Lynda V. Wilton

Postmarketing surveillance of enalapril. I: Results of prescription-event monitoring.

To identify and measure the incidence of adverse effects of the angiotensin converting enzyme inhibitor enalapril 13,713 patients were studied for one year by prescription-event monitoring. Precise information about the duration of treatment was available for 12,543 patients. The frequency of many events was calculated, including dizziness (483 patients; 3.9%), persistent dry cough (360; 2.9%), headache (310; 2.5%) hypotension (218; 1.7%), and syncope (155; 1.2%). Less common reactions included angioedema, urticaria, and muscle cramps. Altogether 1098 (8%) patients died and the notes of 913 of them (83%) were obtained for detailed scrutiny. With the exception of a few patients with renal failure who deteriorated during treatment (reported on separately), no death was attributed to enalapril. Enalapril was considered to be effective, even in patients with advanced cardiac failure. These results for enalapril are reassuring and provide further evidence of the value of prescription-event monitoring.

Prevalence of Churg–Strauss syndrome, vasculitis, eosinophilia and associated conditions: retrospective analysis of 58 prescription-event monitoring cohort studies

Churg–Strauss syndrome is characterised by hypereosinophilia, systemic vasculitis and asthma. The cause is usually unknown, but there have been reports of an association with particular drugs, including anti‐asthma drugs. Our aim was to estimate the prevalence of Churg–Strauss syndrome and related conditions in post‐marketing safety studies of new anti‐asthma drugs.

The pharmacovigilance of olanzapine: results of a post-marketing surveillance study on 8858 patients in England

Olanzapine is an ‘atypical’ antipsychotic indicated for the treatment of schizophrenia. We analysed adverse events (AEs) reported in primary practice in England. Dispensed prescriptions issued between December 1996 and May 1998 provided exposure data. Questionnaires sent to general practitioners provided outcomes. Frequently reported AEs were: drowsiness/sedation (n = 19), extrapyramidal disorder (n = 13) and unspecified side-effects (n = 33). Events with highest incidence density in first month and reason for stopping were: drowsiness/sedation [n = 153, incidence density (ID)1 18.9], weight gain (n = 117, ID1 8.9) and malaise/lassitude (n = 65, ID1 5.2). Extrapyramidal disorders were more common in elderly population (> 70 years, ID1 3.6, risk 26.0 per 1000 patients) compared to < 70 years (ID1 1.1, risk 8.4 per 1000 patients). Serious suspected adverse reactions were neuroleptic malignant syndrome (n = 1) and angioneurotic ooedema (n = 2). There were eight reports of diabetes mellitus assessed as possibly due to olanzapine. Diabetes mellitus was an unlabelled AE and possible signal generated by prescription-event monitoring.

Postmarketing surveillance of enalapril. II: Investigation of the potential role of enalapril in deaths with renal failure.

The possibility that enalapril might damage renal function was investigated in 1098 deaths recorded in a prescription-event monitoring study. Case notes for 913 patients were examined. In seventy five there was a rise in the urea or creatinine concentration of 50% or more above pretreatment values. Enalapril appeared to have contributed to a decline in renal function and subsequent death in 10 of these patients. Several characteristics were identified among these patients, including old age, the use of high dose or potassium sparing diuretics, and pre-existing renal disease. Adding a non-steroidal anti-inflammatory drug was also associated with a deterioration in patients with previously stable renal function. No death was encountered of a patient with uncomplicated hypertension. Enalapril infrequently contributed to a substantial decline in renal function in certain vulnerable patients, especially those receiving other drugs known to be capable of adversely affecting renal function. Awareness of the characteristics of these patients and of their concomitant treatment may serve to reduce the risk.

Unlicensed and off label drug use for paediatric patients: General practitioners prescribe SSRIs to children off label

Editor—Turner et al highlight the fact that children admitted to hospital are often prescribed unlicensed drugs and drugs given outside the terms of their product licence (off label).1 The appropriateness of such prescribing is uncertain, and a high rate of adverse drug reactions has been observed in children prescribed such drugs.2 The problem is not limited to hospitals. General practitioners may be asked to prescribe unlicensed or off label drugs by specialists or may consider initiating such treatment themselves. Little information exists on the extent of such prescribing in primary care. We examined the prescribing of selective serotonin reuptake inhibitors to children in general practice by accessing a computerised database of 100 British general practices (349 doctors) using the AAH Meditel System 5 computer system to enter medical records (Doctors Independent Network).3 We determined the number of children aged 12 and under who had at least one prescription for a selective serotonin reuptake inhibitor between January 1992 and December 1996. For each child we ascertained age at first prescription; sex; name, dose, and formulation of the drug; number of prescriptions issued during the study; and reason for prescription. To be certain that we had identified children, we included only subjects who had an immunisation record in their notes, with dates consistent with their recorded age. Overall we identified 25 children who met the entry criteria for the study, except that we had to exclude six because of doubt over their age. The table shows the reasons for the prescription of the drugs. The commonest antidepressant prescribed was fluoxetine capsules. The British National Formulary states that prescribing these drugs for children is not recommended. These data from a small number of practices (under 1% of all British practices) suggest that nationally there are probably hundreds of children who have been prescribed off label antidepressants in general practice. Research suggests that some children are prescribed these drugs in general practice soon after their launch, when clinical experience is limited.4 We agree with Turner et al that all drugs used to treat children should be evaluated for their paediatric efficacy, safety, and quality. Doctors should have enough information to be able to discuss with parents the likely benefits and risks of using these drugs.5 Research should also assess the appropriateness of such prescribing in general practice.