Syrian Rue + Acetaminophen, Butalbital, Caffeine, Codeine
Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.
Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Read the full interaction reportSyrian Rue and Acetaminophen, Butalbital, Caffeine, Codeine
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, Butalbital, Caffeine, Codeine 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).
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine
Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Syrian Rue interacts with.
Syrian rue contains beta-carboline alkaloids, including harmine, harmaline, harmalol, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids can inhibit CYP2D6 enzymes.
Interaction 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..
Here's the wrinkle with this combo: the codeine in your Fioricet is a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6, and that's the step that gives you pain relief. Syrian Rue's harmala alkaloids appear to block CYP2D6. So in theory, less of your codeine would get turned into morphine, meaning you could get weaker pain control than expected.
I'll be honest, this is a theoretical concern based on lab studies, not real patient cases, so I don't want to alarm you. But Syrian Rue carries its own real toxicity risks and is also an MAO inhibitor, which raises other safety flags. Please loop in your pharmacist or doctor before mixing the two.
- 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.
HEPATOTOXIC DRUGS
2 of 4Acetaminophen, Butalbital, Caffeine, Codeine 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.
Here's the main thing to know about this combo: the acetaminophen part of your Fioricet with Codeine is the player to watch. Acetaminophen is hard on the liver in higher doses, and Syrian Rue, when taken in large amounts, has been linked to liver injury too. Putting two things that can stress the liver together could, in theory, raise that risk.
I'll be honest, this concern is theoretical and comes mostly from reports of people swallowing huge quantities of the seeds (up to 100 grams). It's not a strong, well-proven interaction. Still, since this drug already needs you to stay under acetaminophen limits, I'd skip the Syrian Rue and check with your pharmacist or doctor first.
- 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, Butalbital, Caffeine, Codeine 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 practical picture with this combination pill. Syrian Rue's harmala alkaloids may gently block CYP3A4, one of the liver enzymes that helps clear several ingredients in Fioricet with Codeine. If that enzyme slows down, levels of butalbital and codeine could drift higher than expected. That might mean more drowsiness, dizziness, foggy thinking, slowed breathing, or constipation. Caffeine could also linger longer.
There's an extra wrinkle: Syrian Rue acts like an MAO inhibitor, and mixing MAOIs with opioids like codeine can be genuinely risky. Keep in mind this CYP3A4 concern is theoretical, based only on lab research, not real patient cases. Still, given the sedation and MAOI overlap, 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.
CAFFEINE
4 of 4Acetaminophen, Butalbital, Caffeine, Codeine also falls under CAFFEINE.
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.
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 thing to know about this combo product: it contains caffeine, and that's the piece that interacts with Syrian Rue. The harmala alkaloids in the seeds (like harmaline) can cause body tremors, and animal studies suggest caffeine may make those tremors stronger and last longer. So pairing the two could leave you feeling jittery, shaky, restless, or on edge, on top of the caffeine you're already getting in this medication.
I want to be honest that this is a theoretical concern based mostly on lab and animal research, not solid human studies, so I don't want to scare you. Still, Syrian Rue is risky on its own and isn't something to self-treat with. Please run it by your pharmacist or doctor before combining them.
- 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.
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, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 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: 15 major · 245 moderate · 45 minor.
Open the Acetaminophen, Butalbital, Caffeine, Codeine interaction page
Where Syrian Rue and Acetaminophen, Butalbital, Caffeine, Codeine 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.
#749 of 1,452 supplements looked up here in the last 7 days
#121 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 ›
- Ivermectin ›
- Aspirin ›
- Tirzepatide ›
- Ibuprofen ›
- Docusate ›
- Valacyclovir ›
- Isotretinoin ›
- Hydroxyurea ›
- Semaglutide ›
- Metformin ›
- Lisinopril ›
- Bupropion ›
- Bendamustine ›
- Pregabalin ›
- Azithromycin ›
- Levothyroxine, Liothyronine ›
- Lamotrigine ›
- Acyclovir ›
- Gabapentin ›
- Naproxen ›
- Candesartan Cilexetil ›
- Acetylsalicylic Acid ›
- Cephalexin ›
- Cyclopentolate ›
- Ezetimibe ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Insulin Degludec, Liraglutide ›
- Roxithromycin ›
- Levetiracetam ›
- Mannitol ›
- Thyroid Hormone ›
- Spironolactone ›
- Valsartan ›
- Mitomycin ›
- Canagliflozin, Metformin ›
- Alginic Acid, Aluminum Hydroxide ›
- Levothyroxine Sodium ›
- Atenolol ›
- Magnesium Hydroxide (otc Drug) ›
- Minoxidil ›
- Phentermine, Topiramate ›
- Abrocitinib ›
- Acenocoumarol ›
- Sacubitril, Valsartan ›
- Cefaclor ›
- Daptomycin ›
- Bupivacaine, Meloxicam ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Amobarbital, Ephedrine Sulfate ›
- Irbesartan, Hydrochlorothiazide ›
- Pegunigalsidase Alfa-iwxj ›
- Hydroxychloroquine ›
- Flutemetamol F-18 ›
- Avatrombopag Maleate ›
- Digoxin ›
- Atenolol, Chlorthalidone ›
- Hydrochlorothiazide ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Hydrochlorothiazide, Valsartan ›
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, Butalbital, Caffeine, Codeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine 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, Butalbital, Caffeine, Codeine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Butalbital, Caffeine, Codeine?
Why are there 4 interactions listed for Syrian Rue and Acetaminophen, Butalbital, Caffeine, Codeine?
How serious is the Syrian Rue and Acetaminophen, Butalbital, Caffeine, Codeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Butalbital, Caffeine, Codeine 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.