Although serious adverse events associated with the use of tocolytic drugs are rare, it has been found that some combinations of these drugs to prevent preterm labor are better avoided. This was concluded by gynecologists from University Medical Center (UMC) Utrecht together with Dutch and Belgian associates. In the British Medical Journal of Saturday March 14, the investigators presented an analysis of nearly 2,000 pregnancies in which a threatening preterm birth has been delayed through tocolytic drugs.
Doctors from the Netherlands and Belgium analyzed 1,920 women in 28 hospitals who had undergone treatment with tocolytic drugs from 2006 – 2007. The aim of the study was to detect severe adverse events associated with the use of these drugs. Dangerous side effects occurred infrequently. Out of a total of 1,920 births, only 14 (0.7%) serious adverse events occurred.
However, using certain types of tocolytic drugs strongly increases the risk of complications, as does the administration of drug combinations given concomitantly. The risk of serious adverse events associated with drug combinations varies from 1.6 to 2.5 percent. When serious maternal adverse events occur, women have to remain admitted to hospital and there is even a chance that they may die. Examples of adverse events are: severe hypotension, lung edema, extreme shortness of breath or a severe allergic response. Gynecologists use tocolytic drugs if labor is threatening between the 25th and 34th week of pregnancy.
The first author, Roel de Heus, who is a registrar of obstetrics and gynecology at UMC Utrecht, says: “A combination of tocolytic drugs has not been proved to be more effective than a single drug that can be given more often if necessary. But our study has shown that the combination can increase the risk of complications, which is why we advise against such use.”
Most tocolytic drugs are actually used with other purposes in mind, for example, as painkillers or hypotensives. Because they also have a relaxing effect on the uterus, they are often used ‘off label’ to prevent uterine contractions. It is these off label drugs in particular that can cause complications in pregnant women.
One good alternative appears to be the drug atosiban that has been specially developed to prevent uterine contractions. De Heus has shown in this study that atosiban is the safest of all drugs for the mother. However, this drug is more expensive than the off label drugs. Moreover, no studies have been conducted on the effectivity of atosiban compared with the most commonly used alternative nifedipine. De Heus calls for such a study to take place.
The current study was led by Professor Gerard Visser from the Department of Perinatology and Gynaecology of UMC Utrecht. Doctors from 28 hospitals in the Netherlands and Belgium took part in the study.