Macitentan


Concise Prescribing Info
Indications/Uses
Pulmonary arterial hypertension.
Dosage/Direction for Use
Adult : PO As mono- or combination therapy, in patients with WHO functional class II and III PAH: 10 mg once daily.
Dosage Details
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.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food. Swallow whole, do not chew/split/crush.
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.
Special Precautions
Patient with pulmonary veno-occlusive disease, anaemia, severe chronic heart disease. Severe renal (including patients on dialysis) and moderate hepatic impairment.
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.
Patient Counseling Information
This drug may cause headache or hypotension, if affected, do not drive or operate machinery.
MonitoringParameters
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.
Overdosage
Symptoms: Headache, nausea, vomiting. Management: Supportive treatment.
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).
Food Interaction
Reduced serum concentration with St. John’s wort.
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)
Chemical Structure

Chemical Structure Image
Macitentan

Source: National Center for Biotechnology Information. PubChem Database. Macitentan, CID=16004692, https://pubchem.ncbi.nlm.nih.gov/compound/Macitentan (accessed on Jan. 21, 2020)

Storage
Store between 15-30°C.
ATC Classification
C02KX04 - macitentan ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
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.

Disclaimer: This information is independently developed by MIMS based on Macitentan from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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