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OBJECTIVES To examine the safety of tadalafil as used in general practice in England, and to compare the mortality rate due to ischaemic heart disease (IHD) in tadalafil users with that in the male population in England. PATIENTS AND METHODS Patients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by general practitioners (GPs) from February 2003 to November 2004. Demographic and outcome data (clinical events) were requested from patients’ GPs using a postal questionnaire. A standardized mortality ratio (SMR) was calculated using indirect standardization for deaths from IHD in the cohort (where age was known) over a 1-year observation period compared to that in the English male population (2003). A sensitivity analysis was carried out to investigate the effects of missing data for age and cause of death. RESULTS Clinical information was obtained for 16 129 patients (median age 60 years, interquartile range 52–67); the age was not specified for 3212 (19.9%) patients. At least a third of the patients had diabetes mellitus and 29% had hypertension. Comparison of the mortality rate due to IHD for the patients of known age with that in the English male population provided an SMR of 0.57 (95% confidence interval 0.38–0.83) indicating fewer observed deaths in the cohort than expected. The results of the sensitivity analyses investigating the effect of missing data for age and cause of death produced similar SMR estimates. One confirmed case of non-arteritic anterior ischaemic optic neuropathy (NAION) was reported during tadalafil therapy in a patient with other risk factors for this condition. CONCLUSION The results from this prescription-event monitoring study suggest that tadalafil is generally well tolerated when used in general practice in England. The most frequently reported adverse clinical events were in keeping with clinical trial data and include headache, dyspepsia and back pain. There was no evidence of a greater mortality rate due to IHD in the tadalafil cohort than in the general male population. However, these results are limited by the use of an external comparator group and might be explained by a ‘healthy cohort effect’. One event of NAION was reported, and although a causal relationship was not established it indicates that NAION occurs rarely in patients prescribed tadalafil. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study which examined the safety profiles of the anti-obesity agents orlistat and sibutramine using prescription-event monitoring. Licensed in Great Britain in December 1998 and May 2001 for the treatment of obesity, orlistat is a gastrointestinal lipase inhibitor while sibutramine is a serotonin-noradrenaline reuptake inhibitor. Several side effects of orlistat include diarrhea, flatus and oily or fatty stools.

Introduction A modified prescription-event monitoring (PEM) study was conducted to examine the safety of the introduction of the metered dose inhaler (MDI) Flixotide EvohalerTM (fluticasone with the propellant HFA 134a). Methods Patients were identified from the first NHS prescriptions dispensed in England for Flixotide EvohalerTM. 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 EvohalerTM. Results The cohort comprised 13 413 patients that were prescribed Flixotide EvohalerTM. 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 EvohalerTM; these were minor with the exception of one case of angioneurotic facial oedema. Six of these events were assessed as possibly related to Flixotide EvohalerTM. During the study period there were an additional 13 patients with events assessed as possibly related to Flixotide EvohalerTM, including two reports of allergic reactions. Discussion The results suggest that the transition to Flixotide EvohalerTM was generally well tolerated. The modified methodology has contributed to the risk management of the introduction of this product. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE To examine the cardiovascular safety of tadalafil, a phosphodiesterase type-5 inhibitor used for treating erectile dysfunction in patients prescribed this drug by general practitioners (GPs) in England in 2003, focusing on mortality due to ischaemic heart disease (IHD). PATIENTS AND METHODS Patients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by GPs from February to November 2003. Demographic and outcome data were requested from patients’ GPs using a postal questionnaire. A standardized mortality ratio (SMR) was calculated using indirect standardization for all deaths from IHD or myocardial infarction (MI) in male patients who were prescribed tadalafil, regardless of whether they were taking tadalafil at the time, compared to those in the English male population (2002). RESULTS Clinical information was obtained for 6266 patients; patient sex could not be confirmed for 37 but in the remaining 6229 the median age was 61 years (interquartile range 53–68). The age was not specified for 2361 (37.7%) of the patients. Excluding patients not taking tadalafil at the time of the event, cardiovascular events included chest pain in 20, angina in 18, MI in 15 (including six fatal) and IHD in 11 (including five fatal). There were also six deaths where the cause was not ascertained; five of these patients were known to be male. Comparison of mortality due to IHD or MI for men with those in the English male population (2002) provided an SMR of 0.91 (95% confidence interval 0.50–1.48). CONCLUSIONS The results from this study suggest a similar incidence of death due to IHD or MI in men prescribed tadalafil to that in the male English population. However, due to possible under-reporting and the limitations of using an external comparator, these results should be interpreted in context with other studies on the cardiovascular effects and safety of tadalafil. [ABSTRACT FROM AUTHOR]

OBJECTIVES To examine the safety and use of apomorphine as prescribed in general medical practice in England as a treatment for erectile dysfunction (ED). PATIENTS AND METHODS Apomorphine hydrochloride (marketed as Uprima®, Abbott Laboratories Ltd, UK) is licensed in the UK as a sublingual therapy for ED. It is the first treatment for ED with a central mode of action. This postmarketing observational cohort study was conducted using prescription-event monitoring (PEM) methods. Exposure information was obtained from dispensed prescription data for patients first prescribed apomorphine between October 2001 and December 2002. Outcome data were derived from Green-Form questionnaires posted to prescribing physicians ≥6 months after the date of the first apomorphine prescription for each patient. The study cohort comprised 11 185 patients, 99.3% (11 111) of whom were men, with a median (interquartile range) age of 61 (54–68) years. RESULTS The most frequently reported prescribing indication was ED and the most frequently reported reason for stopping apomorphine was that it was ‘not effective’. In addition, the percentage of patients for whom apomorphine was reported to have been effective was relatively low. Headache was the most commonly reported adverse drug reaction, and the most frequently reported clinical condition occurring in the first month of observation. A small number of events (24) were reported that were not listed in the current Summary of Product Characteristics (SPC) and were considered by the prescribing general practitioner (GP) to be associated with apomorphine use. CONCLUSION The proportion of patients for whom apomorphine was reported to be effective was low. Also, ‘not effective’ was the most frequently reported event and a high percentage of patients stopped apomorphine because it was ‘not effective’. The most frequently reported clinical adverse events (headache and nausea) were those listed in the SPC. A small number of reports for unlabelled events were thought by prescribers to be related to apomorphine use. The confounding factors of patient age and coexisting disease should be considered when assessing data from this study. [ABSTRACT FROM AUTHOR]

To evaluate cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) reported in a prescription event monitoring study of Yasmin®, an oral contraceptive. Reports of DVT/PE and events suggestive of DVT/PE were followed up by questionnaire. Thirteen cases (DVT five; PE eight), each with possible risk factor(s), were identified in 15 645 females using Yasmin®. Applying complete case analysis, the crude incidence rate was 13.7 cases per 10 000 woman-years (95% confidence interval 7.3, 23.4). Yasmin is associated with venous thromboembolism. An incidence rate has been calculated, but this may be subject to bias and should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Aims A postmarketing Prescription-Event Monitoring study was undertaken to monitor the safety of rofecoxib, a cyclo-oxygenase (COX)-2 selective inhibitor prescribed in primary care in England. Methods Questionnaires requesting clinical event data were sent to prescribing physicians between February and November 2000, and the data analysed for all events. Results There were 15 268 patients identified, mean age 62 years, 67% female. The commonest specified indication was osteoarthritis (24%). Dyspepsia and nausea were the most frequently reported adverse events. A history of dyspeptic or upper gastrointestinal (GI) conditions, recent use of other nonsteroidal anti-inflammatory drugs (NSAIDs), use of selected concomitant gastroirritant drugs (NSAIDs, aspirin, anticoagulants, antiplatelet drugs), or gastroprotective drugs (misoprostol, antacids, proton-pump inhibitors, histamine-2 antagonists), and age (≥ 65 years) modified the risk of having minor GI events. During treatment or within 1 month of stopping, 110 serious GI events were reported (including 76 upper GI bleeds/peptic ulcers, one perforated colon), 101 thromboembolic events, three reports of acute renal failure, one each of Stevens–Johnson syndrome, severe anaphylaxis and angio-oedema. Conclusions Doctors should continue to prescribe NSAIDs including COX-2 selective inhibitors with caution. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Our aim was to monitor the use of gabapentin (GBP) by patients prescribed this drug by primary care physicians in England soon after it was marketed in the United Kingdom. Methods: A noninterventional observational cohort study was conducted by using the technique of prescription-event monitoring. Patients were identified from dispensed National Health Service prescriptions. Outcome data were obtained from questionnaires sent to the doctor ∼6 months after the initial prescription. These data included demographic information, events reported since starting GBP, and reason for stopping the drug, if it was stopped. Incidence rates were calculated for given periods for all events reported. Additional information was requested for selected events of medical interest, including pregnancies. Standardised mortality ratio (SMR) was calculated. Results: The cohort comprised 3,100 patients, of whom 136 (4%) were children. The median duration of treatment was 8.1 months. The most frequently reported adverse events reported during the first month of treatment, drowsiness/sedation, dizziness, and malaise/lassitude, also were the commonest reasons for discontinuing GBP and reported as suspected adverse drug reactions (ADRs). There were no congenital anomalies in the 11 babies born to women who used GBP during the first trimester of pregnancy. Crude mortality rate was 5 times that in general population but similar to that in other published studies. Conclusions: Neurologic-related events were the most frequently reported adverse events. They also were the commonest reasons for discontinuing treatment and reported as suspected ADRs. No previously unrecognised adverse events were detected in this large cohort of patients who were among the first treated with gabapentin in England. [ABSTRACT FROM AUTHOR]

To evaluate cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) reported in a prescription event monitoring study of Yasmin®, an oral contraceptive. Reports of DVT/PE and events suggestive of DVT/PE were followed up by questionnaire. Thirteen cases (DVT five; PE eight), each with possible risk factor(s), were identified in 15 645 females using Yasmin®. Applying complete case analysis, the crude incidence rate was 13.7 cases per 10 000 woman-years (95% confidence interval 7.3, 23.4). Yasmin is associated with venous thromboembolism. An incidence rate has been calculated, but this may be subject to bias and should be interpreted with caution. [ABSTRACT FROM AUTHOR]