Kaletra must not be administered once daily in combination with nevirapine. Coadministration decreased lopinavir AUC, Cmax and Cmin by 27%, 19% and 51% respectively. The Kaletra tablets dosage should be increased to 500/125 mg twice daily when coadministered with nevirapine.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Kaletra ONCE DAILY in combination with nevirapine is not recommended. The dose of Kaletra must be increased when administered in combination with nevirapine.  The recommended dose of Kaletra tablets is 500/125 mg twice daily (such as two 200/50 tablets and one 100/25 tablet). The recommended dose of Kaletra oral solution for adults is 520/130 mg (6.5 mL) twice daily. Coadministration of nevirapine (200 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) to 22 HIV+ subjects resulted in decreases in lopinavir Cmax, AUC and Cmin of 19%, 27% and 51% respectively, when compared to data from 19 subjects receiving lopinavir/ritonavir alone. Coadministration of nevirapine (200 once daily for 14 days, escalating to 200 mg twice daily for 6 days) and lopinavir/ritonavir (400/100 mg for 20 days) to 5 HIV- subjects resulted in increases in nevirapine Cmax, AUC and Cmin of 5%, 8% and 15% respectively, when compared to data from 6 subjects receiving nevirapine alone.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Coadministration of nevirapine and lopinavir/ritonavir (400/100 mg twice daily) decreased lopinavir AUC, Cmax and Cmin by 27%, 19% and 46%, respectively. An increase in the dose of lopinavir/ritonavir to 533/133 mg (4 capsules) or 500/125 mg (5 tablets with 100/25 mg each) twice daily with food is recommended in combination with nevirapine. Dose adjustment of nevirapine is not required when co-administered with lopinavir. Coadministration of nevirapine and lopinavir/ritonavir oral solution (300/75 mg/m2) to paediatric patients decreased lopinavir AUC, Cmax and Cmin by 22%, 14% and 55%, respectively. For children, increase of the dose of lopinavir/ritonavir to 300/75 mg/m2 twice daily with food should be considered when used in combination with nevirapine, particularly for children in whom reduced susceptibility to lopinavir/ritonavir is suspected.
Viramune Summary of Product Characteristics, Boehringer Ingelheim Ltd, November 2019.

Coadministration of nevirapine (200 mg once daily for 2 weeks then 200 mg twice daily for 2 weeks) with Kaletra (400/100 mg lopinavir/ritonavir twice daily) in 22 patients was compared to lopinavir/ritonavir alone in 19 patients. Patients taking nevirapine had 27%, 19% and 51% lower lopinavir AUC, Cmax and Cmin, respectively. Coadministration of nevirapine (7 mg/kg or 4 mg/kg twice daily) and lopinavir/ritonavir (300/75 mg/m2 to was studied in 15 pediatric subjects (6 months to 12 years). When compared to data from 12 subjects taking lopinavir/ritonavir alone, nevirapine decreased lopinavir AUC, Cmax and Cmin by 22%, 14% and 55%, respectively. The effect on nevirapine pharmacokinetics was not significant when compared to adult and pediatric historical controls. Dosing in adult patients: A dose adjustment of lopinavir/ritonavir to 500/125 mg tablets twice daily or 533/133 mg (6.5 mL) oral solution twice daily is recommended when used in combination with nevirapine. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine. Dosing in pediatric patients: Please refer to the Kaletra® prescribing information for dosing recommendations based on body surface area and body weight. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine.
Viramune Prescribing Information, Boehringer Ingelheim Pharmaceuticals Inc, October 2019.

The aim of this study was to assess the influence of nevirapine on lopinavir pharmacokinetics in order to optimise dosing regimens. The study included 15 HIV+ subjects, who received LPV/r (533/133 mg twice daily) and NVP (200 mg once daily for 2 weeks followed by NVP 200 mg twice daily). Steady state pharmacokinetic parameters were measured at week 4 and compared with data from patients (n=23) receiving LPV/r (400/100 mg twice daily) + 2 NRTIs. Following an increase in the LPV/r dosage, the mean ± sd LPV Ctrough was 5240 ± 4029 ng/ml, which was not significantly different from the mean Ctrough for LPV 400/100 mg bid + 2NRTI (4272 ± 3114 ng/ml, P=0.637). No statistically significant difference was observed in the mean AUC for LPV 400/100 mg bid + 2NRTI or with LPV/r 533/133 mg bid + NVP 200 mg bid (82746 ± 41019 vs 100940 ± 48871 ng.h/ml, P=0.3286). The findings suggest that an increase in LPV/r dose to 533/133 mg (4 capsules twice daily) is appropriate when co-administered with NVP. Data is awaited on the new tablet formulation of lopinavir in the presence of nevirapine.
The steady state pharmacokinetics (PK) of lopinavir/ritonavir 533/133 mg bid plus nevirapine (200 mg bid) in adult HIV-1-infected individuals (the NRTI sparing study). Youle M, et al. 16th International AIDS Conference, Toronto, August 2006, abstract TUPE0094.

Coadministration of an NNRTI (n=25; nevirapine n=9, efavirenz n=16) with lopinavir/ritonavir (400/100 mg twice daily) resulted in a 39% decrease in lopinavir Ctrough but no change in Cmax, compared in patients taking lopinavir/ritonavir (400/100 mg twice daily alone n=125). There was no difference in lopinavir Ctrough between patients taking efavirenz and nevirapine. There was no difference in lopinavir Ctrough between patients taking lopinavir (400/100 mg twice daily, n=125) and those taking lopinavir/ritonavir (533/133 mg twice daily, n=32) with an NNRTI (NVP n=3, EFV n=29). There was no statistically significant difference in ritonavir Ctrough or Cmax in patients taking lopinavir/ritonavir 400/100 mg twice daily with or without an NNRTI but patients taking lopinavir ritonavir 533/133 mg twice daily with an NNRTI had higher ritonavir Ctrough and Cmax. The number of patients with lopinavir concentrations below the 3000 ng/ml threshold was higher in those taking lopinavir/ritonavir 400/100 with an NNRTI compared to those without an NNRTI. However, the number of patients with suboptimal levels was comparable between those taking lopinavir/ritonavir 400/100 mg alone to those taking lopinavir/ritonavir 533/133 mg plus an NNRTI. Similar results were observed when a lower threshold (1500 ng/ml) was used.
Therapeutic drug monitoring of lopinavir/ritonavir given alone or with an non-nucleoside reverse transcriptase inhibitor. Solas C, Poizot-Martin I, Drogoul M, et al., Br J Pharmacol, 2003, 57: 436-440.

The coadministration of nevirapine to 2 patients receiving lopinavir/ritonavir resulted in lopinavir Cmin values of 1420 and 5240 ng/ml and Cmax values of 3920 and 12300 ng/ml. Mean lopinavir concentrations in a group of patients (n=4) receiving lopinavir/ritonavir alone were 5690 (1420-11120) ng/ml for Cmin and 12400 (3920-17300) ng/ml for Cmax. Nevirapine concentrations were 769 and 1610 ng/ml for Cmin and 2290 and 2490 ng/ml for Cmax.
Steady state pharmacokinetics of lopinavir in combination with nevirapine or efavirenz. Degen O, Kurowski M, van Lunzen J, et al. 14th International AIDS Conference, Barcelona, July 2002, abstract TuPeB4573.

Five HIV+ patients receiving nevirapine (200 mg bd), amprenavir (600 mg bd) and lopinavir/ritonavir (400/100 mg bd) were studied. Amprenavir concentrations were in the expected ranges (Cmin 560-3090 ng/ml; Cmax 1760-8040 ng/ml; AUC0-12h 13230-75170 ng/ml.h). However, lopinavir concentrations were quite variable (Cmin 620-5980 ng/ml; Cmax 2710-12600 ng/ml; AUC0-12h 998-175140 ng/ml.h) and 40-60% lower than reported by the manufacturer. The combination of amprenavir, lopinavir and nevirapine may result in unpredictable lopinavir concentrations and pharmacological monitoring is advisable in patients treated with such combinations.
Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients. Fatkenheuer G, Romer K, Kamps R, et al. AIDS, 2001, 15:2334-2335.