Daclatasvir 30 mg/day is the correct dose for patients taking atazanavir/cobicistat

Atazanavir is boosted with the cytochrome P450 (CYP) 3A4 inhibitor ritonavir. When combined with the CYP3A4 substrate daclatasvir, the daclatasvir dosage should be reduced from 60 to 30 mg once daily. Recently, cobicistat was licensed as a CYP3A booster and used with atazanavir. To determine whether...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2017-02, Vol.72 (2), p.486-489
Main Authors: Smolders, E J, Colbers, E P H, de Kanter, C T M M, Velthoven-Graafland, K, Drenth, J P H, Burger, D M
Format: Article
Language:English
Subjects:
Adult
Anti-HIV Agents - adverse effects
Anti-HIV Agents - pharmacokinetics
Anti-HIV Agents - therapeutic use
Atazanavir Sulfate - pharmacokinetics
Atazanavir Sulfate - therapeutic use
Cobicistat - pharmacokinetics
Cobicistat - therapeutic use
Cross-Over Studies
Cytochrome P-450 CYP3A Inhibitors - pharmacokinetics
Cytochrome P-450 CYP3A Inhibitors - therapeutic use
Female
HIV Infections - drug therapy
Humans
Imidazoles - administration & dosage
Imidazoles - pharmacokinetics
Imidazoles - therapeutic use
Male
Middle Aged
Prospective Studies
Ritonavir - pharmacokinetics
Ritonavir - therapeutic use
Young Adult
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Summary:Atazanavir is boosted with the cytochrome P450 (CYP) 3A4 inhibitor ritonavir. When combined with the CYP3A4 substrate daclatasvir, the daclatasvir dosage should be reduced from 60 to 30 mg once daily. Recently, cobicistat was licensed as a CYP3A booster and used with atazanavir. To determine whether the fixed-dose combination of atazanavir/cobicistat has an influence on daclatasvir pharmacokinetics comparable to that of the separate agents atazanavir and ritonavir. A prospective, open-label, two-period, randomized, cross-over trial was performed in 16 healthy subjects (NCT02565888). Treatment consisted of 300/100 mg of atazanavir/ritonavir plus 30 mg of daclatasvir once daily (reference) and a second period of 300/150 mg of atazanavir/cobicistat plus 30 mg of daclatasvir once daily (test). A 24 h pharmacokinetic, steady-state curve was recorded for all drugs. Geometric mean ratios (GMRs) with 90% CI were calculated for daclatasvir and atazanavir AUC  and C to compare the effect of both treatments (test versus reference). Laboratory safety and adverse events were evaluated throughout the trial. All 16 healthy subjects completed the study. Median (range) age and BMI were 48.5 (21-55) years and 24.5 (19.0-29.2) kg/m , respectively. Pharmacokinetic parameters of ritonavir and cobicistat were comparable to those in the literature. The GMRs (90% CI) of daclatasvir AUC and C (test versus reference) were 101% (92%-111%) and 97% (89%-106%), respectively. Atazanavir GMRs (90% CI) of AUC and C were 82% (75%-79%) and 74% (68%-81%), respectively. No serious adverse events were reported. Atazanavir/cobicistat and atazanavir/ritonavir had a similar influence on daclatasvir pharmacokinetics in healthy volunteers. Daclatasvir at 30 mg once daily is the correct dose when combined with atazanavir/cobicistat.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkw429