Dear Editor,

Dr. Westafer’s commentary on diphenhydramine makes several valid points about some misuses (e.g,. sleep aid) or overuses (routine adjunct in treating migraine headache) of the drug.¹ However, I disagree that emergency physicians are unfamiliar with the “not-so-commonly-known side effects” of sedation, anti-muscarinic effects, and a “high” with rapid IV push. Taken together, these points are conflicting. The well-known sedating effect is the reason why some physicians may suggest it for sleep and why most over-the-counter sleep aids contain diphenhydramine. Likewise, the antimuscarinic effect is the intended effect for avoiding or treating akathisia caused by dopamine antagonists.

Her strong recommendation for IV cetirizine over IV diphenhydramine overlooks their large cost difference. Intravenous (IV) cetirizine has a wholesale cost of over $300.^2,3 Charges to patients are likely much higher. Meanwhile, IV diphenhydramine costs less than $1.⁴ This large cost difference provides a non-inferior drug that may be slightly better. This large cost difference with modest incremental benefit is the reason why many hospitals (including my own) have not rushed to add IV cetirizine to their formularies. While cetirizine has less sedation, we generally know well that diphenhydramine is sedating and give discharge instructions to avoid driving or operating machinery.

The patent for IV cetirizine will expire in 2039, so we have 17 years to wait for the cost of IV cetirizine to approach the cost of diphenhydramine. To paraphrase a quote attributed to Mark Twain, rumors of the death of diphenhydramine are greatly exaggerated.⁵

Michael E. Mullins MD, FACEP, FAACT practices emergency medicine at St. Louis Children’s Hospital and Barnes-Jewish Hospital in St. Louis.

References

1. Westafer L. The death of diphenhydramine. ACEP Now. 2022; 41(7):18.
2. Intravenous cetirizine (Quzyttir) for acute urticaria. Med Lett Drugs Ther. 2020 Apr 6;62(1595):55-56.
3. Amrol DJ. Intravenous cetirizine for acute urticaria. NEJM Journal Watch. Oct 29, 2020.
4. Banerji A, Long A, Camargo C. Diphenhydramine versus non-sedating antihistamines for acute allergic reactions: A literature review. Allergy Asthma Proc. 2007; 28:418-426.
5. http://www.twainquotes.com/Death.html (accessed 6 August 2022)