Selexipag Accord: Uses, Dosage & Side Effects
A generic selective prostacyclin (IP) receptor agonist for the long-term treatment of pulmonary arterial hypertension (PAH) in adults
Selexipag Accord is a generic formulation of selexipag, a first-in-class oral selective prostacyclin (IP) receptor agonist used for the long-term treatment of pulmonary arterial hypertension (PAH) in adults. PAH is a progressive, life-threatening condition in which the small arteries of the lungs become narrowed and stiff, forcing the right side of the heart to work harder and eventually leading to right heart failure. Selexipag mimics the action of prostacyclin, a natural vasodilator produced by the endothelium, and helps reduce pulmonary artery pressure, relieve symptoms such as breathlessness and fatigue, and slow disease progression. As a generic medicine, Selexipag Accord contains the same active substance as the originator product (Uptravi) and has been demonstrated to be bioequivalent, providing clinicians and patients with a cost-effective option backed by the same evidence base, including the landmark GRIPHON trial (N Engl J Med, 2015).
Quick Facts: Selexipag Accord
Key Takeaways
- Selexipag Accord is a generic version of selexipag, a selective prostacyclin (IP) receptor agonist that activates the prostacyclin pathway to relax and widen narrowed pulmonary arteries in adults with pulmonary arterial hypertension (PAH).
- The 200-microgram film-coated tablet is used for the initial titration dose and as a building block to reach the individualized maintenance dose, which can be up to 1,600 micrograms taken twice daily, approximately 12 hours apart, with food.
- Common side effects – headache, jaw pain, flushing, diarrhea, nausea, and muscle pain – are related to the prostacyclin mechanism, most pronounced during titration, and often improve with time or with supportive treatment such as paracetamol.
- Selexipag Accord 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.
- As a bioequivalent generic, Selexipag Accord shares the clinical evidence of the originator, including the GRIPHON trial (N Engl J Med, 2015), which demonstrated a 40% reduction in the risk of PAH disease progression events.
What Is Selexipag Accord and What Is It Used For?
Selexipag Accord contains the active substance selexipag, a first-in-class, orally active, selective prostacyclin (IP) receptor agonist. The prostacyclin pathway is one of three major vasoregulatory pathways implicated in pulmonary arterial hypertension, alongside the endothelin and nitric oxide pathways. In healthy individuals, prostacyclin is continuously produced by the endothelial cells that line the pulmonary arteries, where it acts as a potent vasodilator and also inhibits the aggregation of platelets and the proliferation of vascular smooth muscle cells. In PAH, however, the production of endogenous prostacyclin is reduced, contributing to the vasoconstriction, vascular remodeling, and in situ thrombosis that characterize the disease.
Selexipag and its active metabolite ACT-333679 (also known as MRE-269) bind to and activate the prostacyclin (IP) receptor on pulmonary artery smooth muscle cells. The active metabolite is approximately 37 times more potent than the parent compound at the IP receptor and is responsible for most of the pharmacodynamic activity in humans. IP-receptor activation causes the smooth muscle to relax, leading to vasodilation of the pulmonary arteries. This reduces the abnormally high pressure in the pulmonary circulation, decreases the hemodynamic workload on the right ventricle, and helps preserve right heart function over time. Unlike older prostacyclin analogues such as epoprostenol (which requires continuous intravenous infusion) or iloprost (which requires frequent inhalation several times a day), selexipag is taken conveniently as an oral tablet twice daily.
An important pharmacological feature of selexipag is its selectivity for the IP receptor. Traditional prostanoid analogues activate multiple prostanoid receptor subtypes (EP, DP, FP, TP) in addition to the IP receptor, which may contribute to off-target effects. Selexipag and its active metabolite display high selectivity for the IP receptor with minimal activity at other prostanoid receptors. This selectivity is thought to contribute to a more predictable pharmacological profile, although characteristic prostacyclin-related adverse effects such as headache, jaw pain, flushing, and gastrointestinal symptoms are still expected and tend to be most pronounced during the dose-titration period.
Selexipag Accord is indicated for the long-term treatment of PAH in adult patients with WHO Functional Class II or III disease. It is used in two main clinical settings. First, as add-on therapy in patients whose disease is not adequately controlled by treatment with an endothelin receptor antagonist (such as bosentan, ambrisentan, or macitentan) and/or a phosphodiesterase type 5 (PDE-5) inhibitor (such as sildenafil or tadalafil). Second, as monotherapy in patients for whom these classes of PAH medicines are not considered suitable. In both settings, treatment should be initiated and monitored only by a physician with expertise in the management of PAH.
Pulmonary arterial hypertension is a progressive disease in which the small arteries in the lungs become narrowed, thickened, and stiff as a result of abnormal vascular remodeling, endothelial dysfunction, and in situ thrombosis. The resulting increase in pulmonary vascular resistance forces the right ventricle of the heart to generate much higher pressures to propel blood through the lungs. Over months to years, this leads to right ventricular hypertrophy and, ultimately, right heart failure. Patients with PAH commonly experience breathlessness on exertion, fatigue, reduced exercise capacity, palpitations, chest pain, light-headedness, and syncope (fainting). Without targeted pharmacological treatment, PAH is associated with substantial morbidity and reduced survival, which is why modern guidelines emphasize early diagnosis, risk stratification, and combination therapy.
Three main pharmacological pathways are targeted in PAH: the endothelin pathway (endothelin receptor antagonists such as bosentan, ambrisentan, macitentan), the nitric oxide pathway (PDE-5 inhibitors such as sildenafil and tadalafil, and soluble guanylate cyclase stimulators such as riociguat), and the prostacyclin pathway (oral selexipag and parenteral/inhaled prostanoids such as epoprostenol, iloprost, and treprostinil). By targeting the prostacyclin pathway with a convenient oral tablet, Selexipag Accord addresses a distinct mechanism and can be used together with medicines acting on the other two pathways to achieve comprehensive combination therapy.
What Does “Generic Medicine” Mean?
Selexipag Accord is a generic medicine, meaning it contains the same active substance, in the same amount and dosage form, as the reference originator product (Uptravi). Before a generic medicine can be approved in Europe or other strictly regulated markets, the manufacturer must demonstrate bioequivalence to the reference product. Bioequivalence studies show that the generic delivers the same amount of active substance into the bloodstream, at the same rate, so that the expected clinical efficacy and safety are essentially identical. Generic medicines undergo strict manufacturing and quality controls in line with Good Manufacturing Practice (GMP) and the requirements of the European Medicines Agency (EMA) or equivalent authorities.
In practical terms, prescribers can expect the same indications, dosing regimen, efficacy, and safety profile from Selexipag Accord as from Uptravi. Differences are limited to the list of inactive ingredients (excipients), the appearance of the tablets, the pack sizes, and in some markets the available strengths offered by a particular manufacturer. Because inactive ingredients may differ, patients who have a known allergy or intolerance to a specific excipient should check the pack leaflet carefully. Switching between selexipag products should always be done under the supervision of a PAH specialist.
What Should You Know Before Taking Selexipag Accord?
Selexipag Accord is a specialist medicine that should be prescribed and monitored only by physicians with experience in the management of pulmonary arterial hypertension. Before starting treatment, your doctor will carry out a detailed clinical assessment, including cardiac evaluation (typically right heart catheterization, echocardiography, ECG, and laboratory testing) and a full medication review. The following contraindications, warnings, and special populations are particularly important to understand before the first dose.
Contraindications
There are specific clinical situations in which Selexipag Accord must not be used. These absolute contraindications reflect situations where the hemodynamic or metabolic risks outweigh any potential benefit, and they should be discussed carefully with your prescribing physician before initiating therapy.
- Hypersensitivity: Do not take Selexipag Accord if you have a known allergy to selexipag or to any of the other ingredients of the tablet (see “What Does Selexipag Accord Contain?” below).
- Severe coronary heart disease or unstable angina: Patients with impaired blood flow to the heart muscle, including severe coronary artery disease or unstable angina causing chest pain, should not use this medicine because further vasodilation could worsen coronary perfusion.
- Myocardial infarction within the past 6 months: Patients who have experienced a heart attack within the last six months must not take Selexipag Accord.
- Decompensated heart failure: Use is not appropriate in patients with severe, uncontrolled heart failure that is not under close medical supervision.
- Severe cardiac arrhythmias: Patients with seriously irregular heart rhythms must not use selexipag.
- Significant valvular heart disease: Congenital or acquired heart-valve defects that cause the heart to function poorly (independent of 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 Selexipag Accord.
- Concomitant use of gemfibrozil: Gemfibrozil is an absolute contraindication because it strongly inhibits the UGT1A3, UGT2B7, and CYP2C8 enzymes responsible for the metabolism of the active metabolite of selexipag, leading to an approximately 11-fold increase in metabolite exposure and an unacceptable risk of toxicity.
Warnings and Precautions
Even outside the absolute contraindications, several clinical situations require particular caution. Your prescribing physician will evaluate these before treatment and during follow-up visits. Report any new symptoms or new medicines during the course of therapy so that your dose and overall treatment plan can be adjusted as needed.
- Concomitant antihypertensive medicines: Because Selexipag Accord causes vasodilation, it can enhance the blood-pressure-lowering effect of antihypertensives. Your doctor may need to adjust the doses of other cardiovascular medicines to avoid symptomatic hypotension.
- Pre-existing hypotension: If you already have low blood pressure with symptoms such as dizziness, light-headedness, or fainting, tell your doctor before starting treatment. Dose escalation may need to be slower.
- Recent significant blood or fluid loss: Major blood loss or fluid depletion (for example from severe diarrhea, vomiting, or recent surgery) should be corrected before starting or continuing Selexipag Accord, because dehydration can worsen hypotensive effects.
- Thyroid disorders: Selexipag has been associated with changes in thyroid function, including hyperthyroidism. If you have pre-existing thyroid disease, inform your doctor. Periodic thyroid function testing may be advisable during long-term treatment.
- Severe renal impairment or dialysis: Limited data are available in patients with severe kidney disease or those receiving dialysis. Use with caution, monitor closely, and consider a more cautious titration schedule.
- Hepatic impairment: Patients with moderate hepatic impairment (Child-Pugh class B) should start at a reduced dose of 100 micrograms twice daily with careful titration. Selexipag has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should be avoided in that population.
- Pulmonary veno-occlusive disease (PVOD): Because PVOD can be difficult to distinguish clinically from PAH, vasodilator therapy (including selexipag) may precipitate pulmonary edema. If signs of pulmonary edema develop after initiating treatment, the diagnosis should be reconsidered.
Cases of angioedema (swelling of the face, lips, mouth, tongue, or throat) have been reported with selexipag. Angioedema can progress rapidly and may cause difficulty swallowing or breathing. If you experience angioedema while taking Selexipag Accord, stop the medicine and seek immediate medical attention.
Children and Elderly Patients
Selexipag Accord is not authorized for use in children and adolescents below 18 years of age. The safety and efficacy of selexipag in pediatric PAH have not been established in pivotal trials; clinical studies evaluating the use of selexipag in younger patients are ongoing.
Clinical experience with selexipag in patients older than 75 years is limited. The medicine should be used with caution in this age group, with careful monitoring during dose titration and maintenance therapy. Older patients may be more susceptible to the vasodilatory effects and prostacyclin-related side effects, and concomitant medicines and comorbidities should be reviewed in detail before treatment is started.
Pregnancy and Breastfeeding
Selexipag Accord is not recommended during pregnancy. Animal studies have not shown direct harmful effects with respect to pregnancy or fetal development, but the potential risk in humans is unknown. Because PAH itself carries a very high risk of maternal morbidity and mortality during pregnancy, contraception and pregnancy planning should always be part of the shared decision-making with the PAH specialist team.
Women of childbearing potential should use effective contraception during treatment with Selexipag Accord. If you are pregnant, think you may be pregnant, or are planning a pregnancy, consult your doctor before continuing this medicine. In the event of an unplanned pregnancy, urgent specialist input is required to balance the risks of the medicine against the risks of uncontrolled PAH.
It is not known whether selexipag or its active metabolite is excreted into human breast milk. Because of the potential for serious adverse reactions in breastfed infants, a decision should be made either to discontinue breastfeeding or to discontinue Selexipag Accord, taking into account the importance of the medicine to the mother.
Driving and Operating Machinery
Selexipag Accord may cause side effects such as headache and low blood pressure (hypotension) that can affect your ability to drive or operate machinery safely, particularly during the dose-titration period. The underlying symptoms of PAH, including dizziness and fatigue, can also impair concentration and reaction time. If you experience symptoms that affect your alertness, avoid driving or using machinery until the effects resolve.
How Does Selexipag Accord Interact with Other Drugs?
Drug interactions with Selexipag Accord primarily involve the metabolism of selexipag and its pharmacologically active metabolite ACT-333679. Selexipag is first hydrolyzed by hepatic carboxylesterases to its active metabolite, which is then further metabolized by the UDP-glucuronosyltransferases UGT1A3 and UGT2B7 (glucuronidation) and by cytochrome P450 enzymes CYP2C8 and CYP3A4 (oxidation). Medicines that inhibit or induce these enzymes can substantially alter exposure to the active metabolite, with potential impact on both efficacy and safety. For this reason, it is essential to inform your doctor and pharmacist about every medicine you take, including over-the-counter products, herbal remedies, and dietary supplements.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Gemfibrozil | Approximately 11-fold increase in active metabolite exposure (inhibits UGT1A3, UGT2B7, and CYP2C8) | Absolute contraindication – do not combine |
| Clopidogrel | Approximately 2-fold increase in active metabolite exposure (CYP2C8 inhibition) | Caution advised; consider 100-microgram reduced titration scheme; closer monitoring for prostacyclin-related adverse effects |
| Deferasirox | Inhibits CYP2C8 and UGT enzymes; may increase active metabolite levels | Use with caution; consider lower starting dose and slower titration |
| Carbamazepine | Potent CYP3A4 and CYP2C8 inducer; can significantly reduce active metabolite levels | May reduce efficacy of selexipag; consider an alternative anticonvulsant when feasible |
| Rifampicin / Rifapentine | Potent CYP enzyme inducers; decrease selexipag and active metabolite exposure by around 50% | May substantially reduce therapeutic effect; avoid the combination when possible |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Teriflunomide | Inhibits CYP2C8; may modestly increase active metabolite levels | Monitor for increased prostacyclin-related adverse effects |
| Phenytoin / Valproic acid | CYP enzyme inducers or UGT substrates; potential for altered exposure | Monitor clinical response; adjust dose if therapeutic effect diminishes |
| Fluconazole | Inhibits CYP2C9 and CYP3A4; modest increase in selexipag exposure | Use with caution; monitor for dose-dependent adverse effects |
| Probenecid | Inhibits OAT1/OAT3 and UGT enzymes; may alter metabolite clearance | Monitor for increased adverse effects during co-administration |
| Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) | No clinically significant pharmacokinetic interaction observed | Safe to combine; commonly used together as part of PAH combination therapy |
| PDE-5 inhibitors (sildenafil, tadalafil) | No clinically significant pharmacokinetic interaction observed | Safe to combine; routinely used together with selexipag in triple PAH therapy |
| Warfarin | No effect on INR or warfarin pharmacokinetics | No dose adjustment of warfarin required; safe to co-administer |
Selexipag Accord is often used as part of a combination regimen in modern PAH care. The pivotal GRIPHON trial evaluated selexipag as add-on therapy in patients already receiving endothelin receptor antagonists, PDE-5 inhibitors, or both, and did not identify clinically meaningful pharmacokinetic interactions with these standard PAH treatments. However, when starting or stopping concomitant medicines that affect UGT, CYP2C8, or CYP3A4, your specialist may need to re-evaluate the dose of selexipag to preserve both efficacy and tolerability. Always check with your PAH team before starting any new prescription, over-the-counter medicine, or herbal product – including St John’s wort, which is a notable CYP3A4 inducer.
What Is the Correct Dosage of Selexipag Accord?
Selexipag Accord should only be prescribed by a physician experienced in the treatment of pulmonary arterial hypertension. Dosing follows a carefully structured individual titration: the dose is increased step-by-step until the highest dose the patient can tolerate is identified. This approach allows the body to adapt to the prostacyclin-related effects while maximizing the therapeutic benefit, in line with the approach used in the GRIPHON trial and reflected in current ESC/ERS and FDA/EMA prescribing information.
Adults: Standard Titration
Standard Starting Dose and Titration
Starting dose: 200 micrograms of selexipag taken once in the morning and once in the evening, approximately 12 hours apart.
Titration step size: Add one 200-microgram tablet to each of the morning and evening doses, usually once a week (the interval between increases may be longer if tolerability issues occur). It is often recommended to take the first higher dose in the evening.
Maximum dose: 1,600 micrograms in the morning and 1,600 micrograms in the evening.
Example trajectory: Week 1: 200 mcg twice daily. Week 2: 400 mcg twice daily. Week 3: 600 mcg twice daily, and so on, until the highest individually tolerated dose is reached.
Selexipag Accord 200-microgram tablets provide the flexibility needed to start titration from the lowest recommended dose and to incrementally increase the daily dose. Where higher-strength selexipag tablets (for example 400, 600, 800, 1,000, 1,200, 1,400 or 1,600 micrograms) are available in a given market, your physician and pharmacist will typically combine strengths to minimize the number of tablets taken at each dose step. Selexipag Accord 200 mcg can therefore be used either alone throughout titration or in combination with higher-strength tablets at later steps.
Reduced Titration (100-Microgram Regimen)
Patients with Hepatic Impairment or Specific Drug Interactions
Who qualifies: Adults with moderate hepatic impairment (Child-Pugh class B) and patients taking certain CYP2C8 inhibitors such as clopidogrel or deferasirox.
Starting dose: 100 micrograms of selexipag taken twice daily, approximately 12 hours apart.
Titration step size: Add 100 micrograms to each of the morning and evening doses, usually once a week.
Maximum dose: 800 micrograms twice daily.
Children and Adolescents
Selexipag Accord is not authorized for use in patients younger than 18 years of age. The safety and efficacy of selexipag in pediatric pulmonary arterial hypertension have not been formally established. Children and adolescents with PAH should be managed in specialized centers, where pediatric-specific therapeutic protocols are used.
Elderly Patients
No specific dose adjustment is required on the basis of age alone. However, clinical experience with selexipag in patients older than 75 years is limited, and increased caution is warranted in this population. Titration may need to be slower, and blood pressure and volume status should be monitored closely. Drug-drug interactions are more likely in older patients because of polypharmacy, so a complete medication review at each visit is particularly important.
Patients with Renal Impairment
No dose adjustment is required in patients with mild or moderate renal impairment (eGFR 30–89 mL/min/1.73 m²). In patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²) and in those on dialysis, data are limited; treatment should be initiated with caution and with close monitoring.
How to Take Selexipag Accord
- Take Selexipag Accord once in the morning and once in the evening, approximately 12 hours apart, to keep plasma levels of the active metabolite relatively steady.
- Take tablets with food, as this improves tolerability of the prostacyclin-related side effects.
- Swallow tablets whole with a glass of water. The film coating helps the tablet pass the stomach and protects the active substance.
- Do not split, crush, or chew the tablets.
- Follow exactly the schedule your prescriber has given you, including the titration plan and maintenance dose.
Missed Dose
If you forget to take a dose of Selexipag Accord, take it as soon as you remember, and then continue your normal schedule. However, if it is less than 6 hours before the next scheduled dose, skip the missed dose and take the next one at the regular time. Never take a double dose to make up for a forgotten one, as this could increase side effects.
If you miss treatment for more than 3 consecutive days (i.e. 6 or more consecutive doses missed), contact your prescribing physician immediately. The dose may need to be restarted at a lower level and gradually re-titrated 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 an emergency department immediately. An overdose may intensify prostacyclin-related effects such as severe headache, flushing, jaw pain, nausea, vomiting, diarrhea, and marked hypotension (low blood pressure). Treatment of overdose is supportive and symptomatic; there is no specific antidote for selexipag.
Stopping Treatment
Do not stop taking Selexipag Accord suddenly unless your doctor tells you to do so. Abrupt discontinuation may lead to worsening of PAH symptoms and hemodynamic deterioration. If treatment needs to be stopped, the dose will usually be reduced gradually under the supervision of the PAH team before complete discontinuation.
What Are the Side Effects of Selexipag Accord?
Like all medicines, Selexipag Accord can cause side effects, although not everyone experiences them. Side effects may occur during the titration period when the dose is being increased, and some may also appear during long-term maintenance treatment at a stable dose. The majority of adverse effects are directly related to the prostacyclin receptor agonist mechanism of action and are therefore dose-dependent. Many of these effects improve over time as the body adjusts, or they can be managed with simple supportive treatments such as analgesics, antiemetics, or antidiarrheals.
If you experience swelling of the face, lips, mouth, tongue, or throat (angioedema) that makes it difficult to swallow or breathe, stop taking Selexipag Accord and seek emergency medical care immediately.
If you develop any of the following side effects and find them intolerable or not adequately managed, contact your physician: headache, diarrhea, nausea, vomiting, jaw pain, muscle pain, leg pain, joint pain, or flushing. Your doctor may slow the titration, adjust the dose, or recommend specific supportive treatments, such as paracetamol (acetaminophen) for headache or musculoskeletal pain, antiemetics for nausea, or oral rehydration for diarrhea.
Very Common Side Effects
May affect more than 1 in 10 people
- Headache
- Flushing (reddening of the face)
- Nausea and vomiting
- Diarrhea
- Jaw pain
- Muscle pain (myalgia)
- Joint pain (arthralgia)
- Pain in extremities (leg pain)
- Nasopharyngitis (nasal congestion, runny nose)
Common Side Effects
May affect up to 1 in 10 people
- Anemia (low red blood cell count) or decreased hemoglobin
- Hyperthyroidism (overactive thyroid gland)
- Decreased appetite
- Weight loss
- Hypotension (low blood pressure)
- Abdominal pain and dyspepsia (indigestion)
- General pain
- Changes in blood test results (blood cell counts, thyroid function tests)
- Skin rash and urticaria (hives), sometimes with burning or stinging sensation and redness
- Angioedema (swelling of the face, lips, tongue, or throat)
Uncommon Side Effects
May affect up to 1 in 100 people
- Tachycardia (increased heart rate)
Rare / Post-Marketing Reports
May affect fewer than 1 in 1,000 people or frequency not known
- Severe hypersensitivity reactions
- Marked, symptomatic hypotension
- Syncope (fainting) during dose escalation
- Pulmonary edema in patients with undiagnosed pulmonary veno-occlusive disease
The prostacyclin-related side effects (headache, jaw pain, diarrhea, nausea, vomiting, flushing, and musculoskeletal pain) are the most characteristic adverse effects of selexipag and directly reflect its pharmacological mechanism. These side effects are generally most intense during the titration phase and tend to stabilize or diminish once the maintenance dose is reached. However, they can also re-emerge during long-term treatment at a stable dose, particularly if the dose is increased again or if a concomitant interacting medicine is added. If previously tolerable side effects become bothersome, the dose may need to be reduced rather than treatment stopped entirely.
During long-term treatment, your PAH specialist will arrange regular monitoring that typically includes assessment of thyroid function, full blood count (because of the potential for anemia), blood pressure, and clinical assessment of exercise capacity and symptoms. In patients with significant intolerance to one dose step, down-titration and a slower re-escalation approach often produce a better long-term outcome than prematurely stopping a potentially effective therapy.
Reporting Side Effects
You are encouraged to report any suspected side effects to your healthcare professional and to the national pharmacovigilance system (for example, the Yellow Card scheme in the United Kingdom, the FDA MedWatch program in the United States, or the EudraVigilance system used by EU national authorities). Reporting side effects helps provide more information on the safety profile of Selexipag Accord and all other medicines.
How Should You Store Selexipag Accord?
Proper storage is important to maintain the stability, efficacy, and safety of Selexipag Accord. Always keep the medicine in its original blister or container, protected from moisture and excessive light. Do not transfer the tablets to another container, as the original packaging is designed to protect the active substance throughout its approved shelf life.
Store Selexipag Accord at room temperature, avoiding places with high heat or humidity such as bathrooms or near kitchen stoves. The exact storage temperature (usually below 25°C or 30°C, depending on the market approval) is printed on the outer carton and should be followed precisely. If the pack indicates specific handling instructions – for example, use within a certain number of months after first opening a bottle – follow those instructions exactly.
Do not use Selexipag Accord 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. If the tablets show signs of unusual appearance (crumbling, discoloration, or visible moisture damage), do not use them and consult your pharmacist for advice.
Always keep this medicine out of the sight and reach of children. Do not dispose of Selexipag Accord via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help protect the environment and reduce the risk of accidental ingestion by children, pets, or other people.
What Does Selexipag Accord Contain?
The active substance in Selexipag Accord is selexipag. Each 200-microgram film-coated tablet delivers a defined amount of selexipag that is then hydrolyzed in the body to the active metabolite responsible for most of the pharmacological activity. As with all generics, the qualitative and quantitative composition of the active substance matches that of the reference product Uptravi 200 micrograms film-coated tablets.
Composition of Selexipag Accord 200 mcg
| Component | Ingredient | Function |
|---|---|---|
| Active substance | Selexipag 200 micrograms | Selective prostacyclin (IP) receptor agonist |
| Tablet core | Mannitol (E421) | Diluent |
| Tablet core | Maize (corn) starch | Diluent / binder |
| Tablet core | Low-substituted hydroxypropylcellulose | Disintegrant |
| Tablet core | Hydroxypropylcellulose | Binder |
| Tablet core | Magnesium stearate | Lubricant |
| Film coating | Hypromellose (E464) | Film former |
| Film coating | Propylene glycol (E1520) | Plasticizer |
| Film coating | Titanium dioxide (E171) | Opacifying agent / pigment |
| Film coating | Iron oxides (E172) | Color |
| Film coating | Carnauba wax | Polishing agent |
Minor differences in excipients between Selexipag Accord and other selexipag-containing products (including the originator brand) are expected and do not affect bioequivalence. However, patients with a known intolerance or allergy to any of the inactive ingredients, or to colorants such as specific iron oxide pigments, should check the current package leaflet carefully and consult their pharmacist before starting treatment.
Appearance and Packaging
Selexipag Accord 200-microgram tablets are round, film-coated tablets. Details such as the tablet size, color, imprint, and pack size are specified in the current approved product leaflet and may vary slightly depending on the country of marketing. Typical packaging consists of blister packs supplied in cartons, with pack sizes tailored to the titration and maintenance phases of therapy. Not all pack sizes may be marketed in every country. Always check the outer carton and the patient information leaflet for the exact description of your pack.
Marketing Authorization Holder and Manufacturer
Selexipag Accord is manufactured and marketed by Accord Healthcare, a global pharmaceutical company specializing in high-quality generic medicines. Accord manufactures products under strict Good Manufacturing Practice (GMP) standards and holds marketing authorizations in many markets worldwide. Regulatory oversight is provided by the European Medicines Agency (EMA) and national competent authorities, who also monitor the product’s ongoing quality and safety through pharmacovigilance.
Frequently Asked Questions About Selexipag Accord
Yes, in terms of clinical effect. Selexipag Accord is a generic version of the originator product Uptravi. Both contain the same active substance – selexipag – at the same strength in the same film-coated tablet form. Generic products must be shown to be bioequivalent to the originator, meaning that they deliver the same amount of active ingredient to the bloodstream in the same way. Differences are limited to inactive ingredients (excipients), tablet appearance, manufacturer, and packaging. The indication, mechanism of action, dosing regimen, warnings, and safety profile are the same.
Pulmonary arterial hypertension (PAH) is a rare but serious progressive disease in which the small arteries of the lungs become narrowed and stiff. This increases the pressure in the pulmonary circulation and forces the right side of the heart to pump harder to push blood through the lungs. Over time, the right ventricle enlarges and may eventually fail. Symptoms include shortness of breath (especially during exercise), fatigue, dizziness, chest pain, and fainting. PAH requires expert management in specialized centers and is usually treated with a combination of targeted therapies including endothelin receptor antagonists, PDE-5 inhibitors, and prostacyclin pathway agents such as Selexipag Accord.
The dose titration of Selexipag Accord typically takes several weeks. Starting from 200 micrograms twice daily, the dose is usually increased by 200 micrograms per step, about once a week. In principle, reaching the maximum dose of 1,600 micrograms twice daily could take up to 7 weeks, but many patients settle at a lower individually tolerated maintenance dose earlier. The goal is not simply to reach the maximum but to identify the highest dose each patient can tolerate comfortably, as this is associated with the best therapeutic benefit. If side effects slow titration, longer intervals between dose increases are acceptable and often advisable.
Yes, combination therapy is common in modern PAH care. The pivotal GRIPHON trial evaluated selexipag as add-on therapy in patients already receiving endothelin receptor antagonists (such as bosentan, ambrisentan, or macitentan), PDE-5 inhibitors (such as sildenafil or tadalafil), or both. No clinically significant pharmacokinetic interactions were identified between selexipag and these classes. International guidelines (ESC/ERS 2022) often recommend combination therapy targeting multiple pathways for optimal outcomes. Your PAH specialist will select the specific combination based on risk stratification, tolerability, and individual response.
In many cases, yes. The prostacyclin-related side effects (headache, jaw pain, diarrhea, nausea, and flushing) are generally most pronounced during the titration phase and often improve as the body adjusts to the medicine. Once a stable maintenance dose is reached, many patients find that these effects become more manageable or diminish noticeably. Simple supportive treatments – paracetamol for headache and pain, antiemetics for nausea, and antidiarrheals for loose stools – can be helpful. If side effects remain intolerable at a particular dose, your doctor can slow the titration, reduce the dose, or try again more gradually at a later point.
The primary evidence supporting selexipag (and therefore Selexipag Accord) comes from the GRIPHON trial, published in the New England Journal of Medicine in 2015. This large, event-driven, phase III, randomized controlled trial enrolled 1,156 PAH patients across 181 sites in 39 countries. Patients receiving selexipag had a 40% reduction in the risk of the composite primary endpoint (death or complications of PAH, including hospitalization for PAH worsening or clinical worsening) compared with placebo. Benefits were consistent across subgroups, including patients already on dual background PAH therapy. On the basis of these data, selexipag is approved by the FDA (2015) and EMA (2016) and is recommended in current ESC/ERS 2022 pulmonary hypertension guidelines. As a bioequivalent generic, Selexipag Accord is expected to share this evidence base.
Selexipag Accord is a convenient oral tablet taken twice daily, whereas older prostacyclin therapies are administered parenterally or by inhalation. Epoprostenol (Flolan, Veletri) requires continuous intravenous infusion via a central venous catheter, iloprost (Ventavis) requires 6–9 inhalations per day via a special nebulizer, and treprostinil (Remodulin, Tyvaso, Orenitram) can be given by subcutaneous or intravenous infusion or by inhalation. Beyond the route of administration, selexipag is also a selective IP-receptor agonist with a distinct chemical structure from traditional prostacyclin analogues, which can contribute to a somewhat different tolerability profile. The choice between these therapies depends on disease severity, patient preference, tolerability, and available support for parenteral therapies.
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.
- European Medicines Agency. Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1). London: EMA; 2010.
- 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.
- 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.
- British National Formulary (BNF). Selexipag. National Institute for Health and Care Excellence (NICE). Last updated 2025.
- World Health Organization. WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
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 officially approved product labeling in your country.