Sofosbuvir + Rifampin = Prohibited

Effect on Concentration

Sofosbuvir
Decrease
Applies within class?
No
Rifampin
Unknown
Applies within class?
No

Pharmacologic Effects

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

Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis C virus NS5B polymerase inhibitor sofosbuvir. ^

Study Design

This was an open-label, randomized, cross-over Phase 1 study in healthy subjects to evaluate the effect of rifampin (RIF) on sofosbuvir (SOF) pharmacokinetics (PK). Participants received single doses of SOF 400mg alone and one day after 7 consecutive daily doses of RIF 600mg. All doses were administered under fasting conditions. Geometric mean ratios (GMR %) and 90% confidence intervals (CI) for SOF and major circulating metabolite, GS-331007 AUC and Cmax were estimated with PK equivalence boundaries of 70-143%

Study Results

Using the GMR%, RIF-mediated induction caused SOF AUC and Cmax to decrease by ~72 % and ~77 %, respectively. The AUC of GS-331007 did not change, however, Cmax increased by ~24%. Using GMR and 90% CI, the Cmax and AUC of SOF were 0.95 (0.68-1.33) and 1.30 (1.00-1.69), respectively, while those for GS-331007 (major circulating metabolite) were 0.73 (0.65-0.83) and 1.04 (0.89-1.22), respectively. These changes were not deemed clinically relevant and no effect on the PK parameters of methadone was observed with co-administration of these agents (PK parameters not reported).

Study Conclusions

The authors state that the decrease in SOF exposure when co-administered with RIF is clinically significant and expected to alter its therapeutic effect. This is consistent with current labeling of SOF which states that co-administration of SOF with RIF and other potent P-gp inducers is not recommended. There were no reports of subjective methadone withdrawal symptoms or indications of decreased methadone efficacy based on the Short Opiate Withdrawal Scale (SOWS), Desires for Drugs Questionnaire (DDQ) or pupil diameter measurements.

References

Kirby BJ, Symonds WT, kearney BP, Mathias AA. Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis c virus ns5b polymerase inhibitor sofosbuvir. Clinical Pharmacokinetics. 2015; 7: 677-690.