title: Comparative safety and tolerability of endothelin receptor antagonists in pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a condition that leads to progressive right heart failure and death unless recognized and treated early. Endothelin, a potent endogenous vasoconstrictor, has been identified as an important mediator of PAH. Endothelin receptor antagonists (ERAs) have been associated with an improvement in exercise capacity and time to clinical worsening in patients with Group 1 PAH, and three different ERAs are currently approved for use in this population: bosentan, ambrisentan, and macitentan. While all three ERAs are generally well-tolerated, they each have important adverse effects that need to be recognized and monitored. In particular, they may cause anemia, peripheral edema, and mild cardiac, respiratory, neurologic, and gastrointestinal adverse effects to varying degrees. Although bosentan increases a patient's risk of developing liver transaminitis, ambrisentan and macitentan do not appear to confer the same risk of hepatotoxicity at this time. Important drug-drug interactions, particularly involving other drugs metabolized via the cytochrome P450 pathway, are important to recognize when prescribing ERAs. In this review, we provide a brief overview of the current state of knowledge as it relates to the adverse effect profiles, tolerability, and drug-drug interactions of this class of medication as informed by the results of randomized clinical trials, drug surveillance programs, and regulatory agencies.
authors: Toronto General Hospital, 11-124 Munk building, 585 University Ave, Toronto, Ontario, Canada.
authors: Meghan
authors: M
authors: Aversa
authors: Sandra
authors: S
authors: Porter
authors: John
authors: J
authors: Granton
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000077300:Bosentan; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000517:prevention & control; D004347:Drug Interactions; D016903:Drug Monitoring; D065128:Endothelin Receptor Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010666:Phenylpropionates / Q000009:adverse effects* / Q000627:therapeutic use; D011724:Pyridazines / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C467894:ambrisentan; D000077300:Bosentan; C533860:macitentan