2016 年 8 巻 1 号 p. 21-31
Purpose: Exposure to sodium valproate (VPA) during pregnancy may increase the risk of fetal malformations and cognitive developmental deficits. We therefore assessed a clinically practical method to change treatment from VPA monotherapy to lamotrigine (LTG) monotherapy in Japanese women of childbearing potential whose seizures were controlled by VPA.
Methods: In an open-label, single arm, multicenter study, we evaluated the reduction in VPA dose and change in seizure frequency from baseline when VPA monotherapy was switched to LTG monotherapy in female patients by the following protocol. (1) The LTG dose was increased up to 200 mg/day while the initial VPA dose was maintained. (2) The VPA dose was reduced to 0 mg/day while the LTG dose was maintained. (3) When VPA was removed, the LTG dose was simultaneously increased by up to 100 mg/day. (4) The LTG dose was further adjusted. Due to the risk of break-through seizures during adjustment of VPA and LTG doses, LTG trough serum concentration was measured for seizure control.
Results: Of 33 patients enrolled, 20 completed the entire protocol, with VPA removal in 19 patients. Thirteen patients were withdrawn from the study during LTG escalation, mainly due to LTG-related skin rash (n = 8) in the early stage of LTG initiation (10 days on average). Seizures were observed once in 2 patients during LTG monotherapy (7 and 13 weeks after VPA removal).
Discussions: By paying careful attention to the occurrence of skin rash or any sign of hypersensitivity at the beginning of LTG escalation, Japanese women receiving VPA monotherapy can be converted to LTG monotherapy.