Selexipag STADA: Uses, Dosage & Side Effects
A generic selective prostacyclin (IP) receptor agonist containing 200 micrograms of selexipag, used for the long-term treatment of pulmonary arterial hypertension (PAH) in adults.
Selexipag STADA is a generic oral medicine containing 200 micrograms of selexipag, a first-in-class selective prostacyclin (IP) receptor agonist authorised for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO Functional Class II or III disease. As a generic version of the originator medicine Uptravi, it delivers the identical active substance in a bioequivalent formulation and is used in the same way. Selexipag acts on the prostacyclin pathway, mimicking the action of the natural vasodilator prostacyclin to relax and widen the small pulmonary arteries, thereby lowering pulmonary artery pressure, easing the workload on the right ventricle, and slowing disease progression. The landmark GRIPHON trial demonstrated a significant reduction in PAH-related morbidity and mortality events with selexipag, supporting its role as add-on therapy or as monotherapy when endothelin receptor antagonists and phosphodiesterase 5 inhibitors are inappropriate.
Quick Facts: Selexipag STADA
Key Takeaways
- Selexipag STADA is a generic 200-microgram oral tablet of selexipag, therapeutically equivalent to the originator Uptravi, indicated for pulmonary arterial hypertension (PAH) in adults with WHO Functional Class II or III disease.
- It is a selective prostacyclin receptor agonist that targets the prostacyclin pathway, one of three major signalling pathways in PAH, working alongside endothelin receptor antagonists and phosphodiesterase 5 inhibitors for multi-pathway treatment.
- Dosing begins at 200 micrograms twice daily (or 100 micrograms for patients with moderate hepatic impairment or certain interactions) and is titrated weekly to the highest individually tolerated maintenance dose, up to 1,600 micrograms twice daily.
- Very common side effects include headache, jaw pain, diarrhoea, nausea, flushing and musculoskeletal pain – these are prostacyclin-related, most intense during titration, and can usually be managed with supportive treatment or dose adjustment.
- Selexipag STADA must not be taken with gemfibrozil, and it is contraindicated in severe ischaemic heart disease, recent myocardial infarction or stroke, decompensated heart failure, severe arrhythmias, and significant valvular defects.
What Is Selexipag STADA and What Is It Used For?
Selexipag STADA is a generic medicinal product containing the active substance selexipag. Generic medicines are authorised on the basis of bioequivalence to an originator (reference) product — in this case Uptravi from Janssen-Cilag — meaning that the rate and extent of absorption of the active substance into the bloodstream are statistically equivalent to the originator. Once bioequivalence has been demonstrated through regulatory studies, the clinical efficacy and safety data established for the originator are accepted as applicable to the generic, allowing patients to benefit from the same therapeutic outcomes at typically lower cost. Selexipag STADA is distributed in Europe by STADA Arzneimittel AG and its affiliates.
Selexipag is a first-in-class, orally available, selective prostacyclin (IP) receptor agonist. The prostacyclin pathway is one of three major endothelial signalling pathways involved in the regulation of pulmonary vascular tone, smooth muscle proliferation and platelet function, alongside the endothelin pathway (targeted by endothelin receptor antagonists) and the nitric oxide pathway (targeted by phosphodiesterase 5 inhibitors and soluble guanylate cyclase stimulators). In healthy individuals, prostacyclin (prostaglandin I₂) is produced by endothelial cells lining the pulmonary arteries and acts as a potent pulmonary vasodilator, an inhibitor of platelet aggregation and a suppressor of vascular smooth muscle cell proliferation. In patients with PAH, prostacyclin synthesis is markedly reduced, contributing to the vasoconstriction, thrombosis and progressive vascular remodelling that characterise the disease.
Selexipag and its pharmacologically active metabolite ACT-333679 (also known as MRE-269) act selectively on the IP receptor expressed on pulmonary artery smooth muscle cells. Activation of this receptor triggers a rise in intracellular cyclic AMP, which relaxes the vascular smooth muscle and causes vasodilation of the pulmonary arteries. The net result is a reduction in pulmonary vascular resistance and pulmonary artery pressure, decreased right ventricular afterload, and improved cardiac output. In pre-clinical studies, the active metabolite has been shown to be approximately 37 times more potent at the IP receptor than the parent compound, and both molecules display high selectivity for the IP receptor over the other prostanoid receptor subtypes (EP1-4, DP, FP and TP). This selectivity distinguishes selexipag from intravenous or subcutaneous prostacyclin analogues (such as epoprostenol or treprostinil) and contributes to its distinctive pharmacological profile.
Selexipag STADA is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO Functional Class II or III disease. It is used either in combination with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor in patients whose disease is not adequately controlled on these background therapies, or as monotherapy in patients for whom ERAs and PDE-5 inhibitors are not suitable. Because selexipag targets the prostacyclin pathway, it is pharmacologically complementary to the other two drug classes used in modern PAH therapy, and the three classes together form the foundation of the multi-pathway strategy recommended by the 2022 ESC/ERS pulmonary hypertension guidelines.
Pulmonary arterial hypertension is a rare, progressive and life-threatening disorder characterised by abnormally high pressure in the pulmonary arteries. The small precapillary pulmonary vessels become narrowed, thickened and stiff through a process of vascular remodelling that involves intimal thickening, medial hypertrophy, adventitial fibrosis and, in advanced disease, the formation of plexiform lesions. The increased pulmonary vascular resistance forces the right ventricle to generate higher pressures to maintain pulmonary blood flow, leading first to right ventricular hypertrophy and ultimately to right heart failure. Clinically, patients typically present with exertional dyspnoea, fatigue, light-headedness, palpitations, chest pain and, in later stages, syncope and signs of right heart failure such as peripheral oedema and ascites. Without effective treatment, median survival from diagnosis in historical registries was of the order of 2.8 years, although contemporary multi-drug regimens have substantially improved prognosis.
Three major pathways are addressed in modern PAH treatment. The endothelin pathway is blocked by endothelin receptor antagonists such as bosentan, ambrisentan and macitentan. The nitric oxide–cyclic GMP pathway is enhanced by PDE-5 inhibitors (sildenafil, tadalafil) and by soluble guanylate cyclase stimulators (riociguat). The prostacyclin pathway is activated by oral selexipag (as in Selexipag STADA) and by parenteral or inhaled prostanoids (epoprostenol, treprostinil, iloprost). By targeting the prostacyclin pathway with an oral medicine, Selexipag STADA provides a route to triple combination therapy without the need for an indwelling catheter or frequent inhalations.
What Should You Know Before Taking Selexipag STADA?
Selexipag STADA is a specialist medicine that should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension. Before prescribing, the physician will review your full medical history, current medications, recent investigations (including echocardiography, right heart catheterisation and blood tests) and any planned procedures. The following sections summarise the main contraindications and precautions documented in the European Medicines Agency Summary of Product Characteristics for selexipag, which apply equally to the originator product and to generic versions such as Selexipag STADA.
Contraindications
There are specific medical conditions and circumstances in which Selexipag STADA must not be used at all. These absolute contraindications reflect situations where the vasodilatory, platelet-inhibiting or pharmacokinetic properties of selexipag would create unacceptable risk. Each should be actively excluded before the first tablet is taken.
- Hypersensitivity: Do not use Selexipag STADA if you are allergic to selexipag or to any of the excipients listed in the package leaflet (including mannitol, maize starch, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate, hypromellose, propylene glycol, titanium dioxide, iron oxide pigments and carnauba wax).
- Severe coronary artery disease or unstable angina: Patients with symptomatic severe coronary heart disease or unstable angina must not use Selexipag STADA, because vasodilation could precipitate ischaemic events.
- Recent myocardial infarction: Patients who have had a heart attack within the previous 6 months must not use the medicine.
- Decompensated heart failure: Patients with decompensated cardiac failure not under close medical supervision should not be started on Selexipag STADA.
- Severe arrhythmias: Clinically significant or severe cardiac rhythm disturbances are an absolute contraindication.
- Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension: If the primary cause of heart dysfunction is valvular disease, Selexipag STADA must not be used.
- Recent cerebrovascular events: Patients who have had a stroke or transient ischaemic attack (TIA) within the past 3 months must not use the medicine.
- Concomitant use of gemfibrozil: Gemfibrozil, a fibrate used to lower blood lipids, is an absolute contraindication because it strongly inhibits UGT1A3, UGT2B7 and CYP2C8, leading to an approximately 11-fold increase in exposure to the active metabolite ACT-333679 and an unacceptable risk of toxicity.
Warnings and Precautions
Even in the absence of an absolute contraindication, several conditions call for particular caution when prescribing Selexipag STADA. These situations do not necessarily preclude treatment, but they require careful assessment, often with dose adjustment, additional monitoring or coordination with other specialists. Discuss all of the following issues honestly with your prescribing physician before starting and at each follow-up appointment.
- Concurrent antihypertensive therapy: Because selexipag lowers systemic as well as pulmonary vascular resistance, it can produce additive blood-pressure-lowering effects in patients already treated for systemic hypertension. Your antihypertensive regimen may need to be re-evaluated or adjusted during titration.
- Pre-existing hypotension: Patients who have low blood pressure with symptoms such as dizziness, light-headedness or syncope should be assessed carefully before initiation. Dose titration should be slower, and the lowest tolerated maintenance dose should be targeted.
- Recent significant blood or fluid loss: Volume depletion from diarrhoea, vomiting, diuretic over-treatment or recent haemorrhage can exacerbate hypotensive effects; correct these disturbances before continuing Selexipag STADA.
- Thyroid function abnormalities: Hyperthyroidism has been reported during selexipag treatment. Thyroid function tests should be performed in patients with symptoms suggestive of thyroid dysfunction, and the results should inform ongoing management.
- Renal impairment: Selexipag has been used in patients with mild to moderate renal impairment without specific dose adjustment, but experience in severe renal impairment and end-stage renal disease is limited. Use with caution and consider slower titration.
- Hepatic impairment: In patients with moderate hepatic impairment (Child-Pugh class B), the starting dose should be 200 micrograms once daily, with increments of 200 micrograms once daily at weekly intervals as tolerated. Selexipag is not recommended in patients with severe hepatic impairment (Child-Pugh class C).
- Pulmonary veno-occlusive disease (PVOD): As with all pulmonary vasodilators, pulmonary oedema has been reported when drugs from this class are used in patients with undiagnosed PVOD. If signs of pulmonary oedema develop, consider this diagnosis and stop Selexipag STADA.
Cases of angioedema with swelling of the face, lips, tongue or throat have been reported with selexipag, particularly in patients who are also taking angiotensin-converting enzyme (ACE) inhibitors. Swelling of the airway can be life-threatening. If you experience any swelling that makes it difficult to swallow or breathe, stop taking Selexipag STADA and seek emergency medical attention immediately.
Children, Adolescents and Elderly Patients
The safety and efficacy of selexipag have not been established in children and adolescents below 18 years of age. Selexipag STADA is therefore not recommended for paediatric use outside clinical trial settings. Investigational studies of selexipag in paediatric pulmonary hypertension are ongoing in specialist centres, and where a child appears to need prostacyclin-pathway therapy, referral to an expert paediatric PAH programme is appropriate.
Clinical experience with selexipag in patients older than 75 years is limited. In this age group, polypharmacy, age-related pharmacokinetic changes and a higher baseline risk of hypotension and cardiovascular events make careful, individualised titration particularly important. Older patients should be monitored closely for side effects such as dizziness, falls and musculoskeletal pain, and the titration schedule should be slowed or paused whenever these occur.
Pregnancy, Breastfeeding and Fertility
Pregnancy in women with PAH is associated with substantially increased maternal morbidity and mortality, and international PAH guidelines strongly recommend that women of childbearing potential use highly effective contraception throughout treatment. Selexipag STADA is not recommended during pregnancy unless the clinical situation requires treatment with selexipag. Animal reproduction studies have not shown a direct harmful effect on pregnancy or embryo-fetal development, but human data are limited. The risk-benefit balance must therefore be considered on an individual basis in consultation with a PAH specialist and an obstetrician experienced in high-risk pregnancies.
It is not known whether selexipag or its active metabolite is excreted into human breast milk. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants, a decision must be made either to discontinue breastfeeding or to discontinue the medicine, taking into account the importance of treatment to the mother.
In animal studies, selexipag produced reversible disturbances of testicular function in male rats at clinically relevant exposures. The clinical relevance of these findings is unknown. If fertility is a concern, discuss available data with your physician before starting treatment.
Driving and Operating Machinery
Selexipag STADA has a minor influence on the ability to drive and use machines. Headache and low blood pressure can occur during treatment and may, on an individual basis, impair concentration or reaction time. Underlying PAH symptoms — including fatigue, breathlessness and syncope — can also affect driving. You should not drive or operate machinery while experiencing symptoms of hypotension or significant headache, and the same caution applies during the early days after each dose increase in the titration schedule.
How Does Selexipag STADA Interact with Other Drugs?
Drug interactions with Selexipag STADA primarily concern the metabolic pathways of selexipag and its pharmacologically active metabolite ACT-333679. Selexipag is first hydrolysed by hepatic carboxylesterases to the active metabolite, which is subsequently cleared mainly by glucuronidation (UGT1A3 and UGT2B7) and oxidative metabolism (CYP2C8 and, to a lesser extent, CYP3A4). Medicines that inhibit or induce these enzymes can substantially alter the systemic exposure to the active metabolite, with consequences for both efficacy and side-effect burden. Always provide your prescriber and pharmacist with a complete, up-to-date list of prescription medicines, over-the-counter products and herbal remedies so that potential interactions can be identified and managed.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Gemfibrozil | Approximately 11-fold increase in active metabolite exposure (dual inhibitor of UGT1A3/2B7 and CYP2C8) | Absolute contraindication – never combine with Selexipag STADA |
| Clopidogrel | Approximately 2-fold increase in exposure to the active metabolite (CYP2C8 inhibition) | Reduce Selexipag STADA to once-daily dosing during concomitant use; resume twice-daily dosing when clopidogrel is stopped |
| Deferasirox | Inhibits CYP2C8 and UGT enzymes; may increase exposure to the active metabolite | Caution advised; slower titration and closer clinical monitoring recommended |
| Carbamazepine | Strong inducer of CYP3A4 and CYP2C8; may reduce exposure to selexipag and the active metabolite and thus efficacy | Avoid combination where possible; consider alternative anticonvulsant |
| Rifampicin / Rifapentine | Potent CYP enzyme inducers; reduce selexipag and active metabolite exposure by approximately 50% | May substantially reduce efficacy; titrate up to maximum tolerated dose if combination is unavoidable |
| St. John's Wort (Hypericum perforatum) | Herbal CYP3A4 and P-glycoprotein inducer; may reduce efficacy of selexipag | Advise patients to avoid St. John's Wort during treatment with Selexipag STADA |
Minor and Other Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Teriflunomide | Weak CYP2C8 inhibitor; may modestly increase exposure to the active metabolite | Monitor for prostacyclin-related side effects; dose titration as tolerated |
| Phenytoin / Valproic acid | Enzyme induction or UGT substrate competition; variable effect on exposure | Monitor clinical response and adjust dose if needed |
| Fluconazole | Moderate CYP2C9 and CYP3A4 inhibitor; modest increase in selexipag exposure | Use with caution; monitor for adverse effects during co-administration |
| Probenecid | Inhibits OAT1/OAT3 and UGT enzymes; may affect clearance of the active metabolite | Monitor for increased side effects during combined use |
| Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) | No clinically significant pharmacokinetic interaction observed | Safe to combine; this combination is the basis of multi-pathway PAH therapy |
| PDE-5 inhibitors (sildenafil, tadalafil) | No clinically significant pharmacokinetic interaction observed | Safe to combine; complementary mechanism of action |
| Warfarin | No effect on INR or warfarin pharmacokinetics | No dose adjustment required; safe to co-administer |
| ACE inhibitors and ARBs | No pharmacokinetic interaction, but additive hypotensive effect possible | Monitor blood pressure; adjust antihypertensive therapy if symptomatic hypotension occurs |
The GRIPHON trial specifically evaluated selexipag in patients already receiving endothelin receptor antagonists, PDE-5 inhibitors, or both, and demonstrated both clinical benefit and absence of significant pharmacokinetic interactions with these classes. Selexipag STADA can therefore be used confidently as add-on therapy in modern multi-drug PAH regimens. When any new medicine, including over-the-counter products, is started or stopped, it is good practice to re-evaluate the selexipag regimen; this applies equally to inhibitors or inducers of UGT1A3, UGT2B7, CYP2C8 and CYP3A4.
What Is the Correct Dosage of Selexipag STADA?
Selexipag STADA should only be prescribed and dose-titrated by a physician experienced in the management of pulmonary arterial hypertension. The overall dosing philosophy is individualised titration: each patient is started at a low dose and the dose is gradually increased until either the maximum recommended dose is reached or further increases are limited by side effects. The highest dose the patient can tolerate without unacceptable adverse effects becomes the maintenance dose.
Adults – Standard Titration
Starting Dose and Weekly Titration
Starting dose: 200 micrograms taken twice daily, approximately 12 hours apart, with food.
Titration step: Increase by 200 micrograms in the morning and 200 micrograms in the evening at each step, usually at intervals of at least one week. It is recommended to take the first increased dose in the evening.
Maximum dose: 1,600 micrograms morning and 1,600 micrograms evening.
Example (with 200-microgram tablets only): Week 1 – 1 tablet morning + 1 tablet evening (200 mcg BD). Week 2 – 2 + 2 tablets (400 mcg BD). Week 3 – 3 + 3 tablets (600 mcg BD). Continue up to a maximum of 8 + 8 tablets per day (1,600 mcg BD), always limited by tolerability.
Because Selexipag STADA is only authorised as a 200-microgram tablet, patients who tolerate and benefit from higher maintenance doses will end up taking several tablets per dose. This increases pill burden and the risk of dosing errors at higher levels. In practice, treating centres often prescribe the 200-microgram generic during the early titration steps and transition to a presentation with higher-strength tablets (for example the originator's 400, 600, 800, 1000, 1200, 1400 or 1600-microgram tablets) once a stable maintenance dose has been identified, so that patients can take just one or two tablets per administration. This decision depends on local availability and reimbursement arrangements.
Reduced-Titration Regimen
Patients with Moderate Hepatic Impairment or Specific Interactions
Who qualifies: Patients with moderate hepatic impairment (Child-Pugh class B), or those taking clopidogrel (CYP2C8 inhibitor).
Starting dose: 200 micrograms once daily in moderate hepatic impairment; reduce to 200 micrograms once daily when clopidogrel is added to an existing twice-daily regimen.
Titration: Increase by 200 micrograms once daily at weekly intervals, guided by tolerability.
Alternative approach: Where available, use 100-microgram tablets to allow more gradual titration. In moderate hepatic impairment, the recommended maximum is 1,600 micrograms once daily.
Elderly Patients
No specific dose adjustment is required in elderly patients on the basis of age alone. However, experience in patients aged 75 years and older is limited, and pharmacokinetic variability increases with age. Clinical practice is to titrate more slowly, extending the interval between dose increases, and to pay particular attention to orthostatic symptoms, falls, musculoskeletal pain, and interactions with commonly prescribed medicines such as diuretics, statins and anticoagulants.
Patients with Renal Impairment
Selexipag has been studied in patients with mild and moderate renal impairment without the need for dose adjustment. Data in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m²) and those requiring dialysis are limited. In such patients, slower titration, more frequent monitoring, and close coordination with a nephrologist are prudent.
Children and Adolescents
Selexipag STADA is not authorised for use in children and adolescents below 18 years of age, as the safety and efficacy of selexipag in this population have not been established in confirmatory trials. Paediatric PAH is managed in specialist referral centres, where selexipag may be used within clinical research protocols. Parents and guardians should not attempt to adapt adult regimens for children.
Managing Side Effects During Titration
Prostacyclin-related side effects such as headache, diarrhoea, nausea, vomiting, jaw pain, muscle pain, leg pain, joint pain and flushing are common during the titration phase, and are often dose-limiting. Simple supportive measures include taking the tablets with food, staying well hydrated, and using paracetamol (acetaminophen) for headache and musculoskeletal pain. Prochlorperazine or ondansetron may be considered for persistent nausea, and antidiarrhoeal agents for loose stools. If side effects are nevertheless intolerable, the dose can be reduced by one tablet in the morning and one tablet in the evening; if this lower dose is then tolerated, it may be adopted as the maintenance dose.
Your physician may subsequently attempt further cautious dose increases after a period of stability, provided clinical status permits. The overall goal is not to force a particular numerical dose but to find the highest dose that the individual patient can comfortably tolerate, as higher maintenance doses are associated with larger risk reductions in the GRIPHON trial analyses.
Maintenance Dose and Follow-Up
The highest dose reached during individual titration that is well tolerated becomes the long-term maintenance dose. Patients should attend regular follow-up appointments with their PAH centre so that efficacy (6-minute walk distance, WHO functional class, biomarkers such as NT-proBNP, echocardiographic and haemodynamic parameters) and safety (blood pressure, thyroid function, haematology, liver function and symptom inventory) can be reviewed. Dose adjustments may be needed over time in response to changes in clinical status, concomitant medications or new comorbidities.
How to Take Selexipag STADA
- Take tablets twice daily, approximately 12 hours apart, at the same times each day.
- Take with food, because administration with a meal improves tolerability, particularly for gastrointestinal side effects.
- Swallow tablets whole with a glass of water; the film coating must remain intact to ensure predictable drug release.
- Do not split, crush or chew the tablets.
- Keep a written dosing diary, particularly during titration, so that you and your specialist nurse can review tolerability and identify the optimal dose.
Missed Dose
If you forget to take a dose, take it as soon as you remember and then resume your normal schedule. If it is less than 6 hours until your next scheduled dose, skip the missed dose altogether and take the next one at the usual time. Never take a double dose to compensate for a missed one, because this increases the risk of prostacyclin-related side effects.
If you have missed Selexipag STADA for more than 3 consecutive days (6 or more consecutive doses), contact your doctor or PAH specialist nurse before restarting. Your maintenance dose may need to be restarted at a lower level and gradually re-titrated to avoid a marked increase in prostacyclin-related side effects such as headache, flushing and musculoskeletal pain.
Overdose
There is limited clinical experience of deliberate or accidental overdose with selexipag. Reports from single doses up to 3,200 micrograms and daily doses up to 2,400 micrograms have described headache, gastrointestinal disturbances and hypotension as the dominant symptoms. No specific antidote exists. Treatment is supportive: discontinuing the medicine, lying flat if hypotension occurs, intravenous fluids for severe volume depletion, and symptomatic relief for headache and musculoskeletal pain. If you or someone else has taken more tablets than prescribed, contact a poison information service or attend an emergency department promptly.
Stopping Treatment
Do not stop taking Selexipag STADA abruptly on your own initiative. Sudden discontinuation may lead to worsening of PAH symptoms, including increased breathlessness, fatigue and fluid retention, and can precipitate clinical deterioration. If your specialist decides that the medicine should be stopped, the dose will usually be tapered in a stepwise fashion, ideally with alternative PAH therapy in place or under consideration.
What Are the Side Effects of Selexipag STADA?
Like all medicines, Selexipag STADA can cause side effects, although not everybody gets them. The most characteristic adverse effects reflect the prostacyclin-like pharmacology of the molecule and are shared by the entire class of prostacyclin pathway agents. They tend to emerge as the dose is increased and are therefore most prominent during the titration phase, but they can also appear or re-emerge later in long-term treatment, particularly after dose increases, intercurrent illness or drug interactions. Many effects diminish over time as the body adjusts, and most can be managed pragmatically with supportive measures or dose modification rather than by abandoning the drug altogether.
Stop taking Selexipag STADA and seek emergency medical care immediately if you experience swelling of the face, lips, mouth, tongue or throat (angioedema) that makes it difficult to swallow or breathe, sudden severe breathlessness, signs of gastrointestinal bleeding (black or bloody stools, vomiting blood or material resembling coffee grounds), or severe allergic symptoms such as widespread hives with dizziness or collapse.
For less severe side effects that are none the less troublesome — for example persistent headache, jaw pain, diarrhoea, nausea, vomiting, muscle pain, leg pain, joint pain or flushing — contact your PAH specialist or nurse. Options include simple supportive measures, dose reduction, or revised timing of the tablets in relation to meals and rest. It is rarely necessary to discontinue selexipag solely because of class-typical side effects.
Very Common
May affect more than 1 in 10 people
- Headache
- Flushing (redness of the face)
- Nausea and vomiting
- Diarrhoea
- Jaw pain
- Muscle pain (myalgia)
- Joint pain (arthralgia)
- Leg pain / pain in extremity
- Nasopharyngitis (nasal congestion, runny nose)
Common
May affect up to 1 in 10 people
- Anaemia (low red blood cell count), decreased haemoglobin
- Hyperthyroidism or abnormal thyroid function tests
- Decreased appetite
- Weight loss
- Hypotension (low blood pressure)
- Abdominal pain, including dyspepsia (indigestion)
- Non-specific 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)
Rare and Post-Marketing
Less than 1 in 1,000 or reported after market launch
- Severe hypersensitivity reactions
- Pulmonary oedema in undiagnosed pulmonary veno-occlusive disease
- Unusual bleeding events (in the context of concomitant antiplatelet or anticoagulant therapy)
The prostacyclin-related side effects — headache, jaw pain, diarrhoea, nausea, vomiting, flushing and musculoskeletal pain — are the most characteristic adverse effects of selexipag and directly reflect its pharmacological mechanism of action. In clinical trials, these effects were more frequent at higher doses and during periods of dose up-titration, but they also tended to stabilise or diminish once a steady maintenance dose had been achieved. If a previously tolerable maintenance dose becomes associated with intolerable side effects — for example after a concurrent illness or new medicine — the dose can often be reduced to a more comfortable level rather than the treatment being abandoned.
Structured laboratory monitoring during treatment should include regular full blood counts (to detect anaemia), thyroid function tests (because hyperthyroidism and abnormal thyroid biochemistry have been reported), and liver function tests, in line with local PAH-centre protocols. Blood pressure should be measured at each clinic visit, as progressive hypotension is not uncommon and may require antihypertensive dose adjustment. Your PAH specialist will schedule appropriate follow-up visits and laboratory tests to ensure the early detection and management of any adverse effects.
If you notice any adverse reaction that is not listed in the patient leaflet, you can report it directly to your doctor, pharmacist or the national pharmacovigilance authority. Such reports make an important contribution to knowledge about the safety profile of selexipag in real-world clinical practice.
How Should You Store Selexipag STADA?
Correct storage is important to maintain the stability, potency and safety of Selexipag STADA. The film coating of each tablet provides protection against light and moisture, but the intact blister pack provides additional protection and should not be opened until the tablet is due to be taken. Keep the medicine in its original packaging and in the outer carton where relevant.
Store the medicine at room temperature. No specific temperature range is required in the Summary of Product Characteristics, but extremes of heat and cold should be avoided. Do not store Selexipag STADA in the bathroom, where humidity can be high, or in a hot car. Keep the medicine well out of the sight and reach of children and pets at all times; even a single tablet could cause significant symptoms in a young child.
Check the expiry date on the carton and blister pack before each use. The expiry date (EXP) refers to the last day of the stated month. Do not use Selexipag STADA after this date, as the potency of the medicine can no longer be guaranteed. Do not use tablets that appear damaged, discoloured, broken or otherwise abnormal.
Do not dispose of medicines via wastewater or household waste. Unused or expired Selexipag STADA should be returned to your pharmacy for environmentally safe disposal in accordance with local regulations. These measures help to protect the environment and reduce the risk of accidental exposure.
What Does Selexipag STADA Contain?
Each Selexipag STADA film-coated tablet contains 200 micrograms of selexipag as the active pharmaceutical ingredient. The 200-microgram strength corresponds to the starting dose in the standard titration schedule and is used as a building block for higher doses. Selexipag is a white to almost white crystalline powder, poorly soluble in water, and is formulated as a film-coated tablet to support consistent oral absorption.
Excipients (Inactive Ingredients)
In addition to the active substance, each tablet contains the following excipients, which are chosen to ensure consistent manufacturing, dissolution and stability:
- Tablet core: mannitol (E421), maize starch, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate.
- Film coating: hypromellose (E464), propylene glycol (E1520), titanium dioxide (E171), iron oxide pigments (E172), carnauba wax.
The iron oxide pigments provide colour to distinguish tablets and are considered inert at the small quantities used. Selexipag STADA does not contain lactose, and so is suitable for patients with lactose intolerance, nor does it contain any ingredient derived from wheat, and is therefore suitable for patients on a gluten-free diet. Propylene glycol in oral dosage forms is considered safe at the levels used in film-coated tablets for adults, but patients with rare inherited metabolic disorders should discuss this with their pharmacist.
Appearance and Packaging
| Strength | Appearance | Pack Size | Route |
|---|---|---|---|
| 200 micrograms | Small, round, film-coated tablet | Blister packs containing 10, 60 or 140 tablets (not all pack sizes may be marketed in every country) | Oral (by mouth) |
Selexipag STADA is supplied in aluminium blister packs that protect the tablets from moisture and light. A patient information leaflet is enclosed with each pack, describing the medicine, the dosing schedule and the most important warnings. Patients and carers should read the leaflet carefully before starting treatment and keep it for later reference throughout therapy. If any part of the leaflet is unclear, ask your pharmacist or PAH specialist nurse for further explanation.
Marketing Authorisation and Regulatory Status
Selexipag STADA is authorised in the European Union under the centralised or decentralised procedure with STADA Arzneimittel AG (or a designated STADA affiliate) as the marketing authorisation holder. As a generic medicine, its approval is based on demonstrated pharmaceutical and bioequivalence to the originator product Uptravi (selexipag 200 micrograms), combined with the reference product's pharmacology, efficacy and safety data. Availability varies by country and jurisdiction; check with your prescriber or pharmacist for local information about supply, reimbursement and legal status.
Frequently Asked Questions About Selexipag STADA
Yes. Selexipag STADA is a generic version of the originator medicine Uptravi. Both products contain the same active substance (selexipag) at the same dose per tablet (200 micrograms) and are used in the same way for the same indication — the long-term treatment of pulmonary arterial hypertension in adults. Generic medicines are authorised on the basis of pharmaceutical equivalence and bioequivalence to the originator, meaning that they release the active substance into the bloodstream at the same rate and to the same extent. The clinical efficacy and safety documented for the originator therefore also apply to the generic. Changes between brands should nevertheless be discussed with your PAH specialist, because the transition often coincides with a change in tablet shape, colour and markings, which can be confusing for patients on multi-tablet maintenance regimens.
Selexipag STADA is currently authorised only in a single 200-microgram strength. During titration, doses are typically increased in 200-microgram increments per dose, so reaching higher maintenance levels means taking several 200-microgram tablets per administration. For example, a patient on 1,200 micrograms twice daily will take six tablets in the morning and six in the evening. Many treating centres transition patients to a product line that offers higher-strength tablets (for example the originator's 400, 600, 800, 1000, 1200, 1400 and 1600-microgram tablets) once a stable maintenance dose has been identified, so that the number of tablets per dose can be reduced to one or two. This decision depends on availability, reimbursement and patient preference.
Titration of Selexipag STADA typically takes several weeks. Starting from the initial dose of 200 micrograms twice daily, the dose is increased by 200 micrograms per administration at each step, usually once per week. Because the maximum dose is 1,600 micrograms twice daily, it could theoretically take up to 7 weeks to reach the maximum dose, but in practice many patients reach their individually tolerated maintenance dose before this ceiling. Some patients require longer intervals between dose increases to allow side effects to settle. The aim is not to reach a particular numerical target but to identify the highest dose that the individual patient can comfortably tolerate, because this is associated with the greatest long-term benefit.
Yes. Selexipag STADA is commonly used in combination with endothelin receptor antagonists (bosentan, ambrisentan, macitentan) and/or phosphodiesterase 5 inhibitors (sildenafil, tadalafil). The GRIPHON trial specifically evaluated selexipag as add-on therapy in patients already receiving background PAH therapy, and no clinically significant pharmacokinetic interactions were identified with these classes. The 2022 ESC/ERS pulmonary hypertension guidelines support an escalating, multi-pathway approach for patients whose disease is not adequately controlled on mono- or dual-therapy, and selexipag is specifically recommended as an option for targeting the prostacyclin pathway in this setting.
In many patients, prostacyclin-related side effects such as headache, jaw pain, diarrhoea, nausea and flushing improve over time as the body adjusts to the medicine. These symptoms are usually most pronounced during the titration period when the dose is being increased, and tend to become more manageable once a stable maintenance dose is reached. Simple strategies — taking tablets with food, using paracetamol for headache and musculoskeletal pain, and staying well hydrated — can help. If side effects remain intolerable at any dose, your specialist can reduce the dose or slow down titration to find a more comfortable level. Completely abandoning treatment because of class-typical side effects is rarely necessary and should be done only after discussion with a PAH expert.
The pivotal evidence for selexipag is the GRIPHON trial, published in the New England Journal of Medicine in 2015. This international, randomised, double-blind, placebo-controlled phase III study enrolled 1,156 patients with PAH at 181 sites in 39 countries. Patients who received selexipag experienced a 40% reduction in the risk of a primary composite endpoint of death or complications related to PAH (including hospitalisation for worsening PAH and disease progression) compared with placebo, and the benefit was consistent across pre-specified subgroups, including patients already on dual background PAH therapy. Based on GRIPHON, the originator was approved by the FDA in 2015 and the EMA in 2016, and is recommended in the 2022 ESC/ERS pulmonary hypertension guidelines. Because Selexipag STADA is bioequivalent to the originator, the GRIPHON data also apply to this generic product.
Selexipag differs from other prostacyclin-pathway therapies in several important ways. Unlike epoprostenol, which requires continuous intravenous infusion via an indwelling central line, treprostinil, which can be given by continuous subcutaneous or intravenous infusion (or inhaled or orally), and iloprost, which requires several inhalations per day via a nebuliser, selexipag is a simple twice-daily oral tablet. Pharmacologically, selexipag is a selective IP receptor agonist, whereas traditional prostanoids activate multiple prostanoid receptor subtypes, which may partly explain differences in their side-effect profile. Selexipag is also chemically distinct from prostacyclin analogues and has a different metabolic pathway. These features make selexipag — and generic versions such as Selexipag STADA — particularly suited to oral triple-combination therapy in modern PAH regimens.
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 revision 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). N Engl J Med. 2015;373(9):834-844. doi:10.1056/NEJMoa1413687
- Chin KM, Channick R, Kim NH, et al. Selexipag in Pulmonary Arterial Hypertension: Hemodynamic Characterisation 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.
- European Medicines Agency. Guideline on the Investigation of Bioequivalence. CPMP/EWP/QWP/1401/98 Rev. 1. Committee for Medicinal Products for Human Use, 2010.
- Kaufmann P, Okubo K, Bruderer S, et al. Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag. Am J Cardiovasc Drugs. 2015;15(3):195-203. doi:10.1007/s40256-015-0110-y
Medical Editorial Team
Medical Content
iMedic Medical Editorial Team – Specialists in Pulmonary Medicine, Cardiology, and Clinical Pharmacology
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This article was first published on and last medically reviewed on . Content is reviewed regularly and updated when new evidence becomes available. For the most current prescribing information, consult the officially approved product labelling in your country.