“Hit by an unexpected allergic reaction? You may never know what got you, but at least you’ll know what to do about it. Benadryl®.” Have you heard this advertisement before? You probably have, since Benadryl® has many different types of products available for allergies, especially the oral liquid.  But did you know there is a topical version available for your allergy itch or insect bites?


What is Benadryl® Itch Cream?

Benadryl® products by Johnson & Johnson Inc. are available in both oral and topical preparations1. There are three different topical versions available: an itch cream, itch spray, or an itch stick1.  All of these can be conveniently purchased at most grocery stores, pharmacies, gas stations, and more. Although the main active ingredient of all of the Benadryl® products are the same, the formulations of each product are slightly different. Here we will concentrate on the Benadryl® Itch Cream in particular.

The active ingredient in Benadryl® Itch Cream is an antihistamine called diphenhydramine hydrochloride, which is commonly used to help quickly relieve allergy or insect bite symptoms such as itchiness, redness, and swelling1,2,3. According to the Benadryl® website, it can also be used for fast and effective relief of skin itch due to poison ivy or poison oak, minor skin irritations, and even mild sunburn1.

How does Benadryl® Itch Cream work?

The main culprit causing allergic reactions is a substance in the body called histamine4. When the body is exposed to an allergen (something that causes an allergic reaction), histamine is released and binds to specific sites (receptors) that are found in the blood vessels, lungs, skin, and throat4. This causes characteristic allergy symptoms such as breathing difficulties, sneezing, and itchiness5. When you apply Benadryl® Itch Cream onto your skin, the active ingredient diphenhydramine acts in 2 ways:

1)  It blocks local histamine receptors so that histamine can no longer bind to these receptors to cause itching2,3,4.

2)  The topical version may also provide a local numbing effect, further contributing to local relief from itching2,3,6.

Why choose the cream?

One of the greatest advantages of Benadryl® Itch Cream over its oral counterparts is that topical diphenhydramine causes less side effects throughout the body.  Topical diphenhydramine acts locally (only to the area applied) and has very little absorption from the skin to the blood – so low that you can’t even measure it in the blood6! Since there just isn’t enough diphenhydramine to go around, it doesn’t bind to receptors around the body responsible for other side effects (such as drowsiness, dizziness, dry mouth, nausea, and nervousness)7, so these side effects do not occur with Benadryl® Itch Cream use.

So what does the evidence say?

Experts compiled available evidence on topical antihistamines to treat itch (which included Benadryl®), finding 19 studies8; however, most of the studies had a poor design resulting in contradictory outcomes and inconsistent, inconclusive results8,9,10. Ultimately, results from  these studies suggested that other than topical doxepin (another product that can be used for itch), there was not enough evidence to support the use of other topical antihistamines, including diphenhydramine, for treating itching8.  Without reliable evidence from credible studies to back its use, support for recommending Benadryl® has only been from the personal experiences of prescribers and patients themselves9. Moreover, studies have also shown that the frequent use of topical diphenhydramine for itching, especially in adults and elderly patients, can also cause hypersensitivity reactions (reactions produced by the normal immune system)2,6.

Are there any safety concerns?

You should not use the cream if you are allergic to the active ingredient (diphenhydramine) or any other components of the cream (alcohol, glycerin, povidone, tromethamine)11.  It should not be used on premature infants, children less than 2 years old, or on chicken pox or measles12.

There aren’t any major safety concerns associated with this cream but some other cautions should be kept in mind. Side effects you may experience include developing a skin rash or hives, and experiencing increased sensitivity to the sunlight, which can lead to a sunburn11,12.  If you do apply the cream, make sure you are not taking any other diphenhydramine products at the same time, such as oral Benadryl® products for allergies11.  When applying the cream, apply it only to the skin and try to avoid the eyes, nose, ears, and mouth11,12.  Try to also limit cream application to the affected areas, and do not spread it over large regions of the body as this can increase absorption into the blood, which can cause side effects throughout the body11.  Studies have shown that the product may be acceptable for pregnant women11.  As for women who are nursing, it is unknown if the topical product is actually excreted into the breast milk or not.  Nevertheless, pregnant and/or nursing women should consult with a doctor before using any over-the-counter products.

The bottom line

Although topical antihistamines are widely available and frequently used, there is a lack of evidence from credible studies to fully support topical diphenhydramine as being effective in relieving itching. It is important to keep in mind that topical antihistamines do have fewer side effects than oral antihistamines. Benadryl® Itch Cream is also not very expensive (approximately $13.59 for a 30g tube13) so if you do get hit by a sudden itch, perhaps you may want to try  topical Benadryl® if it’s a small area and don’t want the side effects of the oral antihistamines.



Alyssa Aco, Vivian Eng, Amanda Ngo, Sunny Ngo, Kayla Wong, BSc. Pharm Candidate(s)

Faculty of Pharmacy and Pharmaceutical Sciences

University of Alberta

Edited and Reviewed by the Health Aisle Team 



  1. Benadryl®. (2013, July). Benadryl® Itch Cream. Retrieved from http://www.benadryl.ca/topical-relief-medicine/itch-cream
  2. Clinical Key. (n.d.). Retrieved from https://wwwclinicalkeycom.login.ezproxy.library.ualberta.ca/#!/ContentPlayerCtrl/doPlayContent/6-s2.0-197/{“scope”:”all”,”query”:”diphenhydramine”}
  3. Woo, T. M., & Wynne, A. L. (2011, August). Pharmacotherapeutics for Nurse Practitioner Prescribers. Philadelphia, PA: F.A. Davis Company.
  4. (n.d.). How do antihistamines work? Retrieved from http://health.howstuffworks.com/diseases-conditions/allergies/allergy-treatments/how-do-antihistamines-work.htm
  5. C-Health. (n.d.). Benadryl. Retrieved from http://chealth.canoe.ca/drug_info_details.asp?brand_name_id=1874
  6. Yaffe, S. J., Bierman, C. W., Cann, H. M., Gold, A. P., Kenny, F. M., Riley, H. D., … Stern L. (1973). Antihistamines in topical preparations. Pediatrics, 51(2), 299-301. Retrieved from http://pediatrics.aappublications.org/content/51/2/299.full.pdf
  7. e-CPS. (2012, June). Benadryl® Retrieved from  https://www-e-therapeutics ca.login.ezproxy.library.ualberta.ca/cps.showMonograph.action?newSearch=true&simpleIndex=brand_generic&simpleQuery=benadryl&brandExactMatch=false#
  8. Eschler, D. C., & Klein, P. A. (2010, August). An evidence-based review of the efficacy of topical antihistamines in the relief of pruritus [Abstract]. The Journal of Drugs in Dermatology, 9(8), 992-7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20684150
  9. Elmariah, S. B., & Lerner, E. A. (2011, June). Topical therapies for pruritus. Seminars in Cutaneous Medicine and Surgery, 30(2). 118-126. Retrieved from http://europepmc.org/articles/PMC3139917
  10. Klein, P. A., & Clark R. A. (1999). An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Archives of Dermatology, 135(12), 1522-5. http://dx.doi.org/10.1001/archderm.135.12.1522
  11. (n.d.). Diphenhydramine Topical (OTC). Retrieved from http://reference.medscape.com/drug/benadryl-itch-stopping-diphenhydramine-d-diphenhydramine-999685#0
  12. (2010, August). Diphenhydramine Topical. Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601044.html
  13. Well.ca. (n.d.). Benadryl®. Retrieved from http://well.ca/brand/benadryl.html