Dose adjustment to 30 mg daily is preferred when using daclatasvir with CYP 3A inhibitors.
Lopinavir/Ritonavir versus Daclatasvir
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Study Design
In an open-label, non-randomized, one-way study (AI444-093), 14 healthy subjects received daclatasvir (DCV) 60 mg once daily for 4 days (Days 1-4), then DCV 30 mg once daily with lopinavir/ritonavir (LPV/r) 400/100 mg twice daily on Days 5-14.1,2 Blood samples were collected for the pharmacokinetic (PK) assessment of DCV on Days 4 and 14. Geometric mean ratios (GMRs; LPV/r + DCV 30 mg/ DCV 60 mg) [90% CI] of AUC and Cmax, for DCV were 1.15 [1.07, 1.24] and 0.67 [0.61, 0.74], respectively.
Study Results
In the AI444-043 sub-study, coadministration of LPV/r (400/100 mg twice daily) and DCV 30 mg once daily with a pegylated interferon with ribavirin (PEG-IFN/RBV) regimen was studied in HIV/HCV genotype I co-infected patients (n = 6).2 Patients were on treatment with LPV/r (400/100 mg twice daily) based combination antiretroviral therapy (cART) and were well suppressed on antiretroviral therapy (ART; HIV viral load < 40 cp/mL). PK sampling was conducted 1 day before study start (Day -1) and 14 days after receiving LPV/r (400/100 mg twice daily) plus DCV 30 mg once daily with pegINF/RBV (Day 14). GMRs (LPV/r + DCV + pegINF/RBV / LPV/r) [90% CI] of AUC, Cmax and Cmin, for LPV were 1.15 [0.77, 1.72], 1.22 [1.06, 1.41] and 1.54 [0.46, 5.07], respectively.
Study Conclusions
Investigators concluded that no dose adjustment is required for either drug when DCV is coadministered with LPV/r.
References
Ghandi Y, Adamczyk R, Wang R, Stonier M, Kandoussi H, Hesney M. Assessment of drug–drug interactions between daclatasvir and darunavir/ritonavir or lopinavir/ritonavir. International Workshop On Clinical Pharmacology Of Hiv And Hepatitis T Herapy . Washington DC, USA. 16; May 2015.
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