There is no long-term safety data on cobicistat BID. Data also suggests that when etravirine and darunavir are used together, it may be warranted to boost darunavir with ritonavir instead of cobicistat
Darunavir/cobicistat vs elvitegravir or etravirine
^
Study Design
This was a pharmacokinetic (PK) study in healthy volunteers. After subjects recieved darunavir/ritonavir (DRV/r 600/100mg) twice daily (BID), a seven-day washout, then (DRV/cobicistat 600/150mg) BID. The group was split into two subsets (n=12 in each) and randomized to DRV/cobicistat 600/150mg BID plus elvitegravir (EVG) 150mg daily or etravirine. All study treatments were adminstered for 10 days. DRV exposure was assessed using geometric mean ratios, with 90% confidence interval (CI) bounds of 80-125% and EVG PK was compared against historial data.
Study Results
Coadminitration of ETR did not affect DRV or ETR PK.
References
S Ramanathan, H Wang, J Szwarcberg, BP Kearney. Safety/tolerability, pharmacokinetics and boosting of twice-daily cobicistat administered alone or in combination with darunavir or tipranavir [poster p08]. 13th International Workshop On Clinical Pharmacology Of Hiv Therapy. Barcelona, Spain. ; 2012.
Etravirine versus Darunavir/Cobicistat when used alone
^
Study Design
in this single center, open-label, fixed sequence, phase I two cohort trial, HIV infected patients were receiving stable antiviral therapy including darunavir/cobicistat (DRV/COBI) 800/150 mg once daily (DRV cohort) or etravirine (ETV) 400 mg once daily (ETV cohort). Patients continued taking their respective antiretroviral therapies and patients in the DRV cohort were given ETV on days 1-14, while patients in the ETV cohort were given DRV/COBI on days 1-7. Pharmacokinetic profiles were obtained on days zero and 14 in the DRV cohort and on days zero and 7 in the ETV cohort. Drug concentrations were determined using validated LCMS/MS methods and drug geometric means ratios (GMRs) and 90% confidence intervals (Cis) were derived from the long transformed AUC0-24, Cmax and C24 using linear mixed models. Safety and continued efficacy were monitored throughout the study using standard methods.
Study Results
plasma concentration time profile and PK for etravirine were not affected by darunavir/cobicistat. However the GMRs (90% CI) of darunavir/cobicistat when coadminstered with etravirine compared to darunavir/cobicistat alone were 0.70 (0.56-0.87) for cobicistat AUC0-24, 0.86 (0.75-0.98) for COBI Cmax, 0.34 (0.23-0.50) for COBI C24, 0.99 (0.86-1.13) for DRV AUC0-24, 1.11 (0.99-1.24) for DRV Cmax, and 0.44 (0.33-0.58) for DRV C24. Treatments remained effective and were well tolerated during the duration of the study.
Study Conclusions
ETV PK remain unchanged by DRV/COBI, but there is a marked decrease in COBI exposure and in DRV C24 when DRV/COBI is coadministered with ETV. The authors did not propose a mechanism for this drug drug interaction, but did suggest that boosting darunavir with ritonavir instead of with cobicistat may be preferred if dual therapy with darunavir plus etravirine is to be used in clinical practice.
References
Molto J, Curran A, Valle M, Miranda C, Ribera E. Pharmacokinetics of darunavir/cobicistat and etravirine alone and coadministered in hiv-infected patients . International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
Etravirine versus Darunavir/Cobicistat when used alone
^
Study Design
in this single center, open-label, fixed sequence, phase I two cohort trial, HIV infected patients were receiving stable antiviral therapy including darunavir/cobicistat (DRV/COBI) 800/150 mg once daily (DRV cohort) or etravirine (ETV) 400 mg once daily (ETV cohort). Patients continued taking their respective antiretroviral therapies and patients in the DRV cohort were given ETV on days 1-14, while patients in the ETV cohort were given DRV/COBI on days 1-7. Pharmacokinetic profiles were obtained on days zero and 14 in the DRV cohort and on days zero and 7 in the ETV cohort. Drug concentrations were determined using validated LCMS/MS methods and drug geometric means ratios (GMRs) and 90% confidence intervals (Cis) were derived from the long transformed AUC0-24, Cmax and C24 using linear mixed models. Safety and continued efficacy were monitored throughout the study using standard methods.
Study Results
plasma concentration time profile and PK for etravirine were not affected by darunavir/cobicistat. However the GMRs (90% CI) of darunavir/cobicistat when coadminstered with etravirine compared to darunavir/cobicistat alone were 0.70 (0.56-0.87) for cobicistat AUC0-24, 0.86 (0.75-0.98) for COBI Cmax, 0.34 (0.23-0.50) for COBI C24, 0.99 (0.86-1.13) for DRV AUC0-24, 1.11 (0.99-1.24) for DRV Cmax, and 0.44 (0.33-0.58) for DRV C24. Treatments remained effective and were well tolerated during the duration of the study.
Study Conclusions
ETV PK remain unchanged by DRV/COBI, but there is a marked decrease in COBI exposure and in DRV C24 when DRV/COBI is coadministered with ETV. The authors did not propose a mechanism for this drug drug interaction, but did suggest that boosting darunavir with ritonavir instead of with cobicistat may be preferred if dual therapy with darunavir plus etravirine is to be used in clinical practice.
References
Molto J, Curran A, Valle M, Miranda C, Ribera E. Pharmacokinetics of darunavir/cobicistat and etravirine alone and coadministered in hiv-infected patients . International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
icon on your home screen.