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Comparative Tolerability of Second Generation Antihistamines

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Abstract

Second generation histamine H1 receptor antagonists, the so-called ‘nonsedating’ antihistamines, have high potency and additional antiallergic properties as well as H1 antagonism and are associated with fewer adverse effects compared with the first generation antihistamines. A number of drugs in this class are approved for use: acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine and terfenadine. All of them have a more favourable risk-benefit ratio with regard to the CNS adverse effects. Even those second generation antihistamines that are not actually ‘nonsedating’ are less impairing than their predecessors, but not one of them is entirely devoid of CNS activity.

Under certain circumstances some antihistamines may affect cardiac repolarisation resulting in cardiovascular adverse effects. Serious cardiovascular effects have been reported with terfenadine and astemizole when they are used in high dosages or when they are given to ‘at risk’ patients. Animal models indicate that there might be a potential risk of cardiovascular adverse effects with other antihistamines as well. However, up to now there is no clinical evidence for this assumption, despite some confusing reports. Likewise there has been much discussion about a link between these agents and carcinogenicity. However, there is no evidence that any of the second generation antihistamines increase the risk of tumour growth in humans.

Small children, elderly patients and persons with chronic renal or liver impairment are special groups in which the individual adverse effects of the second generation antihistamines must be kept in mind. The dosage for an individual has to be modified with respect to their metabolic situation.

Despite the fact that some of the second generation antihistamines are listed in the US Food and Drug Administration pregnancy risk classification as class B, the use of second generation antihistamines should be avoided during pregnancy and they should never be administered to nursing mothers.

Taking into account their negligible CNS activity, the low incidence of cardiovascular adverse effects, their lack of anticholinergic effects and other benefits, this class of antiallergic drugs represents a definite advance in therapy.

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    Friedrich Horak & Ursula Petra Stübner

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Horak, F., Stübner, U.P. Comparative Tolerability of Second Generation Antihistamines. Drug-Safety 20, 385–401 (1999). https://doi.org/10.2165/00002018-199920050-00001

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