Asunaprevir/Daclatasvir (Clinical Trial) + Digoxin = Precautionary

Effect on Concentration

Asunaprevir/Daclatasvir (Clinical Trial)
No change
Applies within class?
No
Digoxin
Increase
Applies within class?
No

Pharmacologic Effects

Asunaprevir/Daclatasvir (Clinical Trial)
Effect
N/A
Applies within class?
No
Digoxin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Effect of steady-state daclatasvir plus asunaprevir on the single-dose pharmacokinetics of the P-glycoprotein substrate digoxin in healthy adult subjects. ^

Study Design

This was an open-label, single sequence, one-way interaction study to assess the combined effect of asunaprevir (ASV) and daclatasvir (DCV) on the pharmacokinetics (PK) of digoxin in healthy subjects (n=16). Participants received single doses of digoxin 0.25mg QD on days 1 and 16, and DCV 60mg QD + ASV 100mg BID on days 6-20. Blood samples for digoxin PK analysis were collected pre-dose and for 120 hours postdose on day 1 (without DCV + ASV) and day16 (with DCV + ASV).

Study Results

Mean plasma concentrations of digoxin were higher following coadministration with multiple doses of DCV + ASV than when administered alone. Using geometric mean ratios (GMR) and 90% confidence intervals (CI), the Cmax, AUC0-t and AUCinf for digoxin were 1.766 (1.504-2.073), 1.343 (1.265-1.425) and 1.288 (1.197-1.385), respectively. Coadministration of these agents did not appear to alter the Tmax or T1/2 of digoxin.

Study Conclusions

The authors state that this effect was not greater than that observed previously with DCV or ASV alone, indicating that there is no additive effect of these agents on P-gp inhibition and that the predominant sites for P-gp inhibition are non-renal. The recommendation from the manufacturer for co-administration of daclatasvir with digoxin should also be applied to this combination: "Digoxin should be used with caution when coadministered with daclatasvir. The lowest dose of digoxin should be initially prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical effect." Monitor the patient closely.

References

Garimella T, Adamczyk R, Stonier M, Kandoussi H, Hesney M, Coulston E, Bifano M. Effect of steady-state daclatasvir plus asunaprevir on the single-dose pharmacokinetics of the p-glycoprotein substrate digoxin in healthy adult subjects. Id Week. 2014; : 8-12.