Macitentan

Endothelin (ET)-1 and its receptors (ETA and ETB ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage. Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ETA and ETB 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.

Recommended Dosage: The recommended dosage of Macitentan is 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended.

Pregnancy Testing in Females of Reproductive Potential: Obtain a pregnancy test in females of reproductive potential prior to Macitentan treatment, monthly during treatment and one month after stopping Macitentan. Initiate treatment with Macitentan in females of reproductive potential only after a negative pregnancy test.

Pediatric Use: The safety and efficacy of Macitentan in children have not been established.

Geriatric Use: Of the total number of subjects in the clinical study of Macitentan for PAH, 14% were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Strong CYP3A4 Inducers: Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of Macitentan with strong CYP3A4 inducers should be avoided.

Strong CYP3A4 Inhibitors: Concomitant use of strong CYP3A4 inhibitors like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of Macitentan with strong CYP3A4 inhibitors. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment

The most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection.

Macitentan may cause fetal harm when administered to a pregnant woman. Macitentan is contraindicated in females who are pregnant. Macitentan was consistently shown to have teratogenic effects when administered to animals. If Macitentan is used during pregnancy, advise the patient of the potential risk to a fetus.

There are no data on the presence of Macitentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants from Macitentan advise women not to breastfeed during treatment with Macitentan.

• ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated.
• Fluid retention may require intervention.
• Decreases in hemoglobin.
• Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment.
• Decreases in sperm count have been observed in patients taking ERAs.

Anti-hypertensive

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.