Ledipasvir/Sofosbuvir + Famotidine = Unknown or no reaction

Effect on Concentration

Ledipasvir/Sofosbuvir
No change
Applies within class?
No
Famotidine
No change
Applies within class?
No

Pharmacologic Effects

Ledipasvir/Sofosbuvir
Effect
N/A
Applies within class?
No
Famotidine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Famotidine dosing should NOT exceed 40 mg BID

Sources

Clinical pharmacokinetics and pharmacodynamics of ledipasvir/sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis C ^

Study Design

The drug-drug interaction potential of ledipasvir/sofosbuvir (LDV/SOF) with famotidine was assessed. LDV/SOF was administered as a 90/400mg once daily, while famotidine was given as 40mg. Pharmacokinetic evaluations of both simultaneous and 12-hour staggered single dose administration were conducted (n=12).

Study Results

Using geometric mean ratios (GMR) and 90% confidence intervals (CI), the Cmax and AUC for SOF, GS-331007 (major circulating metabolite for SOF) and LDV were as follows: SOF: 1.15 (0.88-1.50) and 1.11 (1.00-1.24); GS-331007: 1.06 (0.97-1.14) and 1.06 (1.02-1.11); LDV: 0.80 (0.69-0.93) and 0.89 (0.76-1.06), respectively, with simultaneous co-administration, and SOF: 1.00 (0.76-1.32) and 0.95 (0.82-1.10); GS-331007: 1.13 (1.07-1.20) and 1.06 (1.01-1.12); LDV: 0.83 (0.69-1.00) and 0.98 (0.80-1.20), respectively, when famotidine was administered 12 hours prior to LDV/SOF.

Study Conclusions

The authors state that an H2-receptor antagonist may be administered simultaneously or 12 hours apart from LDV/SOF at a dose not exceeding famotidine 40mg BID.

References

German P, Mathias A, Brainard D, Kearney BP. Clinical pharmacokinetics and pharmacodynamics of ledipasvir/sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis c. Clinical Pharmacokinetics. 2016; 11: 1337-1351.