Coadministration has not been studied and may increase bosentan concentrations but decrease concentrations of cobicistat and darunavir. The European product label for darunavir/cobicistat does not recommended coadministration as it may lead to decreased cobicistat concentrations and consequently those of darunavir being boosted, leading to loss of therapeutic effect and possible development of resistance. However, the US product label suggests the following dose modifications. For patients stable on darunavir/cobicistat, start bosentan at 62.5 mg once daily or every other day based on individual tolerability. When starting darunavir/cobicistat in patients stable on bosentan, discontinue bosentan at least 36 h prior to starting cobicistat and resume bosentan at 62.5 mg once daily or every other day based on individual tolerability after at least 10 days following starting darunavir/cobicistat. To switch from ritonavir to cobicistat, maintain bosentan dose.