Kratom + Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine
Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine brand name: Conar-A.
Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls into 4 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Read the full interaction reportKratom and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Kratom interacts with whole categories of medication. Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls into 4 of those categories, so it can interact with Kratom in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine
Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Kratom interacts with.
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity. However, human research shows that a single low dose of kratom tea 2 grams does not inhibit CYP2D6 activity. However, this kratom dose is lower than what is normally taken for psychoactive effects. In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP2D6-mediated metabolism of buspirone and consequently increased systemic exposure to serotonin. In another case, a 37-year-old male stable for 15 years on amitriptyline presented with anticholinergic symptoms including xerostomia, dry eyes, and constipation, along with mildly elevated bilirubin and liver enzymes after taking progressively higher doses of up to 14 grams of kratom daily for 12 weeks. It was hypothesized that the adverse effects of amitriptyline were precipitated by CYP2D6 inhibition by kratom.
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.
In this combo cold-and-cough product, the piece that matters here is dextromethorphan, the cough suppressant. Your body relies on a liver enzyme called CYP2D6 to break it down. Kratom may slow that enzyme down, so dextromethorphan could build up and hit harder than expected. That can mean more drowsiness, dizziness, confusion, or feeling out of it. There's also a real concern for serotonin syndrome (agitation, racing heart, shivering, sweating) since both kratom and dextromethorphan affect serotonin.
Honestly, this is mostly theoretical and based on lab work and a few case reports, not strong human proof. Lower kratom amounts may not matter much, but bigger doses could. Please run this past your pharmacist or doctor before mixing the two.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
- Vanani NB, Stevanovic SG, Stevanovic N. Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Cureus 2023;15(1):e33809. PubMed
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
2 of 4Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2. In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP1A2-mediaed metabolism of ziprasidone which consequently increased systemic exposure to serotonin.
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.
Here's the gist with this combo cold-and-cough product. Lab studies hint that kratom may slow down a liver enzyme called CYP1A2. If that enzyme is doing some of the clearing, the medicines it handles could linger a bit longer and feel stronger. With this formula, the piece most likely affected is the acetaminophen (the Tylenol part), and to a lesser degree the dextromethorphan. None of these are prodrugs, so the worry is buildup, not weaker effect.
In plain terms, you might notice more drowsiness, dizziness, or stomach upset, and over time more strain on the liver from acetaminophen. This is theoretical, based on lab data, not real-world reports for this product, so don't panic. Still, please run it by your pharmacist or doctor before pairing them.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom. In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin.
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.
This combo cold-and-cough product has one piece worth flagging with kratom: the dextromethorphan (the cough suppressant). Kratom appears to block a liver and gut enzyme called CYP3A4, which is one route your body uses to clear dextromethorphan. If that breakdown slows, dextromethorphan can build up and you may feel more drowsy, dizzy, or lightheaded. Both kratom and dextromethorphan also nudge serotonin, so combining them adds a small theoretical risk of jitteriness, confusion, fast heartbeat, or sweating.
Honestly, this is based mostly on lab work and a few case reports, not strong human studies, so it is more caution than alarm. Still, since kratom carries its own real risks, please check with your pharmacist or doctor before using these together.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
SEROTONERGIC DRUGS
4 of 4Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine also falls under SEROTONERGIC DRUGS.
A 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited the cytochrome P450 3A4-, 2C9-, 2D6-, and 1A2-mediated metabolism of several of these serotonergic medications, consequently increasing systemic exposure to serotonin.
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.
Of the four ingredients in Conar-A, the one that matters here is dextromethorphan, the cough suppressant. It nudges serotonin activity in the brain, and kratom does too. Combining the two could, in theory, push serotonin too high. That's called serotonin syndrome, and signs include agitation, a racing heart, shivering or muscle twitching, sweating, and feeling confused. Kratom may also slow the liver enzymes that clear dextromethorphan, letting more of it build up.
To be fair, this is mostly theoretical and based on a single case report, not strong proof. Acetaminophen, guaifenesin, and phenylephrine aren't the concern. Still, since kratom carries real risks on its own, I'd check with your pharmacist or doctor before pairing it with any cough or cold product.
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Kratom Also Interacts With Other Medications
Kratom has 982 moderate, 12 minor known drug interactions in our database — the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Kratom
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Covers the 2,830 medications we’ve checked against Kratom. Pick one to open its full report.
Questions About Kratom or Acetaminophen, Dextromethorphan, Guaifenesin, 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 Kratom or Acetaminophen, Dextromethorphan, Guaifenesin, 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.
See Every Supplement That Interacts With Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine
This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine page lists 261 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: 12 major · 206 moderate · 43 minor.
From our pharmacist’s overview on the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine page
“Picture the week someone takes Conar-A (acetaminophen, dextromethorphan, guaifenesin, phenylephrine): a miserable cold, coffee to push through, maybe wine at night or an herbal remedy on top. Those habits are exactly where this list turns serious.”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine interaction page
Taking Kratom as Part of a Dietary Supplement Product? Check It for Interactions
We hold 8 real supplement products containing Kratom, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kratom. Your product may carry other ingredients that interact with Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine too, on top of Kratom — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Kratom and Acetaminophen, Dextromethorphan, Guaifenesin, 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.
#322 of 1,452 supplements looked up here in the last 7 days
#214 of 2,830 medications looked up here in the last 7 days
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.
About Kratom
What is Kratom?
- Pain relief
- Opioid withdrawal symptoms
- Anxiety and stress
- Low energy or fatigue
- Mood enhancement
Kratom is a Southeast Asian plant whose leaves act on the brain's opioid receptors and can produce both stimulant-like and opioid-like effects. It is not approved or proven safe by health regulators, carries real risks of dependence and serious harm, and its legal status varies widely. Talk to a pharmacist or doctor before considering it.
Other Drugs & Kratom
Browse every other medication we’ve checked against Kratom — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
982 interactions
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Phenylephrine ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meprobamate ›
- Nortriptyline ›
- Oxymorphone ›
- Propoxyphene ›
- Rifampin ›
- Selegiline ›
Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.
12 interactions
No interaction 1,835 drugs checked — show the list
We also checked Kratom against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Doxycycline ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Spironolactone ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Lenvatinib ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Procainamide ›
- Tenecteplase ›
- Amoxicillin, Clavulanate Potassium ›
- Hydroxychloroquine ›
- Digoxin ›
- Azelaic Acid ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Diclofenac Sodium ›
- Hydrochlorothiazide ›
- Pizotifen ›
- Tocainide ›
- Rocuronium ›
- Succimer ›
- Telmisartan ›
Showing the 60 most looked-up of 1,835 medications checked with no known interaction — see the full Kratom list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine as a medicine that can lower these. This is not an interaction with Kratom — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Kratom and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine Together: Common Questions
Can you take Kratom with Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine?
Why are there 4 interactions listed for Kratom and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine?
How serious is the Kratom and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine and Kratom?
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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.