Macitentan works by blocking endothelin, a substance made by the body that causes 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 allows people to be more active, as shown by research studies.

• Macitentan is a once-daily oral 10 mg tablet (round and white with a “10” on both sides.)
• Tablets should be swallowed whole. Do not split, crush or chew tablet.
• May be taken with or without food.
• Macitentan can be taken alone or with PDE-5 inhibitors or inhaled prostanoids, which are types of PAH medicines. Talk to your doctor about how this therapy can be part of your treatment plan.

Macitentan has limited distribution, which means you can’t fill the prescription at a local pharmacy. A specialty pharmacy specified by your insurance plan will ship the medicine to you. Those specialty pharmacies include Accredo, Aetna, Alliance Rx Walgreens Prime, Axium, BriovaRx, Cigna, CVS specialty, Humana and Kaiser Permanente.

Because of the risk of serious birth defects, women of reproductive potential must take monthly pregnancy tests and adhere to contraception requirements.

You might need insurance approval before starting therapy.

Macitentan is generally well tolerated. The most frequent side effects are:

• Nasal inflammation (stuffy nose).
• Headache.
• Anemia.
• Bronchitis (irritation of the airways).
• Urinary tract infection.
• Flu-like illness.

 

More serious side effects include:

Birth defects: Macitentan can cause serious birth defects if taken during pregnancy. Because of the potential harm to the fetus, women of childbearing potential must have pregnancy tests before starting therapy and every month as long as they take macitentan.

Liver problems: Liver problems can occur with endothelin receptor antagonists like macitentan. Although monthly blood tests to measure your liver enzymes (liver function tests) aren’t required while taking macitentan, your doctor will test your liver function before you start treatment and periodically afterward. Your doctor will guide you in managing elevated liver enzymes if you have signs and symptoms of abnormal liver function or injury or your total bilirubin has increased to twice the normal level (as shown on another blood test for liver function). In some cases, the doctors will stop the medication.

Low red blood cell levels: Low red blood cell levels can occur in the first weeks after starting therapy. In some cases, a blood transfusion may be needed, but this isn’t common. Your doctor will check your red blood cell count before you start macitentan therapy and periodically thereafter.

Fluid retention: Fluid retention is a known side effect of endothelin receptor antagonists. You might need to reduce salt and fluid in your diet, as well take a diuretic. The diuretic will help move fluid through the kidneys, causing frequent urination. It is important to notify your physician if you experience swelling or other side effects.

Altered sperm production: Sperm production may change, as observed in animal studies. Men should discuss this with their health care providers.

Allergies: Allergic reaction is possible but not likely.

Tell your health care provider about any medications you take (including over the counter and herbal supplements), to avoid potential or known drug interactions. Possible drug interactions include:

• Macitentan blood levels could increase if your take ketoconazole for fungal infections. Your doctor should adjust your macitentan dosage.
• Ritonavir or ritonavir-containing combination drugs to treat HIV/AIDS haven’t been studied but are likely to increase blood levels of macitentan, similar to ketoconazole. Your doctor should adjust your macitentan dosage.
• While drug levels in the blood can change with combined use of sildenafil and macitentan, the differences don’t appear to be clinically important.
• Macitentan doesn’t appear to alter the effect of warfarin (Coumadin).

Certain patient populations must take precautions while taking macitentan, while others should avoid it. Learn about who can and who shouldn’t take this medication:

Pregnant and breastfeeding patients: Macitentan shouldn’t be used during pregnancy. Macitentan causes serious birth defects, as show in animal studies.

Patients shouldn’t become pregnant while taking macitentan. Women must use two acceptable methods of contraception when taking macitentan to prevent pregnancy, such as tubal ligation or a copper T380A, or an LNg 20 intrauterine device.

If you become pregnant while taking macitentan, immediately notify your health care provider and stop the medication.

It isn’t known whether macitentan passes into breast milk, so nursing mothers shouldn’t take macitentan.

Children and teens: There hasn’t been research to determine whether macitentan is safe or effective for children.

People with liver and kidney disease: Macitentan isn’t recommended for people with significant liver disease. People with significant kidney disease don’t need changes to their macitentan dosage.