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Update on tocolytic therapy
1College of Pharmacy, University of Georgia, Athens 30602, USA.
Objective:
To review medications currently being used or investigated for the treatment of preterm labor. Adverse effects, pharmacoeconomic issues, and therapeutic controversies are included.
Data Sources:
A MEDLINE search, limited to English-language articles and publication years of 1989-1994, was used to identify pertinent literature. Additional references were identified from articles retrieved in the search.
Study Selection:
Studies were chosen on drugs that are available or whose approval is anticipated in the US: ritodrine, terbutaline, hexoprenaline, and magnesium sulfate. Several studies comparing indomethacin and nifedipine with currently used medications are also included. Oxytocin antagonists, now in Phase II clinical trials, are discussed. Studies focusing on adverse reactions were included because of serious concerns that these reactions raise.
Data Extraction:
Part of the controversy surrounding tocolytic agents involves the difficulty in comparing data from different trials, particularly because the criteria for diagnosis of preterm labor vary significantly. Therefore, no attempt was made to directly compare data from different sources; individual study data are presented.
Data Synthesis:
Most studies reviewed using the beta-agonists showed each to be comparable in effectiveness when given parenterally during early preterm labor. These drugs usually delay delivery for 24-48 hours. There is less evidence that they are consistently effective in the long-term treatment of preterm labor. The adverse effects vary somewhat, but all beta-agonists have been reported to cause pulmonary edema, which is the most serious adverse effect associated with the use of these medications to inhibit labor. Indomethacin and nifedipine may be alternative choices for tocolytic therapy, but each has different adverse reactions that also make them less than ideal agents. Oxytocin antagonists may provide more specific therapy and are currently being investigated.
Conclusions:
The beta-agonists are effective in delaying delivery for 24-48 hours in most patients; however, there are potential risks involved. Magnesium sulfate, prostaglandin synthetase inhibitors, calcium-channel blockers, and oxytocin antagonists may provide alternative choices for the treatment of preterm labor associated with neonatal morbidity and mortality. Each of the medications has advantages and disadvantages at different stages of gestation.