Darunavir/Ritonavir + Daclatasvir = Precautionary

Effect on Concentration

Darunavir/Ritonavir
No change
Applies within class?
No
Daclatasvir
Increase
Applies within class?
No

Pharmacologic Effects

Darunavir/Ritonavir
Effect
N/A
Applies within class?
No
Daclatasvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Recommendations suggest using Daclatasvir 30 mg when combined with CYP3A inhibitors

Sources

Darunavir/Ritonavir versus Daclatasvir ^

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 darunavir/ritonavir (DRV/r) 800/100 mg once 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; DRV/r + DCV 30 mg / DCV 60 mg) [90% CI] of AUC and Cmax, for DCV were 1.41 [1.32, 1.50] and 0.77 [0.70, 0.85], respectively.

Study Results

In the AI444-043 sub-study, coadministration of DRV/r (600/100 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=11).2 Patients were on treatment with DRV/r (600/100 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 DRV/r (600/100 mg twice daily) plus DCV 30 mg once daily with pegINF/RBV (Day 14). GMRs (DRV/r + DCV + pegINF/RBV / DRV/r) [90% CI] of AUC, Cmax and Cmin for DRV were 0.90 [0.73, 1.11], 0.97 [0.80, 1.17] and 0.98 [0.67, 1.44], respectively.

Study Conclusions

Investigators concluded that no dose adjustment is required for either drug when DCV is coadministered with DRV/r.2,3 However, coadministration of DCV and DRV/r should be undertaken with caution as this may result in increased DCV plasma concentrations and an increased risk of adverse effects. If concomitant use is required, consider monitoring for toxicity and adverse events associated with DCV.

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.