Table 4 Monitoring and dosage of pulmonary arterial hypertension pharmacotherapy in renal insufficiency
Drug | Degree of renal elimination | Dosage adjustments | Monitoring | Recommendations |
|---|---|---|---|---|
Phosphodiesterase type 5 inhibitors | Â | Â | ||
Sildenafil [8] | Nonrenal metabolism to active metabolites; 13% of dose excreted in urine as metabolites | No dose adjustment is required. In patients with CrCl ≤30 ml/minute, exposure to parent drug and active metabolite increased twofold | Worsening of side effects (hypotension, epistaxis, nasal congestion, headache, dyspepsia, flushing, insomnia, erythema, dyspnea and/or rhinitis) | Monitor for worsening of side effects and decrease dosage if indicated. |
Tadalafil [11] | Nonrenal metabolism; however, renal impairment results in twofold to fourfold increase in tadalafil exposure | CrCl 31 to 80 ml/minute: start dosing at 20 mg once daily; increase to 40 mg once daily based on individual tolerability. CrCl ≤30 ml/minute or hemodialysis: avoid use. | Worsening of side effects (hypotension, headache) | Monitor for hypotension, consider dose reduction. Severe impairment: hold dose if side effects worsened |
Endothelin-receptor antagonists | Â | Â | ||
Ambrisentan [17] | Nonrenal elimination | No adjustment for mild-moderate renal failure; severe renal failure and hemodialysis not studied | Fluid overload | Hold if fluid overload is problematic |
Bosentan [13] | <3% eliminated in urine | No adjustment necessary | Fluid overload | Hold if fluid overload is problematic |
Macitentan [13] | Nonrenal elimination | No adjustment necessary | Worsening of side effects (anemia, nasopharyngitis, pharyngitis, bronchitis, headache, influenza, and urinary tract infection) | Likely safe to use in patients with renal dysfunction |
Soluble guanylate cyclase stimulator | Â | Â | ||
Riociguat [19] | 40% drug eliminated in urine (mostly as inactive metabolites) | Not recommended in patients with CrCl <15 ml/minute or those receiving dialysis | Possible hypotension bleeding or other side effects (headache, dizziness, dyspepsia/gastritis, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux, and constipation) | Monitor for hypotension, consider dose reduction. Severe impairment (anuria): hold dose if side effects worsened |
Intravenous prostacyclin therapy | Â | Â | ||
Nonrenal elimination; metabolites recovered in urine, some of which are minimally active | No adjustment necessary; if initiating therapy, consider starting at a low dose and titrating slowly | Possible hypotension or side effects (headache, jaw pain, flushing) | Titrate slowly during initiation phase; consider gradual dosage reduction if patient is hypotensive and experiencing increased side effects (flushing, headache, jaw pain); do not abruptly discontinue therapy | |
Treprostinil [41] | 4% of unchanged drug eliminated in urine; all metabolites (inactive) renally eliminated | No specific recommendation available | Possible hypotension or side effects (headache, jaw pain, flushing) | Titrate slowly during initiation phase; consider gradual dosage reduction if patient is hypotensive and is experiencing increased side effects (flushing, headache, jaw pain); do not abruptly discontinue therapy |
Inhaled vasodilators (prostacyclin and nonprostacyclin) | Â | Â | ||
Inhaled nitric oxide [42] | Combines with oxyhemoglobin to produce methemoglobin and nitrate; nitrate is renally eliminated | No dosage adjustments recommended/required | Methemoglobin | Probably safe to use in patients with renal dysfunction |
Treprostinil, inhaled [21] | 4% of unchanged drug eliminated in urine; all metabolites (inactive) renally eliminated | No specific recommendation available | Possible hypotension or side effects (headache, jaw pain, flushing) | Titrate slowly during initiation phase; consider increasing dosing interval if patient is hypotensive and experiencing increased side effects (flushing, headache, jaw pain) |
Iloprost, inhaled [20] | Nonrenal elimination | Not studied in patients with renal impairment; based on drug elimination, accumulation not expected | Possible syncope or side effects (headache, flushing, dizziness, nausea, vomiting or diarrhea) | Probably safe for use in patients with renal dysfunction. Continue usual monitoring |