Adrafinil + Aspirin, Caffeine, Orphenadrine
Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.
Aspirin, Caffeine, Orphenadrine falls into 4 drug categories that Adrafinil can interact with; the most serious is rated moderate. Theoretically, adrafinil might reduce the levels and clinical effects of CYP1A2 substrates.
Read the full interaction reportAdrafinil and Aspirin, Caffeine, Orphenadrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Adrafinil interacts with whole categories of medication. Aspirin, Caffeine, Orphenadrine falls into 4 of those categories, so it can interact with Adrafinil 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 Aspirin, Caffeine, Orphenadrine
Aspirin, Caffeine, Orphenadrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Adrafinil interacts with.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP1A2 activity in vitro.
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 for this combo pill (aspirin, caffeine, and orphenadrine). Adrafinil turns into modafinil in your body, and modafinil may slightly speed up a liver enzyme called CYP1A2. The caffeine portion is cleared by that same enzyme, so in theory adrafinil could make caffeine wear off a bit faster, meaning you might feel a touch less of its pick-me-up effect.
I want to be honest: this is a theoretical concern based on lab data, not real-world reports, and the effect is described as weak. The aspirin and orphenadrine pieces aren't really driven by this pathway. Still, since adrafinil is unregulated and hard on the liver, please run it by your pharmacist or doctor before combining the two.
- Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
- Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
- Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 4Aspirin, Caffeine, Orphenadrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP3A4 activity.
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 product blends aspirin (a pain reliever), caffeine, and orphenadrine (a muscle relaxer). Here's the connection: once your liver turns adrafinil into modafinil, that modafinil can gently speed up a liver enzyme called CYP3A4. Orphenadrine is partly handled by that same enzyme, so in theory it could be cleared a little faster, which might make the muscle-relaxing effect feel slightly weaker.
I want to be honest with you though, this is a theoretical concern based on how these drugs work, not from real patient reports, and modafinil is only a weak enzyme booster. The effect, if any, is likely small. Still, since adrafinil is unregulated and hard on the liver, please run this past your pharmacist or doctor before combining them.
- Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
- Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
STIMULANT DRUGS
3 of 4Aspirin, Caffeine, Orphenadrine also falls under STIMULANT DRUGS.
Adrafinil is a precursor to the prescription drug modafinil, which has stimulant effects.
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 product you're asking about combines aspirin, caffeine, and a muscle relaxant called orphenadrine. The piece that matters here is the caffeine. Adrafinil is a prodrug, meaning your liver turns it into modafinil, which has stimulant-like, wakefulness-promoting effects. So you'd essentially be stacking two stimulating agents on top of each other.
In plain terms, combining them could add up to more stimulation than you want. Think jitteriness, a racing or pounding heart, trouble sleeping, anxiety, or feeling wired. This concern is theoretical and based on how these compounds work rather than strong studies, so it's a caution, not an alarm. Still, since adrafinil is unregulated and hard on the liver, please check with your pharmacist or doctor before pairing them.
- Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
- Chariot J, Appia F, Vaille C, Rozé C. Effect of modafinil on pancreatic exocrine secretion in rats. A comparison with adrafinil and related drugs. Fundam Clin Pharmacol 1987;1(4):243-52. PubMed
CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES
4 of 4Aspirin, Caffeine, Orphenadrine also falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP2B6 activity in vitro.
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 of this one. When you take adrafinil, your liver turns it into modafinil. Lab studies hint that modafinil can mildly speed up a liver enzyme called CYP2B6. The orphenadrine in this combo product (the muscle relaxant piece) is partly handled by that enzyme, so in theory the body might clear it a touch faster, which could make it work a bit less well for pain and muscle tightness.
I want to be honest though: this is purely theoretical, based on test-tube data, and the effect looks weak. The aspirin and caffeine parts aren't really the concern here. I wouldn't lose sleep over it, but since adrafinil is unregulated and rough on the liver, please loop in your doctor or pharmacist before combining them rather than changing anything yourself.
- Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
- Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
- Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
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.
Adrafinil Also Interacts With Other Medications
Adrafinil has 1 major, 1,057 moderate known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Adrafinil
We haven’t checked that one against Adrafinil yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Adrafinil. Pick one to open its full report.
See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine
This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 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), Danshen (major) and Ephedra (major).
By severity: 14 major · 289 moderate · 47 minor.
From our pharmacist’s overview on the Aspirin, Caffeine, Orphenadrine page
“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”
Reviewed by 2 · Jul 18, 2026
Taking Adrafinil as Part of a Dietary Supplement Product? Check It for Interactions
We hold 7 real supplement products containing Adrafinil, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adrafinil. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Adrafinil — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Adrafinil and Aspirin, Caffeine, Orphenadrine 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.
#707 of 1,452 supplements looked up here in the last 7 days
#90 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 Adrafinil
What is Adrafinil?
- Wakefulness and alertness
- Fatigue
- Focus and concentration
- Cognitive enhancement (nootropic)
- Daytime sleepiness
Adrafinil is a synthetic compound that the body converts into modafinil, a prescription wakefulness-promoting drug. It is sometimes sold as a nootropic supplement, but it is unregulated, carries real risks (especially to the liver), and is banned in some sports and countries. Talk with a doctor or pharmacist before using it.
Other Drugs & Adrafinil
Browse every other medication we’ve checked against Adrafinil — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1 interaction
1,057 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Phentermine ›
- Hydrocortisone ›
- Methylphenidate ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Phenylpropanolamine ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Bupropion ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Nicotine ›
- Orphenadrine ›
- Oxybutynin ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Miconazole ›
- Phenylephrine ›
- Pseudoephedrine ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Diethylpropion ›
- Everolimus ›
Showing 60 of 1,057 moderate interactions — see all 1,057 on the Adrafinil page.
No interaction 1,771 drugs checked — show the list
We also checked Adrafinil against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Ivermectin ›
- Rosuvastatin ›
- Aspirin ›
- Isotretinoin ›
- Tirzepatide ›
- Levothyroxine, Liothyronine ›
- Docusate ›
- Metformin ›
- Semaglutide ›
- Hydroxyurea ›
- Valacyclovir ›
- Sumatriptan ›
- Methotrexate ›
- Amoxicillin ›
- Azithromycin ›
- Pregabalin ›
- Doxycycline ›
- Gabapentin ›
- Lamotrigine ›
- Acyclovir ›
- Duloxetine ›
- Methylene Blue ›
- Amoxicillin, Clavulanate Potassium ›
- Acetylsalicylic Acid ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Aspirin, Butalbital ›
- Cephalexin ›
- Ezetimibe ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Levetiracetam ›
- Levodopa ›
- Cyclopentolate ›
- Aluminum Hydroxide, Aspirin, Codeine Phosphate, Magnesium Hydroxide ›
- Aspirin, Ethoheptazine, Meprobamate ›
- Canagliflozin, Metformin ›
- Insulin Aspart, Insulin Degludec ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Daunorubicin, Cytarabine ›
- Alginic Acid, Aluminum Hydroxide ›
- Sodium Bicarbonate (otc Drug) ›
- Efgartigimod Alfa-fcab ›
- Saxagliptin, Metformin Xr ›
- Aspirin, Aluminum Hydroxide, Codeine Phosphate, Magnesium Hydroxide ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Measles, Mumps, Rubella Virus Live ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Peginterferon Alfa-2a, Ribavirin ›
- Atropine Methyl Nitrate, Digestive Enzymes ›
- Cytomegalovirus Immune Globulin ›
- Aminolevulinic Acid Hydrochloride ›
- Acarbose ›
- Glycerol Phenylbutyrate ›
- Tubocurarine ›
- Sulfadiazine, Trimethoprim ›
- Alpha-1 Proteinase Inhibitor ›
- Articaine, Epinephrine ›
Showing the 60 most looked-up of 1,771 medications checked with no known interaction — see the full Adrafinil 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, Caffeine, Orphenadrine Is Linked to Lower Levels of 4 Nutrients
Natural Medicines records Aspirin, Caffeine, Orphenadrine as a medicine that can lower these. This is not an interaction with Adrafinil — 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, Caffeine, Orphenadrine 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 Adrafinil and Aspirin, Caffeine, Orphenadrine Together: Common Questions
Can you take Adrafinil with Aspirin, Caffeine, Orphenadrine?
Why are there 4 interactions listed for Adrafinil and Aspirin, Caffeine, Orphenadrine?
How serious is the Adrafinil and Aspirin, Caffeine, Orphenadrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Aspirin, Caffeine, Orphenadrine and Adrafinil?
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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.