BOSENTAN TAB,SUSP,ORAL
Clinical Criteria Summary
Exclusion Criteria
- Known pregnancy
- Baseline hepatic transaminase elevations >3 times the upper limit of normal
- Moderate or severe liver impairment (e.g., Child-Pugh Class B or C)
Inclusion Criteria
- Care provided by a VA/VA Community Care provider experienced in the management of pulmonary arterial hypertension (PAH) (certified and enrolled in the bosentan REMS Program)
- World Health Organization (WHO) Group 1 PAH
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure >25 mmHg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance >3 Wood Units
- Baseline hepatic transaminase testing and commitment to monthly testing
- Intolerance, inadequate response, or unable to use ambrisentan (ambrisentan is the preferred endothelin receptor antagonist when clinically appropriate)
Reproductive Safety & Counseling
- Females who can become pregnant: Pregnancy must be excluded prior to receiving bosentan; counseling on potential risk vs benefit and effective contraception use prior to, during, and one month after stopping treatment is required
- Males of reproductive potential: Counseling provided on the potential risk of bosentan to adversely affect spermatogenesis and impair fertility
Hemodynamic & Clinical Context Considerations
- Hemodynamic definition applies to the majority of PAH patients and is recommended by the 7th World Symposium for Pulmonary Hypertension for consideration of PAH-specific drug therapy including endothelin receptor antagonists
- Decisions for hemodynamic parameters outside specified thresholds should be made by PAH specialists in the context of the individual patient's entire presentation
- mPAP and PVR thresholds have been expanded to include mPAP >20 mmHg and PVR >2 Wood Units, though most PAH therapies were studied in populations meeting the older definition
- Consensus is lacking on whether PAH treatment should be considered in patients with mildly elevated pressures per the 7th World Symposium
- PAWP ≤15 mm Hg is traditionally used to rule out pulmonary hypertension due to left-heart disease, where PAH-specific therapies have not been shown to benefit and may result in harm
- REVEAL U.S. registry data suggests PAH may exist in patients with PAWP 16-18 mmHg; survival did not significantly differ from those with PAWP ≤15 mm Hg at diagnosis