Safety profile of orlistat: results of a prescription-event monitoring study

Abstract

Introduction: Orlistat, the first of a new class of drugs for the treatment of obesity, was launched in the UK in December 1998. The prescribing information recommends that treatment with orlistat should be discontinued after 12 weeks if the patient has not achieved a specified loss of weight. Objective: To monitor the safety of orlistat prescribed in the primary care setting in England using prescription-event monitoring (PEM). Methods: A postmarketing surveillance study using the observational cohort technique of PEM. Patients were identified from dispensed prescriptions issued by primary care physicians for orlistat between December 1998 and November 1999. The outcome data were event reports obtained by sending questionnaires (green forms) to the prescribing doctor at least 6 months after the first prescription for an individual patient. Incidence densities, expressed as number of first reports of an event/1000 patient-months of exposure, were calculated. Significant differences between incidence densities (IDs) for events reported in the 1st month (ID 1 ) and months 2 and 3 (ID 2-3 ) of exposure were regarded as potential signals. Reasons for stopping orlistat were analysed. Follow-up information was requested for selected events and used to assess the causal association with orlistat. Results: Green forms containing clinically useful information on 16 021 patients (median age 45 years (interquartile range 35-54); 80.1% females) were received. The events reported most frequently during the 1st month of treatment were 'not effective' (639; 4.0% of cohort), diarrhoea (371; 2.3%) and weight loss (230; 1.4%). Twelve clinical adverse events were identified for which ID 1 was significantly greater than ID 2-3 . These included non-specific events (e.g. intolerance, malaise/ lassitude, unspecified side effects), weight loss and vaginitis/vulvitis. The remaining events were gastrointestinal in nature and included diarrhoea, pain abdomen, flatulence, nausea/vomiting, rectal discharge, faecal incontinence and 'gastrointestinal unspecified' events. A similar pattern of predominately gastrointestinal events was seen for reasons for stopping and suspected adverse drug reactions. Review of selected events for causality revealed 45 events which were assessed as possibly or probably related to orlistat. Conclusions: This study shows that orlistat is fairly well tolerated. The safety profile of orlistat was similar to the prescribing information and experience reported in the literature.

Orlistat: current status in clinical therapeutics

“…No cases of serious hepatic events were reported; however, two patients had causally related increases in liver function tests (LFTs), and one had LFT elevations deemed as possibly related to orlistat use [103]. Additional case reports considered possibly related are included in Table 5 [102,103]. Five examples of potential drug interactions were reported with metformin, terbinafine, methotrexate, fluoxetine and an unspecified contraceptive [102,103].…”

“…Within the first 3 months of treatment, 30.3% of patients given orlistat and 41.8% given sibutramine had stopped therapy. The most common reason for stopping orlistat within the first 3 months was lack of efficacy (10.6%) in the Acharya et al cohort [102] as opposed to diarrhea (2.1%) in the Perrio et al cohort [103]. The reasons provided for stopping therapy due to adverse events in the first 3 months were: diarrhea (2.1%); intolerance (0.5%); weight gain (0.5%); unspecified (0.4%); abdominal pain (0.3%); flatulence (0.3%); unspecified GI side effects (0.3%); fecal incontinence (0.2%); pregnancy (0.2%) and headache (0.2%).…”

“…Orlistat is a category B medication [41]. A total of 368 severe adverse events (in 315 patients) were reported in the questionnaires [102]. No cases of serious hepatic events were reported; however, two patients had causally related increases in liver function tests (LFTs), and one had LFT elevations deemed as possibly related to orlistat use [103].…”

“…General practitioners (GPs) who prescribed orlistat and/or sibutramine were mailed questionnaires [102,103]. The prescriptions for orlistat were written from December 1998 to November 1999.…”

“…Forty patients were exposed to orlistat during the first trimester and had a live birth; three of these babies were born with congenital abnormalities (congenital dislocation of the hips, translocation of the great vessels and malrotation requiring surgery). An additional infant had shoulder dystocia [102,103]. Orlistat is a category B medication [41].…”