Incidence of Acute Renal Failure in Patients Using Levetiracetam Versus Other Antiseizure Medications: A Voluntary Post-Authorization Safety Study.

INTRODUCTION: Acute kidney injury is an expected adverse drug reaction listed in the European Union (EU) Summary of Product Characteristics (SmPC) for levetiracetam, one of the most widely used modern antiseizure medications (ASMs). OBJECTIVE: We conducted a voluntary post-authorization safety study to characterize the rate of acute renal failure (ARF) in patients exposed to levetiracetam versus other ASMs. METHODS: New users of ASMs without prior renal dysfunction were identified and followed for 30 days in the IBM® MarketScan® database (USA, January 2008-December 2017). ARF was defined as a diagnosis on inpatient or emergency department claims. We estimated adjusted incidence rates, incidence rate ratios (IRRs), and incidence rate differences (IRDs) of ARF in patients initiating levetiracetam versus other ASMs. RESULTS: Overall, 110,336 patients were eligible for the monotherapy cohort and 96,215 were eligible for the polytherapy cohort. The overall crude rate of ARF following a new ASM was 6.0 and 6.5 per 10,000 patients for the 'monotherapy' and 'polytherapy' cohorts, respectively, in the first 30 days after the index date. In the monotherapy cohort, the IRR for ARF was 1.37 (95% confidence interval [CI] 0.80-2.34) and the corresponding IRD was 2.0 (95% CI - 1.12 to 5.12) additional ARFs per 10,000 patient-months. In the polytherapy cohort, the adjusted IRR for ARF was 0.94 (95% CI 0.51-1.74) and the corresponding IRD was - 0.42 cases per 10,000 patient-months (95% CI - 4.01 to 3.17). CONCLUSIONS: The rate of ARFs in ASM new users was very low. In patients without prior ASMs, the estimated difference in risk of ARF associated with initiation of levetiracetam versus initiation of other ASMs was small, with 95% CIs compatible with small protective or harmful effects. In patients receiving polytherapy, the difference was compatible with the null and the 95% CI with small protective or harmful effects.

Delivery outcome after the use of meclozine in early pregnancy.

In some countries, including Sweden, no risk is considered to exist with the use of meclozine for nausea and vomiting in pregnancy (NVP), but in other countries warnings against use during pregnancy are given. Rat tests indicate a teratogenic risk and published epidemiological studies are of restricted size. Delivery outcome was studied in 16,536 women who reported the use of meclozine in early pregnancy and was compared with all 540,660 women who gave birth. Information on drug usage was obtained prospectively in early pregnancy. Risk factors for using meclozine were young maternal age, to have had a previous child, not to smoke, to have a low body mass index. The use of some other drugs (antihypertensives, thyroxine, anticonvulsants) decreased the use of meclozine. Maternal diagnoses of preeclampsia or diabetes were less frequent when the woman had used meclozine. The twinning rate was increased and the sex distribution of the infants low (female excess). Preterm birth, low birth weight, short body length, and small head circumference occurred at a reduced rate after meclozine use, notably for boys. Also the rate of congenital malformations was reduced. If anything, delivery outcome is better than expected when the mother used meclozine. These beneficial effects are probably secondary to NVP. Meclozine can apparently be used without risk at this condition.