Clinical impact of pharmacokinetic interactions between the HCV protease inhibitor Simeprevir and frequently used concomitant medications

Aims

Direct-acting antivirals (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications.

Methods

This post-hoc analysis pooled data from 9 studies which evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of frequently used concomitant medication of interest (CMOI) were analysed (antihypertensive drugs (AHD), anxiolytic drugs (AXD), and lipid-lowering drugs (LLD)) and categorized as amber or green according to their DDI potential with SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant medications not recommended to be co-administered with SMV were not included. The composite primary endpoint was defined as the frequency of either discontinuation, interruption or dose modification of the CMOI during 12 weeks of SMV treatment.

Results

Few patients met the composite endpoint in the various subgroups. Patients on amber CMOI tended to experience CMOI modification more often (13.4-19.4%) than patients on green CMOI (3.1%-10.8%). There was no difference in frequency of adverse events between patients taking green and patients taking amber CMOI.

Conclusions

In this large pooled analysis, co-administration of the evaluated commonly prescribed medications with known or potential PK interactions with SMV was manageable and resulted in few adjustments of concomitant medications.

Our method could serve as a blueprint for the evaluation of the impact of DDIs.

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