Clinical Issues Surrounding the Use of Terbutaline Sulfate for Preterm Labor

Abstract

beta-mimetics have been prescribed by physicians to arrest or prevent premature labor for more than 20 years. Although not approved by the Food and Drug Administration (FDA) for tocolytic use, terbutaline sulfate has been the most widely prescribed beta-mimetic in the United States. Recently, the role of terbutaline in the treatment and prevention of preterm labor has been questioned by the FDA. Because the off-label use of drugs is a formally accepted practice in medicine when scientific studies support such use, we reviewed the currently available clinical literature on terbutaline use in various routes of delivery: intravenous, oral, and subcutaneous via infusion pump. This review describes the clinical evidence that supports the safe and effective use of terbutaline as a tocolytic agent in certain patient populations. Practicing physicians should continue to have unrestricted use of terbutaline for tocolysis as one of the few remaining therapeutic options remaining in the fight against preterm birth.

Disruption of Rat Forebrain Development by Glucocorticoids: Critical Perinatal Periods for Effects on Neural Cell Acquisition and on Cell Signaling Cascades Mediating Noradrenergic and Cholinergic Neurotransmitter/Neurotrophic Responses

“…Nevertheless, it is the enhancement of bAR expression by Dex that may be of particular relevance. Terbutaline, a bAR agonist, is frequently administered to arrest preterm labor (Lam et al, 1998), and this drug also penetrates to the fetus to stimulate bARs in the developing brain, impairing cell acquisition and producing lasting synaptic and structural anomalies (Meyer et al, 2005;Rhodes et al, 2004a, b;Slotkin et al, 2003). Dex and terbutaline are almost always given together in the therapy of preterm labor, and our findings suggest the strong likelihood of additive or synergistic effects on neurodevelopment, a possibility highlighted for future study (Gilstrap et al, 1994).…”

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

“…These regimens elicit robust ␤AR stimulation in the neonate while retaining selectivity toward ␤ 2 ARs (Slotkin et al, 2001). For tocolytic therapy in humans, doses typically lie in the range of 0.5 mg/kg/day but can also be as high as 1 to 2 mg/kg/day (Lam et al, 1998;Goldenberg, 2002). In light of the fact that terbutaline has a much shorter half-life in the rat (Tegner et al, 1984), we used a proportionally higher dose.…”

“…␤ 2 -Adrenoceptor (␤ 2 AR) agonists, especially terbutaline, are frequently administered as tocolytics (Lam et al, 1998), although this use is not endorsed by the manufacturer and is specifically "off-label". In addition to blocking uterine contractions, terbutaline penetrates the placenta to activate fetal ␤ARs, eliciting a number of adverse neonatal effects, including alterations in glucose metabolism and tachycardia (for review, see Slotkin et al, 2003).…”

Critical Prenatal and Postnatal Periods for Persistent Effects of Dexamethasone on Serotonergic and Dopaminergic Systems

“…Additionally, the use of multiple glucocorticoid courses is common (Crowther and Harding, 2003;Dammann and Matthews, 2001), despite the likelihood of subsequent metabolic, cardiovascular and behavioral anomalies (Barrington, 2001;Seckl, 2001;Shinwell et al, 2000;Trautman et al, 1995;Yeh et al, 2004). Recent reviews point out the long-term consequences of the use of antenatal steroids (Blackmon et al, 2002;Coe and Lubach, 2005;Newnham, 2001;Raff, 2004;Seckl, 2004) but isolating an explicit glucocorticoid effect in human populations is confounded by the comorbidities and interventions that are characteristic of preterm labor; as just one example, terbutaline, which is typically given to arrest uterine contractions (Lam et al, 1998) is itself a developmental neurotoxicant (Rhodes et al, 2004;Slotkin et al, 2003).…”