Products
Macitentan is commercially available in the form of film-coated tablets (Opsumit). It was approved in the United States in October 2013 and in many countries in 2014. Macitentan was launched as a successor to bosentan (Tracleer) as it loses patent protection.
Structure and properties
Macitentan (C19H20Br2N6O4S, Mr = 588.3 g/mol) is a brominated pyrimidine derivative. It was developed as a dual and tissue-specific endothelin receptor antagonist. Macitentan exists as a crystalline powder that is insoluble in water.
Effects
Macitentan (ATC C02KX04) and its metabolite ACT-132577 are dual ETA-/ETB–endothelin receptor antagonists and thus abolish the effects of endothelin. They are vasodilators, reduce vascular resistance, and increase blood flow volume without increasing heart rate.
Indications
For the treatment of pulmonary arterial hypertension.
Dosage
According to the SmPC. Tablets are taken once daily, regardless of meals.
Contraindications
- Hypersensitivity
- Pregnancy
- Women capable of childbearing without contraception
- Elevated liver enzymes before starting treatment
Full precautions can be found in the drug label.
Interactions
Macitentan is a substrate of CYP3A4 with minor involvement of CYP2C19. Drug-drug interactions are possible with potent CYP3A inhibitors and inducers.
Adverse effects
The most common potential adverse effects include anemia, nasopharyngitis, pharyngitis, bronchitis, headache, influenza, and urinary tract infection. Other endothelin receptor antagonists have liver toxic properties. Therefore, such side effects should also be watched for with macitentan.
