Reviewing the safety of loratadine for elderly adults: a potential shortcoming of the 2012 Beers criteria.

Abstract

To the Editor: Anticholinergic drugs produce a variety of adverse effects, including dry mouth and eyes, constipation, blurred vision, rapid heart rate, dizziness, sedation, confusion, delirium, hallucinations, and cognitive impairment.1, 2 Furthermore, anticholinergic toxicity has been reported as a common problem in elderly adults, and anticholinergic drug use is closely associated with serious negative outcomes in this population, such as risk of falls, behavioral symptoms (including agitation), and high mortality.1, 2 Anticholinergic drugs are often mentioned in explicit criteria for inappropriate medication use in older adults, such as the Beers criteria.1, 3 In 2012, the American Geriatrics Society revised these criteria and included loratadine on the list of potentially inappropriate medication for elderly adults owing to its strong anticholinergic properties; these drugs were to be avoided in cases of lower urinary tract symptoms, benign prostatic hyperplasia, chronic constipation, and cognitive impairment and delirium.3 Loratadine is a second-generation H1 antihistamine, as are levocabastine, azelastine, bilastine, desloratadine, ebastine, cetirizine, fexofenadine, levocetirizine, and rupatadine; the characteristics of second-generation H1 antihistamines make them more effective and safer than first-generation H1 antihistamines (e.g., diphenhydramine, hydroxyzine, promethazine, clemastine, triprolidine). Moreover, first-generation H1 antihistamines are associated with undesirable sedation and anticholinergic side effects.4-6 Under the umbrella term “sedation” is a range of conditions including somnolence, impaired concentration, and poor learning ability.5 Central nervous system (CNS) and cardiac toxicity have been the most serious adverse effects associated with H1 antihistamines. Cardiac toxicity is rare but is of considerable concern because of the associated risk of death. CNS toxicity produced by first-generation H1 antihistamines is widespread, but even during the years when first-generation H1 antihistamines were widely used, case reports of cardiac toxicity were uncommon, and epidemiological studies involving large sample sizes identified only a few cases of H1 antihistamine–associated ventricular arrhythmias.7 Thereafter, several second-generation H1 antihistamines, the use of which was devoid of any associated cardiac toxicity and significant CNS toxicity,5, 7 became the H1 antihistamines of choice.7 Loratadine is considered a nonsedating antihistamine. At recommended doses (10 mg/d), no significant differences between loratadine and placebo for any measure of cognitive or psychomotor performance, mood, or sedation were observed.5, 6 In contrast, other performance studies that used higher doses of loratadine (20 and 40 mg) showed significant performance impairment and sedation in some tests (e.g., choice reaction time, adaptive tracking, digit-symbol substitution) in comparison with placebo.5 In light of the evidence demonstrating its safety, the inclusion of loratadine in the list of potentially inappropriate medications solely on the basis of the studies that the 2012 revised Beers criteria reference is not justified. Those three studies, which the American Geriatrics Society cited,8-10 do not provide any evidence of loratadine being an antihistamine with strong anticholinergic properties. One of these studies9 gave loratadine 2 points on the Anticholinergic Risk Scale, indicating that it entails intermediate risk; another study8 gave loratadine 0 points, which means that it has no known anticholinergic properties. Moreover, a recent systematic review of anticholinergic risk scales in older adults1 did not mention that loratadine has strong anticholinergic properties or the potential for serious adverse effects in elderly adults. That review1 cited two of the three studies that the 2012 Beers criteria referenced;8, 9 the third study,10 also used as a reference by the American Geriatrics Society, was not included in the systematic review, probably because it was a narrative review that did not provide any evidence of loratadine possessing strong anticholinergic properties. That review1 has great clinical implications because the summarized studies describe different drugs with anticholinergic properties. Although this study was not a systematic review of randomized clinical trials, the data can be applied to clinical practice. The findings of this review provide insights into a broad issue that could have not been addressed through clinical trials. The finding that loratadine is safe for elderly adults is of great consequence to health professionals concerned with providing treatment for people of this age group. In addition, it highlights a probable shortcoming of the Beers criteria, which are currently used as a basis for supporting prescription for elderly adults.3 Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed to review and the preparation of the manuscript. Sponsor's Role: Not applicable.