Tenofovir Alafenamide + Dolutegravir = Unknown or no reaction

Effect on Concentration

Tenofovir Alafenamide
Increase
Applies within class?
No
Dolutegravir
No change
Applies within class?
No

Pharmacologic Effects

Tenofovir Alafenamide
Effect
N/A
Applies within class?
No
Dolutegravir
Effect
N/A
Applies within class?
No

Interaction History

Precautionary, 03-Aug-2018;

Last Updated 03-Aug-2018

Summary

Sources

Tenofovir alafenamide vs ARVs ^

Study Design

This was an open-label, fixed sequence, crossover study to evaluate the effect of dolutegravir (DTG) 50mg on the pharmacokinetics (PK) of tenofovir alafenamide (TAF) 10mg plus emtricitabine (FTC) 200mg (n=9). Treatments were administered in the morning with food as follows:Day 1: FTC + TAF 200/10mg QD; Days 2-14: DTG 50mg QD; Day 15: FTC + TAF 200/10mg + DTG 50mg QD.Plasma samples for PK analysis were collected over 24 hours on days 1, 14 and 15.

Study Results

Using 90% confidence intervals and geometric mean ratios, when DTG was co-administered with FTC and TAF the AUCinf and Cmax for TAF were 1.17 (0.94-1.45) and 1.24 (0.88-1.74), respectively compared to administration of FTC + TAF alone.The exposure of tenofovir (TFV; active form of TAF) was also analyzed with and without DTG; AUCinf and Cmax of TFV were 1.25 (1.06-1.47) and 1.10 (0.96-1.25), respectively compared to administration of FTC + TAF alone.Monitor for tenofovir-associated adverse effects. AUC, Ctau and Cmax of DTG were 0.98 (0.93-1.03), 0.95 (0.88-1.03) and 0.87 (0.79-0.96), respectively.These results informed the authors' decision to pursue dosing of a fixed dose combination of FTC + TAF 200/25mg in combination with integrase inhibitors.

Study Conclusions

With unboosted antiretrovirals, TAF is dosed at 25 mg daily. Because of the pharmacokinetic data above, the manufacturers pursued dosing of TAF at 10 mg, due to inhibition of metabolism by CYP3A.

References

Lawson EB, H Martin, S McCallister, et al. Drug interactions between tenofovir alafenamide and hiv antiretroviral agents. 54th Interscience Conference On Antimicrobial Agents And Chemotherapy. . ; 2014.