PMID- 25933358
OWN - NLM
STAT- MEDLINE
DCOM- 20160617
LR  - 20181202
IS  - 1600-0404 (Electronic)
IS  - 0001-6314 (Linking)
VI  - 132
IP  - 5
DP  - 2015 Nov
TI  - Lacosamide cardiac safety: clinical trials in patients with partial-onset 
      seizures.
PG  - 355-63
LID - 10.1111/ane.12414 [doi]
AB  - OBJECTIVE: To evaluate the cardiac safety of adjunctive lacosamide in a large 
      pool of adults with partial-onset seizures (POS). METHODS: Post-randomization 
      changes from baseline for electrocardiographic (ECG) measurements, diagnostic 
      findings, and relevant adverse events (AEs) were compared for pooled data from 
      three randomized, placebo-controlled trials of adjunctive lacosamide for the 
      treatment of POS. RESULTS: Lacosamide did not prolong the QTc interval or affect 
      heart rate as determined by an analysis of data from patients randomized to 
      lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). 
      After 12-week maintenance treatment, mean changes from baseline for QRS duration 
      were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, 
      -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A 
      small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, 
      and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, 
      respectively). First-degree atrioventricular (AV) block was reported as a 
      non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective 
      groups. Second- or higher degree AV block was not observed. There was no evidence 
      of a PR-interval-related pharmacodynamic interaction of lacosamide with either 
      carbamazepine or lamotrigine. CONCLUSIONS: Evaluation of the pooled cardiac 
      safety data from patients with POS showed that adjunctive lacosamide at the 
      maximum recommended dose (400 mg/day) was not clearly associated with any cardiac 
      effect other than a small, dose-related increase in PR interval that had no 
      evident symptomatic consequence.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Rudd, G D
AU  - Rudd GD
FAU - Haverkamp, W
AU  - Haverkamp W
AD  - Department of Cardiology, Campus Virchow Clinic, Charite'-University Medicine 
      Berlin, Berlin, Germany.
FAU - Mason, J W
AU  - Mason JW
AD  - Cardiology Division, Department of Medicine, University of Utah, Salt Lake City, 
      UT, USA.
FAU - Wenger, T
AU  - Wenger T
AD  - Wenger Consulting, Durham, NC, USA.
FAU - Jay, G
AU  - Jay G
AD  - RAPID Pharmaceuticals, Rockville, MD, USA.
FAU - Hebert, D
AU  - Hebert D
AD  - UCB Pharma, Raleigh, NC, USA.
FAU - Doty, P
AU  - Doty P
AD  - UCB Pharma, Raleigh, NC, USA.
FAU - Horstmann, R
AU  - Horstmann R
AD  - Consulting Early Development, Bonn, Germany.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150430
PL  - Denmark
TA  - Acta Neurol Scand
JT  - Acta neurologica Scandinavica
JID - 0370336
RN  - 0 (Acetamides)
RN  - 0 (Anticonvulsants)
RN  - 563KS2PQY5 (Lacosamide)
SB  - IM
MH  - Acetamides/administration & dosage/*adverse effects/therapeutic use
MH  - Administration, Oral
MH  - Adult
MH  - Anticonvulsants/administration & dosage/*adverse effects/therapeutic use
MH  - Epilepsies, Partial/drug therapy
MH  - Female
MH  - *Heart Rate
MH  - Humans
MH  - Lacosamide
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - PR interval
OT  - cardiac safety
OT  - electrocardiographic intervals
OT  - lacosamide
OT  - partial seizures
EDAT- 2015/05/02 06:00
MHDA- 2016/06/18 06:00
CRDT- 2015/05/02 06:00
PHST- 2015/04/06 00:00 [accepted]
PHST- 2015/05/02 06:00 [entrez]
PHST- 2015/05/02 06:00 [pubmed]
PHST- 2016/06/18 06:00 [medline]
AID - 10.1111/ane.12414 [doi]
PST - ppublish
SO  - Acta Neurol Scand. 2015 Nov;132(5):355-63. doi: 10.1111/ane.12414. Epub 2015 Apr 
      30.