Drug & supplement interaction

Ashwagandha + Acetaminophen, Chlorpheniramine, Phenylephrine

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

Moderate Interaction
The bottom line Moderate

Acetaminophen, Chlorpheniramine, Phenylephrine falls into 4 drug categories that Ashwagandha can interact with; the most serious is rated moderate. Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ashwagandha and Acetaminophen, Chlorpheniramine, Phenylephrine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Ashwagandha interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Phenylephrine falls into 4 of those categories, so it can interact with Ashwagandha in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 4

Why this applies to Acetaminophen, Chlorpheniramine, Phenylephrine

Acetaminophen, Chlorpheniramine, Phenylephrine falls under HEPATOTOXIC DRUGS — the group Ashwagandha interacts with.

Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure.
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

This cold and allergy combo includes acetaminophen (the same active ingredient as Tylenol), which your liver has to process. Ashwagandha has been tied to rare but real cases of liver trouble. So the concern here is mostly about doubling up the workload on your liver. This is a theoretical caution based on how each one behaves, not on strong proof that the two together cause harm.

For most healthy people taking this combo product short-term at normal doses, the risk is low. Still, keep an eye out for signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and don't exceed the acetaminophen limit on the label. If you drink alcohol regularly or have liver concerns, check with your pharmacist or doctor before pairing them.

References
  1. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. PubMed
  2. Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb. 2021;51(4):363-365. PubMed
  3. Suryawanshi G, Abdallah M, Thomson M, Desai N, Chauhan A, Lim N. Ashwagandha-Associated Acute Liver Failure Requiring Liver Transplantation. Am J Ther 2023;30(1):e80-e83. PubMed
  4. Pusec CM, Wolsky R, Llerena C, Sura P. A Case of Supplement-Induced Hepatitis. Cureus 2022;14(10):e30433. PubMed
  5. Lubarska M, Halasinski P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health 2023;20(5):3921. PubMed
  6. Tóth M, Benedek AE, Longerich T, Seitz HK. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep 2023;11(3):e7078.
  7. Bokan G, Glamocanin T, Mavija Z, et al. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. Pharmaceuticals (Basel) 2023;16(8):1129. PubMed
  8. Philips CA, Valsan A, Theruvath AH, et al. Ashwagandha-induced liver injury-A case series from India and literature review. Hepatol Commun 2023;7(10):e0270. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

Acetaminophen, Chlorpheniramine, Phenylephrine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes.
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 combo cold product (acetaminophen for pain and fever, chlorpheniramine for runny nose and sneezing, and phenylephrine as a decongestant) isn't one I'd lose sleep over with ashwagandha. The only signal we have is from lab dish studies suggesting ashwagandha might gently speed up an enzyme called CYP1A2. In theory, that could clear certain medicines a little faster and make them slightly less effective. So you might, in principle, notice a touch less relief from the cold formula.

Here's the honest part: this is theoretical, based only on test-tube data, and rated minor. None of these three ingredients are prodrugs, so I wouldn't expect a real problem. Still, if you take ashwagandha regularly, it's worth a quick chat with your pharmacist.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes.
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 is a combination cold and allergy product, with acetaminophen (pain and fever), chlorpheniramine (an antihistamine), and phenylephrine (a decongestant). The concern here is purely theoretical. In lab dish studies only, ashwagandha appeared to speed up an enzyme called CYP3A4, which helps break down certain medicines. If that happened in the body, it could in theory clear these ingredients a bit faster and make them slightly less effective.

Honestly, I wouldn't lose sleep over this one. The evidence is very weak (test tube data only), and it's rated a minor interaction. You might simply notice the cold relief feels a little less strong, but that's unlikely. If you want to be sure, just check with your pharmacist before combining them.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

Serotonergic Drugs

4 of 4

Acetaminophen, Chlorpheniramine, Phenylephrine also falls under Serotonergic Drugs.

Some animal studies have reported that ashwagandha can enhance serotonergic transmission by altering certain serotonin (5-HT) receptors. However, there is no evidence to suggest that ashwagandha increases the risk of serotonin-related effects, and there have been no published case reports of serotonin syndrome when combined with other serotonergic drugs. Nevertheless, due to the lack of extensive studies on the matter and the fact that ashwagandha appears to affect serotonergic pathways, it would be prudent to exercise caution when combining it with drugs that affect serotonin. [References: - Effects of Withania somnifera (Ashwaga ndha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021 Sep 14; 19: 1468–1495. - A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/]
Severity Minor Likelihood Possible Evidence C

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 combo cold product mixes acetaminophen (a pain and fever reducer), chlorpheniramine (an antihistamine that can make you drowsy), and phenylephrine (a decongestant). The piece that touches on ashwagandha here is the chlorpheniramine, which has a mild effect on serotonin. Animal studies hint that ashwagandha may gently nudge serotonin activity too, so on paper there's a small theoretical overlap.

In real life, this is a minor concern. There are no case reports of problems when these are taken together, and the evidence is weak. If anything, just be aware that both ashwagandha and chlorpheniramine can make you a bit sleepy, so you may feel more drowsy than usual. Check with your pharmacist or doctor before combining them, especially if you take other medicines.

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

Ashwagandha Also Interacts With Other Medications

Ashwagandha has 915 moderate, 456 minor 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.

Taking anything else?

Check Another of Your Medications Against Ashwagandha

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

From our Q&A

Questions About Ashwagandha or Acetaminophen, Chlorpheniramine, 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 Ashwagandha or Acetaminophen, Chlorpheniramine, 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, Chlorpheniramine, Phenylephrine

This page covers Ashwagandha 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

One more smart check

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

We hold 4,964 real supplement products containing Ashwagandha, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ashwagandha. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Phenylephrine too, on top of Ashwagandha — 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 Ashwagandha 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 Ashwagandha
Top 5%

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

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

#336 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 Ashwagandha

What is Ashwagandha?

Ashwagandha
  • Stress and anxiety
  • Sleep problems
  • Fatigue and low energy
  • Athletic performance
  • General well-being (adaptogen)

Ashwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evidence is still limited. It is generally well tolerated for short-term use in healthy adults, but it should be avoided in pregnancy and used cautiously by people with thyroid or liver problems. Talk with your pharmacist or doctor before starting it.

Read the full Ashwagandha monograph & all interactions
Keep checking

Other Drugs & Ashwagandha

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

0Major
915Moderate
456Minor
1,458No known interaction
Moderate

915 interactions

Showing 60 of 915 moderate interactions — see all 915 on the Ashwagandha page.

Minor

456 interactions

Showing 60 of 456 minor interactions — see all 456 on the Ashwagandha page.

No interaction 1,458 drugs checked — show the list
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
Pharmacist Counseling Corner

Taking Ashwagandha and Acetaminophen, Chlorpheniramine, Phenylephrine Together: Common Questions

Can you take Ashwagandha 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 4 interactions listed for Ashwagandha and Acetaminophen, Chlorpheniramine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Phenylephrine belongs to more than one drug category, and Ashwagandha 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 Ashwagandha 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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