Trade Names:Letairis- Tablets 5 mg- Tablets 10 mg
Antagonizes endothelin receptor by binding to endothelin A.
Rapidly absorbed. T max is 2 h.
Plasma protein binding is 99%.
Substrate for P-glycoprotein (P-gp). Metabolized by CYP2C19, CYP3A4, and uridine 5-diphosphate glucuronosyltransferases (UGTs) 1A3S, 1A9S, and 2B7S.
Elimination is primarily nonrenal. Terminal half-life is 15 h; effective half-life is about 9 h.
Treatment of pulmonary arterial hypertension in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.
PO 5 mg once daily. Consider increasing the dosage to 10 mg once daily if 5 mg is tolerated.
Store at 59° to 86°F.
Exposure to ambrisentan may be increased; use with caution.Inducers of P-gp, CYPs, and UGTs
Use ambrisentan with caution.Strong inhibitors of CYP2C19 (eg, omeprazole) and CYP3A (eg, ketoconazole)
Ambrisentan concentrations may be increased; use with caution.
None well documented.
Nasal congestion (6%); nasopharyngitis (3%).
Constipation (4%); abdominal pain (3%).
Dyspnea (4%); sinusitis (3%).
Peripheral edema (17%); fluid retention (postmarketing).
At least a 3-fold increase in ALT or AST occurs in some patients and requires close monitoring.Pregnancy
Because serious birth defects were seen consistently when ambrisentan was administered to animals, use is contraindicated in pregnancy. Pregnancy must be excluded before initiation of treatment and prevented thereafter by use of at least 2 reliable methods of contraception unless patient has had a tubal sterilization or Copper T 380A intrauterine device (IUD) or levonorgestrel (LNg) 20 IUD inserted.Dispensing program
Ambrisentan is available only through a special restricted distribution program called the Letairis Education and Access Program (LEAP), by calling 1-866-664-5327. Only prescribers and pharmacies registered with LEAP may prescribe and distribute. Ambrisentan may be dispensed only to patients who are enrolled in and meet all conditions of LEAP.
Monitor serum aminotransferase levels (and bilirubin if aminotransferase levels are elevated) prior to starting treatment and monthly for the duration of treatment. Measure hemoglobin prior to initiation of treatment, at 1 month after initiation, and periodically thereafter. For women of childbearing potential, order and review a pregnancy test prior to initiation of treatment and monthly during treatment.
Category X .
Safety and efficacy not established.
Peripheral edema was more common in elderly patients.
No information available regarding use in patients with severe renal impairment.
Use with caution in patients with mild hepatic impairment. Not recommended in patients with moderate or severe hepatic impairment. Avoid use in patients with elevated aminotransferases (more than 3 times ULN) at baseline. If liver aminotransferases are accompanied by clinical symptoms of liver injury (eg, abdominal pain, fever, jaundice, nausea, unusual lethargy or fatigue, vomiting) or if increases in bilirubin of more than 2 times ULN occur, stop treatment.
Hemoglobin concentration and hematocrit may decrease within the first few weeks of treatment and stabilize thereafter.
Peripheral edema may occur.
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