Steady-state concentrations of phenytoin were moderately decreased due to CYP2C9 and CYP2C19 induction by Kaletra. Lopinavir concentrations are decreased due to CYP3A induction by phenytoin. Caution should be exercised in administering phenytoin with Kaletra. Phenytoin levels should be monitored when coadministering with lopinavir/ritonavir. An increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice.  Kaletra must not be administered once daily in combination with phenytoin.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration of anticonvulsants, such a phenytoin, may result in decreased concentrations of lopinavir. Kaletra may be less effective due to decreased plasma concentrations in patients taking these agents concomitantly and should be used with caution. In addition, coadministration of phenytoin and Kaletra may cause decreases in steady state phenytoin concentrations. Phenytoin levels should be monitored when coadministering with Kaletra. Kaletra ONCE DAILY in combination with phenytoin is not recommended.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

The pharmacokinetic interaction between lopinavir/ritonavir (LPV/RTV; 400/100 mg bd) and phenytoin (300 mg once daily) was investigated in 12 healthy volunteers. Pharmacokinetic sampling was performed at steady state (study days 11 and 22). Following the addition of phenytoin, lopinavir Ctrough decreased by 46% (from 5.97 ± 3.17 to 3.55 ± 2.31 µg/ml; mean ± sd), AUC decreased by 33% (from 70.89 ± 36.96 to 49.61 ± 25.09 µg/ml.h; mean ± sd) and oral clearance increased from 4.79 ± 3.68 to 9.60 ± 9.76 L/h (mean ± sd). Concentrations of ritonavir were also decreased: Ctrough decreased from 0.28 ± 0.33 to 0.14 ± 0.15 µg/ml (mean ± sd) and AUC decreased from 3.08 ± 2.79 to 1.99 ± 1.09 µg/ml.h (mean ± sd). Following the addition of lopinavir/ritonavir, phenytoin Ctrough decreased by 33% (from 7.04 ± 4.02 to 5.31 ± 4.05 µg/ml; mean ± sd), AUC decreased by 31% (from 191.00 ± 89.21 to 147.75 ± 104.54 µg/ml.h; mean ± sd), and oral clearance increased from 0.61 ± 0.65 to 1.53 ± 1.95 L/h (mean ± sd). The decrease in lopinavir and ritonavir concentrations may be clinically significant and a dose increase to LPV/RTV 533/133 mg or addition of 100 mg extra RTV (i.e. LPV/RTV 400/200 mg) could be considered. Dose monitoring of phenytoin is recommended due to the decrease in phenytoin exposure.
Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. Lim ML, Min SS, Eron JJ, et al. J Acquir Immune Defic Syndr, 2004, 36: 1034-1040.