Long-Term Evaluation of the Impact of the H1-Receptor Antagonist Cetirizine on the Behavioral, Cognitive, and Psychomotor Development of Very Young Children with Atopic Dermatitis

Abstract

The impact of the prolonged use of cetirizine at high dose (0.25 mg/kg twice a day over 18 mo) on behavior and cognitive ability was examined in a double-blind, randomized, placebocontrolled trial (ETAC-Early Treatment of the Atopic Child) designed to establish whether it was possible to prevent young children (1-2 y old at study entry) with atopic dermatitis from developing asthma. Well-validated and standardized measures of behavior (Behavior Screening Questionnaire) and cognition (McCarthy Scales of Children's Abilities) were used. In addition, the ages of attainment of psychomotor milestones were established. These measures were taken between an average of 32 and 53 mo of age, both during the study treatment with cetirizine or placebo and after the study treatment had been discontinued. The Behavior Screening Questionnaire was completed at least once on approximately 300 children in each group and on approximately 200 children on five occasions. The McCarthy Scales of Children's Abilities were administered to approximately 100 in each group at three different times. There were no significant differences between the cetirizine and placebo groups on either of the behavior and cognition measures or in psychomotor milestones during or after the study treatment. These findings suggest that there are no adverse effects on behavior or learning processes associated with the prolonged use of cetirizine in young children with atopic dermatitis. There is evidence that the use of some antihistamines has an effect on behavior and that this is shown most markedly as sedation (1-3). These side effects may have implications for the long-term development of the child. Little is known about the development of histamine receptors with age, and, given that all antihistamines can gain access to the brain (4), it is important to establish whether antihistamines have a deleterious effect on histamine receptor sites and on the cognitive and behavioral systems regulated by histamine (5). There has been no study on the impact of the long-term administration of antihistamines on children's behavioral development. The present study aimed to fill this gap.A number of findings that have suggested that firstgeneration antihistamines can interfere with learning. Sedating (diphenhydramine) and nonsedating (loratadine) antihistamines and a placebo have been used with children suffering from seasonal allergic rhinitis (6). It was found that those on placebo and diphenhydramine learned significantly less well than healthy controls. The nonsedating antihistamine only partially counteracted this effect. A subsequent study of young adults with seasonal allergic rhinitis showed that this learning deficit could be avoided by the use of a combination compound of acrivastine and pseudoephedrine (7). The indications from these previous studies made it essential to determine whether

Adverse Systemic Reactions of Antihistamines: Highlights in Sedating Effects, Cardiotoxicity and Drug Interactions

“…817, 1-2 year-old children using cetirizine for 18 months have been evaluated for the adverse effects of cetirizine on the behavioral, cognitive and psychomotor development. No detrimental effect of cetirizine on any of the outcome measures had been detected [19].…”

Population pharmacokinetics of levocetirizine in very young children: the pediatricians’ perspective

“…An algorithm could be developed for an optimal pediatric levocetirizine dosage regimen: dose in mg twice daily=0.20 mg/L [0.244 L/h+(0.044 L/h/kg·BW)]×12 h, where 0.20 mg/l is mean maximum steady‐state levocetirizine plasma concentration at steady‐state, 0.244 l/h is the extrapolated intercept of the Cl / F vs. body weight plot, and BW is body weight in kg. In daily clinical practice, due to the favorable therapeutic index (benefit‐to‐risk ratio) of levocetirizine arising from cetirizine (23–28), it may not be necessary to apply this formula.…”

“…The children, who had atopic dermatitis and a family history of allergy, and were at high risk for developing asthma and other allergic disorders, were enrolled after informed consent was obtained from their parents or guardians. The inclusion and exclusion criteria for the study, and the methods of monitoring for efficacy and safety have been described in detail in previous ETAC study publications (23–28). Cetirizine 0.25 mg/kg or placebo solution were administered as drops with breakfast and with the evening meal every day for 18 months.…”

“…It is also a newly synthesized chemical entity (19) which is indicated in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria in adults and children. We hypothesized that levocetirizine population PK could be investigated in the young children who received cetirizine in the prospective, randomized, double‐blind, placebo‐controlled Early Treatment of the Atopic Child (ETAC) Study (23–28). Our objective was to demonstrate for pediatricians that the levocetirizine concentrations measured in timed, sparse blood samples obtained at steady‐state for safety monitoring in children in the ETAC study could be utilized to derive clinically relevant pharmacokinetic information.…”

New Oral Antihistamines in Pediatrics and Safety of Antihistamines in Children

“…In the prospective, randomized, double-blind, placebocontrolled Early Treatment of the Atopic Child (ETAC) study conducted over 18 months in children with atopic dermatitis, aged 12-24 months at study entry, cetirizine (0.25 mg/kg twice daily) was found to have a similar safety profile to that of placebo with no adverse affects on behavioral, cognitive or psychomotor development [80]. Accidental overdosage with 180 mg of cetirizine in an 18-month-oldboy had no adverse consequences [81].…”