Drug & supplement interaction

Rhodiola + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 drug categories that Rhodiola can interact with; the most serious is rated minor. Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityMinor
LikelihoodPossible
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Rhodiola and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Why Are There 3 Interactions?

Rhodiola interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 of those categories, so it can interact with Rhodiola in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Rhodiola interacts with.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.
Severity Minor Likelihood Possible Evidence B

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

This combination product is a mouthful, but the part that matters here is the caffeine in it. Caffeine is cleared by a liver enzyme called CYP1A2, and in lab tests Rhodiola can slow that enzyme down a little. In theory, that could let caffeine linger and add to jitteriness, a racing heart, or trouble sleeping. The good news is reassuring: an actual study in healthy people taking Rhodiola for two weeks showed no real effect on how caffeine was handled.

So this is a minor, mostly theoretical concern, and the lab results varied a lot by product. The other ingredients (acetaminophen, the antihistamine, hydrocodone, phenylephrine) aren't the main worry here. Still, if you take this medicine regularly, run the Rhodiola idea past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  2. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.
Severity Minor Likelihood Possible Evidence B

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

This combination product includes hydrocodone, an opioid that your body partly processes through a liver enzyme called CYP3A4. In a test tube, rhodiola can slow that enzyme down, which in theory could let a little more hydrocodone build up. If that happened, you might notice more drowsiness, dizziness, constipation, or slowed breathing.

Here's the reassuring part: this is mostly lab-dish evidence, and the effect varies a lot from product to product. In fact, a human study found rhodiola did not meaningfully slow CYP3A4 in healthy volunteers. So a real-world problem is unlikely. Still, since this medicine already makes many people sleepy, it's worth a quick chat with your pharmacist or doctor before adding rhodiola.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hellum BH, Tosse A, Hoybakk K, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med 2010;76:331-8.
  2. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  3. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

CNS DEPRESSANTS

3 of 3

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CNS DEPRESSANTS.

Theoretically, rhodiola might increase the risk of adverse effects when taken with CNS depressants.
A review of adverse event reports in Poland identified cases of excessive sedation, myoclonus, hypotension, and hallucinations when rhodiola was taken with haloperidol, diazepam, or alprazolam.
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

This combination product (Hycomine Compound) contains hydrocodone, an opioid, plus chlorpheniramine, a sedating antihistamine. Both can make you drowsy, and that's where Rhodiola comes in. The concern here is theoretical and based only on a few anecdotal reports, where people taking Rhodiola alongside calming or sedating drugs noticed things like extra sleepiness, low blood pressure, or muscle twitching.

So in plain terms, pairing Rhodiola with this product might add to the drowsiness and lightheadedness the hydrocodone and chlorpheniramine already cause. The evidence is weak, and many people would notice nothing. Still, since this medicine already slows down your nervous system, it's worth a quick chat with your pharmacist before adding Rhodiola, especially if you'll be driving.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. 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

Rhodiola Also Interacts With Other Medications

Rhodiola has 624 moderate, 646 minor known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 624 Minor 646 No known interaction 1,560 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Rhodiola

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

From our Q&A

Questions About Rhodiola or Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Rhodiola or Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Rhodiola only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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 Ephedra (major).

By severity: 17 major · 276 moderate · 46 minor.

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

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page

One more smart check

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

We hold 2,713 real supplement products containing Rhodiola, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Rhodiola. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Rhodiola — 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 Rhodiola and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Rhodiola
Top 5%

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

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

#467 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 Rhodiola

What is Rhodiola?

Rhodiola
  • Fatigue and low energy
  • Stress and coping (adaptogen)
  • Mental performance and focus
  • Mild depression
  • Physical and exercise performance

Rhodiola is an herb traditionally used to fight fatigue and help the body cope with stress. Some small studies suggest it may modestly reduce fatigue and improve mood, but the evidence is limited and not strong. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before trying it, and avoid it during pregnancy and breastfeeding.

Read the full Rhodiola monograph & all interactions
Keep checking

Other Drugs & Rhodiola

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

0Major
624Moderate
646Minor
1,559No known interaction
624 Moderate 646 Minor 1,559 No interaction
Moderate

624 interactions

Showing 60 of 624 moderate interactions — see all 624 on the Rhodiola page.

Minor

646 interactions

Showing 60 of 646 minor interactions — see all 646 on the Rhodiola page.

No interaction 1,559 drugs checked — show the list

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

Showing the 60 most looked-up of 1,559 medications checked with no known interaction — see the full Rhodiola list.

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

Can you take Rhodiola with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Rhodiola and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine belongs to more than one drug category, and Rhodiola 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 Rhodiola and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Rhodiola?

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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.