Uptravi: Uses, Dosage & Side Effects
A selective prostacyclin (IP) receptor agonist for the long-term treatment of pulmonary arterial hypertension (PAH) in adults
Uptravi (selexipag) is the first and only oral selective prostacyclin (IP) receptor agonist approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adults. PAH is a progressive, life-threatening condition characterized by abnormally high blood pressure in the pulmonary arteries, which places increasing strain on the right side of the heart. Uptravi mimics the action of prostacyclin, a natural substance that relaxes and widens blood vessels, thereby reducing pulmonary artery pressure, relieving symptoms such as breathlessness and fatigue, and slowing disease progression. The landmark GRIPHON trial demonstrated that selexipag significantly reduced the risk of disease progression events in PAH patients, including hospitalization and clinical worsening.
Quick Facts: Uptravi
Key Takeaways
- Uptravi (selexipag) is the only oral selective prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH), targeting the prostacyclin pathway to relax and widen narrowed pulmonary arteries.
- The dose is individually titrated from 200 micrograms twice daily up to a maximum of 1,600 micrograms twice daily, with weekly increases to find the highest tolerated dose for each patient.
- Common side effects include headache, jaw pain, diarrhea, nausea, flushing, and muscle pain – these are related to the prostacyclin mechanism and often improve over time or with dose adjustment.
- Uptravi must not be used with gemfibrozil and is contraindicated in patients with severe coronary heart disease, recent myocardial infarction, decompensated heart failure, or recent stroke.
- The GRIPHON trial (N Engl J Med, 2015) demonstrated that selexipag significantly reduced the risk of PAH disease progression events, supporting its use as add-on therapy or as monotherapy when other PAH treatments are unsuitable.
What Is Uptravi and What Is It Used For?
Uptravi contains the active substance selexipag, a first-in-class oral selective prostacyclin (IP) receptor agonist. The prostacyclin pathway is one of three major signaling pathways involved in the regulation of pulmonary vascular tone and remodeling, alongside the endothelin and nitric oxide pathways. In healthy individuals, prostacyclin is produced by the endothelial cells lining the pulmonary arteries and acts as a potent vasodilator and inhibitor of platelet aggregation and vascular smooth muscle cell proliferation. In patients with PAH, prostacyclin production is reduced, contributing to the characteristic vasoconstriction, vascular remodeling, and thrombosis that define the disease.
Selexipag and its active metabolite ACT-333679 (also known as MRE-269) act selectively on the prostacyclin (IP) receptor located on pulmonary artery smooth muscle cells. By activating these receptors, Uptravi causes the smooth muscle to relax, leading to vasodilation of the pulmonary arteries. This reduces the abnormally high pressure in the pulmonary circulation and decreases the workload on the right ventricle of the heart. Unlike earlier prostacyclin analogues such as epoprostenol (which requires continuous intravenous infusion) or iloprost (which requires frequent inhalation), selexipag is administered as a convenient oral tablet taken twice daily.
The selectivity of selexipag for the IP receptor is a distinguishing feature. Unlike non-selective prostanoids that can activate multiple prostanoid receptors (EP, DP, FP, TP), selexipag and its active metabolite show high selectivity for the IP receptor with minimal activity at other prostanoid receptors. This selectivity is thought to contribute to a more favorable side effect profile compared with non-selective prostacyclin analogues, although characteristic prostacyclin-related adverse effects such as headache, jaw pain, and gastrointestinal symptoms still occur, particularly during dose titration.
Uptravi is indicated for the long-term treatment of PAH in adult patients with WHO Functional Class II or III disease. It is used in patients whose disease is not adequately controlled by treatment with other types of PAH medications, specifically endothelin receptor antagonists (ERAs) such as bosentan, ambrisentan, or macitentan, and phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil or tadalafil. Uptravi can also be used as monotherapy when these other medication classes are not suitable for a particular patient.
Pulmonary arterial hypertension is a progressive disease in which the small arteries in the lungs become narrowed, thickened, and stiff due to abnormal vascular remodeling. This increased pulmonary vascular resistance forces the right side of the heart to pump harder to push blood through the lungs. Over time, this leads to right ventricular hypertrophy and eventually right heart failure. Patients with PAH experience symptoms such as breathlessness on exertion, fatigue, dizziness, chest pain, and syncope (fainting). Without treatment, PAH is associated with significant morbidity and mortality.
Three major pathways are targeted in PAH treatment: the endothelin pathway (treated with ERAs like bosentan), the nitric oxide pathway (treated with PDE-5 inhibitors like sildenafil or sGC stimulators like riociguat), and the prostacyclin pathway (treated with Uptravi or parenteral prostanoids). By targeting the prostacyclin pathway, Uptravi addresses a distinct mechanism of disease and can be combined with medications from the other two pathways for a comprehensive treatment approach.
What Should You Know Before Taking Uptravi?
Contraindications
There are specific medical conditions and circumstances in which Uptravi must not be used. Understanding these absolute contraindications is critical for patient safety and should be discussed with your prescribing physician before starting treatment.
- Hypersensitivity: Do not take Uptravi if you are allergic to selexipag or any of the other ingredients in the tablets (including mannitol, corn starch, hydroxypropylcellulose, magnesium stearate, hypromellose, propylene glycol, titanium dioxide, iron oxides, or carnauba wax).
- Severe coronary heart disease or unstable angina: Patients with poor blood flow to the heart muscle, including those with severe coronary artery disease or unstable angina presenting with symptoms such as chest pain, should not use Uptravi.
- Recent myocardial infarction: Patients who have had a heart attack within the past 6 months must not take Uptravi.
- Decompensated heart failure: Patients with severe heart failure that is not under close medical supervision should not use this medication.
- Severe cardiac arrhythmias: Patients with seriously irregular heart rhythms must not take Uptravi.
- Significant valvular heart disease: Congenital or acquired heart valve defects that cause the heart to function poorly (unrelated to pulmonary hypertension) are a contraindication.
- Recent cerebrovascular events: Patients who have had a stroke or transient ischemic attack (TIA) within the past 3 months must not use Uptravi.
- Concomitant use of gemfibrozil: Gemfibrozil, a fibrate used to lower blood lipid levels, is an absolute contraindication because it strongly inhibits the UGT1A3 and UGT2B7 enzymes responsible for the metabolism of the active metabolite of selexipag, leading to a dramatic (approximately 11-fold) increase in exposure to the active metabolite and an unacceptable risk of toxicity.
Warnings and Precautions
Before starting Uptravi and throughout the course of treatment, it is important to discuss the following with your PAH specialist or nurse. These precautions help ensure that the medication is used safely and that any risks are appropriately managed.
- Antihypertensive medications: If you are taking medications for high blood pressure, Uptravi may cause an additional lowering of blood pressure due to its vasodilatory effect. Your doctor may need to adjust your blood pressure medications.
- Hypotension: If you already have low blood pressure with symptoms such as dizziness, lightheadedness, or fainting, tell your doctor. The vasodilatory action of Uptravi can further reduce blood pressure.
- Recent significant blood or fluid loss: If you have recently experienced major blood loss or fluid depletion (for example, from severe diarrhea or vomiting), this should be addressed before starting or continuing Uptravi, as dehydration can exacerbate hypotensive effects.
- Thyroid disorders: Uptravi has been associated with thyroid function changes, including hyperthyroidism (overactive thyroid). If you have pre-existing thyroid problems, inform your doctor. Regular thyroid function monitoring may be advisable.
- Severe renal impairment or dialysis: If you have severe kidney problems or are undergoing dialysis, use Uptravi with caution. Limited data are available for these patient populations, and dose adjustments may be necessary.
- Severe hepatic impairment: If you have or have had severe liver dysfunction, Uptravi should be used with extreme caution or may not be appropriate. Patients with moderate hepatic impairment (Child-Pugh class B) should start at a lower dose of 100 micrograms twice daily. Uptravi has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should be avoided in these patients.
Cases of angioedema (swelling of the face, lips, mouth, tongue, or throat) have been reported with Uptravi. This can make it difficult to swallow or breathe. If you experience angioedema, stop taking Uptravi and seek immediate medical attention.
Children and Elderly Patients
Uptravi is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of selexipag have not been established in pediatric patients. Clinical trials are ongoing to evaluate the potential use of selexipag in children with PAH.
Experience with Uptravi in patients older than 75 years is limited. Uptravi should be used with caution in this age group, with careful monitoring during dose titration and maintenance therapy. Elderly patients may be more susceptible to the vasodilatory effects and prostacyclin-related side effects of the medication.
Pregnancy and Breastfeeding
Uptravi is not recommended during pregnancy. Animal studies have not shown direct harmful effects on pregnancy or fetal development, but the potential risk in humans is unknown. Given the serious nature of PAH and the limited data on selexipag use in pregnant women, the decision to use Uptravi during pregnancy must be made carefully with the prescribing physician, weighing the potential benefits against the unknown risks.
Women of childbearing potential should use effective contraception during treatment with Uptravi. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medication.
It is not known whether selexipag or its active metabolite is excreted into human breast milk. Because many drugs are excreted into breast milk and because of the potential for adverse effects in nursing infants, a decision should be made whether to discontinue breastfeeding or to discontinue Uptravi, taking into account the importance of the drug to the mother.
Driving and Operating Machinery
Uptravi may cause side effects such as headache and low blood pressure (hypotension) that could affect your ability to drive safely or operate machinery. The symptoms of PAH itself, including dizziness and fatigue, may also impair these abilities. If you experience any symptoms that affect your concentration or reaction time, refrain from driving or operating machinery until these symptoms resolve.
How Does Uptravi Interact with Other Drugs?
Drug interactions with Uptravi primarily involve the metabolism of selexipag and its active metabolite ACT-333679. Selexipag is hydrolyzed by hepatic carboxylesterases to its active metabolite, which is then further metabolized by UGT1A3 and UGT2B7 (glucuronidation) and CYP2C8 and CYP3A4 (oxidation). Medications that affect these enzymes can alter the exposure to the active metabolite, potentially affecting both efficacy and safety. It is essential to inform your doctor about all medications, supplements, and herbal products you are taking.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Gemfibrozil | Approximately 11-fold increase in active metabolite exposure (inhibits UGT1A3, UGT2B7, and CYP2C8) | Absolute contraindication – never combine |
| Clopidogrel | Approximately 2-fold increase in active metabolite exposure (inhibits CYP2C8) | Caution advised; dose reduction of Uptravi may be needed; use 100 mcg titration |
| Deferasirox | Inhibits CYP2C8 and UGT; may increase active metabolite levels | Use with caution; consider 100 mcg starting dose |
| Carbamazepine | Potent CYP3A4 and CYP2C8 inducer; may significantly reduce active metabolite levels | May reduce efficacy of Uptravi; consider alternative anticonvulsant |
| Rifampicin / Rifapentin | Potent CYP enzyme inducers; decrease selexipag and active metabolite exposure by approximately 50% | May substantially reduce efficacy; avoid combination if possible |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Teriflunomide | Inhibits CYP2C8; may modestly increase active metabolite levels | Monitor for prostacyclin-related side effects |
| Phenytoin / Valproic acid | CYP enzyme inducers or UGT substrates; potential for altered exposure | Monitor response and adjust dose if necessary |
| Fluconazole | Inhibits CYP2C9 and CYP3A4; modest increase in selexipag exposure | Use with caution; monitor for side effects |
| Probenecid | Inhibits OAT1/OAT3 and UGT; may affect metabolite clearance | Monitor for increased side effects |
| Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) | No clinically significant pharmacokinetic interaction observed | Safe to combine; commonly used together in PAH treatment |
| PDE-5 inhibitors (sildenafil, tadalafil) | No clinically significant pharmacokinetic interaction observed | Safe to combine; commonly used together in PAH treatment |
| Warfarin | No effect on INR or warfarin pharmacokinetics observed | No dose adjustment required; safe to co-administer |
Uptravi is commonly used in combination with other PAH-specific therapies. The GRIPHON trial evaluated selexipag as add-on therapy in patients already receiving ERAs, PDE-5 inhibitors, or both. No clinically meaningful pharmacokinetic interactions were identified between selexipag and commonly used PAH medications. However, when initiating or discontinuing concomitant medications that affect UGT or CYP2C8 enzymes, your physician may need to re-evaluate your Uptravi dose to maintain optimal efficacy and tolerability.
What Is the Correct Dosage of Uptravi?
Uptravi should only be prescribed by a physician experienced in the treatment of PAH. The dosing of Uptravi follows a carefully structured titration process, which is designed to gradually increase the dose to find the optimal maintenance dose for each individual patient. This individualized approach ensures that the body can adapt to the prostacyclin-related effects of the medication while maximizing the therapeutic benefit.
Standard Titration (200-Microgram Tablets)
Starting Dose and Titration
Starting dose: 200 micrograms taken once in the morning and once in the evening, approximately 12 hours apart.
Titration: The dose is increased by adding one 200-microgram tablet to the morning dose and one to the evening dose at each step, usually once per week (but intervals may be longer). It is recommended to start the higher dose in the evening first.
Maximum dose: 1,600 micrograms morning and 1,600 micrograms evening.
Example: Week 1: 200 mcg AM + 200 mcg PM. Week 2: 400 mcg AM + 400 mcg PM. Week 3: 600 mcg AM + 600 mcg PM. And so on, until the highest tolerated dose is reached.
At step 5 (1,000 micrograms), patients transition to higher-strength tablets. For example, 1,000 micrograms can be taken as one 800-microgram tablet plus one 200-microgram tablet, rather than five 200-microgram tablets. This simplifies the regimen at higher doses.
Reduced Titration (100-Microgram Tablets)
Patients with Hepatic Impairment or Certain Drug Interactions
Who qualifies: Patients with moderate hepatic impairment (Child-Pugh class B), or those taking certain CYP2C8 inhibitors such as clopidogrel or deferasirox.
Starting dose: 100 micrograms taken once in the morning and once in the evening, approximately 12 hours apart.
Titration: The dose is increased by adding one 100-microgram tablet to the morning dose and one to the evening dose at each step, usually once per week.
Maximum dose: 800 micrograms morning and 800 micrograms evening.
Managing Side Effects During Titration
During the titration phase, patients may experience prostacyclin-related side effects such as headache, diarrhea, nausea, vomiting, jaw pain, muscle pain, leg pain, joint pain, or flushing. If these effects are not tolerable, patients should speak with their doctor. Supportive treatments are available: for example, paracetamol (acetaminophen) for headache and pain, and anti-emetics for nausea.
If side effects remain intolerable despite supportive measures, the doctor may reduce the dose by decreasing the number of tablets by one in the morning and one in the evening. If the lower dose is well tolerated, it becomes the maintenance dose. The doctor may subsequently attempt further dose increases if clinically appropriate.
Maintenance Dose
The highest dose tolerated during the titration phase becomes the maintenance dose. This is the dose that should be taken regularly on an ongoing basis. The doctor will prescribe the appropriate tablet strength(s) for the maintenance dose, which may allow patients to take just one tablet in the morning and one in the evening instead of multiple tablets. The maintenance dose may be adjusted over time based on clinical response and tolerability.
How to Take Uptravi
- Take Uptravi once in the morning and once in the evening, approximately 12 hours apart.
- Take tablets with food, as this improves tolerability.
- The film coating provides protection; swallow tablets whole with a glass of water.
- Do not split, crush, or chew the tablets.
Missed Dose
If you forget to take a dose of Uptravi, take it as soon as you remember. Then continue taking your tablets at the usual times. However, if it is less than 6 hours before your next scheduled dose, skip the missed dose and take the next one at the regular time. Do not take a double dose to make up for a forgotten one.
If you have missed taking Uptravi for more than 3 consecutive days (missing 3 morning and 3 evening doses, or 6 consecutive doses in total), contact your doctor immediately. Your dose may need to be restarted at a lower level and gradually increased back to the previous maintenance dose to avoid an increased risk of side effects.
Overdose
If you have taken more tablets than prescribed, contact your doctor or seek medical attention immediately. An overdose may lead to intensified prostacyclin-related effects such as severe headache, flushing, jaw pain, nausea, vomiting, diarrhea, and significant hypotension (low blood pressure). Treatment is supportive and symptomatic.
Stopping Treatment
Do not stop taking Uptravi suddenly unless your doctor tells you to do so. Abrupt discontinuation may lead to worsening of PAH symptoms. If your doctor decides that treatment should be stopped, the dose may need to be reduced gradually before complete discontinuation.
What Are the Side Effects of Uptravi?
Like all medications, Uptravi can cause side effects, although not everyone experiences them. Side effects may occur during the titration period when the dose is being increased, and they can also appear later during long-term treatment at a stable maintenance dose. The majority of side effects are related to the prostacyclin receptor agonist mechanism of action and are dose-dependent. Many of these effects improve over time as the body adjusts to the medication, or they can be managed with supportive treatments.
If you experience swelling of the face, lips, mouth, tongue, or throat (angioedema) that makes it difficult to swallow or breathe, stop taking Uptravi and seek emergency medical care immediately.
If you experience any of the following side effects and find them intolerable or they cannot be adequately managed, contact your doctor. The dose may need to be reduced: headache, diarrhea, nausea, vomiting, jaw pain, muscle pain, leg pain, joint pain, or flushing.
Very Common
May affect more than 1 in 10 people
- Headache
- Flushing (redness of the face)
- Nausea and vomiting
- Diarrhea
- Jaw pain
- Muscle pain (myalgia)
- Joint pain (arthralgia)
- Leg pain
- Nasopharyngitis (nasal congestion, runny nose)
Common
May affect up to 1 in 10 people
- Anemia (low red blood cell count)
- Hyperthyroidism (overactive thyroid gland)
- Decreased appetite
- Weight loss
- Hypotension (low blood pressure)
- Abdominal pain, including dyspepsia (indigestion)
- Pain
- Changes in blood test results (blood cell counts, thyroid function)
- Skin rash, including urticaria (hives) with burning or stinging sensation and redness
- Angioedema (swelling of face, lips, tongue, or throat)
Uncommon
May affect up to 1 in 100 people
- Tachycardia (increased heart rate)
The prostacyclin-related side effects (headache, jaw pain, diarrhea, nausea, vomiting, flushing, and musculoskeletal pain) are the most characteristic adverse effects of Uptravi and reflect its pharmacological mechanism of action. These side effects are generally most intense during the titration phase and tend to stabilize or diminish once the maintenance dose is established. However, they can also emerge or re-emerge during long-term treatment at a stable dose. If side effects that were previously tolerable become intolerable during maintenance therapy, the dose may need to be reduced.
Regular monitoring during treatment with Uptravi should include assessment of thyroid function, as changes in thyroid hormone levels and clinical hyperthyroidism have been observed. Blood cell counts should also be monitored, as anemia has been reported. Your PAH specialist will schedule appropriate follow-up visits and laboratory tests to ensure early detection and management of any adverse effects.
How Should You Store Uptravi?
Proper storage of Uptravi is important to maintain the effectiveness and safety of the medication. Keep the medicine out of the sight and reach of children at all times. Do not use Uptravi after the expiration date printed on the carton, blister pack, or bottle label. The expiration date refers to the last day of the stated month.
For the 100-microgram film-coated tablets supplied in bottles, use within 5 months of first opening the bottle or before the expiration date, whichever comes first. This is because the smaller tablets in bottle packaging may be more susceptible to moisture after the container is opened.
No special storage conditions are required for Uptravi. Store at room temperature away from excessive heat and moisture. Do not dispose of medications via household waste or wastewater. Ask your pharmacist how to properly dispose of unused or expired medications to help protect the environment.
What Does Uptravi Contain?
The active substance in Uptravi is selexipag. Each tablet contains a specific amount of selexipag corresponding to its labeled strength. The various strengths are designed to facilitate the dose titration process and simplify maintenance dosing once the optimal dose has been identified.
Available Strengths and Appearance
| Strength | Color | Imprint | Shape & Size |
|---|---|---|---|
| 100 mcg | Light yellow | 1 | Round, 3.0 mm |
| 200 mcg | Light yellow | 2 | Round, 7.3 mm |
| 400 mcg | Red | 4 | Round, 7.3 mm |
| 600 mcg | Light purple | 6 | Round, 7.3 mm |
| 800 mcg | Green | 8 | Round, 7.3 mm |
| 1,000 mcg | Orange | 10 | Round, 7.3 mm |
| 1,200 mcg | Dark purple | 12 | Round, 7.3 mm |
| 1,400 mcg | Dark yellow | 14 | Round, 7.3 mm |
| 1,600 mcg | Brown | 16 | Round, 7.3 mm |
Inactive Ingredients
In addition to the active substance selexipag, each tablet contains the following inactive ingredients:
- Tablet core: Mannitol (E421), corn starch, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate
- Film coating: Hypromellose (E464), propylene glycol (E1520), titanium dioxide (E171), iron oxides (E172), carnauba wax
The different colors of the various tablet strengths are achieved using different combinations of iron oxide pigments (yellow, red, and black iron oxides). The 100-microgram tablets also contain talc. These colorants help distinguish the different strengths from one another, reducing the risk of dosing errors, which is particularly important given the wide range of available strengths and the individualized titration process.
Packaging
Uptravi 100-microgram tablets are supplied in bottles containing 60 or 140 tablets (titration pack). Uptravi 200-microgram tablets are available in blister packs of 10 or 60 tablets, and in packs of 60 or 140 tablets (titration packs). All higher-strength tablets (400 through 1,600 micrograms) are supplied in blister packs of 60 tablets. Not all pack sizes may be marketed in every country. A titration guide for patients is included with the titration packs to assist with the dose-escalation process.
Frequently Asked Questions About Uptravi
Pulmonary arterial hypertension (PAH) is a serious, progressive disease characterized by abnormally high blood pressure in the arteries of the lungs (pulmonary arteries). In PAH, the walls of these arteries become thickened, stiff, and narrowed due to vascular remodeling. This forces the right side of the heart to work much harder to pump blood through the lungs, eventually leading to right heart failure. Symptoms include breathlessness (especially during physical activity), fatigue, dizziness, chest pain, and fainting. PAH requires specialist management and is treated with a combination of targeted medications, including endothelin receptor antagonists, PDE-5 inhibitors, and prostacyclin pathway agents like Uptravi.
The dose titration of Uptravi typically takes several weeks. Starting from the initial dose of 200 micrograms twice daily, the dose is increased by 200 micrograms at each step, usually once per week. Since the maximum dose is 1,600 micrograms twice daily, it could theoretically take up to 7 weeks to reach the maximum dose. However, in practice, many patients reach their individually tolerated maintenance dose before this maximum. Some patients may require longer intervals between dose increases if side effects need to resolve. The goal is not necessarily to reach the highest possible dose, but to find the highest dose each patient can comfortably tolerate, as this provides the best therapeutic benefit.
Yes, Uptravi is commonly used in combination with other PAH medications. The GRIPHON clinical trial specifically evaluated selexipag as an add-on therapy in patients already receiving endothelin receptor antagonists (ERAs) like bosentan or ambrisentan, phosphodiesterase 5 inhibitors (PDE-5i) like sildenafil or tadalafil, or both. No clinically significant drug interactions were found between Uptravi and these medication classes. Modern PAH treatment guidelines often recommend combination therapy targeting multiple pathways for optimal outcomes.
In many cases, the prostacyclin-related side effects of Uptravi (such as headache, jaw pain, diarrhea, nausea, and flushing) do improve over time as the body adjusts to the medication. These effects are generally most pronounced during the titration period when the dose is being increased. Once a stable maintenance dose is reached, many patients find that side effects become more manageable or diminish significantly. Supportive treatments, such as paracetamol for headache and pain, can also help manage these effects. If side effects remain intolerable at any dose, your doctor can reduce the dose to find a more comfortable level.
The primary evidence supporting Uptravi comes from the GRIPHON trial (published in the New England Journal of Medicine, 2015), the largest event-driven randomized controlled trial ever conducted in PAH. This phase III trial enrolled 1,156 patients across 181 sites in 39 countries. Patients receiving selexipag had a 40% reduction in the risk of disease progression events (composite of death, hospitalization for PAH worsening, or clinical worsening) compared with placebo. The benefit was consistent across subgroups, including patients already receiving dual background PAH therapy. Based on this landmark trial, Uptravi was approved by the FDA (2015) and EMA (2016) and is recommended in the ESC/ERS 2022 pulmonary hypertension guidelines.
Uptravi differs from other prostacyclin pathway therapies in several important ways. Unlike epoprostenol (Flolan), which requires continuous intravenous infusion via a central line, or iloprost (Ventavis), which requires 6–9 inhalations per day via a nebulizer, or treprostinil (Remodulin), which can be given by subcutaneous or intravenous infusion, Uptravi is taken as a simple oral tablet twice daily. Additionally, selexipag is a selective prostacyclin (IP) receptor agonist, whereas traditional prostanoids activate multiple prostanoid receptor subtypes. This selectivity may contribute to a more predictable side effect profile. Uptravi is also chemically distinct from prostacyclin analogues and has a different metabolic pathway.
References
- Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(26):2522-2533. doi:10.1056/NEJMoa1503184
- European Medicines Agency. Uptravi (selexipag) – Summary of Product Characteristics. EMA/258513/2016. Last updated 2025.
- U.S. Food and Drug Administration. Uptravi (selexipag) – Prescribing Information. Actelion Pharmaceuticals US, Inc. Revised 2024.
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237
- Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317
- Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension (AMBITION study). N Engl J Med. 2015;373(9):834-844. doi:10.1056/NEJMoa1413687
- Chin KM, Channick R, Kim NH, et al. GRIPHON: Hemodynamic Characterizations and Long-term Outcomes. Chest. 2022;162(6):1340-1349.
- World Health Organization. WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- British National Formulary (BNF). Selexipag. National Institute for Health and Care Excellence (NICE). Last updated 2025.
- Coghlan JG, Channick R, Galiè N, et al. Targeting the Prostacyclin Pathway in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. Eur Respir Rev. 2023;32(170):230089.
Medical Editorial Team
Medical Content
iMedic Medical Editorial Team – Specialists in Pulmonary Medicine, Cardiology, and Clinical Pharmacology
Medical Review
iMedic Medical Review Board – Independent panel of medical experts reviewing content according to ESC/ERS, WHO, EMA, and FDA guidelines
Evidence Standard
Level 1A – Based on systematic reviews, meta-analyses of randomized controlled trials, and international clinical guidelines (GRADE framework)
Conflict of Interest
None – Independent medical editorial content with no pharmaceutical company funding, sponsorship, or advertising
This article was last medically reviewed on . Content is reviewed regularly and updated when new evidence becomes available. For the latest prescribing information, consult the official product labeling approved by your national regulatory authority.