Use has been restricted to 48 hours’ maximum parenteral use under specialist supervision, after a European safety review.
Article date: November 2013
Salbutamol and terbutaline are short-acting β2 agonists (SABAs) with the obstetric indication of inhibition of premature labour. They are available in various formulations in the UK, including oral tablets, oral solutions, and parenterals (solutions for injection). In some European countries, these SABAs are also indicated at minimum doses and short duration of use for external cephalic version or emergency use in specified conditions. However, these are not licensed indications in the UK.
Oral SABA preparations
The oral SABA preparations were found to be ineffective in the provision of acute tocolysis in premature labour, and are not consistently effective at maintaining uterine quiescence. Clinical trials showed that maintenance of tocolysis with SABAs did not have a significant effect on perinatal morbidity and mortality.
Use of oral SABAs has been associated with a risk of serious and potentially fatal cardiovascular eventssuch as myocardial infarction and pulmonary oedema in the mother and cardiomegaly in the fetus, which increased with duration of use. Therefore, the risks associated with use of the oral formulations were considered to outweigh the benefits.
The product information for salbutamol and terbutaline will be amended to remove the obstetric indications from the oral products; there will also be no reference to use of oral products in the product information for parenteral formulations.
Parenteral SABA formulations
The parenteral SABA formulations were considered to be efficacious in short-term use up to 48 hours. A short delay to the onset of premature labour enables transfer of the patient to facilities that enable administration of corticosteroids and that can support neonatal care. Therefore, the obstetric indication of tocolysis is only to be used for a maximum duration of 48 hours under specialist supervision. Furthermore, the risk of serious adverse events increases with dose. Consequentially, it is recommended that the minimum effective dose should be titrated for the individual.
Additional advice will be added to the product information for parenteral SABA formulations to promote pretreatment screening for pre-existing heart disease, and to advise continuous monitoring of mother and fetus during treatment.
Particular attention is directed towards heart rate, electrocardiography (ECG), and blood pressure to help minimise the risk of serious cardiovascular events, with additional monitoring of potassium levels to manage the risk of hyperkalaemia-induced cardiac arrhythmia. Electrolyte and fluid balance should also be monitored during infusion of a SABA to help minimise the risk of pulmonary oedema. Glucose levels should also be monitored, particularly in women with diabetes, because SABAs are associated with an increase in blood glucose.
Advice for healthcare professionals:
- Oral SABAs should not be used in any obstetric indication: the benefits do not outweigh the risks in these indications
- The use of parenteral SABAs should be limited to 48 hours maximum and administered under specialist supervision in the authorised indication of inhibition of premature labour
- Tocolysis should not be initiated when:
- Gestational age is less than 22 weeks, or when there is any condition to mother or fetus for which prolongation of pregnancy would be hazardous
- (Pre-existing) risk factors for ischaemic heart disease or a pre-existing medical condition mean that use of a SABA would be harmful (eg, pulmonary hypertension, cardiac disorders such as hypertrophic obstructive cardiomyopathy or aortic stenosis)
- Recommendations for maternal, and where appropriate fetal, monitoring have been introduced as follows:
- blood pressure and heart rate
- electrolyte and fluid balance
- glucose and lactate levels
- potassium levels
- In patients with pre-existing heart disease there are further warnings, including the need for assessment by a physician experienced in cardiology
Letter for healthcare professionals sent October, 2013
European Medicines Agency announcement
Article citation: Drug Safety Update volume 7 Issue 4, November 2013: A3.