Using geometric mean ratios (GMR) and 90% confidence intervals (CI), the Cmax, AUC and Cmin for daclatasvir was 1.06 (0.98-1.15), 1.10 (1.01-1.21) and 1.15 (1.02-1.30), while that for tenofovir was 0.95 (0.89-1.02), 1.10 (1.05-1.15) and 1.17 (1.10-1.24), respectively. Exposures for both agents were within the boundaries of bioequivalence during coadministration. The manufacturer states the 10% increase in tenofovir exposure is not expected to increase tenofovir-related adverse events, eg. renal effects.
No dose adjustment of either agent is required when utilizing this combination.
Tenofovir Disoproxil Fumarate vs Daclatasvir
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Study Design
This combination has not been studied, but given what is known about the metabolic and transport pathways of both of these agents, an interaction is not expected.
Study Results
When used as part of an antiretroviral regimen, in patients who are coinfected with HCV and HIV, zidovudine exposures are not expected to change in the presence of daclatasvir. Similarly, daclatasvir concentration is not expected to be altered due to zidovudine.
Study Conclusions
Manufacturer states that an interaction with NRTIs or Entry Inhibitors is not expected and a dose adjustment is not required for either agent. Given the role of other agents in the antiretroviral regimen, daclatasvir concentrations may be altered. Please see other drugs for individual interaction potential.
References
Bifano M, Howang C, Oosterhuis B, Hartstra J, Grasela D, Tiessen R, Bertz R. Assessment of pharmacokinetic interactions of the hcv ns5a replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir. Antiviral Therapy. 2013; 7: 931-940.
Tenofovir Disoproxil Fumarate versus Daclatasvir Marinaro
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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).
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.
Tenofovir Disoproxil Fumarate versus Daclatasvir Marinaro
^
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).
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.
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