Letairis

ambrisentan

(am-bri-sen-tan) ,

Letairis

(trade name),

Volibris

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: endothelin receptor antagonists
Pregnancy Category: X

Indications

Pulmonary arterial hypertension (WHO Group 1).

Action

Antagonizes endogenous endothelin, resulting in vasodilation.

Therapeutic effects

Improved exercise capacity and delayed clinical worsening.

Pharmacokinetics

Absorption: Absorbed following oral administration. Bioavailability unknown.
Distribution: Unknown.
Protein Binding: 99%.
Metabolism and Excretion: Highly metabolized.
Half-life: 15 hr (effective half-life 9 hr).

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown2 hr24 hr

Contraindications/Precautions

Contraindicated in: Obstetric / Lactation: Pregnancy or lactation; Idiopathic pulmonary fibrosisModerate/severe hepatic impairment; Significant anemia.
Use Cautiously in: Mild hepatic impairment; Pediatric: Safety and efficacy not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)

Cardiovascular

  • peripheral edema (most frequent)

Genitourinary

  • ↓ sperm count

Respiratory

  • pulmonary veno-occlusive disease (life-threatening)

Hematologic

  • ↓ hemoglobin (most frequent)

Interactions

Drug-Drug interaction

Blood levels may be ↑ by cyclosporine ; do not exceed ambrisentan dose of 5 mg once daily.

Route/Dosage

Oral (Adults) 5 mg once daily, may ↑ to 10 mg once daily.

Availability

Tablets: 5 mg, 10 mg

Nursing implications

Nursing assessment

  • Assess for signs and symptoms of primary pulmonary hypertension (dyspnea, exercise intolerance) prior to and periodically during therapy.
  • Assess for peripheral edema during therapy. If clinically significant peripheral edema occurs, with or without weight gain, evaluate for underlying cause, such as heart failure, and treat.
  • Monitor for symptoms of acute pulmonary edema (dyspnea, cough with frothy sputum, anxiety, restlessness, palpitations) during initiation of therapy. Consider the possibility of pulmonary veno-occlusive disease; if confirmed discontinue ambrisentan.
  • Lab Test Considerations: Obtain pregnancy test prior to, monthly during therapy, and 1 month following completion of therapy.
    • Monitor hemoglobin prior to and at 1 mo and periodically during therapy. May cause ↓ hemoglobin; usually occurs during first few weeks and stabilizes. If clinically significant and other causes have been excluded, discontinue therapy.

Potential Nursing Diagnoses

Impaired gas exchange (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Only available through a special restricted distribution program called Letairis REMS due to risks of birth defects. Frmale patients must be enrolled in Letarin REMS and re-enrolled after first year and then yearly. A limited number of pharmacies are certified to dispense ambrisentan. Provide patients with telephone number (1-866-664-5327) and website (www.letairisrems.com) for information on how to obtain medication.
  • Oral: May be administered without regard to food. Tablets should be swallowed whole; do not crush, break or chew.

Patient/Family Teaching

  • Instruct patient to take ambrisentan as directed, at the same time each day. Review medication guide and patient education brochures with every patient. Explain Letarin REMS to patient. Take missed dose as soon as remembered that day. Take next dose at regular time; do not take two doses at the same time to make up for missed dose.
  • Advise patient to notify health care professional promptly if symptoms of fluid retention (swelling of hands, legs, ankles, feet or all over the body) or hepatotoxicity (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant abdominal discomfort, jaundice, dark urine or itching) occur.
  • May cause fetal harm if taken during pregnancy. Inform patients a pregnancy test is required prior to beginning therapy and acceptable methods of contraception (one highly effective form of contraception: intrauterine devices [IUD], contraceptive implants, or tubal sterilization or a combination of methods: [hormone method with a barrier method or two barrier methods]) must be used throughout therapy and for 1 mo following discontinuationIf a partner’s vasectomy is method of contraception chosen, a hormone or barrier method must be used along with this method. Educate women of childbearing years on the use of emergency contraception in the case of unprotected sex or contraceptive failure.
  • Inform patients that ambrisentan may cause low sperm count.
  • Advise patient of the importance of regular liver and hemoglobin testing.

Evaluation/Desired Outcomes

  • Improved exercise capacity and decreased rate of clinical progression in patients with primary pulmonary hypertension.

Letairis

a trademark for ambrisentan.
References in periodicals archive ?
Sales of its cardiovascular drugs Letairis and Ranexa are north of $1 billion a year together.
Disclosures: The ARIES trials were funded by Gilead Sciences, which manufactures Letairis.
In May 2008, Gilead announced the initiation of ATHENA-1, a Phase IV, randomized, double-blind, placebo-controlled study evaluating Letairis (ambrisentan 5mg and 10mg tablets) in patients with PAH demonstrating a sub-optimal response to sildenafil monotherapy.
Ambrisentan may only be prescribed via the Letairis Education and Access Program.
Of the new drugs approved last year, Gilead's Letairis for pulmonary arterial hypertension and Merck's for HIV-1 are expected to be the most successful.
Letairis Sales of Letairis([R]) (ambrisentan) increased 48 percent to $116.
Confirmed 7 first-to-file (FTF) opportunities including generic versions of Uceris, Letairis, and Mirvaso.
Two of the most frequently prescribed specialty drugs in recent years include the cancer drug Avastin, with an $11,000 average annual price per patient, or the hypertension drug like Letairis, which costs $32,000 per year, according to health insurers.
He disclosed that he is a paid researcher, consultant, and adviser to the makers of Letairis, Gilead Sciences, which funded the study.
Gilead may be interested in expanding its cardiovascular product line that includes lung disorder treatment Letairis, which generated $113 million in sales for the company in 2008, Taller said.
Special Considerations: Because it is teratogenic and can cause liver toxicity, Letairis is available only through a restricted distribution program.