Arne Reimers1, Grethe Helde2, Noémi Becser Andersen3, Dag Aurlien4, Elisabeth Surlien Navjord5, Kathrine Haggag6, Jakob Christensen7, Kari Mette Lillestølen8, Karl Otto Nakken8, Eylert Brodtkorb9. 1. Dept. of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway; Dept. of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: arne.reimers@stolav.no. 2. Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 3. Dept. of Neurology, The Neuroscience Center, Copenhagen University Hospital, Copenhagen, Denmark. 4. Dept. of Neurology, Stavanger University Hospital, Stavanger, Norway. 5. Dept. of Neurology, Drammen Hospital, Drammen, Norway. 6. Dept. of Neurohabilitation, Oslo University Hospital, Ullevål, Norway. 7. Dept. of Neurology, Aarhus University Hospital, Aarhus, Denmark. 8. The National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway. 9. Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Dept. of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, Trondheim, Norway.
Abstract
PURPOSE: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. METHODS: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected. RESULTS: 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24-81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges. CONCLUSIONS: ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.
PURPOSE: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. METHODS: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected. RESULTS: 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24-81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges. CONCLUSIONS:ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.
Authors: Page B Pennell; Jacqueline A French; Ryan C May; Elizabeth Gerard; Laura Kalayjian; Patricia Penovich; Evan Gedzelman; Jennifer Cavitt; Sean Hwang; Alison M Pack; Maria Sam; John W Miller; Steffanie H Wilson; Carrie Brown; Angela K Birnbaum; Kimford J Meador Journal: N Engl J Med Date: 2020-12-24 Impact factor: 91.245