Adult: In patients w/ WHO functional class II and III PAH (idiopathic, heritable, or associated w/ connective tissue diseases): Initially, 5 mg once daily, may be increased up to 10 mg once daily if necessary.
Special Patient Group
Patients taking ciclosporin: Max: 5 mg once daily.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food. Swallow whole, do not split/chew/crush.
Contraindications
Idiopathic pulmonary fibrosis. Severe hepatic impairment or clinically significant elevated hepatic aminotransferases (>3 times the upper limit of normal). Pregnancy and lactation.
Special Precautions
Patient w/ pulmonary veno-occlusive disease, significant anaemia. Severe renal (CrCl <30 ml/min) and moderate hepatic impairment. Patients taking concomitant ciclosporin.
This drug may cause dizziness, asthenia, hypotension, or fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor for signs of hepatic injury, significant peripheral oedema. Monitor ALT and AST, Hb and haematocrit levels. Obtain mthly pregnancy test during treatment.
Overdosage
Symptoms: Headache, dizziness, flushing, nausea, nasal congestion, and potential hypotension. Management: In case of hypotension, give active CV support.
Drug Interactions
Increased exposure w/ ciclosporin. Rifampicin may cause transient increase in ambrisentan exposure.
Action
Description: Mechanism of Action: Ambrisentan, an endothelin antagonist, is selective on endothelin type A (ETA) receptor. Endothelin is a potent vasoconstrictor which plays a pathogenic role in pulmonary arterial hypertension (PAH). Blockade of endothelin receptor leads to vasodilation and inhibition of smooth muscle proliferation. Pharmacokinetics: Absorption: Absorbed rapidly from the GI tract. Time to peak plasma concentration: Approx 2 hr. Distribution: Plasma protein binding: 99%, mainly to albumin and to a lesser extent to α1-acid glycoprotein. Metabolism: Metabolised via glucuronidation by several uridine diphosphate glucuronosyltransferase (UGT) isoenzymes to ambrisentan glucuronide and via oxidation, mainly by CYP3A4 and to a lesser extent by CYP3A5 and CYP2C19, to form 4-hydroxymethyl ambrisentan. Excretion: Mainly via bile; urine (22%, 3.3% as unchanged drug). Terminal elimination half-life: Approx 15 hr.
Chemical Structure
Ambrisentan Source: National Center for Biotechnology Information. PubChem Database. Ambrisentan, CID=6918493, https://pubchem.ncbi.nlm.nih.gov/compound/Letairis (accessed on Jan. 20, 2020)
Storage
Store between 15-30°C.
Wear gloves during receiving, unpacking, and placing in storage.
C02KX02 - ambrisentan ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
References
Anon. Ambrisentan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 31/07/2017.Buckingham R (ed). Ambrisentan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/07/2017.Joint Formulary Committee. Ambrisentan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/07/2017.Letairis Tablets (Gilead Sciences, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 31/07/2017.McEvoy GK, Snow EK, Miller J et al (eds). Ambrisentan. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 31/07/2017.
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