Clinicians should not administer magnesium sulfate to pregnant women for the off-label use of stopping preterm labor for more than 5 to 7 days, lest the treatment lead to low calcium levels and bone abnormalities in the fetus, the US Food and Drug Administration (FDA) announced today.
Magnesium sulfate is FDA-approved to prevent seizures in preeclampsia and to control seizures in eclampsia.
The FDA based its warning partly on 18 cases in the agency's Adverse Event Reporting System of skeletal abnormalities in infants born to women who received injections of magnesium sulfate to stop preterm labor. Fetal exposure to the drug lasted on average for almost 10 weeks. According to published studies of these cases, neonates developed osteopenia and fractured bones, conditions that were transient in nature.
Epidemiological studies also "support an association between maternal administration of magnesium sulfate for more than 5-7 days and neonatal hypocalcemia and skeletal abnormalities," the agency said in a news release. The long-term effects of exposure to the drug are not clear because many of the epidemiological studies lacked follow-up data. In 1 study, bone problems identified at birth did not show up on X-rays of the children at ages 1 and 3 years.
The FDA said it is unknown whether fetal bone problems can result from exposures to magnesium sulfate shorter than 5 to 7 days.
The agency is revising the label of magnesium sulfate injection USP 50% to reflect the risk of prolonged use to stop preterm labor. A new teratogenic effects section of the label notes that the potential benefits from using the drug in pregnant women may outweigh the risks in some situations. The label also advises clinicians that off-label administration of the drug for preterm labor should be performed by trained obstetrical personnel in a hospital with appropriate obstetrical facilities. Companies making other versions of magnesium sulfate injection have revised their labels in similar fashion.
Clinicians who decide that magnesium sulfate is warranted for pregnant patients experiencing preterm labor should inform them about the potential harm to the fetus, according to the FDA.
More information about today's announcement is available on the FDA Web site.
To report problems with magnesium sulfate injection, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at http://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.