Nebenwirkungsprofile von Antihistaminika und ihre klinische Relevanz

Abstract

Antihistamines are therapeutic options of first choice for SAR and CIU. In this review, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine and mizolastine are compared regarding cardiotoxieity, sedative potential, eventual hepatotoxicity and teratogenity as well as their safety in special patient groups (children, elderly, patients with hepatic or renal insufficiency). The literature was searched for relevant publications and the pharmaceutical manufacturers as well as the German regulatory authority were asked for information. Antihistamines' influences on cardiac repolarization are not uniform and their risk of triggering severe ventricular arrhythmias especially in high risk patients differs. Cetirizine, desloratadine and levocetirizine bear the lowest risk. Among the modern antihistamines, cetirizine, levocetirizine and mizolastine are associated with the highest placebo-exceeding incidences of sedative adverse reactions in clinical trials. Some antihistamines already at their therapeutic dosage led to impairments in objective psychomotor and cognitive tests, cetirizine did so even below its therapeutic dosage. Under therapy with desloratadine, ebastine, and fexofenadine, few sedative adverse reactions occur in allergic patients and, to date, these antihistamines have not caused impairments in test batteries in studies with healthy volunteers at therapeutic dosages. It cannot be excluded that antihistamines in single cases cause liver function disorders and hepatitis. However, the risk among the different antihistamines seems to be comparable and not to be different from the background of idiopathic hepatitis. Experiences with exposure to antihistamines during the first trimester of pregnancy are limited. In general, there is no increased risk of teratogenity. Data on a potentially increased risk of hypospadias after exposure to loratadine cannot be definitely judged yet. In Germany, cetirizine and desloratadine are approved for children aged 2 years and older, levocetirizine and loratadine are available for children aged 6 years and older. Cetirizine in some pediatric studies was associated with a higher incidence of somnolence. Antihistamines are suitable for elderly patients. However, dosage adjustments have to be considered in case of hepatic or renal insufficiency.