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A-Z Drug Facts > Ambrisentan

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

Adults

PO 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

Cyclosporine

Because 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.

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

Warnings

Hepatotoxicity

At least a 3-fold increase in ALT or AST occurs in some patients and requires close monitoring.

Teratogenicity

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 IUD or LNg 20 IUD inserted.


Monitor

Monitor 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.