Diphenhydramine Topical

123 interactions 540 cited references
Also sold as: Afterbite with Antihistamine Benadryl® Itch Stopping Gel Dermamycin
About Diphenhydramine Topical

Diphenhydramine, an antihistamine, is used to relieve the itching of insect bites, sunburns, bee stings, poison ivy, poison oak, and minor skin irritation. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information. Read the full Diphenhydramine Topical drug information page →

Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Updated Aug 9, 2026 · Editorial policy · Data sources

Sources: FDA prescribing information (Structured Product Labeling), the published literature cited in each entry, DDInter 2.0 (a major open-access drug-interaction database), and legacy DrugBank interaction data distributed by the NIH's RxNav service (decommissioned in 2024) — analyzed and reviewed by our pharmacist team. How we build this library →

Most serious with: Sodium Oxybate Tranylcypromine Potassium Chloride Magnesium Oxybate Isocarboxazid Calcium Oxybate
8 Contraindicated 102 Major 11 Moderate 2 Minor
All (123) Contraindicated (8) Major (102) Moderate (11) Minor (2)

Contraindicated

Diphenhydramine Topical Calcium Oxybate Xywav An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation... Details Diphenhydramine Topical Isocarboxazid Marplan An increased risk of CNS depression Details Diphenhydramine Topical Magnesium Oxybate Xywav An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation... Details Diphenhydramine Topical Potassium Chloride K-Tab Increased risk of gastrointestinal irritation Details Diphenhydramine Topical Potassium Citrate Urocit-K Increased risk of gastrointestinal irritation Details Diphenhydramine Topical Potassium Oxybate Xywav An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation... Details Diphenhydramine Topical Sodium Oxybate Lumryz An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation... Details Diphenhydramine Topical Tranylcypromine Parnate Increased risk of anticholinergic effects and an increased risk of CNS depression Details

Major

Diphenhydramine Topical Alfentanil An increased risk of respiratory and CNS depression and an increased risk of paralytic ileus Details Diphenhydramine Topical Alprazolam Xanax Increased risk of CNS depression Details Diphenhydramine Topical Amantadine Potentiation of anticholinergic effects Details Diphenhydramine Topical Amifampridine Increased risk of seizures Details Diphenhydramine Topical Benzhydrocodone Increased risk of urinary retention and/or severe constipation leading to paralytic ileus and an increased risk of respiratory dep... Details Diphenhydramine Topical Bromazepam Increased risk of respiratory or cardiovascular depression Details Diphenhydramine Topical Bromopride Potentiation of sedative effects Details Diphenhydramine Topical Buprenorphine Belbuca An increased risk of respiratory and CNS depression and an increased risk of paralytic ileus Details Diphenhydramine Topical Bupropion Aplenzin Increased risk of seizures Details Diphenhydramine Topical Butalbital An increased risk of CNS depression Details Diphenhydramine Topical Butorphanol Butorphic Increased risk of respiratory and CNS depression Details Diphenhydramine Topical Cannabidiol Epidiolex Increased risk of CNS depression and an increased risk of sedation and somnolence Details Diphenhydramine Topical Cannabis An increased risk of CNS depression Details Diphenhydramine Topical Carbamazepine Carbatrol An increased risk of CNS depression Details Diphenhydramine Topical Carbidopa Lodosyn An increased risk of CNS depression Details Diphenhydramine Topical Carbinoxamine Carbzah An increased risk of CNS depression Details Diphenhydramine Topical Cetirizine Aller-Tec Increased risk of CNS depression Details Diphenhydramine Topical Clobazam Onfi Increased risk of sedation Details Diphenhydramine Topical Clomipramine Anafranil Increased clomiPRAMINE exposure, an increased risk of CNS depression, increased anticholinergic effects (dry mouth, urinary retent... Details Diphenhydramine Topical Clonazepam Klonopin Increased risk of CNS depression Details Diphenhydramine Topical Clozapine Clozaril Increased risk of anticholinergic toxicity and gastrointestinal adverse reactions Details Diphenhydramine Topical Codeine Tuzistra XR® (as a combination product containing Chlorpheniramine, Codeine) Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression Details Diphenhydramine Topical Cyclobenzaprine Amrix An increased risk of atropine-like adverse reactions and an increased risk of CNS depression Details Diphenhydramine Topical Cyproheptadine An increased risk of CNS depression Details Diphenhydramine Topical Daridorexant An increased risk CNS depression Details Diphenhydramine Topical Dexmedetomidine Dexased Increased risk of CNS depression Details Diphenhydramine Topical Dextroamphetamine Dexedrine Increased dextroamphetamine or lisdexamfetamine (prodrug of dextroamphetamine) exposure and an increased risk of serotonin syndrom... Details Diphenhydramine Topical Diazepam Diastat Increased risk of CNS depression Details Diphenhydramine Topical Dihydrocodeine Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression Details Diphenhydramine Topical Donepezil Adlarity Reduced seizure threshold Details Diphenhydramine Topical Doxepin Prudoxin An increased risk of CNS depression Details Diphenhydramine Topical Doxylamine Aldex AN Increased risk of CNS depression Details

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Educational information only, not medical advice. Always confirm interactions with your pharmacist or prescriber before making any change to your medications.