What are the side effects of Macitentan (Endothelin receptor antagonist)?

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From the Guidelines

Macitentan can cause several side effects, including headache, nasopharyngitis, anemia, and peripheral edema, as well as more serious side effects such as liver problems and fluid retention, which require immediate medical attention. The most common side effects of macitentan include:

  • Headache
  • Nasopharyngitis
  • Anemia
  • Peripheral edema These side effects were reported in a study published in the journal Chest in 2014, which investigated the long-term treatment with macitentan in patients with pulmonary arterial hypertension (PAH) 1. The study found that the incidences of peripheral edema and of alanine aminotransferase or aspartate aminotransferase levels that were more than three times the upper limit of the normal range were similar across the three groups, but higher percentages of patients in the two macitentan groups had nasopharyngitis, headache, and anemia.

More serious side effects of macitentan include liver problems, which can be symptoms of nausea, vomiting, fever, abdominal pain, or yellowing of skin/eyes, and significant decrease in hemoglobin levels, which may require blood tests during treatment 1. Additionally, macitentan can cause fluid retention, which may worsen heart failure symptoms. Women of childbearing potential must use reliable contraception during treatment and for one month after stopping the medication, as macitentan can cause serious birth defects. Monthly pregnancy tests are typically required 1.

The typical dose of macitentan is 10 mg once daily, taken with or without food. Patients should inform their healthcare provider about all medications they're taking, as macitentan can interact with certain drugs, particularly strong CYP3A4 inhibitors and inducers, which may affect its effectiveness or increase side effect risks. Patients with pulmonary arterial hypertension may experience worsening symptoms if macitentan is stopped abruptly, so the medication should only be discontinued under medical supervision.

From the Research

Side Effects of Macitentan

The side effects of Macitentan, an endothelin receptor antagonist, have been studied in several clinical trials. Some of the common side effects include:

  • Decrease in hemoglobin concentration 2, 3
  • Edema/fluid retention, although the safety profile of macitentan appears to be superior with respect to hepatic safety and edema/fluid retention than bosentan and ambrisentan, respectively 2
  • Hepatic safety issues, with a case report of fulminant hepatitis associated with macitentan 4
  • Embryo-fetal toxicity, making it contraindicated in pregnant women 3

Serious Adverse Events

Some serious adverse events associated with macitentan include:

  • Liver injury, with a reported case of fulminant hepatitis requiring liver transplantation 4
  • All-cause hospitalization and PAH-related hospitalization, although macitentan has been shown to significantly reduce the risk of these events 5

Comparison to Other Endothelin Receptor Antagonists

Macitentan has been compared to other endothelin receptor antagonists, such as bosentan and ambrisentan, in terms of its safety profile. The results suggest that macitentan has a superior safety profile with respect to hepatic safety and edema/fluid retention 2. However, the risk of liver injury associated with macitentan is still a concern, as highlighted by a case report of fulminant hepatitis 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Macitentan for the treatment of pulmonary arterial hypertension.

Drugs of today (Barcelona, Spain : 1998), 2014

Research

Macitentan: A Review in Pulmonary Arterial Hypertension.

American journal of cardiovascular drugs : drugs, devices, and other interventions, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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