Opsumit

Before taking macitentan,

• tell your doctor and pharmacist if you are allergic to macitentan, any other medications, or any of the ingredients in macitentan tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), clarithromycin (Biaxin, in Prevpac); efavirenz (Sustiva); certain HIV protease inhibitors such as nelfinavir (Viracept), indinavir (Crixivan), and ritonavir (Norvir, in Kaletra); itraconazole (Onmel, Sporanox); ketoconazole; nefazodone; nevirapine Viramune); phenobarbital; phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin); and rifampin (Rifadin, Rifamate, Rifater, Rimactane).Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with macitentan, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• 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,
• Tell your doctor if you are breastfeeding.

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).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

>10%

Nasopharyngitis (20%)

Headache (14%)

Anemia (13%)

Bronchitis (12%)

1-10%

Urinary tract infection (9%)

Influenza (6%)

Postmarketing Reports

Hypersensitivity reactions (angioedema, pruritus and rash)

Nasal congestion

Edema/fluid retention

Symptomatic hypotension

Elevations of liver aminotransferases (ALT, AST) and liver injury

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using macitentan and call your doctor at once if you have:

• pain or burning when you urinate;
• swelling, rapid weight gain;
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
• new lung problems--anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

Common side effects may include:

• stuffy nose, sinus pain, sore throat;
• headache; or
• flu symptoms (fever, chills, body aches).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Macitentan lowers blood pressure in your lungs, helping your heart pump blood more efficiently.

Macitentan is used to treat pulmonary arterial hypertension (PAH). It improves your ability to exercise and prevents your condition from getting worse.

Macitentan is available to women only under a special program from a certified pharmacy. You must be registered in the program and understand the risks and benefits of taking this medication.

Macitentan may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using macitentan and call your doctor at once if you have:

• pain or burning when you urinate;

• swelling, rapid weight gain;

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• new lung problems--anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

Common side effects may include:

• stuffy nose, sinus pain, sore throat;

• headache; or

• flu symptoms (fever, chills, body aches).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Risk of fetal harm; importance of advising women of childbearing potential to avoid pregnancy and to use acceptable methods of contraception during and for 1 month following discontinuance of macitentan therapy.1 41 Acceptable methods of contraception include one highly effective form of contraception (intrauterine device [IUD], progesterone implant, or tubal sterilization) or a combination of methods (either one hormonal and one barrier method or 2 barrier methods where one form is the male condom).1 41 Acceptable hormonal methods of contraception include estrogen-progestin combination oral contraceptives or transdermal contraceptive systems, vaginal ring, and progesterone injections.41 Acceptable barrier methods include male condoms, diaphragms with spermicide, and cervical caps with spermicide.41 Even if the partner has had a vasectomy, an additional hormonal or barrier method must be used.1 41

• Importance of advising women to inform their clinician immediately if a menstrual period is missed or pregnancy is suspected; clinicians should perform a pregnancy test if pregnancy is suspected for any reason and provide counseling on the use of emergency contraception in the event of unprotected sexual intercourse or known or suspected contraceptive failure.1 41 Apprise patient of potential risk to fetus if pregnancy occurs.1

• Importance of female patients enrolling in the Opsumit REMS program and complying with all contraceptive and pregnancy testing requirements.1 41 Importance of monitoring reproductive status of prepubertal females and immediately reporting changes to clinician.1 41

• Importance of periodic monitoring of RBC counts during treatment.1 41

• Potential risk of liver toxicity.1 41 Importance of patients informing clinicians of any unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching.1 41

• Importance of taking macitentan as prescribed and of not interrupting or discontinuing therapy without consulting a clinician.41

• Importance of not taking a double dose to make up for a missed dose but instead taking the missed dose as soon as it is remembered, and then resuming next dose at regularly scheduled time.41

• Importance of advising patients to not split, chew, or crush tablets.1 41

• Importance of distributing the FDA-approved medication guide with every prescription and reviewing the information with female patients.1 5 41 (See REMS.) Importance of patients carefully reading the medication guide before initiating therapy and each time prescription is refilled.41

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 41

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., drugs for HIV) and OTC drugs or herbal supplements, as well as any concomitant illnesses.1 41

• Importance of informing patients of other important precautionary information.1 41 (See Cautions.)

Macitentan treats symptoms of pulmonary arterial hypertension, which is high blood pressure in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs. When the small blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Macitentan works by relaxing these blood vessels and increasing the supply of blood to the lungs, which reduces the workload of the heart.

This medicine is available only with your doctor's prescription.

• It is used to treat high blood pressure in the lungs.

Recommended Dosage

The recommended dosage of Opsumit is 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended.

Pregnancy Testing in Females of Reproductive Potential

Initiate treatment with Opsumit in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy test during treatment [see Use in Specific Populations (8.6)].

Opsumit tablets are 10 mg white, film-coated, bi-convex debossed with "10" on both sides and supplied as follows:

15 count /PVC/ PE/PVDC aluminum foil blisters in carton (NDC 66215-501-15)

30 count white high-density polyethylene bottle in carton (NDC 66215-501-30)

Store at 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). [See USP Controlled Room Temperature].

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.