Greetings. My name is Frank Rahaghi. I am a pulmonary physician the Chairman of the Pulmonary Critical Care Department at Cleveland Clinic in Weston, Florida and the Director of the Pulmonary Hypertension Clinic. And today we have the pleasure of talking to you about dosing and adverse effect management as a team.

Hi, I am Starlet Harriman. I am an RN. I serve as the Advanced Lung Disease Coordinator at Cleveland Clinic, Florida. And today we're going to be talking about my role in starting patients on Orenitram therapy.

So we got involved in the FREEDOM trials early on, including the registration trials, and from there, since then, we've learned that we can start the patient at lower doses, maybe titrate them up slower, and go to TID dosing instead of BID dosing for better adverse effect management.

We also noticed in FREEDOM-EV and even earlier, there are patients that achieve higher doses, seem to have better outcomes. And FREEDOM-EV actually did show that patients who get to three milligrams TID or greater have a walk improvement of 25 meters, which actually is a clinically impactful change.

I definitely think that managing their expectations is the biggest part of my job up front. These expectations include how long it's going to take to actually get started on the medication, what their insurance is going to cover. I always try to make them understand that this is a journey. This is not a sprint. We're not getting somewhere super fast, and I want them to understand how they're going to feel along the way before they actually do start to feel better so that we're able to keep them on therapy.

The way we try to address adverse events is by addressing it head on as basically one of the biggest responsibilities. And I think one of the most important things we do is right off the bat, we tend to emphasize the top three adverse effects that are most likely to occur, which in the case of Orenitram would be diarrhea, headache, and nausea. And we try at the visit to prepare them for the fact that these things may happen and are likely to happen, in fact. And they will leave with a prescription in their hand that would help them manage these top three adverse effects.

So I normally come in and speak to them after Dr. Rahaghi has, so I do a lot of reinforcement of what he just talked about. We talk about what the expected side effects are. Again, how do we manage them? We'll talk about some non-pharmaceutical ways to manage the side effects. So we let them know there's things that we can do if they're having trouble. And I want to make sure that we have an open line of communication. So they reach out and they know that we're there to help.

Well, obviously we have a really good relationship with our specialty pharmacy providers. And, you know, it does take a little bit of personal interaction with them for them to know what your needs are and how you manage your patients and to sort of allow communication to occur freely.

Also, when it comes to adverse effect management, at the end of the Orenitram enrollment form, there's an area that says optional and basically allows you to share with the specialty pharmacies some of the strategies that you agree to in terms of adverse effect management that they can help you institute that with the patients.

So as we mentioned earlier, this is all sort of built upon a direct relationship with the patient and clear communication.