Tenofovir Disoproxil Fumarate + Methotrexate = Precautionary

Effect on Concentration

Tenofovir Disoproxil Fumarate
No change
Applies within class?
No
Methotrexate
Decrease
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 19-Jul-2018

Summary

The role of PIs in the significance of this interaction has yet to be studied

Sources

Tenofovir Disoproxil Fumarate versus Methotrexate ^

Study Design

Trial setup involved n=48 participants mainly of male sex which were randomized to either low dose methotrexate (MTX) (n=20) or placebo (n=28) weekly for 24 weeks with close monitoring of viral load and CD4 count. Participants were on stable TFV containing ART. Intensive PK sampling occurred at week 2 and at the time of the 2nd dose of either MTX 10mg or placebo which was dosed with TFV. PK parameter monitored during serial PK sampling were AUC0-6hr and AUC 0-24hr and peak concentration (Cmax).

Study Results

48 participants had PK sampling (20 LDMTX, 28 placebo); all were taking TFV in the form of tenofovir disoproxil fumarate. Participants were 92% male, 48% white and 46% black; characteristics were balanced across treatment arms with the exception of concomitant PI-use (25% LDMTX, 43% placebo). For TFV, there was a 22% reduction in the geometric mean (GM) AUC0-6hr in the context of LDMTX; a similar reduction was apparent for AUC0-24hr and Cmax (Table). Analysis by concomitant protease inhibitor (PI) use, suggested a greater difference in the absence of a PI that appeared driven by 5 participants in the LDMTX arm with low TFV concentrations over the sampling period. A formal interaction test was not significant (P>0.3). For PK of LDMTX, the AUC0-6hr and Cmax are summarized descriptively in the abstract. A5314 follow-up is ongoing; interim safety analyses of VL have raised no concerns.

Study Conclusions

During TFV and LDMTX co-administration, decreases in the TFV AUC0-24hr and Cmax are apparent. These decreases appear driven by a subset of participants in the LDMTX arm who were not on PI’s. The results suggest alterations in TFV dosing during co-treatment with LDMTX are likely unnecessary for patients on PI. Further study of an interaction in patients not on PIs is warranted.

References

Gingich D, Ribaudo H, Kantor A, Stein JH, Currier JS, Hsue P, Aweeka F. Effect of low-dose methotrexate on the pharmacokinetics of tenofovir [abstract]. Conference On Retroviruses And Opportunstic Infections. Seattle, WA, USA. 2017; February 2017.