A paper calling for a “final goodbye” to diphenhydramine – best known as Benadryl, and one of the oldest, but not the safest drugs around – is gaining traction among physicians on social media.
Published in the World Allergy Organisation Journal, the paper gives several reasons why it's time to move on from Benadryl, including the presence of effective and safer second-generation antihistamines, frequent and sometimes severe adverse reactions to first-generation agents, (and) its demonstrated abuse potential.
Lead author James Clark, MD, of Johns Hopkins University School of Medicine in Baltimore, noted that despite its known downsides, use of diphenhydramine in both prescription and over-the-counter forms remain prevalent in the United States.
"Often when patients come into my clinic, they’re already on an oral antihistamine, and it will be something like Benadryl," Clark told MedPage Today. “I see it quite frequently in kids too, and it’s talking to their parents and trying to educate them on the different options and the potential downsides of Benadryl as a medication.”
Other experts in allergy and immunology agree, and have recently started sharing the paper on social media, though it was published earlier this year.
“Anything you would use Benadryl for can be replaced with cetirizine (Zyrtec), loratadine (Claritin), fexofenadine (Allegra), or levocetirizine (Xyzal),” David Stukus, MD, of Nationwide Children’s Hospital in Columbus, Ohio, wrote in an Instagram post about the paper. “If you’re asking if any of these are safer or better, the answer is YES!!!”
“Can I use one of these for an acute allergic reaction? Yes!” he added. “Hives? Yes! Seasonal allergies? Yes! What if I take one of these daily and need another one? Yes! The answer is going to be yes!”
Diphenhydramine is a non-selective binder; it doesn’t only target histamine receptors in the body, Stukus told MedPage Today. “It actually binds to receptors throughout the body, and it can impact just about any organ system, and accordingly, there can be significant side effects.”
In their paper, Clark and colleagues said diphenhydramine can interfere with sleep quality, and side effects include sedation, drowsiness, and psychomotor impairment.
They also cited the TikTok “Benadryl challenge” during the pandemic – which led to deaths and hospitalisations – as an example of its abuse potential.
At the time, and in response to the challenge, the South African Health Products Regulatory Authority (SAHPRA) issued an alert regarding the risk of serious heart problems, seizures, coma and death associated with high doses of diphenhydramine-containing medicines.
Pregnant
“Diphenhydramine is not recommended for people with specific health problems, including closed-angle glaucoma, dry eyes, peptic ulcer, constipation, and urinary retention,” wrote Clark and colleagues.
“In addition, regular use of diphenhydramine poses risks for women who are pregnant or breastfeeding. Due to anticholinergic properties, cumulative use of first-generation antihistamines confers risks for people over 65, including Alzheimer’s disease and other forms of dementia.”
Conversely, second-generation antihistamines mostly target histamine receptors with very few side effects, Stukus said.
“They also have equivalent onset and longer-lasting treatment effects,” Clark and colleagues noted. “Thus, they have much better therapeutic ratios than diphenhydramine.” And they are similarly priced and widely available, they added.
Stukus added that he shared the paper because “people are getting their information on social media these days, and that’s part of the reason that I’m out there”.
Zachary Rubin, MD, a paediatrician specialising in allergy and immunology who practices near Chicago, said in a post that “while [Benadryl] is one of the oldest antihistamines available, [that] does not mean that it is the most effective, nor is it the safest”.
Neither the American College of Allergy, Asthma, & Immunology nor the American Academy of Allergy, Asthma, & Immunology (AAAAI) has an official policy or recommendations about the use of Benadryl.
Outside the US there are countries that have partly moved away from diphenhydramine. In their paper, Clark and colleagues noted that Germany, The Netherlands, and Sweden have made diphenhydramine available by prescription only, and that the Canadian Society of Allergy and Clinical Immunology has recommended first-generation antihistamines be considered solely as behind-the-counter medications.
However, it is unlikely that diphenhydramine will disappear from the American market, experts said.
“Benadryl has its place,” Rubin said. “When you talk about intravenous antihistamines, that’s the only one that’s readily available in most places.”
“Science involves evolution and accumulation of evidence, and we should always be looking at best practices,” Stukus said.
“If a patient has been taking a medication for years and years, we should always be re-evaluating. Do they actually need that? Are there better options available? We should revisit things over time.”
Medpage Today article –Is It Really Time to Say Goodbye to Benadryl? (Open access)
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