Association of terbutaline with maternal deaths and serious cardiovascular adverse events in preterm labour

The Health Sciences Authority (HSA) would like to alert healthcare professionals to overseas reports of maternal deaths and serious cardiovascular adverse events associated with the obstetric use of oral and injectable forms of terbutaline.

Terbutaline, a selective beta-adrenoreceptor agonist, is licensed locally for the prevention and treatment of bronchospasm associated with bronchial asthma, bronchitis and emphysema. It is available as oral tablets or syrups under several generic brand names. The injectable form of terbutaline is not registered locally.

US Food and Drug Administration (FDA)

On 17 February 2011, FDA issued a Drug Safety Communication¹ to inform clinicians not to use injectable terbutaline for the prevention or prolonged treatment (beyond 48 to 72 hours) of preterm labor at both hospital and outpatient settings due to the potential for serious maternal cardiac problems and death. In addition, oral terbutaline should not be used for prevention or treatment of preterm labor as it shares the same safety risks as the injectable form and has not been proven to be effective for this purpose.

The FDA arrived at this regulatory decision following its review of post-marketing reports of maternal cardiac adverse events and deaths associated with the use of terbutaline for obstetric indications. It also took into consideration the medical literature documenting the lack of safety and effectiveness of terbutaline for preventing preterm labour.² Based on these information, FDA concluded that the risk of terbutaline causing serious adverse events outweighed the potential benefit of its use in the prevention and treatment of prolonged preterm labour.

Post-marketing reports of maternal deaths and serious cardiovascular adverse events

Since the initial marketing of terbutaline in 1976 through 2009, 16 maternal deaths associated with the obstetric use of terbutaline had been identified in the FDA's Adverse Event Reporting System (AERS). Three of these deaths were associated with outpatient use of terbutaline administered via a subcutaneous pump while nine reported use of oral terbutaline alone or in addition to subcutaneous or intravenous terbutaline. Of these nine cases, two reported use of oral terbutaline on an outpatient basis and seven involved inpatient use of oral terbutaline. For the remaining four deaths, the routes of terbutaline administration were either subcutaneous, intravenous or unknown.

Between January 1998 and July 2009, 12 maternal cases of serious cardiovascular events associated with the use of terbutaline were received through the AERS. Adverse events that were reported included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia. Three cases involved the use of terbutaline administered via subcutaneous pump while five cases reported oral terbutaline use alone or in addition to subcutaneous terbutaline. Of these five cases, three involved outpatient use of oral terbutaline while two involved inpatient use.

Local situation

To date, HSA has not received any reports of maternal deaths and serious cardiovascular adverse events associated with the obstetric use of terbutaline. The local package inserts of terbutaline-containing products will be updated to and strengthen the warnings and precautions of its use in pregnant women.

Healthcare professionals are advised not to use terbutaline for the treatment of prolonged tocolysis due to the unfavorable benefit/risk profile when used for this purpose.

Healthcare professionals are also encouraged to report all adverse reactions associated with the use of terbutaline to the Vigilance Branch of HSA.

References

1. FDA Drug safety Communication: New Warnings against use of terbutaline to treat preterm labor.
   http://www.fda.gov/Drugs/DrugSafety/ucm243539.htm
   [last accessed on 8 March 2011]

2. FDA News Release: FDA warns against certain uses of asthma drug terbutaline for preterm labor.
   http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm243840.htm
   [last accessed on 8 March 2011]