Raltegravir + Tenofovir Disoproxil Fumarate = Precautionary

Effect on Concentration

Raltegravir
Increase
Applies within class?
No
Tenofovir Disoproxil Fumarate
No change
Applies within class?
No

Pharmacologic Effects

Raltegravir
Effect
N/A
Applies within class?
No
Tenofovir Disoproxil Fumarate
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

The increase in plasma raltegravir levels is not considered to be clinically significant.A second PK analysis in HIV+ individuals, also reported in the referenced article, found that the combination of tenofovir and lamivudine increased the plasma raltegravir geometric mean ratio of AUC, Cmax and trough concentrations. In this dose-ranging study, only 6 subjects were treated with raltegravir 400 mg twice daily, and only the increase in trough concentration produced a 90% CI with a lower limit > 1.

Sources

Tenofovir disoproxil fumarate vs raltegravir ^

Study Design

Ten healthy, HIV-negative adult males were administered raltegravir 400 mg every 12 hours for 7 doses (Period 1). After a washout period, tenofovir disoproxil fumarate 300 mg was administered daily for 7 days (Period 2). Immediately following period 2, the combination of raltegravir 400 mg every 12 hours and tenofovir 300 mg daily was administered for 4 days (Period 3). Tenofovir was administered with food. PK sampling took place on the last day of each period.

Study Results

The addition of tenofovir increased plasma raltegravir Cmax 64% (p=0.029) and AUC 49% (p=0.023). Raltegravir trough concentrations were similar regardless of tenofovir exposure.In the presence of raltegravir, serum tenofovir Cmax decreased by 23% (p=0.001). Serum tenofovir AUC and trough concentrations decreased only slightly, 10% and 13% respectively, which was not found to be statisitically significant.

Study Conclusions

References

Larissa A Wenning, Evan J Friedman, James T Kost, Sheila A Breidinger, Jon E Stek, Kenneth C Lasseter, Keith M Gottesdiener, et al. Lack of a significant drug interaction between raltegravir and tenofovir. Antimicrobial Agents And Chemotherapy. 2008; 9: 3253-3258.