Coadministration of darunavir/ritonavir (400/100 mg twice daily) increased darunavir AUC, Cmin and Cmax by 24%, 2% and 40%, respectively. Nevirapine AUC, Cmin and Cmax increased by 27%, 47% and 18%, respectively. Darunavir and nevirapine can be co-administered without dose adjustments.

Coadministration of nevirapine (200 mg twice daily) and darunavir/ritonavir (400/100 mg twice daily) was studied in 8 subjects. Darunavir Cmax, AUC and Cmin increased by 24%, 40% and 2%, respectively. The effect on nevirapine pharmacokinetics was not significant when compared to historical controls.

Coadministration of nevirapine (200 mg twice daily) and darunavir/ritonavir (at a dose lower than recommended or with a different dosing regimen) increased nevirapine AUC, Cmax and Cmin by 27%, 18% and 47%, respectively. Darunavir concentrations were consistent with historical data. Darunavir/ritonavir increases the plasma concentrations of nevirapine as a result of CYP3A4 inhibition. Darunavir coadministered with low dose ritonavir and nevirapine can be used without dose adjustments.

No dosage adjustments are recommended when darunavir/ritonavir is co-administered with nevirapine. Coadministration of nevirapine (200 mg twice daily) and darunavir/ritonavir (400/100 mg twice daily) was studied in 8 subjects. Darunavir and nevirapine exposure both increased. Based on between study comparison, darunavir Cmax, AUC and Cmin increased by 40%, 24% and 2%, respectively. Nevirapine Cmax, AUC and Cmin increased by 18%, 27% and 47%, respectively. 

An open label, randomised cross over study investigated the pharmacokinetic interaction between darunavir/ritonavir and nevirapine. Nineteen HIV+ patients received nevirapine (200 mg twice daily with 2 or more NRTIs) in combination with darunavir oral solution (300 mg twice daily with ritonavir 100 mg twice daily) or darunavir tablet (400 mg twice daily with ritonavir 100 mg twice daily) in two 14-day sessions. At these lower than licensed doses, darunavir/ritonavir increased mean nevirapine AUC by 27% (least square means ratio 1.27; 95% confidence interval 1.02, 1.58). Mean darunavir and ritonavir exposures were similar to historical data. No dose adjustments are considered to be required based on a) dose proportionality of darunavir PK and b) coadministration of darunavir/ritonavir and nevirapine is generally well tolerated.

Data from TDM and a population PK approach were used to examine the influence of coadministered drugs on nevirapine pharmacokinetics in a cohort of 51 patients. In the final one compartment model there was relationship between nevirapine clearance and the presence of darunavir in the regimen. There was a significant decrease in clearance (CL/f, 3.84 ± 0.92 vs 2.76 ± 1.00 L/h) and an increase in the mean nevirapine trough plasma concentrations (3.68 ± 1.69 vs 5.35 ± 3.20 mg/L) in combination with darunavir. The limitations of the study are that it is TDM data and small numbers. The advantage is that these are results obtained with the recommended twice daily dose of darunavir/ritonavir (600/100 mg) rather than the lower doses (300/100 or 400/100 mg) used in the early interaction studies.