Tenofovir Disoproxil Fumarate + Simeprevir = Unknown or no reaction

Effect on Concentration

Tenofovir Disoproxil Fumarate
No change
Applies within class?
No
Simeprevir
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Drug–drug interactions with the NS3/4A protease inhibitor simeprevir. ^

Study Design

In a randomized, open-label, three-period crossover trial with a washout period of at least 14 days, healthy subjects [n = 24 (12 male)] received simeprevir (150 mg once daily), tenofovir disoproxil fumarate TDF (300 mg once daily) or simeprevir (150 mg once daily) plus TDF (300 mg once daily) for 7 days. In an open-label, randomized, three-period crossover study with a washout period of at least 14 days, 24 healthy subjects (12 male) received simeprevir (150 mg once daily), rilpivirine (25 mg once daily) or simeprevir (150 mg once daily) plus rilpivirine (25 mg once daily) for 10 days under fed conditions. Drug–drug interactions were evaluated in a randomized, open-label, three-period crossover study with a washout period of at least 14 days. Twenty-four healthy subjects (17 male) received simeprevir (150 mg once daily), raltegravir (400 mg twice daily) or simeprevir (150 mg once daily) plus raltegravir (400 mg twice daily) for 7 days under fed conditions.

Study Results

In this study, there was no clinically significant decrease in simeprevir exposure with coadministration (the AUC24h decreased 15 %). Tenofovir DF exposure was not affected to a relevant degree (the AUC24h increased by 1.18-fold) with coadministration. Drug Effect on PK PK Parameters Cmax AUC Cmin Simeprevir Decreased 0.85 (0.73 – 0.99) 0.86 (0.76 – 0.98) 0.93 (0.78 – 1.11) Tenofovir No Change 1.19 (1.1 – 1.3) 1.18 (1.13 – 1.24) 1.24 (1.15 – 1.33) The Cmax of simeprevir increased by 1.10-fold; the minimum plasma concentration (Cmin) and AUC24h were unchanged (Table 2). The mean Cmin of rilpivirine increased by 1.25-fold; the Cmin and AUC24h were unchanged. Drug Effect on PK PK Parameters Cmax AUC Cmin Simeprevir No Change 1.1 (0.97 – 1.26) 1.06 (0.94 – 1.19) 0.96 (0.83 – 1.11) Rilpivirine No Change 1.04 (0.95 – 1.13) 1.12 (1.05 – 1.19) 1.25 (1.16 – 1.35) Coadministration resulted in no clinically relevant difference in simeprevir or raltegravir exposure (although the 90 % CI for the AUC24h ratio of test to reference for simeprevir did not include 1). Drug Effect on PK PK Parameters Cmax AUC Cmin Simeprevir No Change 0.93 (0.85 – 1.02) 0.89 (0.81 – 0.98) 0.86 (0.75 – 0.98) Raltegravir Increased 1.03 (0.78 – 1.36) 1.08 (0.85 – 1.38) 1.14 (0.97 – 1.36)

Study Conclusions

The manufacturer, and the authors of this study, state that no dose adjustment is required for either tenofovir disoproxil fumarate or simeprevir when these drugs are co-administered. Neither simeprevir exposure nor rilpivirine exposure was affected to a clinically relevant degree; therefore, no dose adjustment is required for coadministration of these drugs. Co-administration resulted in no clinically significant change to plasma concentration of raltegravir or simeprevir. These drugs can be administered without dose adjustment.

References

Ouwerkerk-Mahadevan, S, Snoeys J, Peeters M, Beumont-Mauviel M, Simion A. Drug–drug interactions with the ns3/4a protease inhibitor simeprevir. Clinical Pharmacokinetics. 2016; 2: 197-208.