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Paper does not provide any reassurance EDITOR--Shakir et al investigated the possibility of myocardial infarction being an adverse drug reaction among users of sildenafil.[1] However, their paper suffers from the [...]

Sildenafil is used to treat erectile dysfunction, and prescription on the NHS is restricted. We are conducting a study of prescription event monitoring for sildenafil in England, the first phase [...]

Data on side effects of newly launched drugs are limited,[1] highlighting the need for effective postmarketing surveillance. An inverted black triangle (??) on product literature identifies new products. Suspected adverse [...]

The incidence was determined of visual field defects in patients in the Prescription-Event Monitoring (PEM) study, treated for ≥6 months with the antiepileptic drug vigabatrin. Questionnaires were sent to the general practitioners of the 7228 patients in the PEM study, treated with vigabatrin for ≥6 months, to ascertain whether any serious adverse events, including changes in vision, had occurred. Ophthalmologists were asked to give the results of the perimetry tests and their opinion of the cause of the visual field defect for those patients referred to them. 6793 (94%) of the 7228 questionnaires were returned. 5090 (75%) contained clinical data. 328 patients were deceased. Seventy seven cases identified from the 4762 surviving patients, are being followed up with ophthalmologists. To date, 2 weeks after posting, 12 cases of visual field defect have been confirmed by formal perimetry tests. Ten of these 12 were considered to be probably or possibly related to vigabatrin use, giving an incidence of 2.0 per 1000 patients compared with 0.4 per 1000 patients in the original PEM cohort. These interim results show a substantial increase in the incidence of visual field defects associated with long term use of vigabatrin and demonstrate that PEM can be used to assess long latency adverse events. Copyright © 1999 John Wiley & Sons, Ltd.

This study determined the licensed and ‘off label’ (outside the terms of the licence) use of newly marketed medicines in children (2–11 years) and adolescents (12–17 years), by general practitioners in England. In addition, the incidence rates during the first month of therapy (ID1) for three adverse events, in these groups were compared with those of adults (≥18 years). The use of these drugs was monitored in 63 individual prescription-event monitoring (PEM) studies, conducted to monitor the safety of these medicines. Patients and drug exposures were identified from dispensed prescriptions. Outcome data (events and demographic information) were obtained from questionnaires. Although only six of these 63 drugs were licensed for use in children, 44 of the 63 drugs were used to treat children. For the majority of the drugs there was no specific reference to adolescents in the data sheets therefore it has been assumed that the drugs were licensed for those aged ≥12 years unless specified otherwise; 55 have been taken as licensed for use in adolescents. Over 690,000 patients were included in the 63 PEM studies, 9081 (1.3%) of these were children and 15,256 (2.2%) were adolescents. 78% of the 9081 children and 93% of the 15,256 adolescents were treated with ‘licensed’ drugs. There was a significant difference in the incidence rate for rash and nausea/vomiting, two adverse events commonly reported during treatment with lamotrigine, between children and adolescents compared to adults. This survey has shown that although only a small proportion (10%) of newly marketed drugs were licensed for use in children the majority of children (78%) were treated with these licensed products but 22% of children received drugs ‘off label’ during the first few years that the drug was marketed and a small number of children and adolescents were given drugs contraindicated in these age ranges. Copyright © 1999 John Wiley & Sons, Ltd.

A PEM study of nicorandil (Ikorel^TM) was undertaken to assess the drug's overall safety in everyday clinical practice. The prescription data used covered the period December 1994 to October 1996. The event data, which were based on a minimum observation period of 6 months, came from questionnaires returned by the prescribing general practitioners. Incidence densities (IDs) were calculated for all events occurring during month 1, months 2–6, and the overall treatment period. Selected events were followed up. The study was based on a cohort of 13 260 patients and 86 760 patient-months of nicorandil treatment. Major indications for use were angina (8744) and ischaemic heart disease (846). Adverse reactions (258) were reported in 175 (1.3%) of patients—the most frequent being headache (58; 0.4%) and unspecified side effects (36; 0.3%). The most common reasons for stopping treatment (excluding those confounded by indication) were headache (477; 3.5%), dizziness (88; 0.65%) and ‘not effective’ (491; 3.6%). The number of patients still being prescribed nicorandil after 6 months was 74.3%. In those cases where an opinion on effectiveness was given, nicorandil was reported to be effective in 80% (8713) of patients. The event of headache/migraine had the highest ID in the first month of treatment (49.4 per 1000 patient-months) and was not confounded by indication. Follow-up of selected events was reassuring overall; rare side effects included angioneurotic oedema and photosensitivity (3 cases each). This PEM study provides information on the ‘real-world’ use of nicorandil and shows generally that the drug is safe when used in the recommended dosage. Copyright © 1999 John Wiley & Sons, Ltd.

Objective —To compare the safety and side-effect profiles of the four selective serotonin reuptake inhibitor antidepressants (SSRIs), fluvoxamine, fluoxetine, sertraline and paroxetine. Methods —The results from four observational cohort studies of the four SSRIs were compared. Each of these studies was conducted by Prescription-Event Monitoring (PEM). The exposure data were derived from general practitioner (GP) prescriptions confidentially supplied by the Prescription Pricing Authority (PPA) in England. Outcome data were obtained from questionnaires (green forms) on which the prescribing doctor recorded event data. The main findings comprised demographic information, including patients' date of birth and sex; the indication for prescribing the monitored drug; the effectiveness of the drug as perceived by the GP; the reasons for stopping treatment and all events recorded during and after treatment. Results —The final cohort for each of the four SSRIs exceeded 10,000 patients. The sex, age distributions and indications for prescribing the four SSRIs were very similar. Only 36% of the GPs expressing an opinion reported fluvoxamine as effective, compared with approximately 60% for fluoxetine, sertraline and paroxetine. Fluvoxamine was associated with a higher incidence of adverse events than the other three SSRIs. Nausea/vomiting was both the most frequent clinical reason for stopping all four SSRIs and the most frequently reported clinical event. Adverse events reported in patients aged 70 years and over were comparable with the events reported for the total cohorts. Differences were identified between the four SSRIs for less frequently reported adverse events. Withdrawal symptoms were significantly more frequent with paroxetine than the other three SSRIs. Conclusions —The data from the four studies were comparable in terms of age distribution, sex of patients and indication for prescribing the drugs. Fluvoxamine had a considerably higher incidence of side-effects associated with its use than the other three SSRIs. The side-effect profiles of the four SSRIs were comparable for frequently reported events. Important differences were identified between the four SSRIs in respect of less frequently reported events. This study suggests that fluvoxamine compares unfavourably with fluoxetine, sertraline and paroxetine, both in terms of reported effectiveness and the incidence of adverse events. Biases possibly affecting the comparisons involved in this study are unlikely to account for the observed differences between fluvoxamine and the other three SSRIs. © 1997 John Wiley & Sons, Ltd.

In observational cohort studies which monitor drug safety, the patterns of reported events are likely to be influenced by a number of factors. We hypothesized that the distribution of events which are unlikely to be adverse events associated with drug use, differ from that for events which may be adverse drug reactions. In 39 individual Prescription‐Event Monitoring (PEM) studies, the incidence rates for upper respiratory tract infections (URTI) and back pain, in the first month of treatment and in the subsequent 5 months, were compared to those for nausea/vomiting and malaise/lassitude. For URTI and back pain there was no statistically significant difference in the event rates between these time periods. This pattern may be characteristic of events which are independent of the disease being treated and are unlikely to be adverse events associated with drug use. However, for nausea/vomiting and malaise/lassitude, which can be adverse events associated with drug treatments, the event rates in the first month of treatment were significantly greater than in subsequent months. These observations confirm that doctors are reporting events irrespective of whether or not they suspect the event to be an adverse event associated with the drug. This provides a simple validation of the PEM methodology. © 1998 John Wiley & Sons, Ltd.