Ambrisentan

Ambrisentan is a prescription medication used for the treatment of pulmonary arterial hypertension. 

• Ambrisentan is available under various brand names: Letairis

Common side effects of Ambrisentan include:

• trouble breathing,
• headache,
• dizziness,
• chest pain or discomfort,
• nausea, and
• flushing (warmth, redness, or tingly feeling)

Serious side effects of Ambrisentan include:

• severe dizziness,
• fast heartbeats,
• warmth or tingly feeling,
• wheezing,
• chest tightness,
• trouble breathing,
• chest pain or pressure,
• pain spreading to the jaw or shoulder,
• seizure,
• lightheadedness,
• severe headache,
• pounding in the neck or ears,
• sudden numbness or weakness (especially on side of the body),
• slurred speech, and
• balance problems

Rare side effects of Ambrisentan include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 5 mg
• 10 mg

Pulmonary Arterial Hypertension

Adult dosage

• Initiate treatment at 5 mg orally once daily, with or without tadalafil 20 mg orally once daily
• At 4-week intervals, either ambrisentan or tadalafil dose can be increased, as needed and tolerated, not to exceed ambrisentan 10 mg/day or tadalafil 40 mg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ambrisentan has severe interactions with no other drugs.
• Ambrisentan has serious interactions with the following drugs:
  • apalutamide
  • cyclosporine
  • idelalisib
  • lasmiditan
  • lonafarnib
  • sotorasib
  • tepotinib
• Ambrisentan has moderate interactions with at least 36 other drugs.
• Ambrisentan has minor interactions with at least 43 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Pregnancy
• Idiopathic pulmonary fibrosis

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ambrisentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ambrisentan?”

Cautions

• Fetal harm when administered during pregnancy and is contraindicated for use in females who are pregnant (see Pregnancy and Black Box Warnings)
• Caution with hepatic impairment; may be associated with rare cases of hepatic cirrhosis with prolonged use; not recommended in patients with moderate-to-severe hepatic impairment
• Discontinue in patients with elevated aminotransferases above five times ULN, or if elevations are accompanied by bilirubin above twice ULN or signs/symptoms of liver dysfunction
• Reports of decreased hemoglobin concentrations from baseline that persisted for up to 4 years  of treatment; these decreases were observed within the first few weeks of treatment, and stabilized thereafter; the cause of the decrease in hemoglobin is unknown, but it does not appear to result from hemorrhage or hemolysis; measure hemoglobin prior to initiation of therapy, at one month, and periodically thereafter; initiation of therapy is not recommended for patients with clinically significant anemia; if a clinically significant decrease in hemoglobin is observed and other causes have been excluded, consider discontinuing therapy
• Coadministration with cyclosporine or CYP3A4 or CYP2C19 inhibitors
  • Peripheral edema is a known class effect of endothelin receptor antagonists, and also a clinical consequence of pulmonary arterial hypertension (PAH) and worsening PAH; fluid retention in patients with pulmonary hypertension, occurring within weeks of initiating therapy is reported; if clinically significant fluid retention develops, with or without associated weight gain, further evaluation to determine the cause, such as ambrisentan or underlying heart failure, possible need for specific treatment or discontinuation of therapy
  • Risk of fluid retention and peripheral edema; more common in combination with tadalafil, than with ambrisentan or tadalafil alone
  • Decreased sperm counts were observed in human and animal studies with another endothelin receptor antagonist and in animal fertility studies with ambrisentan; therapy may have an adverse effect on spermatogenesis; counsel patients about potential effects on fertility
  • Development of acute pulmonary edema during therapy initiation may occur; if the patient develops acute pulmonary edema during initiation of therapy with vasodilating agents such as ambrisentan, the possibility of pulmonary veno-occlusive disease should be considered, and if confirmed therapy should be discontinued.
• Restricted Distribution Program
  • Because of the risk of birth defects, available only through a restricted distribution program called the Ambrisentan REMS, by calling 1-888-417-3172; only prescribers and pharmacies certified with Ambrisentan REMS may prescribe and distribute ambrisentan or the brand Letairis
  • Requirements of the REMS program include the following:
    • Prescribers must be certified with the program by enrolling and completing training
    • All females, regardless of reproductive potential, must enroll in the Ambrisentan REMS program prior to initiating treatment
    • Male patients are not enrolled in the REMS
    • Females of reproductive potential must comply with pregnancy testing and contraception requirements
    • Pharmacies that dispense ambrisentan must be certified with the program and must dispense to female patients who are authorized to receive ambrisentan

Pregnancy & Lactation

• Based on data from animal reproduction studies, fetal harm may occur when administered to a pregnant woman and is contraindicated during pregnancy
• There are limited data on use in pregnant women
• Advise the patient of the potential hazard to a fetus
• Contraception
  • Female patients of reproductive potential must use acceptable methods of contraception during treatment and for 1 month after stopping treatment
  • Patients should choose one highly effective form of contraception (intrauterine device [IUD], contraceptive implant, or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods)
  • If a partner’s vasectomy is one method of contraception, a hormone or barrier method must be used along with this method
  • Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling
• Infertility
  • Males: Based on findings and preclinical data, endothelin receptor antagonists have an adverse effect on spermatogenesis; counsel patients about the potential effects on fertility
• Lactation
  • Unknown whether present in human milk
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition