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Indications and Dosage
Oral
Pulmonary arterial hypertension Adult: As mono- or in combination therapy, in patients with WHO functional class II and III PAH (idiopathic, heritable, associated with connective tissue diseases or with corrected simple congenital heart disease): 10 mg once daily.
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Hepatic Impairment
Severe: Contraindicated.
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Administration
May be taken with or without food. Swallow whole, do not chew/split/crush.
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Contraindications
Severe hepatic impairment (with or without cirrhosis) or clinically significant elevated baseline values of hepatic aminotransferases (>3 times the upper limit of normal). Women of childbearing potential who are not using reliable contraception. Pregnancy and lactation.
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Special Precautions
Patient with pulmonary veno-occlusive disease, anaemia, severe chronic heart disease. Severe renal (including patients on dialysis) and moderate hepatic impairment.
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Adverse Reactions
Significant: Increased serum liver aminotransferases, hepatotoxicity, liver failure, fluid retention, peripheral oedema, decreased Hb and haematocrit, anaemia, decreased sperm count.
Blood and lymphatic system disorders: Leucopenia, thrombocytopenia. Infections and infestations: Influenza. Nervous system disorders: Headache. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, pharyngitis, bronchitis, nasal congestion. Vascular disorders: Hypotension. |
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Patient Counseling Information
This drug may cause headache or hypotension, if affected, do not drive or operate machinery.
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Monitoring Parameters
Obtain pregnancy test prior to initiation of therapy, monthly during treatment, and 1 month after stopping treatment. Monitor ALT and AST, Hb and haematocrit levels prior to treatment and as clinically indicated. Monitor for signs of hepatic injury, significant peripheral oedema.
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Overdosage
Symptoms: Headache, nausea, vomiting. Management: Supportive treatment.
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Drug Interactions
Decreased serum concentrations with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin). Increased serum concentrations with strong CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, ritonavir).
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Food Interaction
Reduced serum concentration with St. John’s wort.
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Action
Description: Macitentan inhibits the binding of endothelin (ET)-1 from binding to both type A (ETA) and type B (ETB) receptors. ET-1 is a potent vasoconstrictor which plays a pathogenic role in pulmonary arterial hypertension (PAH). Blockade of ET-1 leads to vasodilatation, inhibition of smooth muscle proliferation and improved exercise capacity.
Pharmacokinetics: Absorption: Time to peak plasma concentration: Approx 8 hours. Distribution: Widely distributed into tissues. Volume of distribution: Approx 50 L (active metabolite: 40 L). Plasma protein binding: >99%, mainly to albumin and to a lesser extent to α1-acid glycoprotein. Metabolism: Extensively metabolised, mainly by CYP3A4 and to a lesser extent by CYP2C8, CYP2C9, and CYP2C19 via several metabolic pathways, including oxidative depropylation of the sulfamide to form the active metabolite ACT-132577. Excretion: Mainly via urine (approx 50%); faeces (approx 24%). Elimination half-life: Approx 16 hours (macitentan); approx 48 hours (ACT-132577) |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Macitentan, CID=16004692, https://pubchem.ncbi.nlm.nih.gov/compound/Macitentan (accessed on Jan. 21, 2020) |
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Storage
Store between 15-30°C.
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MIMS Class
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ATC Classification
C02KX04 - macitentan ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
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References
Anon. Macitentan. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/05/2020. Anon. Macitentan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/05/2020. Buckingham R (ed). Macitentan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/05/2020. Joint Formulary Committee. Macitentan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/05/2020. Opsumit (Johnson & Johnson Sdn Bhd). MIMS Malaysia. http://www.mims.com/malaysia. Opsumit Tablet, Film Coated (Actelion Pharmaceuticals US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/05/2020.
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