INTERAZIONI FARMACOLOGICHE DELLA LAMOTRIGINA CON CARBAMAZEPINA E FENITOINA

The modifications of the plasma concentrations of CBZ, PHT and LTG have been analyzed during a multicenter international study on the efficacy of LTG. 21 subjects were treated with PHT monotherapy and 19 with CBZ monotherapy and respectively 9 and 6 patients were dropped out of the study for protocol violations or interruption in an early phase. Only 12 patients treated with PHT and 13 patients treated with CBZ completed the study. Mean PHT concentration, at constant daily dose, was reduced from 18.2 μg/ml during PHT monotherapy to 13.8 μg/ml during PHT + LTG. A detailed analysis shows that 8 patients presented a reduction (median 45%, range 17-59%) while 4 patients presented an increase (median 23%, range 5-36%) of PHT plasma concentrations. Mean CBZ concentration, at constant daily dose, varied from 9.6 to 9.1 μg/ml during CBZ monotherapy and CBZ + LTG respectively, however a deeper analysis shows that 7 patients presented a reduction (median 18%, range 8-40) while 4 patients showed an increase (median 23%, range 6-42%) of CBZ plasma levels, which remained stable in 2 patients. During the passage from bitherapy LTG + PHT or LTG + CBZ to LTG monotherapy all the patients showed an increase of LTG plasma levels at constant LTG daily dose. PHT patients showed a mean LTG concentration of 2 μg/ml during add-on therapy, which raised to 5.9 μg/ml during LTG monotherapy with an increased average of 300%, range 209-890%. CBZ patients showed a mean LTG concentration of 2.2 μg/ml which raised to 4.6 μg/ml during LTG monotherapy with an increased average of 186%, range 130-430%. This trend was still present after 3 months of LTG monotherapy. The data show the existence of a drug interaction between LTG, CBZ and PHT and indicate the usefulness of therapeutic drug monitoring of all these AEDs.