Ambrisentan (ambrisentan)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ambrisentan, a selective propionic-acid endothelin-1 (ET-1) type A receptor antagonist, is a vasodilator.
Ambrisentan, a selective endothelin-1 (ET-1) type A receptor antagonist, is a vasodilator. Increased concentrations of ET-1, a potent vasoconstrictor, have been detected in the plasma and lung tissue of patients with pulmonary arterial hypertension (PAH), suggesting a pathogenic role for ET-1 in this disorder. Two ET-1 receptor subtypes, type A and type B, have been identified; activation of ET-1 type A receptors primarily mediates vasoconstriction and smooth muscle cell proliferation, while activation of ET-1 type B receptors results in vasodilation and facilitates clearance of ET-1.
Ambrisentan is approximately 4000-fold more selective for the type A receptor compared with the type B receptor; however, the clinical implications of this selectivity remain to be established.
Ambrisentan exhibits dose proportional pharmacokinetics in healthy adults. The absolute bioavailability is unknown, and peak concentrations occur approximately 2 hours after oral administration in healthy subjects and PAH patients. Food does not affect bioavailability of the drug.
Ambrisentan is highly protein bound (99%). The drug is predominantly eliminated by non-renal pathways. The terminal half-life is 15 hours, but the effective half-life is about 9 hours.
In vitro evidence indicates that ambrisentan is metabolized by cytochrome P-450 (CYP) isoenzymes 3A4 and 2C19, and by uridine diphosphate-glucuronosyltransferases (UGT) 1A9, 2B7, and 1A3. In vitro studies suggest that ambrisentan also is a substrate of the transporters p-glycoprotein and organic anion transport protein (OATP).
USES: Ambrisentan is used to treat high blood pressure in the lungs (pulmonary arterial hypertension). This condition is thought to be caused by increased levels of a certain natural substance (endothelin-1). This medication blocks the effects of endothelin-1, thereby helping to decrease the blood pressure in the lungs, slow the worsening of symptoms, and improve your ability to exercise.
Generic name: ambrisentan
Pronunciation: (AM-bri-SEN-tan)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ambrisentan
Indications
The following indications are listed for Ambrisentan:
- Pulmonary Arterial Hypertension
Also known as: Hypertensive Pulmonary Arterial Disease, Pulmonary Hypertensive Arterial Disease.
Dosing
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that ambrisentan is metabolized by cytochrome P-450 (CYP) isoenzymes 3A4 and 2C19 and by uridine 5'-diphosphate glucuronosyltransferases (UGTs; uridine diphosphoglucuronosyltransferase, UDP-glucuronate beta-d-glucuronosyltransferase (acceptor-unspecific)) 1A9S, 2B7S, and 1A3S. The drug appears to be a substrate, but not an inhibitor, of the organic anion transport protein (OATP) and the P-glycoprotein (P-gp) transport system. At clinically relevant concentrations, ambrisentan does not inhibit or induce CYP enzymes.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Pregnancy.
*Idiopathic pulmonary fibrosis, with or without pulmonary hypertension (WHO group 3).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (>3%) of ambrisentan in clinical studies were peripheral edema, nasal congestion, sinusitis, and flushing.
When used in combination with tadalafil, the most common adverse effects (>5% compared to either monotherapy) were peripheral edema, headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of ambrisentan have not been established in children and adolescents younger than 18 years of age. Juvenile animal data revealed a reduction in brain weight, but no morphologic or neurobehavioral changes following drug exposures 1.8 to 7 times the human pediatric exposures at 10 mg (based on AUC).
Based on data from animal reproduction studies, ambrisentan may cause embryofetal toxicity, including birth defects and fetal death, when administered to pregnant females and is contraindicated during pregnancy. Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as ambrisentan have not identified an increased risk of major birth defects; however, these data are limited. If ambrisentan is used during pregnancy, or if the patient becomes pregnant while taking ambrisentan, clinicians should advise the patient of the fetal risk.
It is not known whether ambrisentan is distributed into human milk. Because many drugs are distributed into human milk and because of the potential for serious adverse reactions to ambrisentan in nursing infants, a decision should be made to discontinue nursing or the drug.
The manufacturer makes no specific dosage recommendations for geriatric patients.
A higher incidence of peripheral edema has been observed in geriatric patients 65 years of age or older relative to younger adults. Clinical trials of ambrisentan included 21% of patients >=65 years of age and 5% of patients >=75 years of age. Improvement in walk distance was less in elderly compared to younger patients, although the prescribing information states to interpret this information, which comes from subgroup analysis, with caution.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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