Fostemsavir + Raltegravir = Precautionary

Effect on Concentration

Fostemsavir
No change
Applies within class?
No
Raltegravir
Unknown
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Investigators concluded that there were no clinically relevant drug-drug interactions between RAL and a wide range of doses of Fostemsavir. However, caution is warranted because of the broad 90% confidence intervals associated with the magnitude of change in the PK parameters of Fostemsavir.

Sources

Fostemsavir vs raltegravir/tenofovir disoproxil fumarate ^

Study Design

In a phase IIb, randomized, active-controlled, multiple dose study, treatment-experienced HIV-infected subjects (exposure to more than 1 antiretroviral for >1 week; n= 254) were randomized to 4 experimental arms (1:1:1:1) and a reference arm.To compare coadministration of fostemsavir (formerly BMS-663068) and RAL with administration of fostemsaviralone, subjects (n=/10) in each experimental arm received fostemsavir alone for 7 days (Days -7 to 0).Blood samples for pharmacokinetic (PK) analyses were collected on Day 14 for raltegravir (RAL) and temsavir (active metabolite; formerly known as BMS-626529). SequencenFostemsavirRALTDFATV/r150400 mg BID400 mg BID300 mg QD249800 mg BID351600 mg QD4501200 mg QDreference51300/ 100 mg QDRAL= raltegravirTDF= tenofovir disoproxil fumarate

Study Results

When patients were given RAL (400 mg BID) together with various doses of fostemsavir, RAL had no significant effect on geometric mean adjusted Cmax and AUC of temsavir. Geometric mean adjusted Ctau showed greater variability, which the authors attributed to inter-subject variability. nFostemsavir(Dose/freq)RAL(Dose/freq)TDF(Dose/freq)PK parameters (90% CI) of TemsavirCmaxAUCCtau50400 mg BID400 mg BID300 mg QD0.82 (0.61, 1.11)0.98 (0.78, 1.23)1.92 (0.93, 3.98)49800 mg BID0.90 (0.57, 1.40)0.95 (0.66, 1.37)0.99 (0.35, 2.89)51600 mg QD0.96 (0.74, 1.24)1.16 (0.95,1.42)2.06 (1.11, 3.81)501200 mg QD1.23 (0.92, 1.64)1.07 (0.84,1.34)1.17 (0.59, 2.32)

Study Conclusions

References

I Landry, D C Cui, J Wang, et al. Hiv-1 attachment inhibitor prodrug bms-663068: assessment of interaction with raltegravir in treatment-experienced hiv-1 infected subjects. 16th International Workshop On Clinical Pharmacology Of Hiv ; Hepatitis Therapy. Washington, DC. ; 2015.