Ledipasvir/Sofosbuvir + Rifampin = Prohibited

Effect on Concentration

Ledipasvir/Sofosbuvir
Decrease
Applies within class?
No
Rifampin
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir. ^

Study Design

The drug-drug interaction potential of ledipasvir and sofosbuvir (LDV and SOF) administered separately with several drugs was assessed in pharmacokinetic evaluations.

Study Results

Co-administration of LDV and SOF with rifampin resulted in a reduced Cmax and AUC by 77% and 72%, respectively, for SOF, and the AUC of the major circulating metabolite of SOF, GS-331007 did not change, however the Cmax increased by ~24 %, and the Cmax and AUC reduced 35% and 59%, respectively, for LDV.

Study Conclusions

The authors state that rifampin and other P-gp inducers should not be utilized in combination with LDV/SOF. Prescribing information for Harvoni (LDV/SOF - coformulated) states that "coadministration of HARVONI with rifampin, a P-gp inducer, is not recommended".

References

German P, Mathias A, Brainard DM, Kearney BP. Drug–drug interaction profile of the fixed-dose combination tablet regimen ledipasvir/sofosbuvir. Clinical Pharmacokinetics. 2018; : 1-15.

Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir. ^

Study Design

The drug-drug interaction potential of ledipasvir and sofosbuvir (LDV and SOF) administered separately with rifampin was assessed in pharmacokinetic evaluations.

Study Results

Co-administration of LDV and SOF with rifampin resulted in a reduced Cmax and AUC by 77% and 72%, respectively, for SOF, and the AUC of the major circulating metabolite of SOF, GS-331007 did not change, however the Cmax increased by ~24 %, and the Cmax and AUC reduced 35% and 59%, respectively, for LDV.

Study Conclusions

The authors state that rifampin and other P-gp inducers should not be utilized in combination with LDV/SOF. Prescribing information for Harvoni (LDV/SOF - coformulated) states that "coadministration of HARVONI with rifampin, a P-gp inducer, is not recommended".

References

Mathias A, German P, Brainard DM, Kearney BP. Drug–drug interaction profile of the fixed-dose combination tablet regimen ledipasvir/sofosbuvir. Clinical Pharmacokinetics. 2018; : 1-15.