Macitentan (Opsumit) for Pulmonary Arterial Hypertension
The recommended dosage of macitentan (Opsumit) for treating pulmonary arterial hypertension is 10 mg once daily for oral administration. 1
Dosing and Administration
- Macitentan is administered orally at a fixed dose of 10 mg once daily
- Doses higher than 10 mg once daily have not been studied in PAH patients and are not recommended 1
- No dose adjustments are required based on age, gender, or mild to moderate hepatic impairment
Clinical Evidence Supporting Efficacy
Macitentan's efficacy was established in the landmark SERAPHIN trial, which was the first large-scale, long-term event-driven study in PAH with morbidity and mortality as the primary endpoint:
- The trial included 742 patients with PAH (predominantly WHO Functional Class II-III) treated for an average of 100 weeks 2
- Patients receiving macitentan 10 mg once daily showed a 45% reduction in the risk of morbidity and mortality compared to placebo 3
- The primary endpoint occurred in 31.4% of patients in the macitentan 10 mg group versus 46.4% in the placebo group 3
- Benefits were demonstrated both in treatment-naïve patients and those already receiving PAH therapy 2
Patient Population
Macitentan is indicated for:
- Adults with PAH (WHO Group I) to reduce the risks of disease progression and hospitalization 1
- Patients with predominantly WHO Functional Class II-III symptoms 1
- Various PAH etiologies including:
- Idiopathic and heritable PAH (57% of studied patients)
- PAH associated with connective tissue disorders (31%)
- PAH associated with congenital heart disease with repaired shunts (8%) 1
Monitoring Requirements
- Pregnancy testing: Must exclude pregnancy before initiating treatment in females of reproductive potential 1
- Liver function: Obtain baseline liver enzyme tests and monitor as clinically indicated 1
- Incidence of elevated aminotransferases >3× ULN was 3.4% with macitentan versus 4.5% with placebo
- Discontinue if clinically relevant aminotransferase elevations occur or if accompanied by increased bilirubin >2× ULN
- Hemoglobin levels: Monitor for potential anemia
- Reduction in blood hemoglobin ≤8 g/dl was observed in 4.3% of patients receiving 10 mg macitentan 2
Adverse Effects
The most common adverse reactions (more frequent than placebo by ≥3%) include:
- Anemia
- Nasopharyngitis/pharyngitis
- Bronchitis
- Headache
- Influenza
- Urinary tract infection 1
Fluid retention and peripheral edema may occur (21.9% incidence with macitentan versus 20.5% with placebo) 1
Important Contraindications and Warnings
- Pregnancy: Macitentan is contraindicated during pregnancy due to potential fetal harm 1
- Reproductive considerations: Females of reproductive potential must use effective contraception before, during, and for one month after treatment 1
- Hypersensitivity: Contraindicated in patients with history of hypersensitivity to macitentan 1
Advantages Over Other ERAs
Macitentan offers several potential advantages compared to other endothelin receptor antagonists:
- Once-daily dosing (compared to twice-daily dosing for bosentan) 2
- No dose titration required (unlike bosentan which requires titration) 2
- Lower incidence of liver toxicity compared to bosentan (no liver toxicity shown in pivotal trials) 2
- Demonstrated reduction in morbidity and mortality in a long-term outcome study 3
Drug Interactions
- Strong CYP3A4 inducers (e.g., rifampin): Avoid co-administration as they reduce exposure to macitentan 1
- Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): Avoid co-administration as they increase exposure to macitentan 1
- Moderate dual CYP3A4 and CYP2C9 inhibitors (e.g., fluconazole, amiodarone): Avoid co-administration 1
Macitentan represents an important treatment option for PAH with proven efficacy in reducing disease progression and hospitalization, supported by robust clinical evidence from the largest and longest prospective trial in PAH to date.