Product: Opsumit

Company: Actelion

Pharmacologic class: Endothelin receptor antagonist

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Active ingredient: Macitentan 10 mg; tabs.

Indication: Treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression. In clinical studies, treatment delayed disease progression (death, initiation of IV or subcutaneous [SC] prostanoids, or clinical worsening of PAH [decreased six-minute walk distance, worsened PAH symptoms, and need for additional PAH treatment]) and reduced hospitalization for PAH.

Pharmacology: Macitentan prevents the binding of endothelin (ET)-1 to both ETA and ETB receptors with displays of high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. 

Clinical trials: The efficacy of macitentan was demonstrated in a multicenter, long-term, placebo-
controlled study involving 742 patients with symptomatic (WHO functional class [FC] II-IV) PAH. Patients were randomized to placebo (n=250), 
macitentan 3 mg (n=250), or macitentan 10 mg (n=242) once daily.

The primary end point was death or time to the first occurrence of a significant morbidity event, defined as atrial septostomy, lung transplantation, initiation of IV or SC prostanoids, or “other worsening of PAH” during double-blind treatment plus seven days.

Other worsening was defined as: (1) a sustained ≥15% decrease from baseline in six-minute walk distance; (2) worsening of PAH symptoms (worsening of WHO FC); and (3) need for additional treatment for PAH. A critical secondary end point was time to PAH death or PAH hospitalization.

The median treatment durations were 101 and 118 weeks in the placebo and Opsumit 10 mg groups, respectively, with a maximum of 188 weeks. Treatment with Opsumit 10 mg resulted in a 45% reduction (HR 0.55, 97.5% CI: 0.39-0.76; P <0.0001) in the occurrence of the primary end point up to end of treatment compared with placebo. The beneficial effect of Opsumit 
10 mg was mainly due to a reduction in clinical worsening events. 

In the secondary end point, the risk of PAH- related death or hospitalization for PAH was reduced by 50% in patients receiving Opsumit 10 mg vs. placebo (HR 0.50, 97.5% CI: 0.34-0.75; P <0.0001).

Treatment with Opsumit resulted in a placebo-corrected mean increase in six-minute walk distance of 22 meters at month 6 (97.5% CI: 3-41; P=0.0078), with significant improvement in six-minute walk distance by month 3; in addition, improvement of at least one WHO FC at month 6 in 22% of patients was seen compared with 13% of patients treated with placebo.

Adults: 10 mg once daily. Doses >10 mg once daily are not recommended.

Children: Not established. 

Contraindications: Pregnancy (Category X).

Warnings/Precautions: In females of reproductive potential, exclude pregnancy prior to starting, monthly during, and for one month after treatment discontinuation; must use acceptable methods of contraception. Obtain liver function tests prior to initiation and repeat during treatment as clinically indicated. Discontinue if clinically relevant aminotransferase elevations occur, or if elevations are accompanied by clinical symptoms of hepatotoxicity.

Not recommended in patients with severe anemia. Measure hemoglobin prior to initiation and repeat during treatment as clinically indicated. Consider pulmonary veno-occlusive disease if signs of pulmonary edema occur; discontinue if confirmed. Potential decrease in sperm count; counsel men on fertility effects. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (e.g., ketoconazole [Nizoral], ritonavir [Norvir]); avoid concomitant use. Antagonized by strong CYP3A4 inducers (e.g., rifampin [Rifadin]); avoid concomitant use. 

Adverse reactions: Anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, urinary tract infection; decreased hemoglobin.

Note: For all female patients: available only through the Opsumit REMS program. To enroll call 866.228.3546 or

How supplied: Tabs—15, 30.

For more information, 
call 866.228.3546 or