AimsLittle is known about the frequency with which suspected adverse drug reactions are seen by general practitioners after the prescription of newly marketed drugs. We investigated age and sex specific incidence rates of suspected adverse drug reactions recorded by general practitioners in England after the prescription of selected newly marketed drugs. Methods Information was collected from 48 national cohort studies of newly marketed drugs studied by prescription-event monitoring. Questionnaires were sent to prescribers asking for details of events and suspected adverse drug reactions recorded in the patients' notes occurring after the drugs were prescribed. Results During the 48 cohort studies, a total of 513 608 patients were investigated, of which 221 781 (43.2%) were males and 285 862 (55.7%) were females. The overall incidence of suspected adverse drug reactions in males was 12.9 per 10 000 patientmonths of exposure (95% confidence limits 12.3 to 13.5), and in females was 20.6 per 10 000 patient-months of exposure (95% confidence limits 19.9 to 21.3). The overall age-standardised relative risk of an adverse drug reaction in females compared with males was 1.6 (1.5-1.7). This sex difference was significant in all age groups above 19 years of age, and was relatively consistent across all age groups (x 2 test for heterogeneity= 9.2, P=0.3). The highest rate of recording in males was in the 50-59 year age group, and in females was in the 30-39 year age group. Conclusions In general practice in England, suspected adverse drug reactions to newly marketed drugs are recorded more often in adults aged between 30 and 59 years of age and are 60% more common in women than in men. The sex difference occurs in all age groups over 19 years of age.

Summary:Purpose: To examine the safety of lamotrigine (LTG) used in general practice to treat epilepsy.Methods: Information was collected on 11,316 patients who were included in a noninterventional observational cohort study conducted by means of Prescription-Event Monitoring (PEM). A follow-up study provided information on the first 3,994 patients who had taken LTG for 3 6 months. Incidence density (ID) measurements were used to rank the frequency of the reported events.Results: Rash was the most frequently reported nonepileptiform event (ID, 19.7/1,000 patient-months) in the first month of treatment and resulted in LTG being stopped in 2% of the 11,316 patients. Rash was reported more frequently among children aged 2-12 years (ID, 29.4/1,000 patient-months) than adults. Other events associated with the use of LTG included headache, drowsiness, nausea, vomiting, malaise, and lassitude.Rare serious events possibly associated with LTG included 12 cases reported as Stevens-Johnson syndrome, four cases of neutropenia, three cases of thrombocytopenia, and two cases of disseminated intravascular coagulation. There were also individual cases of leucopenia, a meningitic reaction, acute renal failure, hepatotoxicity, and a "lupus-like'' reaction possibly associated with the drug. No foetal abnormalities were specifically associated with the use of the drug in pregnancy. No death was attributed to LTG.Conclusions: Patients had severe epilepsy, inadequately controlled by other antiepileptic agents. The results of these two studies suggest that LTG is acceptably safe when used for the treatment of refractory epilepsy. Key Words: LamotrigineEpilepsy-Drug safety-Prescription-Event MonitoringRash.Lamotrigine (LTG) is a relatively new antiepileptic agent (AED) initially licensed as add-on therapy for seizures inadequately controlled by other drugs. LTG is therefore usually prescribed for patients with chronic, severe epilepsy, already being treated by other agents. The safety of LTG in these patients is of importance to both neurologists and general practitioners (GPs).A study was conducted by Prescription-Event Monitoring (PEM) to establish the safety of LTG. PEM identified events over an observation period of -6 months. As LTG is routinely intended for long-term use, a follow-up study was carried out to identify long-latency events in those patients who took the drug for >6 months.We report the results of the PEM study and the follow-up study.

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1 The safety in everyday clinical usage of three 4‐quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription‐Event Monitoring (PEM) during the early post‐marketing period. 2 In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow‐up of all pregnancies and the patients' life‐time medical record. 3 The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4 The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4‐quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with ofloxacin; 1.2 for dizziness with norfloxacin. Uncommon events (reported in less than 1:1000 patients) included rare cases of allergic phenomena, convulsions and pseudomembranous colitis. There were no reports of tendinitis, tenosynovitis or tendon rupture in children but tendon disorders were reported in the two months following the start of treatment in 20 adults. A total of 307 pregnancies were reported. Thirty‐eight of the 55 women who received these drugs during the first trimester of pregnancy gave birth to healthy babies. No congenital abnormalities were reported. Apart from one case of unconfirmed pseudomembranous colitis, none of the other 2468 deaths that occurred in these studies was attributed to the antibiotics. 5 These five antibiotics are acceptably safe antimicrobial agents when used in general medical practice. PEM is an effective method for monitoring the safety of recently introduced antimicrobial agents.

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Objective To determine the proportion and nature of congenital anomalies in babies born to Design Non-interventional observational cohort studies. MethodsThe women were identified in confidence by the Prescription Pricing Authority. The doctor was sent a questionnaire to determine clinical events, including pregnancy, occurring after the drug was dispensed. A supplementary questionnaire determined the outcome of each reported pregnancy.women exposed to newly marketed drugs during the first trimester.Setting General medical practice in England. Population Women exposed to newly marketed drugs in whom pregnancy was recorded.Main outcome measures Outcomes of pregnancies, the proportion and nature of congenital anomalies in the babies born.Results 251 1 pregnancies were reported. In 831 of these pregnancies a newly marketed drug had been taken during the first trimester and in 74 during the secondkhird trimester. The outcome was ascertained for 780 (94'1/0) of these 831 pregnancies: 547 (66'Yo) births; 10 (1%) ectopic pregnancies; 94 (1 1%) spontaneous miscarriages; 5 (< 1%) missed abortions; 120 (14%0) legal abortions; and 4 (C 1%) intrauterine deaths. 557 infants were born, of whom 14 (2.5%) had congenital anomalies. ConclusionsThe proportion of live infants with a congenital abnormality born to mothers exposed to newly marketed drugs in the first trimester was similar to the percentage of congenital anomalies estimated by the Ofice for National Statistics. These data add valuable information to the safety database of these drugs.

Proportional reporting ratios indicate differential reporting of possible reactions, not necessarily differential occurrence. There was no indication of an actual increase of risk of all causes or cardiac deaths during sertindole treatment, but only an increased risk of its being reported. The suspension of sertindole was rescinded by Committee on Proprietary Medicinal Products (CPMP) in October 2001.

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