Diphenhydramine interactions
Overview
Diphenhydramine (Benadryl, ZzzQuil) is a sedating antihistamine for allergies and sleep. In our database it has 37 known interactions with common medicines and substances: 7 serious, 25 that need caution and 5 minor.
Avoid / serious 7 interactions
Too much sedation and slowed breathingCodeine
Too much sedation and slowed breathingHydrocodone
Too much sedation and slowed breathingKratom
Too much sedation and slowed breathingMorphine
Too much sedation and slowed breathingOxycodone
Too much sedation and slowed breathingTramadol
Too much sedation and slowed breathing
Use caution 25 interactions
Alcohol adds to drowsiness and dizzinessAlprazolam
Extra drowsiness and slowed reactionsAmitriptyline
Combined drowsinessBaclofen
Combined drowsinessCannabis
Combined drowsinessClonazepam
Extra drowsiness and slowed reactionsClonidine
Combined drowsinessCyclobenzaprine
Combined drowsinessDiazepam
Extra drowsiness and slowed reactionsDoxylamine
Two drowsy antihistaminesGabapentin
Combined drowsinessHydroxyzine
Two drowsy antihistaminesLevetiracetam
Combined drowsinessLorazepam
Extra drowsiness and slowed reactionsMeclizine
Two drowsy antihistaminesMethocarbamol
Combined drowsinessMirtazapine
Combined drowsinessNyQuil
Two drowsy antihistaminesParoxetine
Stacked anticholinergic side effectsPregabalin
Combined drowsinessPromethazine
Two drowsy antihistaminesQuetiapine
Combined drowsinessTizanidine
Combined drowsinessTrazodone
Combined drowsinessZolpidem
Extra drowsiness and slowed reactions
Minor 5 interactions
A bit more drowsinessCetirizine
Doubling up on antihistaminesFexofenadine
Doubling up on antihistaminesLoratadine
Doubling up on antihistaminesMelatonin
A bit more drowsiness
In-depth guides
No known interaction found
Our rules found no interaction between Diphenhydramine and: Acetaminophen, Acyclovir, Albuterol, Allopurinol, Amlodipine, Amoxicillin, Amoxicillin-clavulanate, Amphetamine salts, Apixaban, Aripiprazole, Aspirin, Atenolol, Atorvastatin, Azithromycin, Birth control pills, Bismuth subsalicylate, Bupropion, Buspirone, Caffeine, Calcium carbonate, Carvedilol, Celecoxib, Cephalexin, Ciprofloxacin, Citalopram, Clindamycin, Clopidogrel, Colchicine, Creatine, DayQuil, Dextromethorphan, Diclofenac, Digoxin, Doxycycline, Duloxetine, Empagliflozin, Escitalopram, Esomeprazole, Estradiol, Excedrin, Famotidine, Finasteride, Fish oil, Fluconazole, Fluoxetine, Furosemide, Glipizide, Grapefruit juice, Guaifenesin, Hydrochlorothiazide, Hydroxychloroquine, Ibuprofen, Insulin, Iron supplements, Isotretinoin, Lamotrigine, Levofloxacin, Levothyroxine, Lisdexamfetamine, Lisinopril, Lithium, Loperamide, Losartan, Magnesium, Meloxicam, Metformin, Methotrexate, Methylphenidate, Methylprednisolone, Metoprolol, Metronidazole, Montelukast, Naltrexone, Naproxen, Nicotine, Nitrofurantoin, Omeprazole, Ondansetron, Oseltamivir, Pantoprazole, Paxlovid, Phentermine, Phenylephrine, Potassium supplements, Pravastatin, Prednisone, Probiotics, Propranolol, Pseudoephedrine, Rivaroxaban, Rosuvastatin, Semaglutide, Sertraline, Sildenafil, Simvastatin, Spironolactone, St. John's wort, Sulfamethoxazole-trimethoprim, Sumatriptan, Tadalafil, Tamsulosin, Tirzepatide, Topiramate, Turmeric, Valacyclovir, Venlafaxine, Vitamin D, Warfarin, Zinc.
Add at least two medicines, supplements or alcohol.
Sources
Source: FDA label for Diphenhydramine on DailyMed (effective 2026-09), plus the labels of each interacting medicine.
This list covers the 147 medicines and substances in our database. It is not a complete list of every possible interaction. Always tell your doctor and pharmacist about every medicine, supplement and herbal product you take.