How Treatment May Help Improve PAH Risk Status Pulmonary arterial hypertension (PAH) is a progressive disease that involves narrowing of the lung’s blood vessels. This narrowing can prevent proper blood flow to the heart. People with the disease often have nonspecific symptoms, such as fatigue, dizziness, shortness of breath, and swelling of lower extremities. A variety of tests, such as an echocardiogram and right heart catheterization, can be performed to help rule out other diseases and diagnose PAH. Once diagnosed with PAH, it is important that your goals are aligned with your healthcare team’s goals. Some common goals are to be more physically active, have fewer symptoms, and prevent those symptoms, and the disease, from getting worse. To aid in achieving these goals, it is important to understand, measure, and monitor your PAH risk status. What is PAH risk status? PAH risk status is a prediction of how your disease will progress over the next 5 years. It is determined using a variety of measures, many of which your healthcare provider already assesses. These include how far you can walk in 6 minutes, whether levels of a certain biomarker in the blood are raised, if there is any strain to the heart, and how well you are functioning in daily life. Your healthcare provider will use these and other tests to calculate your PAH risk score to help determine how far your disease has progressed and how it may be responding to any treatments thus far. There are three risk status classifications: low, intermediate, and high risk. Intermediate and high-risk classifications suggest a worse prognosis of PAH over the next 5 years, while achieving and maintaining a low-risk status has been shown to improve a patient’s 5-year prognosis. Having routine risk assessments to evaluate disease progression and treatment decisions is important for helping to achieve low-risk status and determine if any adjustments to therapy should be considered. Current treatment guidelines recommend healthcare providers assess their PAH patients’ risk status every 3 to 6 months. How does treatment help? Do you know how specific treatments for PAH work to avoid further narrowing of your blood vessels and worsening of symptoms? Understanding some basics about how your medicine may impact your disease, and ultimately affect your PAH risk status, may empower you to help your healthcare provider identify the treatment plan that works best for you. One fundamental thing to know about PAH is that it can involve multiple pathways that affect the blood vessels in the lungs. There are often imbalances in the natural substances in these pathways, and there are several PAH medications that target each of these specific pathways. One of these pathways is the prostacyclin pathway. Prostacyclin is a substance found in blood vessels that helps keep the vessels open, but it may be lower than normal in people with PAH. The prostacyclin class of medications acts like natural prostacyclin to help combat the narrowing of blood vessels in the lungs. These medications can be administered through oral, inhaled, or pump therapy routes. Targeting more than one pathway may help your symptoms While doctors will often start patients with PAH on one oral therapy, combining treatments to target multiple pathways is often highly beneficial for patients. Prostacyclin class therapies tend to be added on after the other treatments, especially when a patient still hasn’t reached low-risk status while on other medications. When it is appropriate to add on a drug that targets the prostacyclin pathway, PAH patients may be prescribed Orenitram (treprostinil) in addition to their initial therapy. Orenitram, which is indicated for PAH patients to delay disease progression and improve exercise capacity, is the first oral prostacyclin class treatment to be approved by the U.S. Food and Drug Administration (FDA). It is the tablet form of the same proven and trusted type of medicine that has been available as a pump therapy for more than 18 years. What to expect with Orenitram (treprostinil) Taking Orenitram may impact your PAH risk status. In a clinical study, 9 of 10 patients who added Orenitram to their treatment plan maintained or improved their PAH risk status. Improvement in risk status was seen in over 30% of patients, and it occurred as early as three months after starting treatment. In clinical studies, patients taking Orenitram have also: • Decreased their shortness of breath • Reduced strain on their heart • Maintained or improved their functional class, and • Increased their 6-minute walk. Many of these parameters are what healthcare providers use to assess your PAH risk status, and ultimately, predict disease progression. In fact, patients taking Orenitram in a clinical study were found to have a 61% less likely chance of disease progression compared to those who didn’t add Orenitram to their treatment plan. Patients taking Orenitram may experience side effects. Some of the most common side effects are headache, diarrhea, nausea, vomiting, flushing, and pain in arms, legs, and jaw. Some patients taking Orenitram find that they feel worse before they feel better, but they may eventually see improvements in PAH symptoms that they did not experience with other therapeutic approaches. Your healthcare team will discuss possible side effects with you before starting Orenitram so you know what to expect and can create a plan for how to manage these side effects. Takeaway Improving risk status is a major goal of PAH treatment, but there is no one-size-fits-all solution for achieving this goal. Orenitram is an add-on medication for PAH patients whose disease may still be progressing despite the use of other therapy. With this medication, patients may be able to improve their overall PAH risk status and slow the progression of their disease. Ask your healthcare provider if adding Orenitram may help you do more and help control your PAH. IMPORTANT SAFETY INFORMATION FOR ORENITRAM

Who should not take Orenitram?

Do not take Orenitram if you have severe liver problems.

What should I tell my healthcare provider before taking Orenitram?

Tell your healthcare provider: • If you have liver problems or diverticulosis. • If you are pregnant, breastfeeding, and/or plan to become pregnant or breastfeed. It is not known if Orenitram will harm your unborn baby or if Orenitram passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Orenitram. • About all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Orenitram and other medicines may affect each other causing side effects. Do not start any new medicine until you check with your healthcare provider. Especially tell your healthcare provider if you take another medicine that contains treprostinil, such as Remodulin® or Tyvaso®.

How should I take Orenitram?

• Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider. • Orenitram is usually taken 3 times a day (about every 8 hours) or 2 times a day (about every 12 hours). Your healthcare provider will tell you how often you should take Orenitram. If you have side effects, your healthcare provider may tell you to change your dose or when you take Orenitram. Take Orenitram with food. • Swallow Orenitram tablets whole. Do not split, chew, crush, or break your Orenitram tablets. Do not take Orenitram tablets that are damaged or broken. If Orenitram tablets are not taken whole, they may release too much medicine at one time. This can lead to side effects. • If you miss your dose of Orenitram, take the missed dose as soon as possible with food. • If you miss 2 or more doses of Orenitram, call your healthcare provider to see if you need to change your dose. • If you take too much Orenitram, call your healthcare provider or go to the nearest hospital emergency room right away. • You may see the tablet shell in your stools (bowel movements). This is usually normal. The tablet shell is not digested. If you have diverticulosis, the tablet shell may get stuck in a blind pouch or diverticulum in your intestine.

What are the possible side effects of Orenitram?

Orenitram can cause serious side effects, including worsening of PAH symptoms. •Stopping Orenitram suddenly may cause worsening of your PAH symptoms. Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider. • The most common side effects of Orenitram include headache, diarrhea, nausea, vomiting, flushing, and pain in arms, legs, and jaw. These are not all of the possible side effects of Orenitram. Tell your healthcare provider if you have any side effect that bothers you or does not go away. • Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at www.fda.gov/MedWatch or call 1-800-FDA-1088.

What is Orenitram?

Orenitram is a prescription medicine used to treat pulmonary arterial hypertension (PAH) which is high blood pressure in the arteries of your lungs. Orenitram can help slow down the progression of your disease and improve your ability to exercise. It is not known if Orenitram is safe and effective in children. The risk information provided here is not comprehensive. To learn more about Orenitram, talk with your healthcare provider. Please see Full Prescribing Information and Patient Information at www.orenitram.com or call Customer Service at 1-877- UNITHER (1-877-864-8437). OREISIconOCT19 References