Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials.
OBJECTIVE
To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959).


METHODS
Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations.


RESULTS
Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥ 5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received <1,600 mg/day (n = 174) and ≥ 1,600 mg/day (n = 29) carbamazepine. Cyclodextrin exposure was not associated with clinically relevant changes in AEs or renal biomarkers. Seizure control was maintained as patients transitioned between oral and IV carbamazepine.


CONCLUSIONS
IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations.
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Deborah
D
Lee
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Uwa
U
Kalu
Comprehensive Epilepsy Center, Medical University of South Carolina, Charleston, South Carolina, U.S.A.
Jonathan J
JJ
Halford
Arkansas Epilepsy Program, Little Rock, Arkansas, U.S.A.
Victor
V
Biton
Center for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, U.S.A.
James
J
Cloyd
Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Maryland, U.S.A.
Pavel
P
Klein
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Ihor
I
Bekersky
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Guangbin
G
Peng
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Suresh
S
Dheerendra
Lundbeck LLC, Deerfield, Illinois, U.S.A.
Dwain
D
Tolbert
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage*; D002220:Carbamazepine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D002220:Carbamazepine
Cyclodextrin; Epilepsy; Intravenous carbamazepine; Tolerability