Pulmonary arterial hypertension, or PAH, is a medical condition affecting the heart and lungs. People who have PAH develop high blood pressure (hypertension) in the arteries of their lungs (the pulmonary arteries). In order to push enough blood through pulmonary arteries narrowed by PAH, the heart must work harder. Over time, the heart loses its ability to pump as much blood as the body needs. Symptoms, such as a reduced ability to exercise, begin to develop.

The symptoms of PAH may include:

• Shortness of breath—especially with physical activity
• Feeling tired
• Chest discomfort or pain
• Dizziness
• Light-headedness or fainting
• Swelling of arms and legs

People with PAH may feel no symptoms for some time. When symptoms do appear, they tend to be mild at first, and may gradually become worse. Because these symptoms can also be caused by many common, less serious illnesses, special tests are usually needed to determine if you have PAH.

PAH has many causes, some of which are known and some of which have not yet been identified.

PAH is divided into multiple subgroups, including:

• Idiopathic PAH (IPAH)—no specific cause can be identified
• Heritable PAH—PAH that runs in families and can be inherited through certain genes
• Drug- and toxin-induced PAH—PAH that occurs in people who have taken certain prescription, over-the-counter, or street drugs
• Associated PAH—PAH that develops in individuals with other diseases or conditions linked to PAH, for example, connective tissue disease, liver disease, HIV infection, or certain birth defects involving the heart

To confirm your diagnosis and to rule out other possible conditions, your doctor will likely schedule a series of tests. These may include:

• Chest x-ray (can reveal clues about the health of your heart and lungs)
• Echocardiogram (measures blood flow through the heart)
• Right heart catheterization (measures blood pressure in the pulmonary arteries and how much blood the heart is able to pump)
• 6-minute walk test (6MWT) (assesses your ability to perform physical activity)

This list is not complete and does not necessarily represent the order in which these tests should be performed.

LETAIRIS is a prescription medicine used to treat pulmonary arterial hypertension (PAH) (WHO Group 1) in people with WHO functional class II or III symptoms. LETAIRIS can improve your ability to exercise (as measured by how far you can walk in 6 minutes), and it can help slow the worsening of your physical condition and symptoms.

The worsening of PAH is defined as a need to go to the hospital for worsening PAH symptoms, a need to take additional PAH treatment, discontinuation of treatment due to worsening PAH symptoms, lung transplantation or other surgical procedures to reduce pulmonary pressures, or death.

• Serious birth defects.
  LETAIRIS can cause serious birth defects if taken during pregnancy. Women must not be pregnant when they start taking LETAIRIS or become pregnant during treatment. Women who are able to get pregnant must have a negative pregnancy test before beginning treatment with LETAIRIS and each month during treatment. Your doctor will decide when to do the test, depending on your menstrual cycle.

  
  Women who are able to get pregnant must use two acceptable forms of birth control during LETAIRIS treatment and for one month after stopping LETAIRIS. If you have had a tubal sterilization or have an IUD, these methods can be used alone and no other form of birth control is needed. Talk with your doctor or gynecologist (a doctor who specializes in female reproduction) to find out about how to prevent pregnancy. Do not have unprotected sex. Talk to your doctor or pharmacist right away if you have unprotected sex or if you think your birth control has failed. Tell your doctor right away if you miss a menstrual period or think you may be pregnant.

The most serious side effects of LETAIRIS are:

Serious birth defects. LETAIRIS can cause serious birth defects if taken during pregnancy. Women must not be pregnant when they start taking LETAIRIS or become pregnant during treatment. (Please see the Important Safety Information for more information on this WARNING.)

Swelling all over the body (fluid retention) can happen within weeks after starting LETAIRIS. Tell your doctor right away if you have any unusual weight gain, tiredness, or trouble breathing while taking LETAIRIS. These may be symptoms of a serious health problem. You may need to be treated with medicine or need to go to the hospital.

Sperm count reduction. Reduced sperm counts have been observed in some men taking a drug similar to LETAIRIS, an effect which might impair their ability to father a child. Tell your doctor if remaining fertile is important to you.

Low red blood cell levels (anemia) can happen during the first weeks after starting LETAIRIS. Your doctor will do blood tests to check your red blood cells before starting LETAIRIS. Your doctor may also do these tests during treatment with LETAIRIS.

• Swelling of hands, legs, ankles, and feet (peripheral edema)
• Stuffy nose (nasal congestion)
• Inflamed nasal passages (sinusitis)
• Hot flashes or getting red in the face (flushing)
• Feeling your heart beat (palpitations)
• Red and sore throat and nose
• Stomach pain
• Constipation
• Shortness of breath
• Headache

Some medicines that are like LETAIRIS can cause liver problems. Tell your doctor if you get any of these symptoms of a liver problem while taking LETAIRIS:

• Loss of appetite
• Nausea or vomiting
• Fever
• Achiness
• Generally do not feel well
• Pain in the upper right stomach (abdominal) area
• Yellowing of your skin or the whites of your eyes
• Dark urine
• Itching

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of LETAIRIS. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

LETAIRIS is used to treat PAH in patients in WHO Group 1 with WHO Class II or III symptoms. Your doctor can determine if LETAIRIS is right for you.

Do not take LETAIRIS if you are pregnant, plan to become pregnant, or become pregnant during treatment with LETAIRIS. LETAIRIS can cause serious birth defects. Serious birth defects from LETAIRIS happen early in pregnancy.

Tell your doctor about all your medical conditions and all the medicines you take, including prescription and non-prescription medicines, such as vitamins and supplements. LETAIRIS and other medicines may affect each other causing side effects. Do not start any new medicines until you check with your doctor.

Especially tell your doctor if you take the medicine cyclosporine (Gengraf^®, Neoral^®, Sandimmune^®). Your doctor may need to change your dose of LETAIRIS. You should not take more than 5 mg of LETAIRIS each day if you also take cyclosporine.

LETAIRIS has not been studied in children.

LETAIRIS can improve your ability to exercise, as measured by how far you can walk in 6 minutes.

In clinical studies, ability to exercise was measured by the 6-minute walk test (6MWT), in which study participants were asked to walk as far as they could on a flat surface for 6 minutes. At 12 weeks, people with PAH who took either 5 mg or 10 mg of LETAIRIS daily experienced significantly greater improvements in how far they could walk on the 6MWT than those taking a placebo.

In one study, people with PAH who took LETAIRIS for 12 weeks were able to walk up to an average of 59 m (194 feet) farther on the 6MWT than people who took a placebo.

In clinical studies, people with PAH who took LETAIRIS found that LETAIRIS helped to slow down the worsening of their physical condition and symptoms compared with people who took a placebo.

The worsening of PAH was defined as a need to go to the hospital for worsening PAH symptoms, a need to take additional PAH treatment, discontinuation of treatment due to worsening PAH symptoms, lung transplantation or other surgical procedures to reduce pulmonary pressures, or death.

In clinical trials, most patients were able to walk farther at 12 weeks after starting therapy. Each patient responds to medication differently. Talk to your PAH healthcare professional about how to track your progress.

Take LETAIRIS exactly as your doctor tells you. Do not stop taking LETAIRIS unless your doctor tells you.

• Take LETAIRIS by mouth once a day
• You may take LETAIRIS with or without food
• Do not split, crush, or chew LETAIRIS tablets
• It will be easier to remember to take LETAIRIS if you take it at the same time each day
• If you take more than your regular dose of LETAIRIS, call your doctor right away
• If you accidentally miss a dose of LETAIRIS, take it as soon as you remember that day. Then take your next dose at the regular time. Do not take two doses at the same time to make up for a missed dose
• During treatment your doctor may order blood tests from time to time to check your liver and red blood cells

If you miss a dose of LETAIRIS, take it as soon as you remember that day. Take your next dose at the regular time. Do not take two doses at the same time to make up for a missed dose.

Because of the risk of birth defects, LETAIRIS is available only through a special restricted distribution program called the LETAIRIS Education and Access Program (LEAP). To receive LETAIRIS, you must talk to your doctor, understand the benefits and risks of LETAIRIS, and agree to all of the instructions in the LEAP program.

All patients must:

• Have a blood test for anemia (low red blood cell count) before starting LETAIRIS. Your doctor may also do this test during treatment with LETAIRIS

Women who are able to become pregnant must:

• Have a negative pregnancy test before starting LETAIRIS
• Have a monthly pregnancy test while taking LETAIRIS
• Use two acceptable forms of birth control at the same time while taking LETAIRIS and for one month after stopping LETAIRIS
• Avoid unprotected sex. Talk to your doctor or pharmacist right away if you have unprotected sex or if you think your birth control has failed. Tell your doctor right away if you miss a menstrual period or think you may be pregnant

Your doctor must enroll you in LEAP before you can receive LETAIRIS. As part of enrolling you in LEAP, your doctor will explain the benefits and risks of taking LETAIRIS and the requirements of LEAP, including the need for regular pregnancy tests if you are a woman who can become pregnant.

Your doctor will need to re-enroll you after the first 12 months and every year thereafter.

When you enroll in LEAP, you will choose a Certified Specialty Pharmacy. Your Certified Specialty Pharmacy will ship your LETAIRIS refill to you. Each month, you will be called to make sure you are available to receive your LETAIRIS shipment. It is important that your Certified Specialty Pharmacy is able to contact you in order to avoid delays in your refills.

You will need to have all necessary tests completed, and test results must show that you are eligible to take LETAIRIS, before LETAIRIS can be shipped to you. Before starting therapy, you will need to have a blood test to check for signs of anemia (low blood cell count). If you are a woman who is able to become pregnant, you will need to have a negative pregnancy test before starting the medication. Required test must be completed every month while you are taking LETAIRIS. Women who are able to become pregnant must use two acceptable forms of birth control during LETAIRIS treatment and for one month after stopping LETAIRIS.

• There are two places to sign on your LEAP enrollment form. Be sure to read and sign the form in both places
• Be sure to provide one or more phone numbers on your application so you don't miss any important calls from your Certified Specialty Pharmacy
• Complete your pregnancy test (for women who are able to get pregnant) every month
• Ask your doctor about LabSync, which can help you choose a nearby laboratory for testing, schedule your laboratory appointments, and assist in resolving insurance issues related to your laboratory testing
• Be proactive. Call your Certified Specialty Pharmacy once you have completed your monthly test, so that you get your medication on time. In case you forget to call, your Certified Specialty Pharmacy will contact you to confirm that you have completed your test before sending you your refill

Your Certified Specialty Pharmacy can provide updates on the status of your shipment.

If you have questions about LETAIRIS, LEAP, or you would like more information about one of the Gilead^TMSolutions financial assistance programs, please call 1-866-664-LEAP (5327).