UDP-glucuronyl transferases have been identified as the enzymes responsible for metabolism of Lamotrigine. There is no evidence that Lamotrigine causes clinically significant induction or inhibition of hepatic oxidative drug-metabolising enzymes, and interactions between Lamotrigine and drugs metabolized by cytochrome P450 enzymes are unlikely to occur. Lamotrigine may induce its own metabolism, but the effect is modest and unlikely to have significant clinical consequences. (See Table 6.)
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Interactions involving AEDs (see Dosage & Administration): Valproate, which inhibits the glucuronidation of Lamotrigine, reduces the metabolism of Lamotrigine and increases the mean half life of Lamotrigine nearly two-fold.
Certain antiepileptic agents (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes induce the metabolism glucuronidation of Lamotrigine and enhance the metabolism of Lamotrigine.
There have been reports of central nervous system event including dizziness, ataxia, diplopia, blurred vision, and nausea in patients taking carbamazepine following the introduction of Lamotrigine. These events usually resolve when the dose of carbamazepine is reduced.
Interactions of involving hormonal contraceptives: Effect of hormonal contraceptives on Lamotrigine pharmacokinetics: Serum Lamotrigine concentrations gradually increased during the course of the week of inactive medication (e.g. "pill-free week"), with pre-dose concentrations at the end of the week of inactive medication being, on average, approximately two-fold higher than during co-therapy.
Effect of Lamotrigine on hormonal contraceptive pharmacokinetics: The impact of the modest increase in levonorgestrel clearance and the changes in serum FSH and LH, on ovarian ovulatory activity in unknown (see Precautions). The effects of doses of Lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparation have not been conducted.
Interactions involving other medications: Rifampicin increased Lamotrigine clearance and decreased Lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the treatment regimen recommended for Lamotrigine and concurrent glucuronidation inducers should be used (see Dosage & Administration).
Lopinavir/ritonavir approximately halved the plasma concentrations of Lamotrigine probably by induction of glucuronidation. In patients receiving concomitant therapy with lopinavir/ritonavir, the treatment regimen recommended for Lamotrigine and concurrent glucuronidation inducers should be used (see Dosage & Administration).
Atazanavir/ritonavir will reduce the plasma AUC and Cmax of Lamotrigine (see General Dosing Recommendations for Lamotrigine in Special Patient Population under Dosage & Administration).