Drug & supplement interaction

Syrian Rue + Acetaminophen, Caffeine, Pyrilamine

Acetaminophen, Caffeine, Pyrilamine brand name: Midol Max Strength Menstrual.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Caffeine, Pyrilamine falls into 4 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.

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

Syrian Rue and Acetaminophen, Caffeine, Pyrilamine

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, Caffeine, Pyrilamine 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).

Moderate

HEPATOTOXIC DRUGS

1 of 4

Why this applies to Acetaminophen, Caffeine, Pyrilamine

Acetaminophen, Caffeine, Pyrilamine falls under HEPATOTOXIC DRUGS — the group Syrian Rue interacts with.

Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with 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.
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

Here's the gist with Midol Max Strength and Syrian Rue: the concern is really about your liver. The acetaminophen in this product is hard on the liver when you take a lot of it, and large amounts of Syrian Rue seeds have been linked to liver injury too. Stacking two things that can stress the liver may add up.

I want to be honest though, this is a theoretical worry based on how these work, not proven cases of the two together. The reported liver problems came from people swallowing big quantities of seeds (up to 100 grams). Still, since acetaminophen liver damage can sneak up quietly, please run this by your pharmacist or doctor before combining them, and never exceed the acetaminophen dose on the label.

References
  1. 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
  2. Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
  3. 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
  4. 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.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

Acetaminophen, Caffeine, Pyrilamine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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

Here's the gist with this Midol combo. Lab studies suggest the harmala alkaloids in Syrian Rue can slow down a liver enzyme called CYP3A4, which helps clear some medications. If that enzyme is blocked, drugs it handles could build up a bit more than usual. For this product, that mainly applies to the caffeine and the antihistamine pyrilamine, which could mean a touch more jitteriness, a racing heart, drowsiness, or dry mouth.

I want to be honest though: this is theoretical, based on test-tube data, not real patient reports, so I wouldn't lose sleep over it. Still, Syrian Rue carries its own toxicity risks, so please check with your pharmacist or doctor before combining them.

References
  1. 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.
Moderate

ANTICHOLINERGIC DRUGS

3 of 4

Acetaminophen, Caffeine, Pyrilamine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, Syrian rue might decrease the effects of anticholinergic drugs.
Syrian rue contains harmine. Animal research suggests that intravenous administration of harmine potentiates the effects of acetylcholine or increases acetylcholine levels.
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

Here's the piece that matters in Midol Max Strength: the pyrilamine part. Pyrilamine is an antihistamine that has mild anticholinergic activity, meaning it gently blocks acetylcholine. Syrian Rue contains harmine, which animal studies suggest may do the opposite and raise acetylcholine. So in theory, the two could work against each other, and pyrilamine's drying effects (less runny nose, mild sleepiness, dry mouth) might be slightly blunted.

I want to be honest with you: this is a theoretical concern based on lab and animal data, not real cases in people, and pyrilamine is a fairly weak player here. The acetaminophen and caffeine aren't involved. Still, Syrian Rue carries its own real toxicity risks, so please check with your pharmacist or doctor before using it.

References
  1. Slotkin, T. A. and DiStefano, V. Cardiovascular and respiratory effects of harmine. Proc Soc Exp Biol Med 1970;133(2):662-664. PubMed
  2. 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
Moderate

CAFFEINE

4 of 4

Acetaminophen, Caffeine, Pyrilamine also falls under CAFFEINE.

Theoretically, taking Syrian rue with caffeine might increase the risk of adverse effects, including tremors.
Syrian rue contains the constituent harmaline. Animal research suggests that a combination of caffeine and harmaline increases the intensity and duration of harmaline-induced tremors.
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 Midol Max Strength to focus on here is the caffeine. Syrian Rue contains harmala alkaloids (like harmaline) that act as MAO inhibitors. In animal studies, pairing caffeine with harmaline made tremors stronger and longer-lasting. So in theory, taking the two together could leave you feeling extra jittery, shaky, or wired, with a racing heart or trouble sleeping. Caffeine isn't activated by this plant, so it's about stacked stimulant-type effects, not a true metabolism block.

Keep in mind this is theoretical and comes mostly from lab animal work, not solid human studies. Syrian Rue carries its own real risks too, so I wouldn't combine them without checking with your pharmacist or doctor first.

References
  1. Al-Deeb, S., Al-Moutaery, K., Arshaduddin, M., Biary, N., and Tariq, M. Effect of acute caffeine on severity of harmaline induced tremor in rats. Neurosci Lett 2002;325(3):216-218. 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

Syrian Rue Also Interacts With Other Medications

Syrian Rue has 1,121 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Pyrilamine 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 Syrian Rue

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Pyrilamine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Pyrilamine page lists 322 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: 16 major · 260 moderate · 46 minor.

Open the Acetaminophen, Caffeine, Pyrilamine interaction page

How much people look this up

Where Syrian Rue and Acetaminophen, Caffeine, Pyrilamine 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 Syrian Rue
Steady interest

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

29 days ago today
Medication Acetaminophen, Caffeine, Pyrilamine
Top 5%

#136 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 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.

Read the full Syrian Rue monograph & all interactions
Keep checking

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.

0Major
1,121Moderate
0Minor
1,708No known interaction
Moderate

1,121 interactions

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
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

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Pharmacist Counseling Corner

Taking Syrian Rue and Acetaminophen, Caffeine, Pyrilamine Together: Common Questions

Can you take Syrian Rue with Acetaminophen, Caffeine, Pyrilamine?
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 Syrian Rue and Acetaminophen, Caffeine, Pyrilamine?
Acetaminophen, Caffeine, Pyrilamine belongs to more than one drug category, and Syrian Rue 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 Syrian Rue and Acetaminophen, Caffeine, Pyrilamine 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.