Bictegravir/Emtricitabine/Tenofovir Alafenamide + Rifampin = Prohibited

Effect on Concentration

Bictegravir/Emtricitabine/Tenofovir Alafenamide
Decrease
Applies within class?
No
Rifampin
Unknown
Applies within class?
No

Pharmacologic Effects

Bictegravir/Emtricitabine/Tenofovir Alafenamide
Effect
N/A
Applies within class?
No
Rifampin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 03-Dec-2018

Summary

Administration of RIF with twice daily BIC/F/TAF leads to a marked decrease in BIC AUC0-24h and Cmax. The geometric least squares mean BIC Ctrough is lowered by 80% when co-administered with RIF but remains above the 95% effective concentration. Until further information is available, use of twice daily bictegravir with rifampin cannot be recommended.

Sources

Bictegravir versus Rifampin ^

Study Design

Cohort 1 subjects received Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/F/TAF) (50/200/25 mg) once daily (QD), 2 hours postprandial, for 28 days. Cohort 2 subjects received B/F/TAF twice daily (BID) plus Rifampin (RIF) 600 mg QD, 2 hours postprandial, for 28 days. Intensive plasma sampling was conducted on Day 28 for determination of BIC primary PK parameters (AUC0-24h, Cmax, Ctrough). Statistical comparisons for BIC were performed using geometric least squares mean (GLSM) ratios and associated 90% confidence intervals (CI) with B/F/TAF BID plus RIF in Cohort 2 as the test treatment and B/F/TAF QD in Cohort 1 as the reference treatment.

Study Results

Following co-administration of BIC/F/TAF BID plus RIF for 28 days, the BIC AUC0-24h and Cmax were decreased approximately 61% and approximately 47%, respectively, as compared with BIC/F/TAF QD administration alone. Although the observed BIC Ctrough in all subjects was above the protein adjusted 95% effective concentration (paEC95) (162 ng/mL) following BIC/F/TAF BID plus RIF in Cohort 2, the resulting geometric least squares mean BIC Ctrough was approximately 80% lower, as compared with that observed following B/F/ TAF QD in Cohort 1.

Study Conclusions

These findings show that twice daily administration of BIC/F/TAF with RIF does not mitigate the induction effect sufficiently to yield BIC Ctrough concentrations associated with the B/F/TAF registrational Phase 3 studies.

References

Custodio, JM, West, SK, Collins, S. Pharmacokinetics of bictegravir administered twice daily in combination with rifampin. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.