Dr. Anna Wolfson says she sees dangerous misuse of the allergy medication diphenhydramine in her clinic every day.
“If someone has an allergic reaction to a food, people will say, ‘Don’t worry, I have diphenhydramine in my purse,’ and I would say, ‘Really, epinephrine is the first-line treatment for food allergies,’” said Wolfson, an allergist at Massachusetts General Hospital.
Diphenhydramine can be harmful if people take it after having an allergic reaction to food, she said, because the drug – best known by the brand name Benadryl – makes them drowsy and can cause them to miss signs that their symptoms are getting worse.
“It’s time to move on. For every single indication that people are using diphenhydramine, there are better drugs that are more effective at treating the symptoms people are trying to treat with fewer side effects,” she said. “I’ve had patients where I worried that diphenhydramine was impairing their ability to drive or fully participate in their daily lives.”
Wolfson isn’t alone in preferring alternatives. In a review published in February, allergy experts from Johns Hopkins University and the University of California, San Diego called for the removal of diphenhydramine from over-the-counter and prescription markets in the United States, saying it’s outdated, dangerous and eclipsed by safer alternatives.
A first-generation antihistamine approved in 1946, diphenhydramine is widely used for allergies, sleep aid and cold symptoms. It’s a common over-the-counter medication in the US, with usage rising in the summer months as people use it to treat itching from bug bites or poison ivy, as well as sneezing and runny nose caused by grass and pollen allergies, according to the American Pharmacists Association.
Despite its longstanding presence in American homes, the authors of the new review say it poses disproportionate risks, especially for children and older adults, than newer antihistamines.
“Patients should trial alternatives agents like loratadine, which is Claritin, or cetirizine, which is Zyrtec, or fexofenadine, which is Allegra,” to alleviate allergy symptoms, Dr. James Clark of the Department of Otolaryngology-Head and Neck Surgery at the Johns Hopkins University School of Medicine, the lead author of the paper, told CNN.
The Consumer Healthcare Products Association, which represents the OTC medicine industry, says that common side effects associated with products containing diphenhydramine are disclosed on the label. However, it notes, “these products are not intended for long-term use.”
“When used as directed, these medicines provide well-established therapeutic benefits for common health ailments like allergies, the common cold, motion sickness, minor skin irritations, and occasional sleeplessness,” the group said in a statement on behalf of Benadryl’s maker, Kenvue. “Like all medicines, responsible use is essential, and consumers should always follow directions and warnings on the Drug Facts labels and consult healthcare providers if they have questions.”
Antihistamines work by blocking receptors called H1, part of the body’s system for responding to allergens, which trigger symptoms like sneezing, itching and a runny nose. But older drugs like diphenhydramine don’t just block the allergy-related receptors, they can also affect other parts of the brain. Diphenhydramine often causes sedation, cognitive impairment, and in some cases, dangerous cardiac effects, the authors wrote.
In older adults, the drug can stay in the body for up to 18 hours, resulting in lingering sleepiness, disorientation and increasing risk of falling. The review also highlighted a possible link between long-term diphenhydramine use and dementia.
In children, the risks can be even more pronounced. The review’s authors cite cases of accidental overdose; paradoxical reactions such as agitation, extreme sedation and coma; and even death, particularly with pediatric formulations, because of accidental ingestions. The medication was linked to several child hospitalizations and fatalities during the viral “Benadryl Challenge” on TikTok.
Dr. Manuela Murray, director of general pediatrics and urgent care at the University of Texas Medical Branch, says diphenhydramine “should not be used lightly.”
“It should always be used under the guidance of a Medical Professional, and it is only indicated to treat allergic reactions and motion sickness,” Murray wrote in an email.
The medication is often misused and “doesn’t offer a benefit for treatment of cold symptoms, and it is not a safe sleep aid medication,” she said. In fact, it can have the opposite effects in children, leading to hyperactivity.
Dr. Alyssa Kuban, a pediatrician and associate medical director at Texas Children’s Pediatrics, also said that she finds diphenhydramine overused for symptoms it does not directly treat and that there are safer alternatives.
“I see some families use diphenhydramine when the child has a cold or upper respiratory infection, thinking it will help with the congestion and help them to sleep better at night,” she said. “This is not effective for cold symptoms, nor is it very safe.”
She recommends over-the-counter cetirizine to treat children with hives, seasonal allergies or an itchy rash. Cetirizine is also longer-lasting and not as sedating as diphenhydramine, she says.
Murray agrees that loratadine and cetirizine are safer for children over 6 months, and saline drops and suctioning are better alternatives for infants.
Diphenhydramine appears in over 300 OTC formulations, often blended into combination products for coughs, colds and flu. The authors of the review say that, like products with pseudoephedrine, diphenhydramine should at minimum be moved behind the counter, allowing pharmacists to guide patients toward second-generation alternatives.
The American Pharmacists Association says patients should use caution with combination cough and cold products that contain diphenhydramine.
Pharmacists may recommend alternative medications for older adults who have a history of being cognitively affected by certain medications, the group says, and it “encourages patients and parents/caregivers to ask their pharmacist for the most appropriate treatment recommendation for their symptoms” with the least amount of side effects.
The review authors also emphasize that there is no strong clinical data that may suggest that diphenhydramine works better than other options. Although it may reduce symptoms like sneezing and itching, it has minimal effect on nasal congestion and doesn’t outperform second-generation drugs in randomized trials. Newer options, such as oral cetirizine, offer 24-hour coverage with fewer adverse events.
However, in the US, the medication remains a staple. According to the review, more than 1.5 million prescriptions are still written annually, not counting untracked OTC purchases.
“In the past, it has been a useful medication that has helped millions of patients; however, its current therapeutic ratio is matched or exceeded by second-generation antihistamines, especially due to their markedly reduced adverse reactions. It is time to say a final goodbye to diphenhydramine, a public health hazard,” the authors wrote.