Macitentan

590.295

588.27

1308068-626-2

Z9K9Y9WMVL

DTXSID50196063

C87728

C02KX04|C - Cardiovascular system

137

3.7

1.675

692.397°C at 760 mmHg

372.5±34.3 °C

1.634

Not water soluble

|Danger|H360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 44 companies from 2 notifications to the ECHA C&L Inventory.

Macitentan has a black box warning of embryo-fetal toxicity. Special precautions must be taken for all females of child-bearing age, and women who are pregnant must not be given macitentan.

Macitentan is associated with a low rate of serum aminotransferase elevations (0% to 4%) that, in clinical trials, was similar to the rate among placebo recipients. These elevations were usually mild, transient and not associated with symptoms, but were above 8 times the ULN in 2% of subjects (vs 0.4% of controls) in at least one long term study. For these reasons, the product label recommends that patients have serum enzymes tested before starting therapy and be alerted to the possibility and symptoms of liver injury during therapy. While there have been no published reports of clinically apparent liver injury with jaundice associated with macitentan, it has had limited general use. Other endothelin receptor antagonists (bosentan, sitaxentan) have been linked to several instances of acute liver injury, some of which have been severe. The onset of illness was usually within 1 to 6 months of starting bosentan and the enzyme pattern was typically hepatocellular or mixed. Immunoallergic features were not present and autoantibodies absent or present in low titer. Macitentan and ambrisentan have not been linked to similar cases.

Macitentan is >99% bound to plasma proteins, which are mainly albumin

Macitentan is indicated for patients with pulmonary arterial hypertension.|FDA Label|Opsumit, as monotherapy or in combination, is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III.Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.|Treatment of chronic thromboembolic pulmonary hypertension (CTEPH)|Treatment of pulmonary arterial hypertension|Treatment of idiopathic pulmonary fibrosis, Treatment of pulmonary arterial hypertension, Treatment of systemic sclerosis

Macitentan is an endothelin receptor antagonist that is used in the therapy of pulmonary arterial hypertension (PAH). Macitentan has been associated with a low rate of serum enzyme elevations during therapy, but has yet to be implicated in cases of clinically apparent acute liver injury.

Pulmonary Arterial Hypertension Agents

Macitentan blocks simulators of hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction.

Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN A RECECPTORS. (See all compounds classified as Endothelin A Receptor Antagonists.)|Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN B RECEPTORS. (See all compounds classified as Endothelin B Receptor Antagonists.)

Macitentan is administered orally, and it take about 8 hours for maximum plasma concentrations to be reached.|Eliminated 50% through urine and 24% through feces.|Macitentan has a volume of distribution of 50L.|Clearance data was not found.

Macitentan is metabolised to an active metabolite by CYP 3A4 (major) and CYP 2C19 (minor).

The half life of macitentan is 16 hours, and the half life of it's active metabolite is 48 hours.

Macitentan is an antagonist/blocker of endothelin receptors. Endothelin receptors are found in the endothelial cells of blood vessels and smooth muscle. Macitentan binds to the receptors, endothelin A and B (ETA and ETB), which prevents the agonist endothelin -1 (ET-1) from binding and stimulating the ETA and ETB receptors.

ACT 064992

Human drugs -> Orphan -> Opsumit -> EMA Drug Category|Antihypertensives -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients