Sofosbuvir/Velpatasvir + Digoxin = Precautionary

Effect on Concentration

Sofosbuvir/Velpatasvir
No change
Applies within class?
No
Digoxin
Increase
Applies within class?
No

Pharmacologic Effects

Sofosbuvir/Velpatasvir
Effect
N/A
Applies within class?
No
Digoxin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Sofosbuvir/Velpatasvir versus Digoxin ^

Study Design

This was a phase 1, open-label, single- and multiple dose, 5 cohort, crossover study in healthy subjects subjects to evaluate the pharmacokinetic (PK) interaction potential between velpatasvir (VEL) and digoxin (n=22).. Subjects received VEL 100mg plus digoxin (dose not reported) under fasting conditions. Serial blood samples were collected over 96 hours for PK analyses. Geometric least squares ratios and 90% confidence intervals were estimated with 80-125% bounds for analysis.

Study Results

Based on the GMRs and 90% confidence intervals , there was a 34% increase in digoxin AUC (1.13,1.60) and an 88% increase in digoxin Cmax (1.71,2.08) when coadministered with VEL. There was one adverse event (Grade 3 panic attack 2 days after taking a single 0.25mg dose of digoxin) that led to a person’s discontinuation of therapy and removal of the patient from the treatment group. Therefore 21 subjects completed the study.

Study Conclusions

Due to the narrow therapeutic index of digoxin as well as the wide confidence intervals observed, therapeutic drug monitoring is recommended for digoxin during concomitant use with VEL.

References

Mogalian E, McNally J, Shen G, Moorehead L, Sajwani K, Smith B, Mathias A. Drug-drug interaction profile of sofosbuvir/velpatasvir fixed-dose combination. Journal Of Hepatology. 2016; 2: S313-S314.