Advice for healthcare professionals:
- maternal administration of magnesium sulfate for longer than 5–7 days in pregnancy may be associated with adverse effects in the foetus, including hypocalcaemia, skeletal demineralisation, osteopenia, and other skeletal adverse effects
- if prolonged or repeated use of magnesium sulfate occurs during pregnancy (for example, multiple courses or use for more than 24 hours), consider monitoring of neonates for abnormal calcium and magnesium levels and skeletal adverse effects
- report suspected adverse drug reactions to magnesium sulfate following exposure during pregnancy on a Yellow Card
Magnesium sulfate is authorised for the prevention of further seizures associated with eclampsia in pregnancy and for the treatment of magnesium deficiency in hypomagnesemia.
The NICE guideline Preterm labour and birth (NG25) advises offering intravenous magnesium sulfate for foetal neuroprotection in women in preterm labour or having a planned preterm birth within 24 hours, who are between 24 weeks and 29 weeks and 6 days of pregnancy. The guideline also advises considering use in women in preterm labour or having a preterm birth between 30 weeks and 33 weeks and 6 days of pregnancy.
The dose recommended by NICE, if given for a full 24 hours, equates to 28 grams of magnesium sulfate, equivalent to usual minimum dose in eclampsia – see Summary of Product Characteristics for full details. However, the new advice should be considered in case uncertainty around exact timing of delivery results in repeat administration.
Previous safety concerns about prolonged use of magnesium sulfate in pregnancy
In 2013 the US FDA issued a safety communication recommending against use of magnesium sulfate for more than 5–7 days when used as a tocolytic (not an authorised indication in the UK). Such prolonged exposure may result in significantly higher cumulative doses than those encountered with use of magnesium sulfate in the UK for eclampsia or foetal neuroprotection (see FDA data summary for description of doses and period of use associated with reports).
The US FDA alert was based on 4 reports of fractures and 35 reports of osteopenia or radiographical bone abnormalities in neonates, some of which also describe hypocalcaemia and hypermagnesemia in the neonate. The long-term clinical significance of the biochemical and skeletal effects is unknown, with the available evidence suggesting a transient effect.
Although overall, most clinically relevant cases were seen following high doses of magnesium sulfate over prolonged periods, we are aware of reports in the literature of electrolyte imbalances in the neonate following lower doses or after treatment periods of less than 5 days (for example, clinically significant hypocalcaemia in a neonate following cumulative administration of an estimated 100 grams of magnesium sulfate).
National review of risk in prolonged use
The MHRA is not aware of any reports in the UK of skeletal adverse effects or relevant biochemical effects in the neonate following use of magnesium sulfate for foetal neuroprotection. However, following efforts to achieve increased uptake in preterm labour and birth (including through the PReCePT project), data suggests usage is increasing in the UK. Healthcare professionals should therefore be vigilant for any adverse effects in the neonatal period if in-utero exposure to magnesium sulfate is prolonged.
The Commission on Human Medicines and its Expert Advisory Groups the Medicines for Women’s Health Expert Advisory Group and the Paediatric Medicines Expert Advisory Group considered data for the use of magnesium sulfate in the UK. Based on their recommendations, the product information for products containing magnesium sulfate will be updated to warn of skeletal adverse effects observed with administration for more than 5–7 days in pregnancy.
Healthcare professionals are advised to consider monitoring neonates for abnormal calcium and magnesium levels and skeletal adverse effects if maternal treatment with magnesium sulfate is prolonged or repeated beyond current recommendations.
Report suspected adverse drug reactions in pregnancy
Please continue to report any suspected adverse drug reactions via the Yellow Card Scheme. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.
For more about the importance of reporting suspected adverse drug reactions associated with medicines in pregnancy, see Drug Safety Update July 2018.
Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card App. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.
You can also use the app to access the latest safety information from the MHRA about medicines and medical devices on the Newsfeed. The App is also piloting additional questions on medicine use during pregnancy – download the app and try it out for yourself.
Article citation: Drug Safety Update volume 12, issue 10: May 2019: 3.