Macitentan

Severe: Contraindicated.

Macitentan May be taken with or without food. Swallow whole, do not chew/split/crush.

Women of childbearing potential who are not using reliable contraception. Severe hepatic impairment (with or without cirrhosis) or those with elevated baseline values of hepatic aminotransferases (>3 times the ULN). Pregnancy and lactation.

Patient with pulmonary veno-occlusive disease and severe chronic heart failure. Not recommended in patients with severe anaemia. Severe renal (including those undergoing dialysis) and moderate hepatic impairment.

Significant: Increased hepatic aminotransferases (e.g. AST, ALT), hepatotoxicity, liver failure; fluid retention, peripheral oedema, pulmonary oedema, decreased haematocrit and Hb, anaemia (requiring blood transfusion).
Blood and lymphatic system disorders: Leucopenia, thrombocytopenia.
Immune system disorders: Hypersensitivity reactions (e.g. rash, pruritus, angioedema).
Infections and infestations: Influenza.
Investigations: Potential decrease in sperm count.
Nervous system disorders: Headache.
Renal and urinary disorders: UTI.
Reproductive system and breast disorders: Increased uterine bleeding.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, bronchitis, pharyngitis, nasal congestion.
Vascular disorders: Hypotension, flushing.

Women of childbearing potential must use proven birth control methods during therapy and for 1 month after stopping the treatment.

Evaluate pregnancy status in females of childbearing potential before treatment initiation, monthly during treatment, and 1 month after treatment discontinuation. Monitor liver enzymes (prior treatment initiation, monthly during therapy, and as clinically indicated); Hb and haematocrit (prior treatment initiation and as clinically indicated). Assess for signs and symptoms of liver injury (e.g. nausea, vomiting, abdominal pain, anorexia, dark urine, fatigue, fever, itching, jaundice); significant peripheral oedema or fluid retention.

Symptoms: Headache, nausea, vomiting. Management: Supportive treatment.

Decreased serum concentrations with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin). Increased serum concentration with strong CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, saquinavir) and moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g. fluconazole, amiodarone).

Reduced therapeutic effect with St. John's wort.

Description:
Mechanism of Action: Macitentan, a vasodilator, is a nonselective endothelin (ET)-1 receptor antagonist. ET-1 and its receptors (ET_A and ET_B) mediate various pathological effects, including vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. Macitentan exhibits sustained occupancy and high affinity for ET receptors in human pulmonary arterial smooth muscle cells, thus preventing endothelin-mediated activation of second messenger systems that lead to vasoconstriction and smooth muscle cell proliferation.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: Approx 8 hours.
Distribution: Widely distributed in tissues. Plasma protein binding: >99%, mainly to albumin and a lesser extent to α₁-acid glycoprotein.
Metabolism: Extensively metabolised in the liver via several metabolic pathways, including oxidative depropylation of the sulfamide mainly by CYP3A4 and to a lesser extent by CYP2C8, CYP2C9, and CYP2C19 to form its active metabolite.
Excretion: Mainly via urine (approx 50%); faeces (approx 24%). Elimination half-life: Approx 16 hours (macitentan); approx 48 hours (active metabolite).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 16004692, Macitentan. https://pubchem.ncbi.nlm.nih.gov/compound/Macitentan. Accessed May 28, 2025.

Store between 15-30°C.

Other Antihypertensives

C02KX04 - macitentan ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.

Brayfield A, Cadart C (eds). Macitentan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/03/2025.

Janssen-Cilag (New Zealand) Ltd. Opsumit 10 mg Film Coated Tablets data sheet 27 October 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 31/03/2025.

Joint Formulary Committee. Macitentan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/03/2025.

Macitentan. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 31/03/2025.

Macitentan. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 31/03/2025.

Opsumit 10 mg Film-coated Tablets (Janssen-Cilag Limited). MHRA. https://products.mhra.gov.uk. Accessed 31/03/2025.

Opsumit 10 mg Film-coated Tablets (Johnson & Johnson Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 31/03/2025.

Opsumit Tablet, Film Coated (Actelion Pharmaceuticals US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 31/03/2025.