The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England.

INTRODUCTION: Observational cohort studies were conducted using prescription-event monitoring (PEM) to examine the safety profiles of the anti-obesity agents orlistat and sibutramine. Adverse events reported as case reports were also evaluated to determine whether these events were also identified by PEM. RESEARCH METHODS AND PROCEDURES: Patients were identified from dispensed prescriptions written by general practitioners (GPs) in England for orlistat or sibutramine. Patient demographic and clinical event information, including reasons for stopping and adverse drug reactions, were requested on questionnaires posted to GPs at least 6 months after the first prescription for individual patients. Event incidence densities (IDs) (number of first reports of event/1000 patient-months treatment) were calculated for month 1 (ID(1)) and months 2-3 (ID(2-3)). Published case reports were identified by searching Medline and Embase. RESULTS: The cohorts comprised 16,021 and 12,336 patients prescribed orlistat and sibutramine, respectively. Both cohorts had a median age of 45 years, and approximately 80% were female. The most common reason for stopping orlistat within 3 months was diarrhea (332 patients; 2.1% cohort), and for stopping sibutramine it was hypertension (203 patients; 1.6%). Clinical events significantly associated with taking orlistat were mainly gastrointestinal and those for sibutramine included central nervous system effects, nausea/vomiting, palpitation, and sweating. We identified 8 published case reports for orlistat and 10 for sibutramine that had equivalent or similar events assessed as causally related in the PEM studies. CONCLUSIONS: The PEM studies highlighted different adverse event profiles for orlistat and sibutramine that were consistent with their distinct pharmacological mechanisms and other published information.

A modified prescription-event monitoring study to assess the introduction of Seretide Evohaler in England: an example of studying risk monitoring in pharmacovigilance.

INTRODUCTION: Monitoring was required for the introduction of non-chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) to ensure that there were no unexpected adverse events due to the new products. A postmarketing surveillance study has been conducted to evaluate the introduction of the MDI Seretide Evohaler (hydrofluoroalkane-134a inhaler containing salmeterol and fluticasone propionate). OBJECTIVES: To summarise the modified prescription-event monitoring (PEM) study conducted to evaluate the introduction of Seretide Evohaler and discuss the relevance of this type of study towards pharmacovigilance risk-management planning. METHODS: Modified PEM methodology was used to examine the introduction of Seretide Evohaler into general practice in England. Patients were identified from the first National Health Service prescriptions dispensed in England for Seretide Evohaler. One postal questionnaire was sent to the prescribing doctor, requesting demographic information, severity of the indication, concomitant medication for this condition, smoking history, event data 3 months prior to and 3 months after the first prescription for Seretide Evohaler and also reason for stopping if it had been stopped. Pregnancies, deaths and selected events were followed up. Incidence density ratios were calculated to compare event rates 3 months prior to and 3 months after the introduction of Seretide Evohaler. A matched cohort analysis examined oral corticosteroid use and hospital admissions between the pre- and post-exposure periods. RESULTS: The cohort comprised 13,464 patients prescribed Seretide Evohaler, with a response rate of 62%. There was no significant difference in the length of courses of oral corticosteroid use when the pre- and post-exposure periods were compared. A matched cohort analysis showed there was no increase in the use of oral corticosteroids (relative risk [RR] 0.95; 95% CI 0.90, 0.99) or hospital admissions in the post-exposure period (RR 0.87; 95% CI 0.73, 1.04). When the number of patients with events were compared for the periods 3 months before and 3 months after exposure, fewer events were reported in the post-exposure period. There were 64 patients who experienced adverse events within an hour of using Seretide Evohaler, including one report of paradoxical bronchospasm and one of myocardial infarction with fatal outcome that were both assessed as possibly related to treatment. DISCUSSION: The results of the study suggest that the introduction of Seretide Evohaler was generally well tolerated. The modified methodology has allowed a comparison of the event rates before and after the introduction of this CFC-free inhaler into general practice.

A modified prescription-event monitoring study to assess the introduction of Flixotide Evohaler into general practice in England: an example of pharmacovigilance planning and risk monitoring.

INTRODUCTION: A modified prescription-event monitoring (PEM) study was conducted to examine the safety of the introduction of the metered dose inhaler (MDI) Flixotide Evohaler (fluticasone with the propellant HFA 134a). METHODS: Patients were identified from the first NHS prescriptions dispensed in England for Flixotide Evohaler. Postal questionnaires were sent to the prescribing doctor, requesting information including: demographic characteristics, severity of indication, concomitant medication, event data 3 months prior to and 3 months after the first prescription, and any reasons for stopping Flixotide. Pregnancies, deaths and selected events were followed up. Incidence density ratios (IDRs) were calculated to compare event rates 3 months before and 3 months after the introduction of Flixotide Evohaler. RESULTS: The cohort comprised 13 413 patients that were prescribed Flixotide Evohaler. The response rate was 64.0%. When the pre- and post-exposure periods were compared fewer patients had events in the post-exposure period, and there was no significant difference in the length of courses of oral steroid use. Eighteen patients experienced an event within 1 hour of using Flixotide Evohaler; these were minor with the exception of one case of angioneurotic facial oedema. Six of these events were assessed as possibly related to Flixotide Evohaler. During the study period there were an additional 13 patients with events assessed as possibly related to Flixotide Evohaler, including two reports of allergic reactions. DISCUSSION: The results suggest that the transition to Flixotide Evohaler was generally well tolerated. The modified methodology has contributed to the risk management of the introduction of this product.