Bosentan Dosing for Pulmonary Arterial Hypertension
Start bosentan at 62.5 mg orally twice daily for the first 4 weeks, then increase to the maintenance dose of 125 mg twice daily if well tolerated. 1
Initial Dosing Phase
- Begin with 62.5 mg twice daily for the first 4 weeks to assess tolerability and monitor for adverse effects 1, 2
- This lower starting dose allows for evaluation of hepatotoxicity risk before escalating to therapeutic levels 1
Maintenance Dosing
- After 4 weeks, increase to the target dose of 125 mg twice daily if no adverse events have occurred 1, 3
- This 125 mg twice daily dose represents the optimal therapeutic dose for most PAH patients 1
- Higher doses (250 mg twice daily) show greater improvement in 6-minute walk distance but carry significantly increased risk of liver function abnormalities, making them generally not recommended 1
Clinical Context for Use
Bosentan is appropriate for:
- WHO functional class III patients who are not candidates for or have failed calcium channel blocker therapy 1
- PAH associated with congenital heart disease, connective tissue disease, or idiopathic PAH 1, 4
- WHO functional class IV patients may be considered for bosentan, though IV epoprostenol remains the preferred treatment for this advanced group 1
Critical Monitoring Requirements
Monthly liver function tests are mandatory due to hepatotoxicity risk, with elevated liver enzymes occurring in approximately 3-11% of patients 1:
- Check transaminases before initiating therapy and monthly thereafter 1
- Hemoglobin/hematocrit monitoring is necessary due to potential anemia development 1
- Regular pregnancy testing is required in women of childbearing age due to teratogenic effects 1
Important Caveat
Do not initiate bosentan simultaneously with IV epoprostenol in PAH patients starting prostacyclin therapy 5. This combination at initiation is specifically advised against by CHEST guidelines, though the exact mechanism of concern is not fully elucidated in the evidence.