PMID- 8814098
OWN - NLM
STAT- MEDLINE
DCOM- 19961021
LR  - 20190813
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 37
IP  - 9
DP  - 1996 Sep
TI  - Lamotrigine high-dose tolerability and safety in patients with epilepsy: a 
      double-blind, placebo-controlled, eleven-week study.
PG  - 857-62
AB  - PURPOSE: This study was undertaken to evaluate the dose tolerability and safety 
      of a chronic ascending twice-daily (b.i.d.) dosage regimen of < or = 700 mg/day 
      lamotrigine (LTG) and to include determination of the LTG pharmacokinetic profile 
      at doses > or = 500 mg/day in patients receiving concomitant enzyme-inducing 
      antiepileptic drugs (AEDs). METHODS: Twelve adult male epileptic patients treated 
      with enzyme-inducing AEDs received < or = 700 mg/day (b.i.d.) oral LTG (n = 8) or 
      placebo (controls, n = 4). For 3 weeks, as outpatients they had their LTG dosage 
      increased from 100 to 400 mg/day. Then, in a clinical research study unit, 
      patients received regimens of 500, 600, and 700 mg/day for 1 week each. Controls 
      received matching placebo in the same sequence. At study end, dosages were 
      tapered in 2 weeks. Follow-up evaluations were made 7 days later. RESULTS: Five 
      LTG patients tolerated 700 mg/day for 1 week. LTG was reduced to 600 mg/day in a 
      patient with mild diplopia and to 500 mg/day in a patient with mild oscillopsia 
      and diplopia. One patient discontinued 300 mg/day therapy with a moderately 
      intense diffuse papular skin rash, attributed to LTG. Headache, drowsiness, 
      faintness, and diplopia, the common adverse events (AEs), were mild to moderate 
      in intensity and occurred in 50-75% of patients in both groups (except for 
      diplopia, occurring only with LTG). Concomitant AED plasma concentrations were 
      not markedly changed by LTG. LTG pharmacokinetics were linear over the range of 
      500-700 mg/day. CONCLUSIONS: LTG doses < or = 700 mg/day can be tolerated in 
      patients receiving concomitant enzyme-inducing AEDs.
FAU - Matsuo, F
AU  - Matsuo F
AD  - Department of Neurology, University of Utah School of Medicine, Salt Lake City 
      84132, USA.
FAU - Gay, P
AU  - Gay P
FAU - Madsen, J
AU  - Madsen J
FAU - Tolman, K G
AU  - Tolman KG
FAU - Rollins, D E
AU  - Rollins DE
FAU - Risner, M E
AU  - Risner ME
FAU - Lai, A A
AU  - Lai AA
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Placebos)
RN  - 0 (Triazines)
RN  - U3H27498KS (Lamotrigine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/*administration & dosage/adverse effects/pharmacokinetics
MH  - Diplopia/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Epilepsy/*drug therapy
MH  - Headache/chemically induced
MH  - Humans
MH  - Lamotrigine
MH  - Male
MH  - Middle Aged
MH  - Placebos
MH  - Sleep Stages
MH  - Treatment Outcome
MH  - Triazines/*administration & dosage/adverse effects/pharmacokinetics
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
AID - 10.1111/j.1528-1157.1996.tb00038.x [doi]
PST - ppublish
SO  - Epilepsia. 1996 Sep;37(9):857-62. doi: 10.1111/j.1528-1157.1996.tb00038.x.