Key takeaways:
There are many medications FDA approved to manage pulmonary arterial hypertension (PAH). Most options target one of three substances in the body that are out of balance with PAH — nitric oxide, endothelin, or prostacyclin.
PAH medications are taken by mouth, inhaled, and/or infused. Examples of oral options include sildenafil (Revatio, Liqrev), tadalafil (Adcirca, Alyq, Tadliq) and macitentan (Opsumit). Some medications come in multiple dosage forms, including treprostinil (Remodulin, Orenitram, Tyvaso) and selexipag (Uptravi).
Most infused PAH medications are given continuously through a catheter via an infusion pump. Examples include epoprostenol (Flolan, Veletri) and Remodulin. Depending on the medication, you may need to have the catheter surgically placed.
Your PAH specialist will consider your health history, symptom severity, preferences, and other factors when recommending a treatment plan for you.
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Pulmonary hypertension is when blood pressure builds up in the lungs. This can happen for a few different reasons. With pulmonary arterial hypertension (PAH), it happens because blood vessels in the lungs narrow. As a result, the heart has to work harder than normal to pump blood to the lungs. Symptoms include shortness of breath, chest pain, and lower exercise tolerance.
PAH medications work in different ways to increase blood flow through the lungs. Some medications also help slow the progression of PAH, and keep you feeling healthier, for longer. The best options for you depend on your health history, symptom severity, preferences, and other factors.
Pulmonary arterial hypertension medications at a glance
Nitric oxide, endothelin, and prostacyclin are three substances that are often out of balance for those with PAH. Most PAH medications target one of these imbalances to increase blood flow to the lungs. They fall into one of three categories: nitric oxide pathway mediators, endothelin receptor antagonists (ERAs), and prostacyclin analogs or agonists. Nitric oxide pathway mediators can be broken down further into phosphodiesterase-5 (PDE5) inhibitors and soluble guanylate cyclase (sGC) stimulators.
Activin signaling inhibitors are a newer medication class that works differently.
Category | Medication(s) |
|---|---|
Sildenafil (Revatio, Liqrev) Tadalafil (Adcirca, Alyq, Tadliq) | |
sGC stimulator | Riociguat (Adempas) |
Endothelin receptor antagonist | Macitentan (Opsumit) Bosentan (Tracleer) Ambrisentan (Letairis) |
Combination ERA / PDE5 inhibitor | Macitentan / tadalafil (Opsynvi) |
Prostacyclin analog | Epoprostenol (Flolan, Veletri) Treprostinil (Remodulin, Orenitram, Tyvaso) Iloprost (Ventavis) |
Prostacyclin receptor agonist | Selexipag (Uptravi) |
Activin signaling inhibitor | Sotatercept-csrk (Winrevair) |
For people with mild or no PAH symptoms, treatment typically starts with one oral medication from one of the first three groups (PDE5 inhibitor, sGC stimulator, ERA). For people with moderate-to-severe symptoms, adding a second oral medication from these three groups can improve symptoms, slow PAH progression, and lower the risk of hospitalization.
In more advanced cases, intravenous (IV) prostacyclin is added in, usually in combination with a PDE5 inhibitor. A new injectable medication, Winrevair, can be added if symptoms progress.
Below, we cover a few key points about each of these medications. Keep in mind that you may take other medications to manage PAH, such as calcium channel blockers, diuretics, blood thinners, and oxygen, that aren’t covered on this list.
PDE5 inhibitors
PDE5 inhibitors are considered nitric oxide pathway mediators. Nitric oxide is a molecule in the body that widens and relaxes blood vessels. These medications enhance nitric oxide’s effects by blocking an enzyme (protein) called PDE5, resulting in better blood flow in the lungs. There are two PDE5 inhibitors FDA approved for PAH: sildenafil and tadalafil.
Sildenafil
Sildenafil is approved to treat PAH in adults and children ages 1 and older. It can help improve the ability to exercise and slow PAH from worsening. Sildenafil comes in the following dosage forms, all of which are taken or administered 3 times a day:
Oral tablet and powder for oral suspension (Revatio)
Oral suspension (Liqrev; for adults only)
IV injection (usually for hospital use)
Tadalafil
Tadalafil is approved to help improve exercise ability in adults with PAH. Unlike Revatio, it’s not approved for use in children. Depending on your symptom severity and risks, you’ll usually take tadalafil with other PAH medications.
Tadalafil comes as an oral tablet (Adcirca, Alyq) and an oral liquid (Tadliq). Compared with sildenafil, tadalafil lasts longer in the body so you take it only once a day. This can make tadalafil a more convenient option for some people. But if you take the oral tablet, you may need to swallow two tablets at the same time.
Soluble guanylate cyclase stimulators
Soluble guanylate cyclase (sGC) stimulators work on the same nitric oxide pathway as PDE5 inhibitors — but at an earlier step in the process. Specifically, they stimulate an enzyme called sGC. This causes blood vessels to relax and widen, with and without nitric oxide present.
PDE5 inhibitors, such as sildenafil and tadalafil, depend on nitric oxide to work. And nitric oxide levels in the body tend to go down over time with PAH. Since sGC stimulators work differently, they may be a good option for people who don’t respond as well to PDE5 inhibitors.
Riociguat
Riociguat (Adempas) is the only sGC stimulator approved for PAH. It can help improve exercise ability and slow PAH from getting worse in adults.
Riociguat comes as oral tablets that are taken 3 times daily. It isn’t available in liquid form. But you can crush the tablets and mix them with water or soft foods if you have difficulty swallowing them whole.
Riociguat shouldn’t be taken during pregnancy. It has a boxed warning (the strictest FDA warning) since it can cause harm to a growing fetus. If you’re able to get pregnant, riociguat is only available through a Risk Evaluation and Mitigation Strategies (REMS) program that requires pregnancy tests before, during, and for a period of time after taking it. Effective birth control is also required to prevent pregnancy.
Endothelin receptor antagonists
ERAs work by blocking the effects of endothelin, a substance that causes blood vessels to narrow. People with PAH tend to have higher levels of endothelin, which contributes to increased resistance and pressure in their lungs.
There are three ERAs approved for PAH:
Bosentan
Ambrisentan
Macitentan
Bosentan
Bosentan (Tracleer) is an oral ERA approved for adults with PAH. It’s also the only ERA approved for use in children ages 3 and older. Tracleer can help improve exercise ability and slow PAH from worsening. It comes as an oral tablet and a tablet for oral suspension that you take twice a day.
Similar to riociguat, bosentan has a boxed warning about birth defects when taken during pregnancy. It’s also only available through a REMS program that requires pregnancy tests. What’s more, bosentan can interact with hormonal contraceptives. So you may need to use more than one effective birth control method while taking it.
Unlike other ERAs, bosentan also has a boxed warning about liver damage. Because of this, your healthcare team will check your liver health before you start bosentan and monthly thereafter.
Ambrisentan
Ambrisentan (Letairis) is an oral ERA medication approved for use for adults. It can help improve exercise ability and slow PAH from getting worse. When taken with tadalafil, this combination can also help keep you out of the hospital.
Ambrisentan comes as oral tablets that are taken once a day. And unlike bosentan, your liver health doesn’t need to be monitored monthly during treatment. But ambrisentan has a similar boxed warning and REMS program, requiring monthly pregnancy tests and the use of effective birth control.
Ambrisentan seems to work just as well as bosentan for PAH. But ambrisentan may be preferred by some since it doesn’t have the same liver risks.
Macitentan
Macitentan (Opsumit) is the latest oral ERA medication for adults. It’s approved to slow the worsening of PAH and lower the risk of being hospitalized. Macitentan comes as an oral tablet that’s taken once a day.
Macitentan has the same boxed warning and REMS program related to birth defects as other ERAs. And while liver damage may be possible, macitentan doesn’t require monthly liver tests like bosentan.
Macitentan may work as well as bosentan and ambrisentan for PAH. But it may have a lower risk of certain side effects. In fact, real-world data suggests that more people are able to continue taking macitentan compared to other ERAs.
Macitenant is often prescribed with other PAH medications, such as tadalafil. For convenience’s sake, macitentan and tadalafil are available in a once-daily combination pill called Opsynvi. If you take both of these medications, Opsynvi can reduce the number of pills you take every day.
Prostacyclin analogs and agonists
Prostacyclin is a substance that widens (or dilates) blood vessels and blocks platelets (blood clotting cells) from clumping together. These effects can help improve blood flow through the arteries in the lungs to help with exercise ability.
Prostacyclin analogs are lab-made versions of prostacyclin, while prostacyclin receptor agonists bind to its targets in the body. Selexipag is the only prostacyclin receptor agonist. Prostacyclin analogs for PAH include:
Epoprostenol
Treprostinil
Iloprost
IV prostacyclin infusions are typically preferred. But other forms, such as subcutaneous infusions and inhalations, may be an option for those who prefer not to receive an IV.
Epoprostenol
There are two approved epoprostenol medications for PAH: Flolan and Veletri. Both are given as continuous IV infusions through a central venous catheter via a portable infusion pump. This type of catheter is a long, thin tube that’s surgically inserted into a large vein above the heart. IV epoprostenol medications like Flolan and Veletri are typically prescribed for more severe PAH.
You’ll receive your first epoprostenol treatment from a healthcare professional in a medical setting. After that, you or your caregiver may be trained to administer the infusions at home.
Prior to use, both Flolan and Veletri must be mixed with the provided liquid and stored properly.
And since epoprostenol lasts a short time in the body, it needs to be given continuously. While effective, it requires commitment to prevent infections at the catheter insertion site, to store and use the medication properly, and to ensure that the infusion doesn’t suddenly stop.
Treprostinil
Treprostinil is a similar medication to epoprostenol. You can receive it as a continuous infusion, but you can also take it as an oral pill or an inhalation. Infused treprostinil is often reserved for more severe PAH cases.
Infusion: Treprostinil infusions (Remodulin) can be administered in two ways — through a central venous catheter (IV) or an under-the-skin (subcutaneous) catheter. The subcutaneous route doesn’t require surgical placement and is usually preferred. But, infusion-site pain and reactions can make this type of infusion difficult to tolerate. Compared with epoprostenol, treprostinil already comes in liquid form and has easier storage instructions.
Oral tablet: Oral treprostinil (Orenitram) comes as oral tablets that are taken 2 to 3 times a day with food. It’s approved to help improve exercise ability in people with slight to marked limitations in their physical ability and to slow down the progression of PAH. If you’re having difficulty managing treprostinil infusions, you may be able to switch to the tablets.
Inhalation: Inhaled treprostinil (Tyvaso) can help improve exercise ability in people with marked limitations in their physical ability. It comes as a dry powder inhaler or a nebulized inhalation solution that you inhale 4 times a day, spaced 4 hours apart. Inhaled treprostinil has mostly been studied in combination with oral PAH medications.
Iloprost
Iloprost (Ventavis) is an inhaled prostacyclin analog. It’s approved to help improve exercise ability, lessen symptoms, and slow down PAH from getting worse. Iloprost is inhaled 6 to 9 times daily. And it can only be administered using a specific device called an I-neb Adaptive Aerosol Delivery (AAD) system.
If you’re not currently taking iloprost, your PAH specialist will likely prescribe a different medication for you. That’s because you won’t be able to get the I-neb AAD system since it has been discontinued by the manufacturer. The iloprost inhalation solution is still available if you already have the inhalation device.
Selexipag
Selexipag (Uptravi) is a medication that acts on specific prostacyclin receptors (binding sites) in the body. Because of how it works, it may be less likely to cause common prostacyclin analog side effects, such as nausea and vomiting.
Selexipag is usually taken twice daily as an oral tablet. But it also comes as an IV infusion that you receive in a hospital setting if you’re unable to take the tablets for a period of time.
Selexipag is approved to slow down the progression of PAH and to help keep you out of the hospital. It may be prescribed on its own or in combination with other PAH medications. For some people, it can be an alternative to oral treprostinil. When comparing the two medications, one retrospective study found lower hospitalization rates with selexipag.
Activin signaling inhibitor
Activin signaling inhibitors are the newest medication class for PAH. They target pathways involved in the building up and breaking down of cells lining blood vessel walls in the lungs. These processes can be out of balance with PAH, resulting in the blood vessel walls changing shape. Activin signaling inhibitors work to restore this balance.
Sotatercept
Sotatercept-csrk (Winrevair) is the first and only approved activin signaling inhibitor for PAH in adults. It’s considered a biologic — a medication that comes from living sources. Sotatercept may be added onto other PAH medications to help improve exercise ability and lessen PAH symptom severity. It can also lower the risk of issues related to worsening of PAH, such as hospitalization.
Sotatercept is given as a subcutaneous injection every 3 weeks. You’ll receive your initial doses from a healthcare professional in a medical setting. After that, you or your caregiver may be able to administer sotatercept injections at home.
Frequently asked questions
If you’re living with PAH, certain medications can worsen your symptoms. Because of this, it’s best to avoid these medications:
Decongestants, such as pseudoephedrine (Sudafed) and oxymetazoline (Afrin)
Nonsteroidal anti-inflammatory drugs, such as ibuprofen (Motrin, Advil)
Some medications can also interact with PAH treatments. Make sure your PAH care team has your full list of medications to check for potential interactions in advance.
It’s possible. A small study found that albuterol may have some benefits for people with PAH already taking oral vasodilators — medications that relax arteries in the lungs. But it’s not a standard treatment for PAH, and larger studies are needed to confirm potential benefits.
There are currently two inhaled medications for PAH: Tyvaso (treprostinil) and Ventavis (iloprost). Tyvaso and Ventavis are both administered using a portable nebulizer device, but Tyvaso also comes in a dry powder inhaler. The nebulizer device for Ventavis has been discontinued by the manufacturer, so it’s no longer an option if you aren’t already using the medication.
If you’re living with PAH, certain medications can worsen your symptoms. Because of this, it’s best to avoid these medications:
Decongestants, such as pseudoephedrine (Sudafed) and oxymetazoline (Afrin)
Nonsteroidal anti-inflammatory drugs, such as ibuprofen (Motrin, Advil)
Some medications can also interact with PAH treatments. Make sure your PAH care team has your full list of medications to check for potential interactions in advance.
It’s possible. A small study found that albuterol may have some benefits for people with PAH already taking oral vasodilators — medications that relax arteries in the lungs. But it’s not a standard treatment for PAH, and larger studies are needed to confirm potential benefits.
There are currently two inhaled medications for PAH: Tyvaso (treprostinil) and Ventavis (iloprost). Tyvaso and Ventavis are both administered using a portable nebulizer device, but Tyvaso also comes in a dry powder inhaler. The nebulizer device for Ventavis has been discontinued by the manufacturer, so it’s no longer an option if you aren’t already using the medication.
The bottom line
There are many medications available to manage pulmonary arterial hypertension (PAH). Examples of oral options include sildenafil (Revatio, Liqrev), tadalafil (Adcirca, Alyq, Tadliq), and macitentan (Opsumit). Some people need two oral medications to improve their symptoms.
Infused medications are an option for more severe PAH symptoms. You usually add them to the oral medications you are already taking. Some of them, such as epoprostenol (Flolan, Veletri), need to be administered continuously. But there are versions of these medications that can be taken as tablets, or inhaled into the lungs, including Tyvaso (treprostinil) and Ventavis (iloprost).
Your PAH specialist will consider your symptoms, health history, and other factors when recommending options for you.
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