Table 4.
Summary of the effects of coadministration on the pharmacokinetics (PK) of simeprevir and coadministered drugsa
| Coadministered drug | Effect on simeprevir PKb | Effect on coadministered drug PKb | Clinical comment |
|---|---|---|---|
| Erythromycin | ↑ | ↑ | Coadministration not recommended |
| Rifampin | ↓ | ↔ | Coadministration not recommended |
| Escitalopram | ↓ | ↔ | No dose adjustments needed for either drug |
| Ritonavir | ↑ | ↑ | Coadministration not recommended |
| Darunavir | NA | ↑ | No comment |
| Darunavir/ritonavirc | ↑ | NA | Coadministration not recommended |
| Efavirenz | ↓ | ↔ | Coadministration not recommended |
| Rilpivirine | ↔ | ↔ | No dose adjustments needed for either drug |
| Tenofovir | ↓ | ↔ | No dose adjustments needed for either drug |
| Raltegravir | ↔ | ↑ | No dose adjustments needed for either drug |
| Atorvastatin | ↔ | ↑ | Use the lowest necessary dose of atorvastatin, but do not exceed a daily dose of 40 mg when it is coadministered with simeprevir |
| Simvastatin | ↔ | ↑ | Titrate the simvastatin dose carefully and use the lowest necessary dose of it while monitoring for safety when it is coadministered with simeprevir |
AUC 24h area under the concentration-time curve from 0 to 24 h, CI confidence interval, NA not applicable
aSummary of data contained in Tables 2 and 3
bThe arrows signify the effects on the PK of the indicated drug according to the change in the mean ratio of the AUC24h: an increase (↑), decrease (↓) or no change (↔; if the 90 % CI is within the range of 0.80–1.25)
cThe dose of simeprevir was 150 mg once daily when it was administered alone, compared with 50 mg when it was coadministered with darunavir/ritonavir