The second-generation antihistamines were developed principally to avoid sedative actions. Mann and colleagues analyzed side effect data on four second-generation antihistamines to assess the frequency of sedation in patients taking these agents.

Data on loratadine, cetirizine, fexofenadine and acrivastine were obtained from the general practice prescription-event monitoring project in Great Britain. With this monitoring system, pharmacists send all prescriptions to the Prescription Pricing Authority, which then sends information to the Drug Safety Research Unit. The latter group sends questionnaires to general practitioners who wrote the original prescriptions to collect data on side effects. The questionnaires are sent three, six or 12 months after the original prescription is written.

Replies from physicians were received for 50.7 percent of the 9,308 patients treated with loratadine, 50.9 percent of the 16,638 patients treated with fexofenadine, 56.5 percent of the 7,863 patients treated with acrivastine and 57.4 percent of the 9,554 patients treated with cetirizine. In general, antihistamines were more likely to be prescribed to women than to men and to younger patients than to older patients; 62.3 percent of the patients were women, and 40.3 percent of the patients were younger than 30 years. The demographics of the patients who received each drug were quite similar.

The number of reports of sedation or drowsiness was low for all four drugs. When sedation occurred, it did so most often in the first weeks of treatment. Sedation was least common with fexofenadine. Using loratadine as the standard and adjusting for age and sex, the odds ratio for the risk of drowsiness and sedation was 0.63 for fexofenadine, 2.79 for acrivastine and 3.53 for cetirizine.

The authors conclude that the second-generation antihistamines are associated with a low incidence of drowsiness and sedation. Because fexofenadine and loratadine had the lowest incidence of sedation, the authors suggest that either of these agents may be appropriate choices when even an infrequent rate of sedation would be undesirable, such as in patients whose occupations could be hazardous if sedation occurs.