The safety and tolerability of the β2‐agonist salbutamol in an event monitoring study of an oral controlled release formulation (‘Volmax’)

Abstract

AbstractObjective — The original study objective was to assess the safety and tolerability of a controlled release formulation of salbutamol (‘Volmax®’), with particular regard to side‐effects related to the delivery system. As the study progressed, an opportunity to review the tolerability of oral administration of salbutamol became apparent.Design — An observational cohort event monitoring study of patients requiring bronchodilator therapy who were prescribed controlled release salbutamol (Volmax) for the first time. A comparator group of patients prescribed any other orally administered bronchodilator for the first time was included. Patients were monitored for a minimum of six months to a maximum of 24 months.Setting — General Practice in the United Kingdom.Main outcome measures — All clinical events during the observation period were recorded. In the analysis particular attention was paid to those events which might be associated with ‘dumping’ of the active ingredient, an excess of gastrointestinal side‐effects, cardiovascular and respiratory morbidity or mortality.Results — A total of 8731 patients were studied; 7750 on Volmax and 981 on comparators. The comparator group comprised 622 patients receiving xanthines, 346 receiving oral beta2‐agonists other than Volmax, and 13 other patients taking a variety of medications such as ephedrine‐based products. There was no significant difference in mortality rates within 24 months of registration which were 5.5% (95% confidence limits 5.0–6.0%) in the Volmax group and 5.6% (4.16–7.03%) in the comparators. There was no evidence that salbutamol in the controlled delivery system studied produced significant gastrointestinal symptoms or any safety problems. The incidence of dyspepsia, heartburn, nausea and vomiting was higher in the xanthine group at 15.3% (12.48–18.12%) than in the Volmax group or in the beta2‐comparators which had incidences of 5.5% (5.0–6.0%) and 4.6% (2.39–6.80%) respectively.The incidences of tremor and cramp was higher in patients treated with Volmax than in those receiving other beta2‐agonists or xanthines; 12.78% (12.05–13.50%), 5.78% (3.33–8.23%) and 3.37 (1.95–4.78%), respectively. More patients in the Volmax group had experienced previous intolerance to salbutamol than in both the comparator sub‐groups. The incidence of diarrhoea in patients receiving Volmax was 3.07% (2.68–3.45%), in those receiving other beta2‐agonists 2.31% (0.72–3.89%) and in those treated with xanthines 1.13% (0.30–1.96%). Although the incidence of diarrhoea was slightly higher in patients receiving Volmax or other beta2‐agonists than in those receiving xanthines, it did not result in discontinuation of therapy.Conclusion — This study provides extensive safety data on the use of a controlled release formulation of salbutamol in general practice. The methodology used was sensitive enough to detect a previous unrecognized minor side‐effect of oral β2‐agonist treatment, and showed no clinically significant safety problems associated with the OROS delivery system or salbutamol itself.