Per the manufacturer, coadministration of etravirine with daclatasvir is predicted to reduce daclatasvir exposure due to CYP3A4 induction. Although pharmacokinetic data is not currently available, coadministration of these two agents is not recommended unless a boosted protease inhibitor is also a part of the antiretroviral regimen.
Daclatasvir plasma concentration assessment in HIV–HCV-coinfected real-life patients
^
Study Design
A review of various drug interactions (both studied and theoretical) and description of their clinical management
Study Results
Several interactions have not been formally studied, but inferences are made based upon what is known of each drug's pharmacokinetic or pharmacodynamic properties.
Study Conclusions
Daclatasvir is a substrate of CYP3A, and as such inhibitors or inducers may alter drug concentrations and various clinical approaches may manage these interactions.
References
Taton A, Colson, P, Dhiver C, Ruiz JM, Bregigeon S, Tomei C, Lacarelle B. Daclatasvir plasma concentration assessment in hiv–hcv-coinfected real-life patients. Antiviral Therapy. 2017; : 731-733.
Etravirine versus Daclatasvir
^
Study Design
Forty Four HIV/HCV co-infected patients treated with DCV plus sofosbuvir (SOF) for at least 4 weeks and receiving antiretroviral therapy (ARV) were enrolled. DCV was dosed 30 mg with ATV assuming a comparable effect of ATV and ATV/r, 60 mg with ETV, due to lack of data at the time of prescription and 60 mg with RPV. One patient treated with elvitegravir/cobicistat/emtricitabine/tenofovir (E/C/F/TDF) received DCV 60 mg. DCV plasmatic levels (DCVpl) (22±2 hours after last intake) were measured using UPLC-MS/MS validated method and reported as ng/mL. Data are expressed as numbers (percentage) and median (IQR).
Patients received ARV containing following drugs: protease inhibithor (PI) in 18 (7 ATV/r, 3 ATV, 5 DRV/r, 3 LPV/r), RPV in 10, raltegravir or dolutegravir in 12, EFV in 1, ETV in 2. One patient received E/C/F/TDF.
Study Results
Total 233 DCV determinations were obtained. Median DCVpl in study population was 215 ng/ml (118;383). Two patients treated with ETV and DCV 60 mg showed DCVpl 45 ng/mL
(42;45), significantly lower (p= 0.018) compared to other patients. DCVpl was 294 ng/mL (62;294) and 225 ng/mL (181;250) in patients treated with ATV and ATV/r, respectively, with no statistical difference between two group considered; DCVpl was 188 ng/mL (60;301) in those receiving RPV without significant statistical difference with those receiving other ARVs. One patient treated with E/C/F/TDF and DCV 60 mg showed DCVpl 415 ng/mL with no statistical difference with other ARVs (p= 0.201) or with DCVpl with ritonavir boosted or unboosted PIs (p= 0.358).
Study Conclusions
The author’s concluded that their findings confirmed the appropriateness of 30 mg reduced DCV dose not only with ATV/r but also with unboosted ATV and the need to increase DCV to 90 mg when co-administered with ETV without PIs. Moreover, in the first case so far reported of coadministration with E/C/F/TDF, standard 60 mg DCV dose provides adequate DCV levels.
References
Marinaro L, Marco A, Merli M, Alcantarini C, Montrucchio C, Patti F. Daclatasvir (dcv) pharmacokinetics and appropriate dosing in hcv/hiv patients co-administered with antiretroviral drugs. International Workshop On Clinical Pharmacology Of Hiv And Hepatitis T Herapy . Chicago, IL, USA. 17; June 2017.
Etravirine versus Daclatasvir
^
Study Design
Forty Four HIV/HCV co-infected patients treated with DCV plus sofosbuvir (SOF) for at least 4 weeks and receiving antiretroviral therapy (ARV) were enrolled. DCV was dosed 30 mg with ATV assuming a comparable effect of ATV and ATV/r, 60 mg with ETV, due to lack of data at the time of prescription and 60 mg with RPV. One patient treated with elvitegravir/cobicistat/emtricitabine/tenofovir (E/C/F/TDF) received DCV 60 mg. DCV plasmatic levels (DCVpl) (22±2 hours after last intake) were measured using UPLC-MS/MS validated method and reported as ng/mL. Data are expressed as numbers (percentage) and median (IQR).
Patients received ARV containing following drugs: protease inhibithor (PI) in 18 (7 ATV/r, 3 ATV, 5 DRV/r, 3 LPV/r), RPV in 10, raltegravir or dolutegravir in 12, EFV in 1, ETV in 2. One patient received E/C/F/TDF.
Study Results
Total 233 DCV determinations were obtained. Median DCVpl in study population was 215 ng/ml (118;383). Two patients treated with ETV and DCV 60 mg showed DCVpl 45 ng/mL
(42;45), significantly lower (p= 0.018) compared to other patients. DCVpl was 294 ng/mL (62;294) and 225 ng/mL (181;250) in patients treated with ATV and ATV/r, respectively, with no statistical difference between two group considered; DCVpl was 188 ng/mL (60;301) in those receiving RPV without significant statistical difference with those receiving other ARVs. One patient treated with E/C/F/TDF and DCV 60 mg showed DCVpl 415 ng/mL with no statistical difference with other ARVs (p= 0.201) or with DCVpl with ritonavir boosted or unboosted PIs (p= 0.358).
Study Conclusions
The author’s concluded that their findings confirmed the appropriateness of 30 mg reduced DCV dose not only with ATV/r but also with unboosted ATV and the need to increase DCV to 90 mg when co-administered with ETV without PIs. Moreover, in the first case so far reported of coadministration with E/C/F/TDF, standard 60 mg DCV dose provides adequate DCV levels.
References
Marinaro L, Marco A, Merli M, Alcantarini C, Montrucchio C, Patti F. Daclatasvir (dcv) pharmacokinetics and appropriate dosing in hcv/hiv patients co-administered with antiretroviral drugs. International Workshop On Clinical Pharmacology Of Hiv And Hepatitis T Herapy . Chicago, IL, USA. 17; June 2017.
icon on your home screen.