Feverfew + Diphenhydramine Hydrochloride, Naproxen Sodium
Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.
Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 drug categories that Feverfew can interact with; the most serious is rated moderate. Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.
Read the full interaction reportFeverfew and Diphenhydramine Hydrochloride, Naproxen Sodium
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Feverfew interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 of those categories, so it can interact with Feverfew 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 Diphenhydramine Hydrochloride, Naproxen Sodium
Diphenhydramine Hydrochloride, Naproxen Sodium falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Feverfew interacts with.
Laboratory research shows that feverfew might inhibit CYP1A2. So far, this interaction 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.
Aleve PM combines naproxen (a pain and inflammation reliever) with diphenhydramine (the sleepy antihistamine in Benadryl). The concern here is purely theoretical: in lab dishes, feverfew appears to slow down a liver enzyme called CYP1A2. If that happened in real people, these medicines could clear a little slower and build up slightly, which in theory might mean more drowsiness, grogginess, dry mouth, or stomach upset.
The reassuring part: this has only been seen in test-tube and animal studies and has never actually been reported in humans. So I wouldn't lose sleep over it. Still, since both products can make you very drowsy on their own, it's smart to mention to your pharmacist or doctor that you're using feverfew before combining them.
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES
2 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.
Laboratory research shows that feverfew might inhibit CYP2C9. So far, this interaction 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.
Aleve PM combines naproxen (an anti-inflammatory pain reliever) with diphenhydramine (a sedating antihistamine). The naproxen half is partly broken down by a liver enzyme called CYP2C9. In lab studies, feverfew appears to slow that enzyme down a bit. In theory, that could let naproxen build up slightly, which might mean a little more stomach upset, heartburn, or, with regular use, kidney strain. The diphenhydramine isn't really affected here, though it already adds drowsiness on its own.
Here's the honest part: this is based only on test-tube and animal research, and it has not been seen in actual people. So for occasional use, it's likely a small concern. Still, if you take Aleve PM often or have stomach or kidney issues, check with your pharmacist or doctor first.
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
3 of 3Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
Laboratory research suggests that feverfew may inhibit platelet aggregation. Additionally, in one case report, a 36-year-old patient taking feverfew 2400 mg daily for 3 months experienced vaginal bleeding and a prolonged menstrual cycle, with a modest increase in partial thromboplastin time (PTT) and prothrombin time (PT).
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.
Aleve PM combines naproxen (an NSAID pain reliever) with diphenhydramine (the antihistamine that helps you sleep). The piece that matters here is the naproxen. Like other NSAIDs, naproxen already makes your platelets a bit less sticky and can irritate the stomach lining, so it carries its own bleeding risk.
Feverfew, in lab studies, may also make platelets less likely to clump together. Stack the two and you could, in theory, bruise more easily or have a higher chance of stomach upset, dark stools, or harder-to-stop bleeding. To be fair, this is based mostly on test-tube work and one case report, so it is a possibility rather than a sure thing. Still, if you take feverfew regularly or have any bleeding history, it is worth a quick chat with your pharmacist or doctor before combining them.
- Awang DVC. Prescribing therapeutic feverfew (Tancetum pathrnium (L.) Schultz Bip., syn. Chrysanthemumparthenium (L.) Bernh). Int Med 1998;1:11-3.
- Heptinstall S, Groenewegen WA, Spangenberg P, Loesche W. Extracts of feverfew may inhibit platelet behaviour via neutralization of sulphydryl groups. J Pharm Pharmacol 1987;39:459-65. PubMed
- Heptinstall S, White A, Williamson L, Mitchell JR. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. Lancet 1985;1:1071-4. PubMed
- Makheja AN, Bailey JM. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prostaglandins Leukot Med 1982;8:653-60.
- Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. J Pharm Pharmacol 1990;42:553-7. PubMed
- Heptinstall S, Groenewegen WA, Spangenberg P, Losche W. Inhibition of platelet behaviour by feverfew: a mechanism of action involving sulphydryl groups. Folia Haematol Int Mag Klin Morphol Blutforsch 1988;115:447-9.
- Biggs MJ, Johnson ES, Persaud NP, Ratcliffe DM. Platelet aggregation in patients using feverfew for migraine. Lancet 1982;2:776. PubMed
- Alenzi KA, Alharbi FH, Tawhari FM, Fradees GS. Alteration of Coagulation Test Results and Vaginal Bleeding Associated With the Use of Feverfew (Tanacetum parthenium). J Med Cases 2021;12(1):9-12.
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.
Feverfew Also Interacts With Other Medications
Feverfew has 928 moderate known drug interactions in our database — the Diphenhydramine Hydrochloride, Naproxen Sodium one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Feverfew
We haven’t checked that one against Feverfew yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Feverfew. Pick one to open its full report.
See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium
This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 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: 13 major · 320 moderate · 45 minor.
From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page
“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”
Reviewed by 2 · Jul 18, 2026
Open the Diphenhydramine Hydrochloride, Naproxen Sodium interaction page
Taking Feverfew as Part of a Dietary Supplement Product? Check It for Interactions
We hold 520 real supplement products containing Feverfew, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Feverfew. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Feverfew — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Feverfew and Diphenhydramine Hydrochloride, Naproxen Sodium 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.
#273 of 1,452 supplements looked up here in the last 7 days
#295 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 Feverfew
What is Feverfew?
- Migraine prevention
- Headache
- Fever (traditional)
- Arthritis and joint pain
- Menstrual discomfort
Feverfew is a daisy-family herb best known for migraine prevention, where some studies suggest it may modestly lower how often migraines occur, though the evidence is mixed. It is generally well tolerated for short-term use in most adults but should be avoided during pregnancy and breastfeeding and by people allergic to ragweed and related plants. Talk to your pharmacist or doctor before starting it.
Other Drugs & Feverfew
Browse every other medication we’ve checked against Feverfew — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
928 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Isotretinoin ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ketoprofen ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meloxicam ›
- Nortriptyline ›
Showing 60 of 928 moderate interactions — see all 928 on the Feverfew page.
No interaction 1,901 drugs checked — show the list
We also checked Feverfew against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Tirzepatide ›
- Docusate ›
- Sumatriptan ›
- Valacyclovir ›
- Hydroxyurea ›
- Metformin ›
- Semaglutide ›
- Amoxicillin ›
- Levothyroxine, Liothyronine ›
- Methotrexate ›
- Lisinopril ›
- Bupropion ›
- Azithromycin ›
- Pregabalin ›
- Doxycycline ›
- Gabapentin ›
- Lamotrigine ›
- Acyclovir ›
- Methylene Blue ›
- Ciprofloxacin ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Insulin Degludec, Liraglutide ›
- Ezetimibe ›
- Cyclopentolate ›
- Cephalexin ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Thyroid Hormone ›
- Mannitol ›
- Levetiracetam ›
- Carbidopa, Levodopa ›
- Levodopa ›
- Atenolol, Chlorthalidone ›
- Avatrombopag Maleate ›
- Roxithromycin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Magnesium Hydroxide (otc Drug) ›
- Spironolactone ›
- Alginic Acid, Aluminum Hydroxide ›
- Mitomycin ›
- Atenolol ›
- Canagliflozin, Metformin ›
- Enalapril Maleate ›
- Flutemetamol F-18 ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Amobarbital, Ephedrine Sulfate ›
- Acarbose ›
- Levothyroxine Sodium ›
- Charcoal (otc Drug) ›
- Ephedrine, Phenobarbital, Theophylline ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Minoxidil ›
- Articaine, Epinephrine ›
Showing the 60 most looked-up of 1,901 medications checked with no known interaction — see the full Feverfew 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
Diphenhydramine Hydrochloride, Naproxen Sodium Is Linked to Lower Levels of One Nutrient
Natural Medicines records Diphenhydramine Hydrochloride, Naproxen Sodium as a medicine that can lower these. This is not an interaction with Feverfew — 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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 Feverfew and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions
Can you take Feverfew with Diphenhydramine Hydrochloride, Naproxen Sodium?
Why are there 3 interactions listed for Feverfew and Diphenhydramine Hydrochloride, Naproxen Sodium?
How serious is the Feverfew and Diphenhydramine Hydrochloride, Naproxen Sodium 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.