Ambrisentan
Pronouncation: (am-brih-SEN-tan)Class: Endothelin receptor antagonist
Trade Names:
Letairis
- Tablets 5 mg
- Tablets 10 mg
Pharmacology
Antagonizes endothelin receptor by binding to endothelin A.
Pharmacokinetics
Absorption
Rapidly absorbed with C max approximately 2 h after oral administration. Mean trough level at steady state is about 15% of the mean C max .
Distribution
Plasma protein binding is 99%.
Metabolism
Substrate for P-glycoprotein (P-gp). Metabolized by CYP2C19, CYP3A4, and uridine 5-diphosphate glucuronosyltransferases (UGTs) 1A3S, 1A9S, and 2B7S.
Elimination
Elimination is primarily nonrenal. Terminal t ½ is 15 h, while the effective t ½ is about 8 h.
Indications and Usage
Treatment of pulmonary arterial hypertension in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.
Contraindications
Pregnancy.
Dosage and Administration
AdultsPO 5 mg once daily with or without food. Consider increasing the dosage to 10 mg once daily if 5 mg is tolerated.
Storage/Stability
Store at 59° to 86°F.
Drug Interactions
CyclosporineBecause exposure to ambrisentan may be increased, use with caution.
Inducers of P-gp, CYPs, and UGTsUse ambrisentan with caution.
Strong inhibitors of CYP2C19 (eg, omeprazole) and CYP3A (eg, ketoconazole)Ambrisentan concentrations may be increased; use with caution.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Palpitations (5%).
CNS
Headache (15%).
Dermatologic
Flushing (4%).
EENT
Nasal congestion (6%); nasopharyngitis (3%).
GI
Constipation (4%); abdominal pain (3%).
Respiratory
Dyspnea (4%); sinusitis (3%).
Miscellaneous
Peripheral edema (17%).
Precautions
WarningsHepatotoxicityAt least a 3-fold increase in ALT or AST occurs in some patients and requires close monitoring. TeratogenicityBecause 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 IUD or LNg 20 IUD inserted. |
MonitorMonitor serum aminotransferase levels 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. |
Pregnancy
Category X .
Lactation
Undetermined.
Children
Safety and efficacy not established.
Renal Function
No information available regarding use in patients with severe renal function impairment.
Hepatic Function
Use with caution in patients with mild hepatic function impairment. Not recommended in patients with moderate or severe hepatic function impairment.
Hematologic
Hemoglobin concentration and hematocrit may decrease within the first few weeks of treatment and stabilize thereafter.
Peripheral edema
Peripheral edema may occur
Prescribing and distribution
Because of the risk of liver injury and birth defects, ambrisentan is available only through a special restricted distribution program called the Letairis Education and Access Program (LEAP). Ambrisentan may be dispensed only to patients who are enrolled in and meet all conditions of LEAP.
Overdosage
Symptoms
No experience available. Massive overdosage could potentially cause hypotension.
Patient Information
- Advise patient to read the Medication Guide before using product the first time and with each refill.
- Instruct female patients of childbearing potential that reliable contraceptive measures must be used during treatment. Advise patients to use at least 2 reliable methods of contraception unless they have had a tubal sterilization or copper T 380A IUD or LNg 20 IUD inserted.
- Advise patients that monthly liver enzyme tests and pregnancy tests (in female patients of childbearing potential) will be required to use this medication safely.
- Inform patients that, during treatment, their health care provider will test their blood for signs of adverse reactions to the liver and RBC.
- Advise patients that product may be taken without regard to meals.
- Advise patients not to split, crush, or chew tablets.
- Instruct women who become pregnant or miss a menstrual period during therapy to notify health care provider.
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