Evodia + 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 Evodia can interact with; the most serious is rated moderate. Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.
Read the full interaction reportEvodia and Acetaminophen, Butalbital, Caffeine, Codeine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Evodia interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 of those categories, so it can interact with Evodia in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine
Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Evodia interacts with.
Evodia extract and the evodia constituent rutaecarpine induce hepatic CYP1A2 enzyme activity. Evodia decreases levels of theophylline and caffeine, CYP1A2 substrates, by about 70% in animal models.
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 piece that matters most in this combination pill: the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2, and Evodia (mainly a compound in it called rutaecarpine) appears to speed that enzyme up. In animal studies, Evodia dropped caffeine levels by roughly 70 percent. So in real life, the caffeine in your Fioricet or Esgic could be broken down faster and feel weaker, meaning less of the alertness or headache boost it's meant to add.
The good news: this is based on lab and animal research, not solid human studies, so it's far from certain. The other parts (acetaminophen, butalbital, and codeine) aren't the main targets here. Still, since effects vary, check with your pharmacist or doctor before pairing Evodia with this medicine.
- Ueng YF, Tsai TH, Don MJ, et al. Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats. J Pharm Pharmacol 2005;57:227-32.
- Ueng YF, Jan WC, Lin LC, et al. The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes. Drug Metab Dispos 2002;30:349-53. PubMed
- Tsai TH, Chang CH, Lin LC. Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Planta Med 2005;71:640-5.
- Lee SK, Kim NH, Lee J, et al. Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s. Planta Med 2004;70:753-7. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 4Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that evodia extract inhibits hepatic CYP3A4. This effect has not been reported in humans.
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 pill has a few moving parts, but the one to watch with Evodia is butalbital, the barbiturate that your liver clears partly through an enzyme called CYP3A4. In test tube studies, Evodia appears to slow that enzyme down. In theory, that could let butalbital build up a little, which might add to drowsiness, dizziness, and that heavy-headed, slowed-down feeling. Caffeine is also partly handled by liver enzymes, so jitteriness is possible too.
Here is the honest part: this is only laboratory evidence, and it has not actually been shown to happen in people. So I would not panic. Still, since this medicine already makes many folks sleepy, it is worth a quick word with your pharmacist or doctor before pairing it with Evodia.
- Iwata H, Tezuka Y, Kadota S, et al. Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract. Drug Metab Pharmacokinet 2005;20:34-45. PubMed
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
3 of 4Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
Animal research suggests that rutaecarpine, a constituent of evodia, induces CYP2E1 activity. In rats, rutaecarpine increases markers of CYP2E1 activity, and administration of rutaecarpine with chlorzoxazone, a known CYP2E1 substrate, reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%.
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 wrinkle with this combo pill. The piece our database flags is the acetaminophen (Tylenol) part, which the liver partly handles through an enzyme called CYP2E1. In animal studies, a compound in evodia called rutaecarpine seemed to speed that enzyme up. The concern isn't less pain relief, it's that revved-up CYP2E1 can push more acetaminophen down a pathway that makes a toxic byproduct, which is harder on the liver, especially with regular use or alcohol.
Honestly though, this is theoretical and based only on rats, not people, so I wouldn't panic. Stick to the labeled acetaminophen limit, skip alcohol, and run the evodia past your pharmacist or doctor before combining them.
- Bista SR, Lee SK, Thapa D, et al. Effects of oral rutaecarpine on the pharmacokinetics of intravenous chlorzoxazone in rats. Toxicol Res 2008;24(3):195-9. PubMed
CAFFEINE
4 of 4Acetaminophen, Butalbital, Caffeine, Codeine also falls under CAFFEINE.
In animal models, evodia extract decreases caffeine levels by up to 71%. Evodia extract induces hepatic cytochrome P450 1A2 (CYP1A2) enzyme, of which caffeine is a substrate.
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..
The piece of this combination pill that interacts with Evodia is the caffeine. Your liver uses an enzyme called CYP1A2 to clear caffeine, and lab and animal studies suggest Evodia can speed that enzyme up. In one animal study, caffeine levels dropped by as much as 71 percent. If that holds true in people, the caffeine portion could be cleared faster and feel less effective, so you might not get the same little lift it normally adds to this headache medicine.
I want to be honest that this is theoretical and based only on test tube and animal work, so it's not a reason to panic. The other ingredients (acetaminophen, butalbital, codeine) aren't the concern here. Still, before adding Evodia, run it by your pharmacist or doctor.
- Tsai TH, Chang CH, Lin LC. Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Planta Med 2005;71:640-5.
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.
Evodia Also Interacts With Other Medications
Evodia has 949 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 Evodia
We haven’t checked that one against Evodia yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Evodia. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine, Codeine
This page covers Evodia 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
Taking Evodia as Part of a Dietary Supplement Product? Check It for Interactions
We hold 182 real supplement products containing Evodia, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Evodia. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Evodia — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Evodia 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.
#427 of 1,452 supplements looked up here in the last 7 days
#1,019 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 Evodia
What is Evodia?
- Digestive upset and nausea
- Headaches
- Menstrual cramps
- Abdominal pain
- Diarrhea
Evodia is a fruit used in traditional Chinese medicine, most often for digestive complaints, headaches, and menstrual pain. Human evidence for these uses is very limited, and it is mostly studied in laboratory and animal research. Talk with a pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.
Other Drugs & Evodia
Browse every other medication we’ve checked against Evodia — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
949 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Miconazole ›
- Procainamide ›
- Trimipramine ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Griseofulvin ›
- Ivabradine ›
- Ketoprofen ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Nortriptyline ›
- Rifampin ›
- Sotalol ›
- Sumatriptan Succinate ›
- Testosterone Undecanoate ›
- Aripiprazole ›
Showing 60 of 949 moderate interactions — see all 949 on the Evodia page.
No interaction 1,880 drugs checked — show the list
We also checked Evodia against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Metoprolol ›
- Ivermectin ›
- Rosuvastatin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Methamphetamine ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Lisdexamfetamine ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Doxycycline ›
- Methotrexate ›
- Lamotrigine ›
- Amphetamine ›
- Gabapentin ›
- Pregabalin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Dexmethylphenidate ›
- Spironolactone ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Vancomycin ›
- Phenylephrine ›
- Hethylphenidate Hcl ›
- Phentermine, Topiramate ›
- Bentoquatam ›
- Dirithromycin ›
- Codeine Sulfate ›
- Amoxicillin, Clavulanate Potassium ›
- Digoxin ›
- Azelaic Acid ›
Showing the 60 most looked-up of 1,880 medications checked with no known interaction — see the full Evodia 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 Evodia — 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 Evodia and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions
Can you take Evodia with Acetaminophen, Butalbital, Caffeine, Codeine?
Why are there 4 interactions listed for Evodia and Acetaminophen, Butalbital, Caffeine, Codeine?
How serious is the Evodia and Acetaminophen, Butalbital, Caffeine, Codeine interaction?
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.