The FDA today advised clinicians not to give pregnant women magnesium sulfate to prevent preterm labor for more than 5 to 7 days because it may harm developing fetal bones.
Longer off-label administration of magnesium for tocolysis, which is approved only for the prevention of seizures in preeclampsia, can lead to low calcium levels and osteopenia or fractures in the baby, the agency explained.
A warning to this effect is being added to the drug's labeling, and the teratogenicity category is being changed from Pregnancy category D rather than A.
The labeling will also be amended to stress that injectable magnesium sulfate is not indicated for prevention of preterm labor, that its efficacy and safety for this use have not been established, and that it should only be administered by trained healthcare professionals in well equipped hospitals
"Pregnant women should discuss with their healthcare professional the possibility of going into labor before term and the risks and benefits of any treatments that may be used," the FDA advisory stated.
The decision to issue this advisory was based on a review of 18 case reports in the agency's Adverse Event Reporting System.
In these cases, women were given the drugs for an average of 9.6 weeks, with an average total dose of 3,700 mg.
Abnormalities resulting in their offspring included fractures of the long bones and ribs, which may have been caused by fetal hypermagnesemia and the resulting hypocalcemia.
The agency also reviewed the epidemiologic evidence. In one study, significantly more bone anomalies were seen in newborns who had been exposed to magnesium for more than 1 week compared with only 3 days of exposure.
Another study found differences in levels of osteocalcin, magnesium, calcium, and phosphorus at birth in babies exposed for longer than a week.
In those two studies, the abnormalities seen in neonates after exposure of more than 5 to 7 days "included radiographic findings of radiolucent transverse metaphyseal bands of long bones such as the humerus," according to the FDA's data summary.
However, the long-term significance of these findings is not known because of inadequate follow-up, and "it is unknown whether a shorter duration of treatment is associated with calcium and bone abnormalities in the neonate."