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Clinical Data Support 30 mg Daclatasvir
with ATV or ATV/r, 90 mg With Etravirine
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18th International Workshop on Clinical Pharmacology of Antiviral Therapy, June 14-17, 2017, Chicago
Mark Mascolini
Analysis of daclatasvir trough concentrations in HCV/HIV-coinfected patients found evidence that 30 mg once daily is an appropriate dose with atazanavir/ritonavir (ATV/r) or unboosted ATV [1]. In regimens without a protease inhibitor (PI), etravirine lowered daclatasvir trough, a finding justifying a 90-mg daclatasvir dose with etravirine.
Daclatasvir (Daklinza), a direct-acting antiviral for chronic HCV infection given with sofosbuvir [2,3], has a standard dose of 60 mg once daily. Product information calls for a 30-mg dose with strong CYP3A inhibitors and a 90-mg dose with moderate CYP3A inducers [2]. Researchers in Turin and Milan who conducted this study noted that atazanavir, ritonavir, and cobicistat inhibit CYP3A4, while the nonnucleosides efavirenz, nevirapine, and etravirine induce CYP3A4. But little research has addressed potential interactions between daclatasvir and cobicistat or the nonnucleoside rilpivirine.
To learn more about daclatasvir interactions with antiretrovirals, the researchers conducted this analysis of HIV/HCV-coinfected patients taking daclatasvir with sofosbuvir in clinical practice. The 44 study participants took sofosbuvir for at least 4 weeks then added daclatasvir at 30 mg daily with ATV/r or ATV and at 60 mg daily with other antiretrovirals. Eighteen people took a PI (7 ATV/r, 3 unboosted ATV, 5 darunavir/r, 3 lopinavir/r), 10 took rilpivirine, 12 took raltegravir or dolutegravir, 1 took efavirenz, 2 took etravirine, and 1 took elvitegravir/cobicistat/TDF/FTC.
Thirty-five of 44 participants (79.5%) were men, and 35 had HCV genotype 3. Median age stood at 52 and median body mass index at 25 kg/m(2). Metavir scores were 4, 3, and 1 in 30, 9, and 1 participants, and 98% had Child-Pugh class A.
Median daclatasvir trough concentration measured 215 ng/mL (interquartile range [IQR] 118 to 383) in 233 samples analyzed. Two people who received 60 mg of daclatasvir with etravirine had a daclatasvir trough of 45 ng/mL (IQR 42 to 45), significantly lower than levels in other participants (P = 0.018). Daclatasvir troughs were similar in people taking ATV/r (225 ng/mL, IQR 181 to 250) and ATV alone (294 ng/mL, IQR 62 to 294).
People taking rilpivirine had a median daclatasvir trough of 188 ng/mL (IQR 60 to 301), a level not statistically different from those recorded with other antiretrovirals. The 1 person taking E/C/F/TDF with 60 mg of daclatasvir had a daclatasvir trough of 415 ng/mL, a value not statistically different from those with other antiretrovirals (P = 0.201) or from ritonavir-boosted or -unboosted PIs (P = 0.358).
The Turin/Milan team believes their findings support a daclatasvir dose of 30 mg once daily with ATV or ATV/r and a dose of 90 mg once daily with etravirine not given with a PI. Results from the single person taking E/C/F/TDF suggest that the standard 60-mg daclatasvir dose provides adequate daclatasvir levels.
References
1. Marinaro L, Barco A, Merli M, et al. Daclatasvir (DCV) pharmacokinetics and appropriate dosing in HCV/HIV patients co-administered with antiretroviral drugs. 18th International Workshop on Clinical Pharmacology of Antiviral Therapy, June 14-17, 2017, Chicago. Abstract P_43.
2. Daklinza product information. http://packageinserts.bms.com/pi/pi_daklinza.pdf
3. Daklinza (daclatasvir) 60 mg tablets. http://www.daklinza.bmscustomerconnect.com/
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