The Food and Drug Administration (FDA) is now requiring a black box warning on the terbutaline label stating that the use of injectable terbutaline should be limited to a maximum of 72 hours to treat preterm labor and that oral terbutaline shouldn't be used at all to treat preterm labor or prevent its recurrence. Terbutaline also shouldn't be used in the home or outpatient setting.
Terbutaline is a β-adrenergic agonist approved for use in treating respiratory disorders, such as asthma, because it causes bronchial dilation and relaxation of vascular smooth muscle. However, its use in the treatment of asthma is very limited these days because inhaled β2-adrenergic agonists, such as albuterol, are considered preferable for quick relief from asthma symptoms. In addition, Terbutaline has been used off label for years as a tocolytic (a drug that stops preterm labor), but its safety and efficacy when used for this purpose have been questioned for a number of years. In fact, in 1997 the FDA issued a letter to health care professionals about the safety concerns related to long-term subcutaneous administration of terbutaline, and the drug label was revised at that time to emphasize the risks of serious cardiovascular adverse effects. Professional organizations have also voiced concern over the use of tocolytics such as terbutaline. The recommendation in the clinical practice guideline on the management of preterm labor from the American College of Obstetricians and Gynecologists published in the May 2003 issue of Obstetrics and Gynecology was that tocolytics be used for only two to seven days, to allow glucocorticosteroids to create their effect in fetal lung development. Furthermore, the guideline specifically states that "[n]either maintenance treatment with tocolytic drugs nor repeated acute tocolysis improve[s] perinatal outcome; neither should be undertaken as a general practice." Despite these warnings, the offlabel use of terbutaline has continued.
The FDA's decision to include a warning on the product's labeling was made after reviewing postmarketing reports of maternal deaths and serious cardiovascular adverse effects (such as arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia). There have been 16 maternal deaths since terbutaline was originally marketed in 1976, the latest occurring in July 2009; nine were related to oral administration. Twelve cases of serious cardiovascular events have also been reported to the FDA; five were related to oral terbutaline use.
Nurses should be aware of these new warnings. Nurse mid-wives may wish to consider different drugs for tocolysis: calcium channel blockers, which appear to have the fewest adverse effects in pregnant women and fetuses; magnesium sulfate; or a nonsteroidal antiinflammatory drug that inhibits prostaglandin synthetase, such as indomethacin (Indocid, Indocin) or ketorolac (Toradol). Women with a history of preterm birth may be able to take the new drug hydroxyprogesterone caproate (Makena; see the next abstract).
Nurses who administer terbutaline to patients in hospitals should monitor them for cardiovascular adverse effects. Because of the drug's potential for stimulating β1-adrenergic receptors, cardiovascular adverse effects could occur even with short-term use (less than 72 hours). A baseline electrocardiogram may be helpful.