Salbutamol, a selective beta2-adrenoreceptor agonist, is available in several dosage forms with varied uses. Parenteral preparations of salbutamol are registered for the management of uncomplicated premature labour in the last trimester of pregnancy though it is known that salbutamol tablets may sometimes be used for this purpose.

The advice by GSK follows a company-initiated review of the available data from published literature, clinical trials and spontaneous reports of myocardial ischaemia in association with salbutamol. The review found eight spontaneously reported cases in the company database and nine reports in published literature, suggestive of a causal association with myocardial ischaemia when salbutamol was given for the treatment of premature labour.

The reported events from literature included myocardial ischaemia, myocardial infarction, chest pain and ECG abnormalities indicative of myocardial ischaemia. All the events were reported with the use of intravenous salbutamol except one which was reported with the use of salbutamol tablets. Five cases required hospitalisation and one was considered life-threatening.

The time to onset ranged between 1.5 hours to 4 days with most of the cases occurring within the same day as treatment initiation. No significant pre-disposing factors could be identified for the development of ischaemic events besides preterm labour. In four of the cases, it was specifically stated that the patients had no known risk factors. One patient had a paternal history of cardiovascular disease while another had a possible pre-existing coronary vascular occlusion.

About half of the cases reported a positive dechallenge on salbutamol discontinuation. One case documented ST depression on the re-introduction of salbutamol one year after the first incident of myocardial ischaemia. However, most of the cases did not provide information on rechallenge. Where specified in the reports, actions taken after the occurrence of the adverse event include the discontinuation of salbutamol and treatment with nifedipine, heparin, aspirin, nitroglycerin and verapamil.

Although the effects of sympathomimetics may be exaggerated in preterm labour due to high background sympathetic drive, hyperventilation, dehydration and haemodilution through the use of intravenous fluids, the association between myocardial ischaemia with salbutamol use in preterm labour cannot be ruled out as the reported cases were well-documented and contained no significant pre-disposing factors for the development of ischaemic events other than preterm labour.

To date, HSA has not received any spontaneous local ADR report of myocardial ischaemia associated with the use of salbutamol in preterm labour. Nevertheless, healthcare professionals are advised to be cautious when using salbutamol for this purpose, and to report any serious adverse reactions suspected to be due to its use in pregnancy to the Pharmacovigilance Unit of HSA. The local package inserts of parenteral and oral Ventolin® products has been updated to include this new safety information.