Prescriptions were obtained for each cohort in the immediate post-marketing period. Subjects Event data were obtained for a total of 43 patients. Main outcome measure Reporting of sedation or drowsiness. Results The odds ratios adjusted for age and sex for the incidence of sedation were 0. No increased risk of accident or injury was evident with any of the four drugs.
Conclusions Although the risk of sedation was low with all four drugs, fexofenadine and loratadine may be more appropriate for people working in safety critical jobs.
Introduction Antihistamines are often used to treat the symptoms of allergies such as seasonal and perennial allergic rhinitis and urticaria. The first generation antihistamines have been associated with side effects, particularly sedation.
To further examine the sedative effects of four commonly prescribed antihistamines—loratadine, cetirizine, fexofenadine, and acrivastine—we analysed the results of four non-interventional observational cohort studies of these drugs performed by the Drug Safety Research Unit. These studies correlated prescriptions issued in general practice with events reported by the patients to their general practitioners after the drug was dispensed.
By monitoring these events in a substantial population of allergy sufferers, without the restrictions imposed by clinical trials methodology, it was possible to measure differences in side effects between these drugs. Methods The methods of prescription-event monitoring have been previously described in detail. The pharmacist sends all these prescriptions to the Prescription Pricing Authority, which under conditions of full confidentiality, provides electronic copies of the exposure data to the Drug Safety Research Unit.
These questionnaires seek to determine any event experienced by patients while they were taking the drug and for a period afterwards. General practitioners are also asked to indicate whether the event was considered to be related to the drug, although they are not required to make this connection. Additionally, the prescribers are asked to indicate whether the drug has been stopped and, if so, the reason for this.
All reported pregnancies are followed up to determine the outcome and the cause of all deaths are established. Both the exposure prescription and the outcome event data are computerised for analysis. Statistical analysis The number of events observed during the treatment period in each individual patient is recorded and the incidence density for each event is calculated using the equation: The incidence density is the measure of the number of reports of each event per thousand patient-months of exposure to the drug.
We calculated incidence densities for various time intervals: Incidence densities were calculated for all of the events reported, to give an indication of which events were reported significantly more frequently in the first month of exposure.
We calculated non-adjusted and age and sex adjusted odds ratios for drowsiness or sedation for fexofenadine, cetirizine, and acrivastine using loratadine as baseline. The method of study records only research also complies with the guidelines on the practice of ethics committees in medical research involving human subjects issued by the Royal College of Physicians of London in August Results The data collection periods for the four drugs were May to August for cetirizine and loratadine, May to September for acrivastine, and March to August for fexofenadine.
The demographics of each cohort were roughly similar. A higher proportion of women than men were prescribed antihistamines, and younger people were more likely to receive the drugs than elderly people.