Volume 128, Issue 5 , Pages 1127-1128, November 2011
Comparison of cetirizine and diphenhydramine in the treatment of acute food-induced allergic reactions
Article Outline
To the Editor:
Diphenhydramine has been commonly used as the antihistamine of choice for acute food-induced allergic reactions given its prompt onset of action (15-60 minutes)1 and ready availability, although epinephrine is still the first-line therapy for anaphylaxis. However, sedation is a common side effect of diphenhydramine, which, in our clinical experience, can complicate the assessment of a patient being treated for an acute food-induced allergic reaction. Cetirizine is a second-generation antihistamine with a similar onset (15-30 minutes) but longer duration of action (≥24 hours) compared with diphenhydramine.2, 3 Furthermore, central nervous system effects are less commonly reported.2, 4, 5 Cetirizine has been used by patients in our outpatient clinic for the treatment of acute food-induced allergic reactions, but a direct comparison of the efficacy and side-effect profile of cetirizine to diphenhydramine has not been investigated for the treatment of allergic food reactions. Therefore the aim of this study was to compare the presence of medication-related sedation of cetirizine with that of diphenhydramine and the efficacy of these medications in the treatment of acute food-induced allergic reactions in subjects undergoing oral food challenges.
This was a randomized double-blind study of 70 allergic reactions during oral food challenge involving 64 patients aged 3 to 19 years (5 patients presented for multiple food challenges). There were 35 reactions included in each treatment arm. Written informed consent was obtained from each subject, and the study was approved by the Mount Sinai Institutional Review Board. Subjects who reacted to the challenge food were blindly randomized to receive either liquid diphenhydramine (1 mg/kg) or liquid cetirizine (0.25 mg/kg). Of note, 5 patients presenting for multiple food challenges were rerandomized at each challenge. When indicated, all other medications were administered as per the standard oral food challenge protocol.6 After administration of the antihistamine, each patient was monitored at 10-minute intervals for allergic symptoms and sedation by nursing staff blinded to the medication. Patients were assessed for sedation by using a 5-point validated sedation score (Table I), which has been used in pediatric anesthesiology studies.7, 8
Table I. Description of sedation scores and their distribution in the 2 treatment groups
| Sedation score∗ | Description | Diphenhydramine (% experiencing sedation) | Cetirizine (% experiencing sedation) |
|---|---|---|---|
| 1: Unconscious | Asleep; does not respond to minor motor stimulation | 8.6 | 2.9 |
| 2: Drowsy | Might close eyes but responds to minor motor stimulation | 25.7 | 17.1 |
| 3: Normal | Calm, sitting/lying comfortably with eyes open | 100† | 100† |
| 4: Anxious | Looks frightened but not clinging to parent; might whimper but not crying | 22.9 | 22.9 |
| 5: Very agitated | Crying, struggling, or clinging to parent | 2.9 | 11.4 |
∗Some of the patients who experienced sedation moved along the sedation score scale during the observation period (eg, a patient could have started with a sedation score of 3, then received a score of 1 when heavily sedated, then moved up to a score of 2 while gradually getting more alert, and ended the observation period again with a score of 3). Therefore these patients received more than 1 sedation score, and this explains why the percentages of the scores sum to greater than 100. |
†All subjects started or ended the observation period with this score. |
The primary outcome of the study was the percentage of patients experiencing sedation in the 2 treatment groups. Patients with sedation scores of 1 or 2 were considered to be experiencing sedation. Additionally, the mean time to resolution of urticaria and pruritus was determined in each group to assess the efficacy of diphenhydramine and cetirizine. Although all symptoms experienced by patients were recorded, the cutaneous symptoms were used for analysis because these are the symptoms effectively treated with antihistamines. Additionally, urticaria is an objective finding, which enhances the validity of study outcome. An unpaired t test (GraphPad Software, Inc, La Jolla, Calif) was used for statistical analysis.
The median age for the diphenhydramine-treated group was 8.42 years (range, 3-19 years), and that for cetirizine-treated group was 8.92 years (range, 4-17 years). Milk, egg, and peanut constituted 88.6% of the foods used for challenges in both groups. In the diphenhydramine-treated group 28.6% experienced sedation compared with 17.1% in the cetirizine-treated group, reflecting a difference in sedation of 11.4% (95% CI, −8.4% to 30.2%); however, this did not reach statistical significance, likely because of the small sample size. The distribution of sedation scores is presented in Table I; both the mean and median sedation scores between the 2 treatment groups were not significantly different. The mean time to resolution of urticaria and pruritus was similar in both groups. In the diphenhydramine-treated group the mean time to resolution of the urticaria was 42.3 minutes (SD, 23.15 minutes); in the cetirizine-treated group the mean time to its resolution was 40.8 minutes (SD, 22.11 minutes; P = .86). For pruritus, the mean time to its resolution was 28.6 minutes (SD, 20.54 minutes) for the diphenhydramine-treated group; in the cetirizine-treated group the mean time to resolution was 31.3 minutes (SD, 20.07 minutes; P = .67). Similarly, the mean time to first onset of urticarial or pruritus relief was similar in the 2 treatment groups. There was no difference in administration of other medications. Specifically, 9 patients in each group required administration of steroid or epinephrine for symptoms of abdominal pain, nausea, cough, wheezing, and angioedema. The reactions were promptly resolved by these additional medications, and all patients were discharged home the same day.
In this randomized double-blind study involving 70 allergic reactions during oral food challenges, cetirizine demonstrated similar efficacy compared with diphenhydramine in treating cutaneous symptoms in acute food-induced allergic reactions. No significant difference in the mean time to resolution of urticaria and pruritus with either cetirizine or diphenhydramine was noted. This finding is consistent with the results of prior studies assessing the efficacy of second-generation antihistamines in patients with acute allergic reactions.2
Although the primary outcome of the study was not met because the study was not sufficiently powered to demonstrate a statistically significant difference in sedation, the observed trend showed a higher percentage of sedation in patients receiving diphenhydramine compared with cetirizine, with a difference of 11.4%. In studies assessing antihistamine-related sedation in other non–food-induced allergic reactions, the results suggest a higher incidence of sedation in patients treated with diphenhydramine in comparison with that seen in those treated with the second-generation antihistamines, including cetirizine.2, 4, 5 However, our study on food-induced allergic reactions did not replicate these results. It should also be noted that liquid formulations of antihistamine were used in our study; other formulations that might have different bioavailability might yield different results. In regard to safety, our study showed no adverse events related to the administration of cetirizine, and a number of studies in the past have documented and confirmed the safety of cetirizine in young children.9, 10
In summary, cetirizine has similar efficacy and onset of action compared with diphenhydramine in treating acute food-induced allergic reactions. With added benefits of similar efficacy but longer duration of action compared with diphenhydramine, cetirizine is a good treatment option for acute food-induced allergic reactions. Further studies involving a larger sample size will better elucidate the difference in sedation between the 2 antihistamines.
References
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- . Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis. J Allergy Clin Immunol. 2003;111:770–776
- . Work group report: oral food challenge testing. J Allergy Clin Immunol. 2009;123(suppl):S365–S383
- . Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology. 1988;69:972–975
- . Intravenous ketamine plus midazolam is superior to intranasal midazolam for emergency paediatric procedural sedation. Emerg Med J. 2001;18:39–45
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- . Prospective, long-term safety evaluation of the H1-receptor antagonist cetirizine in very young children with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child. J Allergy Clin Immunol. 1999;104:433–440
J.W. is funded in part by a grant from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (K23 AI083883). H.A.S. is funded in part by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI44236 and AI066738) and the National Center for Research Resources (RR026134). J.H.G. is supported by award number UL1RR029887 from the National Center for Research Resources.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
PII: S0091-6749(11)01392-3
doi:10.1016/j.jaci.2011.08.026
© 2011 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 128, Issue 5 , Pages 1127-1128, November 2011
