Liverpool HEP Interactions

Coadministration of simeprevir (150 mg once daily) and sofosbuvir (400 mg once daily) increased sofosbuvir AUC and Cmax by 3.16- and 1.91-fold, respectively. The AUC of GS-331007 (the main metabolite) increased by 9%, but Cmax decreased by 31%. Simeprevir AUC and Cmax decreased by 6% and 4%, respectively. Comparisons were based on historic controls. The interaction between simeprevir and sofosbuvir was evaluated in a preliminary pharmacokinetic substudy within a phase 2 study in 22 HCV infected patients. The increase in sofosbuvir exposure observed in the preliminary pharmacokinetic substudy is not clinically relevant.The safety and efficacy of simeprevir in combination with sofosbuvir have not been established in a phase 3 study.

Olysio Summary of Product Characteristics, Janssen-Cilag, May 2014.

Simeprevir must not be used as monotherapy and can be administered with sofosbuvir (or with both peginterferon alfa and ribavirin).

The interaction between simeprevir and sofosbuvir was evaluated in a clinical study and no dose adjustments are needed for either drug. When compared to historical controls, coadministration of simeprevir (150 mg once daily) and sofosbuvir (400 mg once daily) to 21 subjects decreased simeprevir Cmax and AUC by 4% and 6%. Data from 22 subjects showed sofosbuvir Cmax increased by 91% and AUC increased by 3.16-fold; Cmax of GS-331007 (the major circulating metabolite of sofosbuvir) decreased by 31%, but AUC increased by 9%.
Olysio US Prescribing Information, Janssen, November 2014.