Liverpool HIV Interactions

No Interaction Expected

Etravirine (ETR)

_ZZDarunavir

Quality of Evidence: Low

Summary:

Etravirine and darunavir/ritonavir can be coadministered without any dose adjustments. Etravirine exposures from Phase 3 trials with darunavir/ritonavir as part of the background regimen were determined to be safe and effective. Coadministration decreased etravirine Cmax, AUC and Cmin by 32%, 37% and 49%, respectively; darunavir Cmax, AUC and Cmin increased by 11%, 15% and 2%, respectively. When etravirine was added to raltegravir/darunavir/ritonavir, raltegravir AUC, Cmax and Cmin increased by 29%, 21% and 54%, respectively and darunavir AUC, Cmax and Cmin increased by 14%, 6%, and 29%, respectively.

Description:

Coadministration of a lower than recommended etravirine dose (100 mg twice daily) and darunavir/ritonavir decreased etravirine AUC, Cmax and Cmin by 37%, 32% and 49%, respectively. Darunavir AUC in creased by 15% and there was no significant effect on Cmax or Cmin. Darunavir coadministered with low dose ritonavir and etravirine 200 mg twice daily can be used without dose adjustments.
Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, June 2012.

The interaction between darunavir/ritonavir and etravirine was evaluated in clinical studies and no dose adjustment is needed for either drug. Coadministration of etravirine (200 mg twice daily) and darunavir/ritonavir (600/100 mg twice daily) was studied in 15 subjects. Darunavir AUC, Cmax and Cmin increased by 15%, 11% and 2%, respectively. Etravirine AUC, Cmax and Cmin decreased by 37%, 32% and 49%, respectively.
Prezista Prescribing Information, Tibotec Inc, June 2012.

Etravirine and darunavir/ritonavir can be used without dose adjustments. Coadministration with darunavir/ritonavir (600/100 mg twice daily) increased darunavir AUC (15%) and Cmax (11%), but had no effect on Cmin. Etravirine AUC decreased by 37%, Cmax decreased by 32% and Cmin decreased by 49%.
Intelence Summary of Product Characteristics, Janssen-Cilag Ltd, March 2012.

The mean systemic exposure (AUC) of etravirine was reduced when etravirine was co-administered with darunavir/ritonavir. Because all subjects in the Phase 3 trials received darunavir/ritonavir as part of the background regimen and etravirine exposures from these trials were determined to be safe and effective, etravirine and darunavir/ritonavir can be co-administered without dose adjustments. Coadministration of darunavir/ritonavir (600/100 mg twice daily) and etravirine was studied in 15 subjects. Data from 14 subjects showed that etravirine Cmax, AUC and Cmin decreased by 32%, 37% and 49%, respectively. Darunavir Cmax, AUC and Cmin increased by 11%, 15% and 2%, respectively.
Intelence Prescribing Information, Tibotec Pharmaceuticals Ltd, March 2012.

The addition of etravirine (200 mg twice daily) to raltegravir (400 mg twice daily) and darunavir/ritonavir (600/100 mg twice daily) lead to significant increases in the AUC, Cmax and Cmin of both raltegravir (29%, 21% and 54%, respectively) and darunavir (14%, 6%, and 29%, respectively). Ritonavir AUC, Cmax and Cmin decreased by 3%, 5% and 11%, respectively. The authors point to the marked variability of raltegravir pharmacokinetics (particularly higher trough concentrations after the evening dose), but do not offer an explanation for the increase.
Pharmacokinetics of etravirine, raltegravir and darunavir/ritonavir in treatment experienced patients. Barrail-Tran A, Yazdanpanah Y, Goldwirt L, et al. AIDS, 2010, 24(16): 2581-3.

The pharmacokinetic interaction between etravirine (100 or 200 mg twice daily) and darunavir/ritonavir (600/100 mg twice daily) was investigated in two groups of HIV- subjects. Coadministration of 100 mg etravirine with darunavir/ritonavir decreased the AUC, Cmax and Cmin of etravirine by 37%, 32% and 49% respectively. Coadministration had no significant effect on the pharmacokinetics of etravirine or ritonavir. Increasing the dose of etravirine to 200 mg (the dose chosen for Phase III trials) resulted in increases in etravirine AUC, Cmax and Cmin of 80%, 81% and 67% respectively when coadministered with darunavir/ritonavir and compared to etravirine 100 mg given alone. Darunavir AUC and Cmax were increased by 15% and 11% respectively, with no change in Cmin. Etravirine (200 mg twice daily) can be coadministered with darunavir/ritonavir without dose adjustments.
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. Scholler-Gyure M, Kakuda TN, Sekar V, et al. Anitviral Ther, 2007, 12: 789-796.

The pharmacokinetics of etravirine and darunavir were determined in 10 HIV+ subjects receiving etravirine (200 mg twice daily, phase III formulation) and darunavir/ritonavir (600/100 mg twice daily). Darunavir exposure was similar to historical controls and etravirine concentrations were similar to those obtained when administered with a boosted PI.
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level resistance. Boffito et al. AIDS, 2007, 21: 1449-1455.

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