Adrafinil + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 3 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Adrafinil interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 3 of those categories, so it can interact with Adrafinil 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 short version: this is mostly a theoretical concern. Adrafinil turns into modafinil in your body, and modafinil may slightly speed up a liver enzyme called CYP1A2. Of the ingredients in Colrex, that enzyme plays only a minor role, so any real-world effect on your cold and cough relief is likely small.
If anything, faster clearance could mean a given ingredient wears off a touch sooner, but the codeine and acetaminophen pieces aren't mainly handled by this pathway, so I wouldn't expect a big change in pain relief or drowsiness. The bigger caution is that both adrafinil and acetaminophen can stress the liver, and stacking a stimulant on top of a sedating combo is just hard on your body. Please run this by your pharmacist 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
- 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 3Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.
Your Colrex combo packs several ingredients, and the one that interacts here is codeine. Once modafinil (the active form of adrafinil) builds up in your body, it can mildly speed up a liver enzyme called CYP3A4. Codeine relies partly on this pathway, so in theory it could be cleared a little faster. On top of that, codeine is itself a prodrug that has to be converted into morphine to relieve your cough or pain, so faster processing could mean slightly less relief.
Honestly, this is a theoretical concern based on how these drugs work, not something proven in real patients. The effect is expected to be weak. Still, since adrafinil is unregulated and hard on the liver, I'd run it past your pharmacist 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 3Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.
This combo product (Colrex) has four ingredients, but the one that matters here is phenylephrine, the decongestant. Phenylephrine is itself a mild stimulant that can raise blood pressure and heart rate. Adrafinil turns into modafinil in your liver, and modafinil is also a stimulant. Stacking the two could add up, so you might feel jittery, notice a racing or pounding heart, have trouble sleeping, or see your blood pressure tick up.
To be fair, this is a theoretical concern based on how these drugs work, not something proven in studies. Still, if you have heart issues or high blood pressure, it's worth a quick chat with your pharmacist or doctor before pairing them, especially since adrafinil is unregulated.
- 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
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, 1,055 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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: 18 major · 275 moderate · 45 minor.
From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page
“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page
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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.
#500 of 1,452 supplements looked up here in the last 7 days
#269 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
1,055 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 1,055 moderate interactions — see all 1,055 on the Adrafinil page.
No interaction 1,773 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 ›
- Aspirin ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Semaglutide ›
- Tirzepatide ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Doxycycline ›
- Methotrexate ›
- Lamotrigine ›
- Gabapentin ›
- Pregabalin ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Mitomycin ›
- Levodopa ›
- Cefaclor ›
- Ezetimibe ›
- Venlafaxine ›
- Lenvatinib ›
- Vancomycin ›
- Phentermine, Topiramate ›
- Bentoquatam ›
- Dirithromycin ›
- Procainamide ›
- Tenecteplase ›
- Codeine Sulfate ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Digoxin ›
- Azelaic Acid ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Sodium Valproate ›
- Tocainide ›
- Flecainide ›
- Pentobarbitone ›
Showing the 60 most looked-up of 1,773 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
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions
Can you take Adrafinil with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Why are there 3 interactions listed for Adrafinil and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
How serious is the Adrafinil and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.