Lamotrigine high-dose tolerability and safety in patients with epilepsy: a double-blind, placebo-controlled, eleven-week study.
OBJECTIVE
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.
Matsuo
F
F
Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Gay
P
P
Madsen
J
J
Tolman
K G
KG
Rollins
D E
DE
Risner
M E
ME
Lai
A A
AA
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004172:Diplopia / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012894:Sleep Stages; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D000927:Anticonvulsants; D010919:Placebos; D014227:Triazines; D000077213:Lamotrigine