Endothelin Receptor Antagonists for the Treatment of Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis

Table 1

Endothelin receptor antagonists.

Endothelin receptor antagonist	Oral dose	Relative ETA/ETB selectivity	Information
Nonselective
Bosentan	Starting: 62.5 mg twice daily; Maintenance: 125 mg twice daily	20x	FDA approved for use in the USA in November 2001 for WHO functional class III/IV PAH then extended to include WHO class II in 2009. Approved in the EU for WHO functional class III PAH in May 2002. In June 2007, the EU approved and extended the indication of bosentan as a therapy to reduce the number of new DU in patients with SSc and ongoing DU disease.
Selective
Ambrisentan	Starting: 5 mg daily; Maintenance: 5 or 10 mg daily	4000x	FDA approved for the once-daily treatment of WHO functional class II/III PAH in June 2007. It was later approved by the European Medicines Agency for the same indication in the EU in April 2008.
Sitaxsentan	100 mg daily	6500x	Approved in the EU in August 2006, then in Canada and Australia in March 2007 for the once-daily treatment of WHO functional class III PAH. On December 10, 2010, the manufacturer voluntarily removed sitaxsentan from the market and halted clinical trials due to concerns about liver toxicity.

FDA: Food and Drug Administration, EU: European Union, PAH: pulmonary arterial hypertension, DU: digital ulcer(s), RP: Raynaud’s phenomenon, and SSc: systemic sclerosis.