Macitentan

IMPORTANT WARNING:

Macitentan may cause life-threatening birth defects or death of the unborn baby. Before taking macitentan, tell your doctor if you are pregnant, or plan to become pregnant. Macitentan should not be used during pregnancy.

You will have to take a pregnancy test before starting treatment. You must use reliable birth control throughout your treatment with macitentan, and for 1 month after your final dose. Your doctor will tell you which forms of birth control are acceptable, and will give you written information about birth control. In most cases you will be required to use two forms of birth control in order to prevent pregnancy while taking macitentan.

Call your doctor right away if you have had unprotected sex, think your birth control failed, missed your period, or think you may be pregnant. He will discuss your medical options with you. Do not wait until your next appointment to discuss this with your doctor.

Your doctor or pharmacist will give you the Medication Guide when you begin treatment with macitentan and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.

WHY is this medicine prescribed?

Macitentan is used to manage the symptoms of pulmonary arterial hypertension (PAH; high blood pressure in the blood vessels that carry blood to the lungs). Macitentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Macitentan comes as a tablet to take by mouth. Take with or without food once a day. Take macitentan at around the same time every day.

Take macitentan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of macitentan and increase your dose after a week.

What SPECIAL PRECAUTIONS should I follow?

Before taking macitentan,

• tell your doctor or pharmacist if you are allergic to this drug, any part of this drug, or any otherdrugs, foods or substances. Tell your doctor or pharmacist about the allergy and whatsymptoms you had.

• some medications should not be taken with macitentan. Make sure you have discussed anymedications you are currently taking or plan to take before starting macitentan with your doctorand pharmacist. Before starting, stopping, or changing any medications while taking macitentan,please get the advice of your doctor or pharmacist.

• you should know that the following nonprescription or herbal product may interact with macitentan: St. John's wort. Be sure to let your doctor and pharmacist know that you are taking St. John's wort before you start taking macitentan. Do not start taking St. John's wort whiletaking macitentan without discussing with your healthcare provider.

• tell your doctor if you have or have ever had anemia (condition in which red blood cells do not bring enough oxygen to the organs) or liver disease.

• you should know that this medication may decrease fertility in men. Talk to your doctor about the risks of taking macitentan.

• do not breastfeed while taking this medication.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it on that day. Then take the next dose at the regular time and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

Macitentan may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• stuffy nose, sore throat, cough, or flu-like symptoms
• headache
• urgent, frequent, or painful urination
• rash

Some side effects can be serious. If you experience any of these symptoms, stop taking macitentan and call your doctor immediately or get emergency medical treatment:

• itchy skin, extreme tiredness, dark urine, yellowing of your skin or eyes, pain in the upper right part of your stomach, unexplained nausea or vomiting, loss of appetite
• fever
• hoarseness; swelling of the face, throat, tongue, lips, and eyes
• coughing up pink, frothy sputum or blood
• unusual weight increase, swelling of the ankles or legs

Macitentan may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Keep all medication out of sight and reach of children as many containers are not child resistant.Always lock safety caps. Place the medication in a safe location – one that is up andaway and out of their sight and reach. https://www.upandaway.org

Dispose of unneeded medications in a way so that pets, children, and other people cannot takethem. Do not flush this medication down the toilet. Use a medicine take-back program. Talk toyour pharmacist about take-back programs in your community. Visit the FDA's Safe Disposal ofMedicines website (https://goo.gl/c4Rm4p) for more information.

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• headache
• nausea
• vomiting

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory. Your doctor may order tests to see how well your liver is working, and to check for anemia before starting treatment and from time to time during your treatment with macitentan.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

Keep a written list of all of the prescription and nonprescription (over-the-counter) medicinesvitamins, minerals, and dietary supplements you are taking. Bring this list with you each timeyou visit a doctor or if you are admitted to the hospital. You should carry the list with you incase of emergencies.