Drug & supplement interaction

Ergot + Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine brand names: Protid, Histex SR, Alka-Seltzer PLUS.

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

Acetaminophen, Chlorpheniramine, Phenylephrine falls into 2 drug categories that Ergot can interact with; the most serious is rated moderate. Certain ergot alkaloids, such as dihydroergotamine, act as serotonin agonists.

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

Ergot and Acetaminophen, Chlorpheniramine, Phenylephrine

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

Why Are There 2 Interactions?

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

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine falls under SEROTONERGIC DRUGS — the group Ergot interacts with.

Certain ergot alkaloids, such as dihydroergotamine, act as serotonin agonists. Theoretically, combining serotonergic drugs with ergot might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using ergot with serotonergic drugs.
Serotonergic drugs include the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft); tricyclic and atypical antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), and imipramine (Tofranil); triptans such as sumatriptan (Imitrex), zolmitriptan (Zomig), and rizatriptan (Maxalt); opioids such as methadone (Dolophine) and tramadol (Ultram); and many other medications.
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

Let me put this combination in plain terms. The cold and allergy product you asked about contains three things: acetaminophen (a pain and fever reducer), chlorpheniramine (an antihistamine), and phenylephrine (a decongestant). Of these, phenylephrine and chlorpheniramine are the pieces that matter here. Phenylephrine tightens blood vessels, and ergot does the very same thing in a much stronger way. Stacking two vessel-narrowing agents could push your blood pressure up and, in theory, add to ergot's circulation problems.

The serotonin concern in our database is mostly theoretical and rests on weak, anecdotal evidence, so I wouldn't lose sleep over serotonin syndrome from this specific product. Still, ergot itself is unsafe as a home remedy. Please run this by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  2. Eadie MJ. Convulsive ergotism: epidemics of the serotonin syndrome? Lancet Neurol 2003;2:429-34. PubMed
Moderate

STIMULANT DRUGS

2 of 2

Acetaminophen, Chlorpheniramine, Phenylephrine also falls under STIMULANT DRUGS.

Co-administration of stimulant drugs with ergot may increase the risk of vasoconstriction.
Some stimulant drugs include albuterol (Proventil, Ventolin), diethylpropion (Tenuate), dopamine, epinephrine, phentermine (Ionamin), pseudoephedrine (Sudafed), and many others.
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

The piece of this cold and allergy combo that matters here is the phenylephrine, which is a decongestant that works by tightening up blood vessels to dry out a stuffy nose. Ergot also has a strong vessel-narrowing effect of its own. Put the two together and those effects can stack, so blood vessels may clamp down more than you'd want. In real life that could show up as a higher blood pressure, a pounding headache, cold or tingling fingers and toes, or feeling jittery.

To be fair, this concern is based on weak, mostly anecdotal evidence, and ergot really shouldn't be used as a home supplement at all because it's toxic. Still, I wouldn't pair them without checking. Please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Eadie MJ. Convulsive ergotism: epidemics of the serotonin syndrome? Lancet Neurol 2003;2:429-34. 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

Ergot Also Interacts With Other Medications

Ergot has 461 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 461 No known interaction 2,369 (incl. Acetaminophen, Chlorpheniramine, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Ergot

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Phenylephrine

This page covers Ergot only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Phenylephrine page lists 292 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 14 major · 232 moderate · 46 minor.

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

“Picture the week you are sick enough to reach for Alka-Seltzer PLUS or another acetaminophen, chlorpheniramine, and phenylephrine combination, while still taking whatever supplements you always take. That is where trouble hides, and with 14 of its 292 supplement interactions rated major, this medicine warrants real vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Phenylephrine interaction page

How much people look this up

Where Ergot and Acetaminophen, Chlorpheniramine, Phenylephrine 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 Ergot
Steady interest

#1,028 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Phenylephrine
Top 25%

#471 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 Ergot

What is Ergot?

Ergot
  • Heavy menstrual or uterine bleeding
  • Bleeding after childbirth
  • Migraine headaches
  • Stimulating uterine contractions

Ergot is a toxic fungus that grows on rye and contains powerful chemicals (ergot alkaloids) that strongly narrow blood vessels and squeeze the uterus. Because raw ergot is poisonous and the dose is impossible to control safely, it should never be used as a home remedy or supplement. Some purified ergot chemicals are used as prescription drugs under strict medical supervision, but the crude herb is not safe to take.

Read the full Ergot monograph & all interactions
Keep checking

Other Drugs & Ergot

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

0Major
461Moderate
0Minor
2,368No known interaction
461 Moderate 2,368 No interaction
Moderate

461 interactions

Showing 60 of 461 moderate interactions — see all 461 on the Ergot page.

No interaction 2,368 drugs checked — show the list

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

Showing the 60 most looked-up of 2,368 medications checked with no known interaction — see the full Ergot list.

See the full Ergot interactions page
See every supplement checked against Acetaminophen, Chlorpheniramine, Phenylephrine, 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
Ergot monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Chlorpheniramine, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Phenylephrine, 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 Ergot and Acetaminophen, Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Ergot with Acetaminophen, Chlorpheniramine, Phenylephrine?
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 Ergot and Acetaminophen, Chlorpheniramine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Phenylephrine belongs to more than one drug category, and Ergot 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 Ergot and Acetaminophen, Chlorpheniramine, Phenylephrine 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.