Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsants. Careful monitoring of serum levels or therapeutic effects is recommended when these medicines are concomitantly administered with ritonavir.

Coadministration may decrease lamotrigine concentrations. A dose increase may be needed for lamotrigine when co-administered with ritonavir and therapeutic concentration monitoring is recommended for this anticonvulsant, if available.

The possible effects of lopinavir/ritonavir, on the pharmacokinetics of lamotrigine were investigated in 18 HIV-subjects. Plasma levels were determined at steady state following lamotrigine (100 mg twice daily) alone (day 10) or in combination (day 20) with lopinavir/ritonavir (400/100 mg twice daily). A dose increase dependent on the magnitude of decrease in lamotrigine concentrations was performed following PK analysis with further PK analysis 10 days later. At day 20, lamotrigine AUC, Cmin and Cmax decreased by 50%, 56% and 46%, respectively, thus all subjects received a dose increase to 200 mg twice daily. Increasing the dose restored bioequivalence on day 31 (lamotrigine AUC and Cmin decreased by 9% and 21%, Cmax increased by 3%; n=15). Lopinavir concentrations were determined in 6 subjects on day 20 and were found to be comparable with historical controls of lopinavir/ritonavir 400/100 mg twice daily. Lopinavir/ritonavir decreased the AUC of lamotrigine, probably by induction of glucuronidation, and a dose increase of lamotrigine (to 200 mg twice daily) was needed to overcome the interaction. From these limited data, lamotrigine does not appear to have an effect on LPV/RTV.