Opsumit Macitentan Film-coated Tablets

1. Indications and Usage
Pulmonary Arterial Hypertension (PAH): Indicated for the treatment of adult patients with pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression.
It is used for the treatment of adult pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression (including death, intravenous or subcutaneous injection of prostaglandins, or clinical deterioration of PAH).
2. Dosage and Administration
Administration: Oral administration, once daily. Can be taken with or without food. Tablets must be swallowed whole; do not chew, split, or crush.
Dose: The recommended dose is 10 mg once daily.
Pregnancy Testing: For females of reproductive potential, pregnancy testing is required prior to initiation and monthly during treatment.
3. Mechanism of Action
Endothelin Receptor Antagonist (ERA): Macitentan is a dual endothelin receptor antagonist (ETA and ETB).
Pathway: It competitively binds to ETA and ETB receptors with high affinity and tissue retention, blocking the vasoconstrictive and proliferative effects of endothelin-1 (ET-1). This leads to pulmonary and systemic vasodilation and inhibition of vascular remodeling.
4. Safety and Warnings
Embryo-Fetal Toxicity: Contraindicated in pregnancy. Macitentan may cause fetal harm. Effective contraception is mandatory during treatment and for at least one month after the last dose.
Hepatotoxicity: Elevations in liver transaminases (ALT/AST) have been observed. Liver function tests (LFTs) must be performed prior to initiation and subsequently as clinically indicated (e.g., monthly).
Fluid Retention: Peripheral edema and fluid retention are known side effects. Monitor for signs of decompensated heart failure.
Decrease in Hemoglobin: Dose-dependent reduction in hemoglobin may occur; monitor hemoglobin levels.
5. Adverse Reactions
Most Common: Anaemia, nasopharyngitis, headache, influenza, diarrhea, bronchitis, rash, pruritus, and fatigue.
6. Drug Interactions
CYP3A4 Inhibitors: Strong inhibitors (e.g., ketoconazole) may increase macitentan exposure.
CYP3A4 Inducers: Strong inducers (e.g., rifampicin) may significantly decrease macitentan exposure and efficacy; concomitant use is not recommended.
Hormonal Contraceptives: May reduce the efficacy of hormonal contraceptives; alternative non-hormonal methods are recommended.
7. Pharmaceutical Information
Chemical Name: N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N’-propylsulfamide.