Safety of zafirlukast: results of a postmarketing surveillance study on 7976 patients in England.

OBJECTIVES: A prescription event monitoring (PEM) postmarketing surveillance study was carried out to examine the safety of zafirlukast as used in general practice in England.

METHODS: Exposure data were obtained from the first National Health Service (NHS) prescription dispensed for patients whose prescription details were processed by the Prescription Pricing Authority between August 1998 and December 2000. Outcome data were obtained from 'green form' questionnaires sent to general practitioners (GPs) at least 6 months following the first prescription issued. Incidence densities (IDs) were calculated for events reported per 1000 months of patient exposure and ID differences between the first month of treatment and months 2-6 combined were analysed. Events of medical interest were followed up by postal questionnaire sent to GPs.

RESULTS: 21 557 green forms were sent to 8051 doctors, of which 9124 (42.3%) were returned. Useful clinical data was obtained for 7976 patients of which 4664 (58.5%) were female and 3265 (40.9%) were male. The patient's sex was not specified in 47 (0.6%) forms. The median age of the cohort was 53 years (interquartile range 38-66 years). The most frequently reported primary indication was the licensed indication of asthma, but for a small proportion of the cohort it was prescribed 'off label'.A total of 152 events in 120 (1.5%) patients were reported as adverse drug reactions (ADRs) by GPs on the green forms. ADRs with the highest reported frequency were headache and nausea. There were 3514 reasons for stopping zafirlukast in 3148 (39.5%) patients, the most frequently reported of which was that the drug was 'ineffective' (2008 patients; 25.2%). The most frequently reported specified clinical reason for stopping was headache (82 patients; 1.0%). There were 28 pregnancies reported in this cohort, 20 of which were reported to have exposure to zafirlukast during the first trimester. Nine live births with no recorded congenital abnormalities were reported for pregnancies with exposure in the first trimester. There were 151 deaths reported during the study period (1.9%). The most frequently reported causes of death were related to the respiratory system (57; 37.7%), including chronic obstructive pulmonary disease, asthma and bronchopneumonia.

CONCLUSION: This study showed that zafirlukast, as used in general practice in England, is a generally well tolerated drug with few associated adverse events.