Investigation of spontaneous abortion and stillbirth adverse events in epilepsy patients treated with levetiracetam: A pharmacovigilance study.

BACKGROUND

The prescription of levetiracetam during pregnancy has become more common due to its lower teratogenic risk profile. However, due to a lack of data about its association with stillbirth and spontaneous abortion, worries remain.

OBJECTIVE

To investigate information on any possible association of spontaneous abortion and stillbirth adverse events with levetiracetam in women with epilepsy.

METHODS

This retrospective pharmacovigilance study used disproportionality analysis to detect signals of adverse reaction of interest reported with Levetiracetam in FAERS, the FDA Adverse Event Reporting System. The ratio of reporting odds (ROR) and information component (IC) indices were used to undertake disproportionality analyses, and change point analyses were carried out to identify variations in the frequency of reporting of relevant adverse events. Sensitivity analyses included subgroup analyses by indication, treatment regimen, and reporting region.

RESULTS

Overall, 2870 cases of spontaneous abortion and stillbirth with commonly used antiseizure medications were analyzed. A total of 65.5 % of these cases had epilepsy as the indication. In the entire dataset, we observed disproportionality signals of spontaneous abortion for 6 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, topiramate, valproic acid) and disproportionality signals of stillbirth for 4 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine). In the epileptic population, disproportionality signals for stillbirth (ROR = 4.60; IC = 1.30) and spontaneous abortion (ROR = 3.98; IC = 1.20) in levetiracetam was identified. These disproportionality signals have been consistently robust over the past years, according to a temporal assessment of them. Sensitivity studies proved how reliable the findings were.

CONCLUSION

Using validated pharmacovigilance methods, we found significant disproportional signals for spontaneous abortion and stillbirth associated with levetiracetam. Of these, the signals for spontaneous abortion were observed after 2011 and for stillbirth after 2014, which may be related to the rise in levetiracetam prescriptions during pregnancy in recent years. The association of spontaneous abortion and stillbirth adverse events with levetiracetam and potential biases confounding this association merit further investigation.