Tips on managing infused prostacyclin therapies

Summer 2016

What is prostacyclin therapy?

You have now been diagnosed with pulmonary arterial hypertension (PAH) and your PH care team may have recommended starting prostacyclin therapy. This class of medication is the oldest class of medication used in the treatment of PH.  The first in the class was epoprostenol, or Flolan, which was approved by the FDA in 1995.  In many ways Flolan was considered a miracle drug since prior to that date we only had calcium channel blockers, a type of blood pressure medication to treat PH. What was once considered a lethal diagnosis with little to no treatment options became a treatable condition with the advent of Flolan.  In fact, our center has a patient that still remains on epoprostenol since those early days.

Prostacyclin, is a naturally occurring compound. It exists in all of us, but they have found that the level of prostacyclin is low in PH patients.  It does numerous things in the body including but not limited to inhibit platelet activation and vasodilation. In other words, it prevents platelets, which are normally responsible for blood clotting, from sticking to each other.  It also relaxes the smooth muscle of blood vessels which in turn lowers blood pressure including the pressure in your lungs.  Prostacyclin may have anti-inflammatory properties as well.

What types of prostacyclin exist?

Prostacyclin was discovered in the 1970’s by Sir John Vane, who eventually won the Nobel prize in Medicine for his discovery and understanding of prostaglandin and its physiological effects.  But it was not until 1995 that the first prostacyclin analogue, epoprostenol was approved by the FDA. Since then three other prostacyclin analogues have come to market, namely treprostinil (or Remodulin, Tyvaso, and Orenitram), iloprost (Ventavis), and room temperature stable epoprostenol (Veletri). In December 2015, a new prostacyclin receptor agonist, selexipag, was approved by the FDA.  It sensitizes the actual prostacyclin receptor, versus the analogue compounds which mimic the actual structure of prostacyclin.  A receptor is a site in the tissue or molecule that when a specific substance binds to it, activates certain biological processes such as vasodilation or overgrowth of vascular smooth muscle cells. In this presentation, we will focus on the prostacyclin analogues.

What are some of the similarities and differences between the different prostacyclin analogue therapies?

The following chart lists all the prostacyclin analogues that are currently FDA approved in the USA. We will focus the rest of this article on the infused prostacyclin therapy.

Going over the specific steps in preparing your infused therapy is beyond the scope of this article. Please refer to the manufacturer’s web sites, your PH center nurses, or specialty pharmacy for further information.

What are some tips in succeeding in taking infused therapies?

The 2 most important issues with infused therapies are to prevent infection and to avoid disruption in your therapy. If you can avoid those 2 things, you will likely do very well on these medications.

First, let’s talk about Infection prevention strategies. I cannot stress enough, the importance of hand hygiene. Whether we like to think about it or not, we live in a germ infected world. Therefore, when preparing your medication, or cleaning you catheter, it is critical that you wash your hands thoroughly and keep your nails short. Second, when you do prepare your medication, dedicate a focused quiet time and employ proper technique. Often times we advise patients to set aside a special tray that you wipe down with alcohol that you do your mixing on. This is not the time to watch TV, chat or text on your phone. A careless touch with a contaminated object can introduce bacteria in your medication which can then be pumped directly into your body where it can multiply and make you very sick, and can even potentially trigger a life threatening complication. Be sure to check your catheter exit site daily to make sure there are no signs of infection. If there is any suspicion of redness, pus, oozing, swelling or pain, no matter how small, check with your PH nurse right away.

Other ways to prevent infection are to cover your catheter exit site with an occlusive dressing and change it immediately if it gets wet. You should also use a valve at the end of your catheter. Common valves supplied by your specialty pharmacy include the BD Q syte and Rymed’s InVision Plus. It is also good practice that you rigorously wring with an alcohol pad (like you are juicing an orange) any connection points before you disconnect any tubing. These measures will prevent bacteria from entering the tubing once tubing is disconnected as well as prevent blood from backing up in your catheter.

Another tip is to prevent water from entering the tubing at catheter connection points. Some patients apply Glad press and seal to these connection points so that when bathing, water, which is not sterile, does not pool in this area.

Second, let’s talk about how to avoid therapy disruption. For those on intravenous therapy, make sure you secure the tubing. You could use a “stat lock” device which is an adhesive backed dressing that has a part that actually holds down the line. I would always make sure you have a “safety loop” in your catheter, so that when the line pulls, when it’s accidentally caught on a door knob, for example, it will tug on the loop instead of your line. You can also fold over tape around the tubing and safety pin it to your clothes or bra strap. If you are on room temperature stable prostacyclin, you can consider tucking your pump under a spandex band worn around your abdomen or chest. That way the pump is concealed and the likelihood the tubing snagging is less likely. Or you could carry your pump in a larger pant pocket, cut the tip of the inside of the pocket and tunnel your tubing through the hole. Remember to be very careful when you take off your clothes!

Always carry your back up supply with you. This is so that if there is an unplanned emergency as innocuous as being stuck in traffic, you will never run out of medication. You cannot get your medications from any pharmacy. Many hospitals do not stock this on their shelves. And when I say carry your back up supply with you, I urge you literally to carry it with you. After all, it’s no good if a fire or earthquake breaks out and your supplies are in the parking garage and you are stuck somewhere else.

Know your dose and other medications. Healthcare providers always stress carrying a medication list with you at all times. This is because knowing the doses and what medicines you are on can help assess your medical condition more accurately, and appropriate treatments can be given. For example, if you did not tell the emergency room personnel that you are on sildenafil, an oral treatment for PH, and they gave you a medicine called nitroglycerin, often given with patients presenting with chest pain, these 2 drugs can interact in your body and cause dangerously low blood pressure. For prostacyclin, this becomes even more critical. You should always attach a sticker, or write on the medication reservoir directly, the pump rate, concentration, and dose in ng/kg/min. If you do not, it will delay getting you prostacyclin if you are admitted to the hospital, or worse yet, they can give you the wrong concentration and either overdose or under dose you.

How do you prepare for and handle prostacyclin related emergencies?

If a prostacyclin therapy is interrupted for whatever reason, this can potentially trigger a life threatening emergency. This is more an issue with epoprostenol as they have a 6 minute half-life. That means (and these are real situations that happened to my patients) when your toddler asks, “Mommy what’s this?” and pulls out your catheter, or you are in a hurry and you hastily buckle your seat belt and accidentally sever your tubing, you have 12 minutes before there is no more epoprostenol in your body. Your pulmonary pressures which were lowered with this medication is suddenly gone, and your pressures can acutely increase. Your heart cannot handle the sudden change in pressure, and you can have a cardiac crisis. Therefore, all the tips already mentioned become vitally important.

So how should we prepare for an emergency? Acknowledge that denial is not a good plan. Emergencies will occur, and your level of preparation can mean life or death. First, I would call your local emergency services on their non-emergency line. Explain that you are on this type of therapy, that it cannot be stopped for any reason. Ask them to put you on your “BOLO” list, or “Be on the look-out” list, so that when there is an emergency in your area they can prioritize serving your household. Your specialty pharmacy and our PH center personnel are happy to talk to your local EMS service to educate them on what to do in an emergency. That way, if you call 911 because your catheter has come out, paramedics can come, insert a regular IV in you, and you can them transfer the infusion to the IV line. Then they can transport you to the closest emergency room and they can make arrangements to place another more permanent line. Some paramedics are reluctant to do this, as they are almost always unfamiliar with prostacyclin medications. If that is the case, call your specialty pharmacy who can speak to the EMS personnel, or call your PH center’s emergency number, and the PH clinician can explain to the paramedics what needs to be done.

Second, wear a Medic-Alert bracelet. You have to pay small fee, but what you are paying for is not just a bracelet, but for the added service of having your basic information in their system. If you are found unconscious and alone, paramedics can call Medic Alert and find out who your PH doctor is. I encourage all my prostacyclin patients to directly print on the pump, for example, “Flolan- DO NOT STOP PUMP.” If you have any questions as to how to fill out your Medic-Alert application, please talk to your PH center nurse. Do not let anyone stop your infusion; even well-meaning yet unknowledgeable medical personnel. Patients are often uncomfortable asserting yourself this way, but trust me by the time you are trained on the use of parenteral therapy, you will be the most knowledgeable person anywhere about this therapy. We have had very sad circumstances where unknowing medical personnel stopped the infusion and the patient had a fatal outcome.

Third, keep a list of your medications and critical contact information on a sheet and have that posted on your fridge. Some centers have an emergency information storage kit where you can stick an emergency alert sticker on your fridge. That alerts paramedics to look in your top shelf of your fridge where this vital information is stored in an empty medication bottle. At Stanford, you can request this by e-mailing VialofLife@stanfordmed.org. Make sure your loved ones know about your disease. All prostacyclin patients must have at least one dedicated care partner that will be trained on the preparation of the medication as well as its pump functions.

Fourth, if your catheter pulls out, do not attempt to push your line back in. This will reintroduce germs into your body. The best is to tape it to avoid further line migration and call your PH center immediately to obtain further advice. If it comes out entirely, call 911 and follow the procedure described previously. If you notice a small hole or fracture in your line, clean that area with alcohol or other supplied antiseptic solution, and tape it with sterile tape. Then call your PH center immediately for further advice.

Now that I have most likely thoroughly scared you from prostacyclin therapy, know that you are not alone. Many before you have travelled and are still traveling on this path, and we are absolutely committed to walk this journey with you. Remember that first prostacyclin therapy patient I mentioned who started epoprstenol in the 90’s? Well, she is still on it, and is doing great. It has allowed her to witness her children grow up and welcome several grand-children; a previously unthinkable dream at the time of initial diagnosis. It is our team’s greatest joy when patients tell us about studying abroad, travelling to remote corners of the world, being able to go back to work all because prostacyclin therapy has given their life back. Is it life style altering? Yes. Will there be difficult days and potential set-backs? Of course. But it is, even today in the era of so many medical advances, that prostacyclin infused therapy remains the most potent, most efficacious and life-saving regimen we have. Until we find a cure, its role in PH treatment will likely remain for hopefully not too distant future.