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Uptravi is a brand name for Selexipag. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Uptravi is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II–III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. 4 Posology Individualised dose titration Each patient should be up-titrated to the highest individually tolerated dose, which can range from 200 micrograms given twice daily to 1 600 micrograms given twice daily (individualised maintenance dose).
The recommended starting dose is 200 micrograms given twice daily, approximately 12 hours apart. The dose is increased in increments of 200 micrograms given twice daily, usually at weekly intervals. At the beginning of treatment and at each up-titration step it is recommended to take the first dose in the evening.
During dose titration some adverse reactions, reflecting the mode of action of selexipag (such as headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, and flushing), may occur. 8). However, if a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous dose level.
In patients in whom up-titration was limited by reasons other than adverse reactions reflecting the mode of action of selexipag, a second attempt to continue up-titration to the highest individually tolerated dose up to a maximum dose of 1 600 micrograms twice daily may be considered.
Individualised maintenance dose The highest tolerated dose reached during dose titration should be maintained. If the therapy over time is less tolerated at a given dose, symptomatic treatment and/or a dose reduction to the next lower dose should be considered.
Interruptions and discontinuations If a dose is missed, it should be taken as soon as possible. The missed dose should not be taken if the next scheduled dose is within approximately 6 hours. If treatment is missed for 3 days or more, Uptravi should be restarted at a lower dose and then up-titrated.
There is limited experience with abrupt discontinuation of selexipag in patients with PAH. No evidence for acute rebound has been observed. However, if the decision to withdraw Uptravi is taken, it should be done gradually while an alternative therapy is introduced.
, clopidogrel, deferasirox and teriflunomide), the total daily dose of Uptravi should be reduced to half by administering half of each dose twice daily. Alternatively, a once daily dosing frequency to achieve half of the daily dose of Uptravi may be continued in patients already well controlled on a once daily dosing regimen or may be applied in patients for whom the appropriate dose strength(s) supporting twice daily dosing with half the dose is not available.
Summary of the safety profile The most commonly reported adverse reactions are headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, and flushing. These reactions are more frequent during the up-titration phase.
The majority of these reactions are of mild to moderate intensity. The safety of selexipag has been evaluated in a long-term, phase 3 placebo-controlled study enrolling 1 156 adult patients with symptomatic PAH (GRIPHON study). 7 weeks) for patients on placebo.
2 years. Tabulated list of adverse reactions Adverse reactions obtained from the pivotal clinical GRIPHON study and post-marketing surveillance are tabulated below. The adverse reactions are ranked by frequency within each system organ class (SOC) and presented in order of decreasing seriousness.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to <1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). System organ class Very common Common Uncommon Blood and lymphatic disorders Anaemia* Haemoglobin decreased* Endocrine disorders Hyperthyroidism* Thyroid-stimulating Hormone decreased Metabolism and nutrition disorders Decreased appetite Weight decrease Nervous system disorders Headache* Cardiac disorders Sinus tachycardia* Vascular disorders Flushing* Hypotension* Respiratory, thoracic and mediastinal disorders Nasopharyngitis (of non-infectious origin) Nasal congestion Gastro-intestinal disorders Diarrhoea* Vomiting* Nausea* Abdominal pain Dyspepsia* Skin and subcutaneous tissue disorders Rash Urticaria Erythema Angioedema† Musculoskeletal and connective tissue disorders Jaw pain* Myalgia* Arthralgia* Pain in extremity* General disorders and administration site conditions Pain * See section Description of selected adverse reactions.
† Cases of angioedema have been reported in post-marketing experience with a latency that can exceed 30 days of treatment. 10 Description of selected adverse reactions Pharmacological effects associated with titration and maintenance treatment Adverse reactions associated with the mode of action of selexipag have been observed frequently, in particular during the phase of individualised dose titration, and are tabulated below: Prostacyclin-like associated adverse reactions Titration Maintenance Selexipag Placebo Selexipag Placebo Headache 64% 28% 40% 20% Diarrhoea 36% 12% 30% 13% Nausea 29% 13% 20% 10% Pain in jaw 26% 4% 21% 4% Myalgia 15% 5% 9% 3% Pain in extremity 14% 5% 13% 6% Vomiting 14% 4% 8% 6% Flushing 11% 4% 10% 3% Arthralgia 7% 5% 9% 5% These effects are usually transient or manageable with symptomatic treatment.
Hypotension Selexipag has vasodilatory properties that may result in lowering of blood pressure. 8). Hyperthyroidism Hyperthyroidism has been observed with Uptravi. 8). Pulmonary veno-occlusive disease Cases of pulmonary oedema have been reported with vasodilators (mainly prostacyclins) when used in patients with pulmonary veno-occlusive disease.
Consequently, if signs of pulmonary oedema occur when Uptravi is administered in patients with PAH, the possibility of pulmonary veno-occlusive disease should be considered. If confirmed, treatment is to be discontinued. 2). Hepatic impairment There is no clinical experience with selexipag in patients with severe liver impairment (Child-Pugh class C), therefore treatment should not be administered in these patients.
2). 2). 73 m2), caution should be exercised during dose titration. 2), therefore Uptravi should not be used in these patients. 6).
1. Severe coronary heart disease or unstable angina. Myocardial infarction within the last 6 months. Decompensated cardiac failure if not under close medical supervision. Severe arrhythmias. , transient ischaemic attack, stroke) within the last 3 months.
Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension. 5). 6
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If the therapy is not tolerated at a given dose, symptomatic treatment and/or a dose reduction to the next lower dose should be considered. When co-administration of a moderate CYP2C8 inhibitor is stopped, the total daily dose of Uptravi should be increased, as applicable.
5). 2). 4). 4). For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of treatment should be 100 micrograms twice daily and increased at weekly intervals by increments of 100 micrograms twice daily until adverse reactions, reflecting the mode of action of selexipag, that cannot be tolerated or medically managed are experienced.
In these patients the maximum dose is 800 micrograms given twice daily. Alternatively, a once daily dosing frequency to achieve half of the daily dose of Uptravi may be continued in patients already well controlled on a once daily dosing regimen or may be applied in patients for whom the appropriate dose strength(s) supporting twice daily dosing with half the dose is not available.
No adjustment to the dose regimen is needed in patients with mild hepatic impairment (Child-Pugh class A). Renal impairment No adjustment to the dose regimen is needed in patients with mild or moderate renal impairment. 4). Paediatric population The safety and efficacy of selexipag in children aged 2 to less than 18 years have not yet been established.
2, but no recommendation on a posology can be made. Administration of selexipag in the paediatric population is not recommended. The safety and efficacy of selexipag in children aged less than 2 years have not been studied, as animal studies indicated an increased risk of intussusception.
3). Method of administration Oral use. The film-coated tablets are to be taken orally in the morning and in the evening. To improve tolerability, it is recommended to take Uptravi with food and, at the beginning of each up-titration phase, to take the first increased dose in the evening.
The film-coated tablets are to be swallowed with water. The tablets should not be split or crushed because the tablet coating protects the active substance from light. Patients who have poor vision or are blind must be instructed to get assistance from another person when taking Uptravi during the titration period.
5% of patients on selexipag discontinued treatment due to these adverse reactions. 5% in the placebo group. In clinical practice, gastro-intestinal events have been observed to respond to anti-diarrhoeal, anti-emetic, and anti-nauseant medicinal products and/or medicinal products for functional gastro-intestinal disorders.
Pain-associated events have frequently been treated with analgesics (such as paracetamol). 25 g/dL in the placebo group. 0% of placebo-treated patients. 28 g/dL in the double therapy group (placebo, macitentan and tadalafil). 5% in the double therapy group.
3%) in the double therapy group. 4). 5 MU/L) in median thyroid-stimulating hormone was observed at most visits in the selexipag group. In the placebo group, little change in median values was apparent. There were no mean changes in triiodothyronine or thyroxine in either group.
Increase in heart rate In the phase 3 placebo-controlled study in patients with PAH, a transient increase in mean heart rate of 3–4 bpm at 2–4 hours post-dose was observed. 1). 8% in the placebo group. 3 mmHg in the placebo group. 7% in the placebo group.
Dyspepsia In a phase 3 placebo-controlled study in patients newly […]