Ambrisentan works by blocking endothelin, a substance made by the body that causes the blood vessels in the arteries of the lungs to constrict. Endothelin causes abnormal growth of the muscular layer in the vessel wall, which narrows the lumen, or space inside the blood vessel. 

This narrowing causes the pressure to increase, making it harder for the right side of the heart to push the blood through the lungs to get oxygen. By blocking the action of endothelin, ambrisentan helps relax the blood vessels so the lung blood pressure goes down. Lower lung pressures reduce stress on the right heart so heart function improves. Improved heart function generally results in the ability to be more active, as shown in research studies. 

Ambrisentan is taken orally, with or without food.

Swallow tablet whole. Do not split, crush or chew tablets.

Available in two doses: 5 mg and 10 mg.

Your health care provider will determine which strength is the right dose for you.

Ambrisentan has limited distribution, which means you can’t buy it a local pharmacy. You usually need approval from your insurance company before starting this therapy. Your insurance company will identify a specialty mail-order pharmacy to fill your prescription every month. Those companies include Accredo, Aetna, Alliance Rx Walgreens Prime, Axium, BriovaRx, Cigna, CVS specialty, Humana and Kaiser Permanente.

If you are a woman of childbearing potential, you likely will need to take monthly pregnancy tests and comply with contraception requirements before filling your prescription. Although the FDA no longer requires monthly testing for all women, regardless of pregnancy potential, this medication carries an FDA black box warning about serious birth defect risks.

Ambrisentan is generally well tolerated. The most common side effects are:

• Swelling of legs or abdomen (fluid retention)
• Nasal stuffiness or congestion
• Inflammation of the sinuses
• Flushing of the skin
• Rapid or skipped heart beats
• Abdominal pain
• Elevated liver-function tests

Less common side effects

Fluid retention: Fluid retention is a known side effect of endothelin receptor antagonists such as ambrisentan. In ambrisentan clinical trial studies, where the fluid retention was first noticed, the swelling was generally mild and occurred more frequently in older adults. Notify your doctor if you experience swelling or any other side effects.

Decreased red blood cell count: For some people, red blood cell count may decrease, but it rarely requires blood transfusion. Your doctor should measure your red blood cell count before you start therapy and one month after starting the medicine. Your doctor should monitor your red blood cell count periodically as long as you take ambrisentan.

Elevated liver enzymes: People taking endothelin receptor antagonists may have elevated liver function. However, it appears to be less common with ambrisentan. Liver function is measured through blood samples and is considered elevated when it’s more than three times higher than normal. Elevated live enzymes can indicate liver damage.

Although the FDA no longer requires monthly blood tests for liver function, it still may be wise to test liver function before beginning treatment and occasionally while taking ambrisentan. Ambrisentan should be stopped if the liver function test results increase to more than five times normal levels or if two other related problems are present: The total bilirubin level (another blood test of the liver function) increases to more than twice the normal level or if the patient develops signs and symptoms of liver harm.

Decreased sperm count: Decreased sperm counts have been observed in human and animal studies with another endothelin receptor antagonist and in animal fertility studies with ambrisentan.

Ambrisentan can interact with cyclosporine, a medication given to people who have had transplant surgery. When ambrisentan and cyclosporine are used together, ambrisentan should be limited to 5 mg daily.

Ambrisentan use with sildenafil or tadalafil doesn’t cause significant interactions.

Patients should ask their physicians about medications (including over the counter and herbal preparations) they take that could cause drug interactions.

Certain patient populations must take precautions while taking ambrisentan, while others should avoid it. This section addresses special populations and considerations.

Pregnant and breastfeeding patients

Ambrisentan shouldn’t be used during pregnancy. Ambrisentan causes serious birth defects, as shown in animal research studies. Patients shouldn’t become pregnant while taking ambrisentan.

While taking ambrisentan, you should use two forms of contraception to prevent pregnancy. One option is surgical treatment to prevent pregnancy, such as tubal ligation. Another is a copper T380A or LNg 20 intrauterine device.

If you become pregnant while taking ambrisentan, immediately notify your doctor.

It’s not known whether ambrisentan passes into breast milk, so nursing mothers shouldn’t take ambrisentan.

Children and teens

No research exists on whether ambrisentan is safe or effective for children.

Other considerations

Ambrisentan isn’t recommended for people with significant liver disease.

Patients with significant kidney disease don’t need to change their dose.