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 withenzyme-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.
RCT Entities:
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 epilepticpatients 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 LTGpatients 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.
Authors: Rachel G Greenberg; Chiara Melloni; Huali Wu; Daniel Gonzalez; Lawrence Ku; Kevin D Hill; Christoph P Hornik; Michael Cohen-Wolkowiez; Jeffrey T Guptill Journal: Clin Neuropharmacol Date: 2016 Sep-Oct Impact factor: 1.379