OPSUMIT

Opsumit Generic Name & Formulations

Legal Class

General Description

Macitentan 10mg; tabs.

Pharmacological Class

Endothelin receptor antagonist.

How Supplied

Tabs—15, 30

Manufacturer

Actelion Pharmaceuticals

Generic Availability

Mechanism of Action

Macitentan inhibits the binding of endothelin (ET)-1 to both ET_A and ET_B receptors. Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. The clinical impact of dual endothelin blockage is unknown.

Opsumit Indications

Indications

Treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce disease progression risks and hospitalization for PAH.

Opsumit Dosage and Administration

Adult

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

Children

Not established.

Opsumit Contraindications

Contraindications

Pregnancy.

Opsumit Boxed Warnings

Boxed Warning

Embryo-fetal toxicity.

Opsumit Warnings/Precautions

Warnings/Precautions

Embryo-fetal toxicity: in females of reproductive potential, exclude pregnancy prior to initiation, monthly during, and for 1 month after treatment discontinuation; must use acceptable methods of contraception. Obtain LFTs prior to initiation and repeat during treatment as clinically indicated. Discontinue if clinically relevant ALT/AST elevations or if elevations accompanied by bilirubin >2×ULN, or by symptoms of hepatotoxicity occur. Underlying left ventricular dysfunction: monitor for fluid retention; evaluate if develops. Severe anemia: not recommended. Measure Hgb 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.

REMS

YES

Opsumit Pharmacokinetics

Absorption

Maximum plasma concentration: ~8 hours after oral administration.

Distribution

>99% plasma protein bound.
Apparent volume of distribution: ~50 L.

Metabolism

CYP3A4 (primarily) with minor contributions of CYP2C8, CYP2C9, and CYP2C19.

Elimination

Renal (50%), fecal (24%). Half-life: ~16 hours.

Opsumit Interactions

Interactions

Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir); avoid concomitant use. May be potentiated by moderate dual or combined CYP3A4 and CYP2C9 inhibitors (eg, fluconazole, amiodarone); avoid concomitant use. Antagonized by strong CYP3A4 inducers (eg, rifampin); avoid concomitant use.

Opsumit Adverse Reactions

Adverse Reactions

Anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, urinary tract infection; hepatotoxicity, decreased hemoglobin.

Opsumit Clinical Trials

See Literature

Opsumit Note

Notes

For all female patients: available only through the Opsumit REMS program. To enroll call (866) 228-3546 or www.OpsumitREMS.com.

Opsumit Patient Counseling