PAH drug | Mechanism of interaction | Interacting drug | Interaction |
Ambrisentan | ? | CyclosporineKetoconazole | Caution is required in the co-administration of ambrisentan with ketoconazole and cyclosporine |
Bosentan | CYP3A4 inducer | Sildenafil | Sildenafil levels fall 50%; bosentan levels increase 50%. May not require dose adjustments of either drug. |
| CYP3A4 substrate | Cyclosporine | Cyclosporine levels fall 50%; bosentan levels increase fourfold. Combination contraindicated. |
| CYP3A4 substrate | Erythromycin | Bosentan levels increase. May not require dose adjustment of bosentan during a short course. |
| CYP3A4 substrate | Ketoconazole | Bosentan levels increase two-fold. |
| CYP3A4 substrate + bile salt pump inhibitor | Glibenclamide | Increase incidence of elevated aminotransferases. Potential decrease of hypoglycaemic effect of glibenclamide. Combination indicated. |
| CYP2C9 and CYP3A4 substrate | Fluconazole, amiodarone | Bosentan levels considerably increase. Combination potentially contraindicated. |
| CYP2C9 and CYP3A4 inducers | Rifampicin, phenytoin | Bosentan levels decrease by 58%. Need for dose adjustment uncertain. |
| CYP2C9 inducer | HMG CoA reductase inhibitors | Simvastatin levels reduce 50%; similar effects likely with atorvastatin. Cholesterol level should be monitored. |
| CYP2C9 inducer | Warfarin | Increases warfarin metabolism, may need to adjust warfarin dose. Intensified monitoring of warfarin recommended following initiation but dose adjustment usually necessary. |
| CYP2C9 and CYP3A4 inducers | Hormonal contraceptives | Hormone levels decrease. Contraception unreliable. |
Sitaxentan | CYP2C9 inhibitor | Warfarin | Inhibits warfarin metabolism, warfarin dose needs to be reduced by 80% when initiating sitaxentan and INR monitoring intensified. |
| ? inhibition of OATP transporter | Cyclosporine | Increases sitaxen levels; combination contraindicated. |
Sildenafil | CYP3A4 substrate | Bosentan | Sildenafil levels fall 50%; bosentan levels increase 50%. May not require dose adjustment of either drug. |
| CYP3A4 substrate | HMG CoA reductase inhibitors | May increase simvastatin/atorvastatin levels through competition for metabolism. Sildenafil levels may increase. Possible increased risk of rhabdomyolysis. |
| CYP3A4 substrate | HIV protease inhibitors | Ritonavir and saquinovir increase sildenafil levels markedly. Sildenafil dose adjustments are usually required. |
| CYP3A4 inducer | Phenytoin | Sildenafil level may fall. |
| CYP3A4 substrate | Erythromycin | Sildenafil levels increase may not require dose adjustment for a short course. |
| CYP3A4 substrate | Ketoconazole | Sildenafil levels increase. May not require dose adjustment. |
| CYP3A4 substrate | Cimetidine | Sildenafil levels increase. May not require dose adjustment. |
| cGMP | NitratesNicorandil | Profound systemic hypotension, combination contraindicated. |
Tadalafil | CYP3A4 substrate | Bosentan | Tadafil plasma levels decrease by 42%, no significant changes in bosentan levels. May not require dose adjustment. |
| cGMP | NitratesNicorandil | Profound systemic hypotension, combination contraindicated. |