decongestant that can nudge your blood pressure up on its own. When you wash it down with coffee, two things can happen. First, the caffeine in coffee and the decongestant can team up to push your blood pressure even higher. Second, phenylpropanolamine appears to slow how your body clears caffeine, so the caffeine sticks around longer and hits harder.

In real life that might mean a racing or pounding heart, jitteriness, restlessness, or trouble settling down (which is a bit odd for a nighttime product that's supposed to help you sleep). This is mostly theoretical and based on limited studies, so don't panic, but if you have high blood pressure or feel wired, check with your pharmacist or doctor.

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

Coffee Also Interacts With Other Medications

Coffee has 8 major, 466 moderate, 116 minor known drug interactions in our database — the Aspirin, Diphenhydramine, Phenylpropanolamine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 466 Minor 116 No known interaction 2,240 (incl. Aspirin, Diphenhydramine, Phenylpropanolamine)
Taking anything else?

Check Another of Your Medications Against Coffee

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Diphenhydramine, Phenylpropanolamine

This page covers Coffee only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Diphenhydramine, Phenylpropanolamine page lists 361 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 · 308 moderate · 36 minor.

From our pharmacist’s overview on the Aspirin, Diphenhydramine, Phenylpropanolamine page

“A cold remedy used for a few nights can still collide with supplements taken daily, and Alka Seltzer Plus Night Time (aspirin, diphenhydramine, phenylpropanolamine) is one to treat with genuine care. Its three ingredients thin the blood, sedate, and stimulate all at once, which is why 361 supplements and herbs are on file here.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Diphenhydramine, Phenylpropanolamine interaction page

One more smart check

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

We hold 716 real supplement products containing Coffee, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Coffee. Your product may carry other ingredients that interact with Aspirin, Diphenhydramine, Phenylpropanolamine too, on top of Coffee — 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 Coffee and Aspirin, Diphenhydramine, 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 Coffee
Top 10%

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

29 days ago today
Medication Aspirin, Diphenhydramine, Phenylpropanolamine
Top 10%

#212 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 Coffee

What is Coffee?

  • Alertness and reducing fatigue
  • Mental focus and concentration
  • Athletic performance
  • Headache relief
  • Weight management

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is generally safe and may have some health benefits, but too much can cause jitteriness, poor sleep, and a faster heartbeat. People who are pregnant, breastfeeding, or sensitive to caffeine should limit their intake and check with a doctor or pharmacist.

Read the full Coffee monograph & all interactions
Keep checking

Other Drugs & Coffee

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

8Major
466Moderate
116Minor
2,239No known interaction
8 Major 466 Moderate 116 Minor 2,239 No interaction
Major

8 interactions

Moderate

466 interactions

Showing 60 of 466 moderate interactions — see all 466 on the Coffee page.

Minor

116 interactions

Showing 60 of 116 minor interactions — see all 116 on the Coffee page.

No interaction 2,239 drugs checked — show the list

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

Showing the 60 most looked-up of 2,239 medications checked with no known interaction — see the full Coffee list.

See the full Coffee interactions page
See every supplement checked against Aspirin, Diphenhydramine, 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
Coffee monograph › Uses, safety, and every drug interaction in one place Aspirin, Diphenhydramine, Phenylpropanolamine supplement interactions › Every supplement checked against Aspirin, Diphenhydramine, 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 Coffee and Aspirin, Diphenhydramine, Phenylpropanolamine Together: Common Questions

Can you take Coffee with Aspirin, Diphenhydramine, 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 3 interactions listed for Coffee and Aspirin, Diphenhydramine, Phenylpropanolamine?
Aspirin, Diphenhydramine, Phenylpropanolamine belongs to more than one drug category, and Coffee 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 Coffee and Aspirin, Diphenhydramine, 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 Aspirin, Diphenhydramine, Phenylpropanolamine and Coffee?

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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.