Syrian Rue + Acetaminophen, Chlorpheniramine, Phenylephrine
Acetaminophen, Chlorpheniramine, Phenylephrine brand names: Protid, Histex SR, Alka-Seltzer PLUS.
Acetaminophen, Chlorpheniramine, Phenylephrine falls into 4 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, Syrian rue might increase the risk of serotonergic adverse effects, including serotonin syndrome, when taken with serotonergic drugs.
Read the full interaction reportSyrian Rue and Acetaminophen, Chlorpheniramine, Phenylephrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Syrian Rue interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Phenylephrine falls into 4 of those categories, so it can interact with Syrian Rue in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
SEROTONERGIC DRUGS
1 of 4Why this applies to Acetaminophen, Chlorpheniramine, Phenylephrine
Acetaminophen, Chlorpheniramine, Phenylephrine falls under SEROTONERGIC DRUGS — the group Syrian Rue interacts with.
Syrian rue contains harmaline and harmine, which have demonstrated strong, reversible inhibition of monoamine oxidase (MAO) A and weak inhibition of MAO B in animal and in vitro research. This may increase the risk for adverse effects with serotonergic drugs.
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 product has three pieces, and the one I'd watch with Syrian Rue is the phenylephrine (the decongestant). Syrian Rue's harmala alkaloids act like an MAO inhibitor, meaning they slow the enzyme that normally clears out certain stimulating chemicals. When you add phenylephrine on top of that, those effects can stack up and push your blood pressure and heart rate higher, which may cause headache, pounding heartbeat, or feeling jittery.
Honestly, this concern is mostly theoretical, based on lab and animal work rather than real patient reports, so I don't want to alarm you. Still, since Syrian Rue isn't well studied and carries its own risks, please run this past your pharmacist or doctor before mixing the two.
- Kawanishi, K., Hashimoto, Y., Fujiwara, M., Kataoka, Y., and Ueki, S. Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice. J Pharmacobiodyn 1981;4(7):520-527. PubMed
- Herraiz, T., Gonzalez, D., Ancin-Azpilicueta, C., Aran, V. J., and Guillen, H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol 2010;48(3):839-845. PubMed
- Fuller, R. W., Wong, C. J., and Hemrick-Luecke, S. K. MD 240928 and harmaline: opposite selectivity in antagonism of the inactivation of types A and B monoamine oxidase by pargyline in mice. Life Sci 1986;38(5):409-412. PubMed
- Abdel-Fattah, A. F., Matsumoto, K., Murakami, Y., Adel-Khalek, Gammaz H., Mohamed, M. F., and Watanabe, H. Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats. Ge PubMed
- Bergstrom, M., Westerberg, G., and Langstrom, B. 11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies. Nucl Med Biol 1997;24(4):287-293. PubMed
- Gerardy, J. Effect of moclobemide on rat brain monoamine oxidase A and B: comparison with harmaline and clorgyline. Prog Neuropsychopharmacol Biol Psychiatry 1994;18(4):793-802.
- Sacher, J., Houle, S., Parkes, J., Rusjan, P., Sagrati, S., Wilson, A. A., and Meyer, J. H. Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study. J Psychiatry
HEPATOTOXIC DRUGS
2 of 4Acetaminophen, Chlorpheniramine, Phenylephrine also falls under HEPATOTOXIC DRUGS.
Cases of hepatotoxicity and hepatic failure have been reported in patients who ingested a large quantity (up to 100 grams) of Syrian rue seeds.
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 combination cold product contains acetaminophen, which your liver has to process. In high amounts, acetaminophen is one of the better-known causes of liver stress. Syrian Rue carries its own concern here: people who swallowed very large quantities of the seeds (we're talking many grams) have had serious liver problems. So the worry is simply that two things hard on the liver, taken together, could add up.
I'll be honest that this is a theoretical concern based on how each one behaves, not on solid studies of the two together. Syrian Rue does not flip acetaminophen into a more toxic form; it's about overlapping liver strain. Don't exceed the acetaminophen dose on the label, skip alcohol, and check with your pharmacist before mixing in Syrian Rue.
- Yuruktumen, A., Karaduman, S., Bengi, F., and Fowler, J. Syrian rue tea: a recipe for disaster. Clin Toxicol (Phila) 2008;46(8):749-752. PubMed
- Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
- Ghizlane EA, Manal M, Ines HA, et al. Fatal poisoning of pregnant women by peganum harmala L.: a case reports. Ann Med Surg (Lond) 2021;68:102649. PubMed
- Durmaz Çelik N, Ger Akarsu F, Ozkan S, Özdemir AÖ, Aykac Ö, Memmedova F. Herbal teas can be harmful: a case of Peganum harmala induced coma in a patient with Parkinson's disease. Neurocase 2021;27(2):117-119.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Acetaminophen, Chlorpheniramine, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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 cold and allergy combo (acetaminophen for pain and fever, chlorpheniramine for sniffles, and phenylephrine as a decongestant). Lab studies hint that compounds in Syrian Rue may slow down a liver enzyme called CYP3A4, which helps clear several medicines. If that enzyme runs slower, parts of this product could linger a bit longer and feel stronger.
In real life that might mean more drowsiness, dry mouth, or dizziness from the chlorpheniramine, or a jittery, racing-heart feeling from the phenylephrine. Keep in mind this is theoretical, based only on test-tube data, not proven in people. Still, Syrian Rue also acts as an MAO inhibitor and carries its own risks, so please check with your pharmacist or doctor before combining them.
- Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
ANTICHOLINERGIC DRUGS
4 of 4Acetaminophen, Chlorpheniramine, Phenylephrine also falls under ANTICHOLINERGIC DRUGS.
Syrian rue contains harmine. Animal research suggests that intravenous administration of harmine potentiates the effects of acetylcholine or increases acetylcholine levels.
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 product includes chlorpheniramine, an antihistamine that works partly by blocking acetylcholine, one of your body's messenger chemicals. Syrian Rue's harmala compounds may push acetylcholine levels in the opposite direction. In theory, that tug-of-war could slightly blunt the antihistamine part, so you might get a little less relief from sneezing, runny nose, or watery eyes.
I want to be honest here: this idea comes only from animal lab work, not real human studies, so it's mostly theoretical. The bigger concern with Syrian Rue is that it acts like an MAO inhibitor and carries genuine toxicity risk, which matters more than this mild interaction. Before mixing the two, please check with your pharmacist or doctor.
- Slotkin, T. A. and DiStefano, V. Cardiovascular and respiratory effects of harmine. Proc Soc Exp Biol Med 1970;133(2):662-664. PubMed
- Javoy, F., Euvrard, C., Herbet, A., Bockaert, J., Enjalbert, A., Agid, Y., and Glowinski, J. Lack of involvement of dopaminergic and GABA neurones in the inhbitory effect of harmaline on the activity of striatal cholinergic neurones in the rat. Naunyn Sch
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.
Syrian Rue Also Interacts With Other Medications
Syrian Rue has 1,121 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.
Check Another of Your Medications Against Syrian Rue
We haven’t checked that one against Syrian Rue yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Syrian Rue. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Phenylephrine
This page covers Syrian Rue 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
Where Syrian Rue 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.
#1,058 of 1,452 supplements looked up here in the last 7 days
#368 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 Syrian Rue
What is Syrian Rue?
- Traditional remedy for digestive complaints
- Used as a sedative or for mood
- Antimicrobial and antiparasitic folk use
- Used as a dye and incense
- Recreational psychoactive use
Syrian Rue (Peganum harmala) is a traditional plant whose seeds contain potent compounds called harmala alkaloids, including MAO-inhibiting harmine and harmaline. There is little reliable human evidence that it safely treats any condition, and it carries real risks of toxicity, so it is not recommended for self-treatment. Talk to a pharmacist or doctor before considering it.
Other Drugs & Syrian Rue
Browse every other medication we’ve checked against Syrian Rue — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,121 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Amoxicillin ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Fenofibrate ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Glycopyrrolate ›
- Methyltestosterone ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Allopurinol ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Ipratropium ›
- Miconazole ›
- Morphine Sulfate ›
- Phenylephrine ›
- Procainamide ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Dimenhydrinate ›
- Everolimus ›
Showing 60 of 1,121 moderate interactions — see all 1,121 on the Syrian Rue page.
No interaction 1,708 drugs checked — show the list
We also checked Syrian Rue against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Aspirin ›
- Ivermectin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Lisinopril ›
- Acyclovir ›
- Bendamustine ›
- Lamotrigine ›
- Gabapentin ›
- Pregabalin ›
- Azithromycin ›
- Isotretinoin ›
- Naproxen ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Minoxidil ›
- Mitomycin ›
- Ezetimibe ›
- Phentermine, Topiramate ›
- Cefaclor ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Pentobarbitone ›
- Hydroxychloroquine ›
- Tenecteplase ›
- Digoxin ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Tocainide ›
- Pizotifen ›
- Acetylsalicylic Acid ›
- Hydrochlorothiazide ›
- Rocuronium ›
- Telmisartan ›
- Succimer ›
Showing the 60 most looked-up of 1,708 medications checked with no known interaction — see the full Syrian Rue 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, Chlorpheniramine, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Phenylephrine as a medicine that can lower these. This is not an interaction with Syrian Rue — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Chlorpheniramine, Phenylephrine nutrient depletion report ›
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 Syrian Rue and Acetaminophen, Chlorpheniramine, Phenylephrine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Chlorpheniramine, Phenylephrine?
Why are there 4 interactions listed for Syrian Rue and Acetaminophen, Chlorpheniramine, Phenylephrine?
How serious is the Syrian Rue and Acetaminophen, Chlorpheniramine, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Chlorpheniramine, Phenylephrine and Syrian Rue?
Our pharmacists answer your medication & supplement questions — free.
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.