Fostemsavir + Rosuvastatin = Precautionary

Effect on Concentration

Fostemsavir
Unknown
Applies within class?
No
Rosuvastatin
Increase
Applies within class?
No

Pharmacologic Effects

Fostemsavir
Effect
N/A
Applies within class?
No
Rosuvastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Per the investigators, in vitro and clinical data suggest that fostemsavir can be co-administered with statins that are substrates of OATP or BCRP, but dose adjustments may be required. In an ongoing Phase III study, doses of ROS and other statins are being modified and/or carefully titrated when co-administered with fostemsavir.Co-administration of ROS with fostemsavir is therefore discouraged until these data are available to help inform final dosing recommendations. However, if these agents are utilized in combination, it is prudent to use the lowest dose of ROS when initiating fostemsavir. Close monitoring for ROS-related adverse events is advised in this case.

Sources

Rosuvastatin vs fostemsavir ^

Study Design

This was a phase I, open-label, single-site, single-sequence study in healthy adults (n=18) to assess the effect of the co-administration of fostemsavir (formerly known as BMS-663068) on the systemic exposure of rosuvastatin (ROS). A single dose of ROS 10 mg was administered on Day 1, followed by a 3-day washout period. On Days 5-8 fostemsavir 600 mg BID was administered, followed by co-administration of fostemsavir and ROS on Day 9. Fostemsavir was then administered alone on Days 10 -12.Blood samples were collected for pharmacokinetic (PK) analysis of ROS on Days 1-5 and 9-13, while those for temsavir (formerly known as BMS-626529; active moiety of fostemsavir) were collected on Days 7-9, 11 and 13.

Study Results

Co-administration of fostemsavir with ROS resulted in an increased peak and total exposure for ROS by 78% and 69%, respectively, compared with exposures observed with rosuvastatin alone.Geometric mean ratios and 90% confidence intervals (GMR; 90% CI) for Cmax and AUCinf of ROS (Fostemsavir + ROS / ROS) were 1.78 [1.52, 2.09] and 1.69 [1.44, 1.99], respectively.The effect of ROS on the PK of fostemsavir or temsavir was not reported.Multiple fostemsavir doses were generally well-tolerated when co-administered with ROS 10mg; there no serious adverse events or adverse events leading to study discontinuation.

Study Conclusions

References

I Landry, B Vakkalagadda, S Lubin, et al. Hiv-1 attachment inhibitor prodrug bms-663068: pk assessment with rosuvastatin. Conference On Retroviruses And Opportunistic Infections. Boston, MA. ; 2016.