The Food and Drug Administration on Thursday issued its strongest warning against the use of a drug prescribed off-label to prevent preterm labor, saying it appears to be ineffective at delaying premature births and poses serious health risks for pregnant woman who take it for longer than 72 hours.
The warning comes less than two weeks after the FDA approved a new drug, called Makena, to reduce the risk of premature delivery. One in eight babies born in the U.S. each year -- 543,000 -- is born prematurely, says the March of Dimes.
Terbutaline, commercially marketed as Brethine and Bricanyl, is a drug approved for the treatment of asthma and chronic obstructive pulmonary disorder, sometimes called emphysema. It relaxes bronchial tubes and is used to ease asthma symptoms. But it is also thought to relax smooth muscles, including the uterus, thereby disrupting contractions in women who have gone into labor too soon. Although widely administered in hospitals as an injection or infusion to forestall labor, physicians also prescribe it in pill form to prevent premature labor in women who are carrying multiple fetuses or have a history of preterm labor.
Several studies have found the drug ineffective in preventing the onset of early labor. And the American College of Obstetricians and Gynecologists concluded in 2003 that while the use of "tocolytic drugs" such as terbutaline can forestall childbirth by two to seven days, babies fare no better when it is used. Neither emergency nor long-term preventive use of such drugs "should be undertaken as a general practice," ACOG concluded. And the FDA said that in spite of its past efforts to warn physicians of the dangers of terbutaline's use, "prolonged use of terbutaline continues, with serious and sometimes fatal consequences."
The agency on Thursday ordered manufacturers of the drug to label as "contraindicated" the use of terbutaline in pill form for the prevention of premature birth, or treatment with the drug's injectable form for longer than 48 to 72 hours for the same purpose. Any use of the drug outside of a hospital setting should be considered unsafe, the agency said, and it should not be considered as a means of preventing premature labor.
Combing through "adverse events" reports filed by physicians and patients, the agency linked 16 maternal deaths over 33 years to the prolonged use of terbutaline, and 12 cardiovascular events associated with terbutaline use for preterm labor between 1998 and mid-2009. Affected women suffered a range of heart woes, including heart attack, arrhythmia and racing heartbeat, elevated blood pressure and fluid-filled lungs.