Macitentan for the Treatment of Pulmonary Arterial Hypertension

@article{Hong2014MacitentanFT,
  title={Macitentan for the Treatment of Pulmonary Arterial Hypertension},
  author={Irene Seunghyun Hong and Holly V Coe and Linda M. Catanzaro},
  journal={Annals of Pharmacotherapy},
  year={2014},
  volume={48},
  pages={538 - 547}
}
Objective: To review the pharmacology, safety, and efficacy of macitentan. Data Sources: PubMed, EMBASE, and ClinicalTrials.gov were searched using the terms macitentan and ACT-064992. Study Selection and Data Extraction: Phase II and III trials were reviewed in our primary analysis; data from phase I trials and other studies were reported as applicable. Data Synthesis: Macitentan is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH… 
11 Citations
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TLDR
Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study.
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TLDR
Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group, and the primary objective was not met.
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Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations and the study was terminated early.
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The pharmacokinetic and tolerability profile of macitentan is consistent with a once-a-day dosing regimen and warrants further investigation in clinical studies.
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TLDR
Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations and the study was terminated early.
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TLDR
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TLDR
Macitentan co-administered with Cs or rifampin was well tolerated and no marked differences in uptake rates of macitentan and ACT-132577 between the wild-type and OATP over-expressing cells over the concentration range tested were demonstrated.
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TLDR
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TLDR
Macitentan metabolism is indeed affected by CYP3A4 inhibition, but the changes are not considered to be clinically significant and macitentan can be administered concomitantly with CYP2C19 isoenzyme without need for dose adjustment.
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