Should we be taking first-generation H1-antihistamines, like Benadryl, off the over-the-counter shelves?
For years, Benadryl has been used as the go-to drug to treat a range of allergic reactions. But many experts are now discouraging its use – especially in children – saying there are safer, newer alternatives that should be used instead.
“It dumbfounds us (allergists) that people still want to use first-generation H1-antihistamines like Benadryl,” says Barrie, Ont., allergist Dr. David Fischer.
When he was chair of the Canadian Society of Allergy and Immunology, the group was unanimous in wanting to issue a statement that H1-antihistamines should be phased out of use. He says, “we were all frustrated…fed up.”
Like allergy experts around the world, Fischer says that they have known for years that first-generation H1-antihistamines, such as diphenhydramine, the active ingredient in Benadryl, have a “poor safety profile” and that “there are many other safer options that work as well or better.”
Despite this, patients and parents continue to use medications containing diphenhydramine. And, doctors continue to recommend them – a lot.
As an example, for the past seven years, Children’s Benadryl has been the most recommended over-the-counter antihistamine for children by physicians and pharmacists in Canada, according to annual surveys by The Medical Post and Pharmacy Practice + Business.
In October, Fischer’s group published a position statement on allergic rhinitis and urticaria (hives), warning that first-generation H1-antihistamines should not be used “in routine circumstances for allergic disease.” Instead, if you have allergies, newer-generation H1-antihistamines are recommended. The statement calls for a campaign to educate doctors and the public. And, the allergists would like to see the older medications moved behind-the-counter in pharmacies.
In a written statement, Health Canada said that they are “currently assessing the Canadian Society of Allergy and Clinical Immunology’s position paper…to determine whether further risk mitigation measures for diphenhydramine-containing products are required.”
What are the potential problems with using diphenhydramine?
Diphenhydramine is a first-generation H1-antihistamine, a class of drugs that works by binding and stabilizing the H1-histamine receptor. It is found in a variety of allergy, cold, and sleep medications, with Benadryl as the best-known product.
First-generation antihistamines are non-specific – they bind to other receptors and they cross the blood brain barrier. As a result, they have a variety of unintended side effects like dry mouth, dry eyes and constipation all the way to more serious things like dizziness, low blood pressure and being overly sedated or confused. Because of this, it’s recommended not to operate heavy machinery or drive after taking a dose of Benadryl.
According to Fischer, “diphenhydramine wears off in four to six hours, makes you drowsy and irritable, and if you take too high a dose or an overdose you will end up in hospital.”
Children are particularly at risk for dosage errors and can experience serious complications, including seizures and death. World Health Organization (WHO) data from a global database of adverse reactions maintained since 1968 showed almost 9,000 reports of adverse reactions and 400 deaths in children associated with many of the H1-antihistamines.
Even at therapeutic doses, studies show that first-generation H1-antihistamines can affect concentration, memory, and alertness, and in rare cases, can cause cardiac dysrhythmias. The sedating effects of diphenhydramine are so reliable that parents sometimes give Benadryl to their children as a sleep aid. This practice, against the advice of the manufacturer, has resulted in infant deaths.
McNeil Consumer Healthcare, a division of Johnson & Johnson Inc. and makers of Benadryl said in a statement, “BENADRYL® products have been trusted by doctors and moms for more than 60 years… are approved for use by Health Canada, and when used as directed, are safe and effective.”
Fischer says newer generation antihistamines can be a safer, better alternatives -they last 24 hours, are not sedating, and can be safer at high doses.
Newer-generation antihistamines have fewer of these side effects because they are more specific for the H1-receptor and do not readily cross the blood brain barrier. In Canada, the newer-generation over-the-counter H1-antihistamines include cetirizine (Reactine), loratidine (Claritin), desloratadine (Aerius) and fexofenadine (Allegra). Many are approved for use by Health Canada for adults and children two years of age and older.
Why is diphenhydramine still being used by doctors?
With diphenhydramine’s established side-effect and risk profiles, and good alternatives for treating allergy symptoms, why are doctors still recommending and using diphenhydramine?
Dr. Anne Ellis, allergist and professor at Queen’s University in Kingston, Ont. says, “It’s everyone’s go-to. It’s that brand-name recognition…The familiarity leads to an over-estimate of the safety and the efficacy…It’s very challenging to convince somebody (that) what (they) have been doing for the past 20 years is wrong.”
Also, studies show that uptake of clinical guidelines, like the allergists’ statement, can be low, but improves with “active interventions,” such as workshops, order sets, and reminders. But, it is common for new knowledge only to be disseminated through a journal publication or conference presentation and not reach a broad audience.
Dr. Sarah Reid, a pediatric emergency physician in Ottawa and editor of the knowledge mobilization network, Translating Emergency Knowledge for Kids (TREKK), says that the way new information travels to healthcare providers is “imperfect and incomplete.”
TREKK has developed recommendations on the treatment of severe allergy, or anaphylaxis – which advise that first-generation H1-antihistamines should not be used due to safety concerns and lack of efficacy in anaphylaxis. One of the challenges TREKK has faced with the recommendations is “unperceived educational need,” according to Reid. Doctors think they already know how to treat anaphylaxis, even though “many unnecessary medications are being given (like diphenhydramine).”
For anaphylaxis, TREKK developed free web-based guidelines, an algorithm and an order set. And, teams of health educators take these tools directly to health care staff by giving workshops in emergency departments across the country.
To bring the research to the bedside locally, the author of the TREKK recommendations, Dr. Waleed Alqurashi, a pediatric emergency physician, worked with his hospital’s pharmacist. At the Children’s Hospital of Eastern Ontario in Ottawa, they are in the process of removing oral diphenhydramine from all clinical protocols and order sets for allergy. But, Alqurashi says not all hospitals are making this change. And, allergies and anaphylaxis can be treated in many places other than hospitals – like at clinics, schools or at home.
Kim Fitzsimmons, a paramedic with the Frontenac Paramedic Services in Kingston, Ont., says that the only antihistamine available to her for treating moderate to severe allergies is diphenhydramine. Until her region’s protocols change, she says, she will have to continue to use it.
In the meantime, Fischer, Ellis and Alqurashi all continue to tell their patients and colleagues that diphenhydramine should not be routinely used.
Michelle Ward is a pediatrician at the Children’s Hospital of Eastern Ontario and is an associate professor at the University of Ottawa. She is currently a fellow in global journalism at the University of Toronto.