PURPOSE: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. METHODS: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study. RESULTS: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. CONCLUSIONS: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.
RCT Entities:
PURPOSE: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. METHODS: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study. RESULTS: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. CONCLUSIONS: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.
Authors: Andreas Hufnagel; Andreas Kowalik; Klaus Rettig; Andreas Schreiner; Barbara Schäuble Journal: Clin Drug Investig Date: 2011-11-01 Impact factor: 2.859
Authors: Thangam Venkatesan; David J Levinthal; Sally E Tarbell; Safwan S Jaradeh; William L Hasler; Robert M Issenman; Kathleen A Adams; Irene Sarosiek; Christopher D Stave; Ravi N Sharaf; Shahnaz Sultan; B U K Li Journal: Neurogastroenterol Motil Date: 2019-06 Impact factor: 3.598