Bulbine Natalensis + Aspirin, Butalbital, Caffeine, Codeine Phosphate
Aspirin, Butalbital, Caffeine, Codeine Phosphate brand name: Fiorinal w/ Codeine.
Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 3 drug categories that Bulbine Natalensis can interact with; the most serious is rated moderate. Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
Read the full interaction reportBulbine Natalensis and Aspirin, Butalbital, Caffeine, Codeine Phosphate
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Bulbine Natalensis interacts with whole categories of medication. Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 3 of those categories, so it can interact with Bulbine Natalensis in 3 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 3Why this applies to Aspirin, Butalbital, Caffeine, Codeine Phosphate
Aspirin, Butalbital, Caffeine, Codeine Phosphate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bulbine Natalensis interacts with.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied 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.
In this combination product, the piece that overlaps with Bulbine natalensis is the caffeine, which your liver clears using an enzyme called CYP1A2. Lab and animal studies suggest this supplement may gently speed up that enzyme. In theory, that could clear caffeine a little faster, so the small pick-me-up boost from the caffeine might wear off sooner. The aspirin, butalbital, and codeine portions are not strongly tied to this particular enzyme, so they aren't the main concern here.
Honestly, this is a weak, test-tube-level finding that hasn't been confirmed in people, so I wouldn't lose sleep over it. The bigger caution is that Bulbine natalensis itself has raised liver and kidney worries in animals. Since this is a controlled medication, please run it by your pharmacist or doctor before mixing the two.
- Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied 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.
Here's the wrinkle with this combo pill (Fiorinal with Codeine). The codeine part is actually a prodrug, meaning your body has to convert it into morphine before it relieves pain. Lab studies suggest Bulbine natalensis may speed up the CYP3A4 enzyme. For codeine, faster processing could nudge more of it toward inactive byproducts, so in theory you might get less pain relief from this medicine.
I want to be honest, though: this is only seen in test-tube and animal research, not in people, so the real-world effect is uncertain. There's also the separate worry that Bulbine may stress the liver and kidneys, which already do a lot of work clearing aspirin and butalbital. Please check with your pharmacist or doctor before pairing these.
- Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
3 of 3Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
In vitro research shows that Bulbine natalensis ground leaf extract inhibits platelet aggregation.
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.
The piece of this combo pill that matters here is the aspirin. Aspirin already works by making your platelets less sticky, which is how it thins your blood a bit and helps prevent clots. In lab (test tube) studies, Bulbine natalensis seems to do something similar, slowing platelet clumping. Stack the two together and, in theory, you could bruise more easily or bleed a little longer than usual, for example nosebleeds, bleeding gums, or stomach upset that turns into something worse.
I want to be honest about the strength of this: it is theoretical, based on how these things behave in a lab, not on real people. Still, since Bulbine also raises liver and kidney concerns, I'd run it past your pharmacist or doctor before mixing it with this medication.
- Mosa RA, Lazarus GG, Gwala PE, Oyedeji AO, Opoku AR. In Vitro Anti-platelet Aggregation, Antioxidant and Cytotoxic Activity of Extracts of Some Zulu Medicinal Plants. J Nat Prod. 2011;4(2011):136-146.
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.
Bulbine Natalensis Also Interacts With Other Medications
Bulbine Natalensis has 918 moderate known drug interactions in our database — the Aspirin, Butalbital, Caffeine, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Bulbine Natalensis
We haven’t checked that one against Bulbine Natalensis yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Bulbine Natalensis. Pick one to open its full report.
See Every Supplement That Interacts With Aspirin, Butalbital, Caffeine, Codeine Phosphate
This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).
By severity: 17 major · 334 moderate · 47 minor.
From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine, Codeine Phosphate page
“Fiorinal with Codeine packs four active drugs into one capsule, and I would treat its supplement list with genuine wariness rather than a quick skim. The aspirin component is why roughly half of the 398 ingredients on file raise bleeding risk, while the codeine and butalbital explain a second large cluster that deepens sedation, someti…”
Reviewed by 2 · Jul 18, 2026
Open the Aspirin, Butalbital, Caffeine, Codeine Phosphate interaction page
Taking Bulbine Natalensis as Part of a Dietary Supplement Product? Check It for Interactions
We hold 51 real supplement products containing Bulbine Natalensis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bulbine Natalensis. Your product may carry other ingredients that interact with Aspirin, Butalbital, Caffeine, Codeine Phosphate too, on top of Bulbine Natalensis — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Bulbine Natalensis and Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.
#430 of 1,452 supplements looked up here in the last 7 days
#233 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 Bulbine Natalensis
What is Bulbine Natalensis?
- Boosting testosterone
- Improving libido
- Muscle building and athletic performance
- General male vitality
Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal studies. Animal research has also raised concerns about possible liver and kidney harm at higher doses, so caution is warranted. Talk to your pharmacist or doctor before trying it.
Other Drugs & Bulbine Natalensis
Browse every other medication we’ve checked against Bulbine Natalensis — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
918 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Methyltestosterone ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Trimipramine ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ivermectin ›
- Ketoprofen ›
- Lofepramine ›
Showing 60 of 918 moderate interactions — see all 918 on the Bulbine Natalensis page.
No interaction 1,911 drugs checked — show the list
We also checked Bulbine Natalensis against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Escitalopram ›
- Metoprolol ›
- Isotretinoin ›
- Tirzepatide ›
- Methamphetamine ›
- Docusate ›
- Valacyclovir ›
- Metformin ›
- Levothyroxine, Liothyronine ›
- Hydroxyurea ›
- Sumatriptan ›
- Semaglutide ›
- Lisdexamfetamine ›
- Amphetamine ›
- Methotrexate ›
- Lisinopril ›
- Amoxicillin ›
- Bupropion ›
- Azithromycin ›
- Pregabalin ›
- Gabapentin ›
- Dextroamphetamine ›
- Lamotrigine ›
- Acyclovir ›
- Duloxetine ›
- Methylene Blue ›
- Ciprofloxacin ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Bisoprolol ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Ezetimibe ›
- Cephalexin ›
- Atenolol, Chlorthalidone ›
- Cyclopentolate ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Levetiracetam ›
- Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate ›
- Levodopa ›
- Enalapril Maleate ›
- Canagliflozin, Metformin ›
- Aminophylline, Amobarbital, Ephedrine ›
- Thyroid Hormone ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Ephedrine, Phenobarbital, Theophylline ›
- Carbidopa, Levodopa ›
- Mannitol ›
- Daunorubicin, Cytarabine ›
- Alginic Acid, Aluminum Hydroxide ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Acarbose ›
- Spironolactone ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Amobarbital, Ephedrine Sulfate ›
- Efgartigimod Alfa-fcab ›
Showing the 60 most looked-up of 1,911 medications checked with no known interaction — see the full Bulbine Natalensis 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
Aspirin, Butalbital, Caffeine, Codeine Phosphate Is Linked to Lower Levels of 4 Nutrients
Natural Medicines records Aspirin, Butalbital, Caffeine, Codeine Phosphate as a medicine that can lower these. This is not an interaction with Bulbine Natalensis — 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate 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 Bulbine Natalensis and Aspirin, Butalbital, Caffeine, Codeine Phosphate Together: Common Questions
Can you take Bulbine Natalensis with Aspirin, Butalbital, Caffeine, Codeine Phosphate?
Why are there 3 interactions listed for Bulbine Natalensis and Aspirin, Butalbital, Caffeine, Codeine Phosphate?
How serious is the Bulbine Natalensis and Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.