200-1600 µg film-coated tabletsPRESCRIBING INFORMATION
ACTIVE INGREDIENT(S): Selexipag
Please refer to the Summary of Product Characteristics (SmPC) before prescribing.
INDICATION(S): Long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO FC II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor, or as monotherapy in patients who are not candidates for these therapies. Efficacy has been shown in idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.
DOSAGE & ADMINISTRATION: Individualised dose titration only a PAH experienced physician should initiate and monitor treatment. Up-titrate patients to the highest individually tolerated dose, which can range from 200 to 1600 microgram (µg) given twice daily (BD). The recommended starting dose is 200 µg BD approximately 12 hours apart. Increase dose in increments of 200 µg BD, usually at weekly intervals, based on tolerability. During titration some adverse reactions reflecting the mode of action of selexipag may occur, these are usually transient or manageable with symptomatic treatment. If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous dose level. Individualised maintenance dose: Maintain the highest tolerated dose a patient can take with tolerable adverse events. If it is necessary to stop treatment withdraw gradually. Administration: Take each tablet orally, morning and evening with food to improve tolerability. During the up‑titration phase take the first increased dose in the evening. Interruptions and discontinuations: Missed doses should be taken as soon as possible, unless the next dose is scheduled within 6 hrs. If treatment is missed for 3 days or more, restart at a lower dose and then up‑titrate. There is limited experience with abrupt discontinuation. No evidence for acute rebound has been observed. Dosage adjustment with co-administration of moderate CYP2C8 inhibitors: When co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide), reduce the dosing of Uptravi to once daily. 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. Revert to twice daily dosing frequency of Uptravi when co-administration of moderate CYP2C8 inhibitor is stopped. Elderly (≥65 yrs): No dose adjustment required. There is limited clinical experience in patients over 75 yrs, therefore Uptravi should be used with caution in this population. Paediatric populations (<18 years): No data are available. Not recommended to use selexipag in paediatric population. Hepatic impairment: Do not treat patients with severe liver impairment (Child-Pugh class C). Moderate hepatic impairment (Child‑Pugh class B): The starting dose of treatment should be 200 micrograms once daily, and increased at weekly intervals by increments of 200 micrograms given once daily until adverse reactions, reflecting the mode of action of selexipag, that cannot be tolerated or medically managed are experienced. Mild hepatic impairment (Child‑Pugh class A): No dose adjustment required. Renal impairment: Mild/moderate: No dose adjustment required. Severe: Caution should be exercised during dose titration.
CONTRAINDICATIONS: Hypersensitivity to active substance/excipients, severe coronary heart disease, unstable angina, myocardial infarction within 6 months, decompensated cardiac failure, severe arrhythmias, cerebrovascular events within 3 months, congenital or acquired valvular defects, concomitant use with strong CYP2C8 inhibitors (e.g. gemfibrozil).
SPECIAL WARNINGS & PRECAUTIONS: Hypotension: Vasodilatory properties may reduce blood pressure. Before prescribing Uptravi, carefully consider whether patients with certain underlying conditions could be adversely affected by vasodilatory effects. Hyperthyroidism: has been observed, monitor thyroid function if clinically indicated. Pulmonary veno‑occlusive disease: If signs of pulmonary oedema occur consider the possibility of pulmonary veno-occlusive disease which has been reported with vasodilators (mainly prostacyclins), if confirmed discontinue treatment.
SIDE EFFECTS: Very common: Headache, flushing, nasopharyngitis, diarrhoea, vomiting, nausea, jaw pain, myalgia, arthralgia & pain in extremity. Common: Anaemia, decreased haemoglobin, hyperthyroidism, decreased thyroid-stimulating hormone, decreased appetite, weight decrease, hypotension, decreased thyroid-stimulating hormone, nasal congestion, abdominal pain, rash, urticaria, erythema, pain. Refer to SmPC for other side effects.
PREGNANCY: There are no data from the use of selexipag in pregnant women. Women of childbearing potential should practise effective contraception. Uptravi is not recommended during pregnancy and in women of childbearing potential not using contraception.
LACTATION: It is unknown if selexipag or its metabolites are excreted in human milk. Uptravi should not be used during breast-feeding.
INTERACTIONS: Consider adjustment of selexipag dose in case of co-administration with CYP2C8 inducers (rifampicin, carbamazepine, phenytoin). Use caution with concomitant use of Uptravi with strong inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, fluconazole). Dosing frequency of Uptravi should be reduced to once daily when co-administered with moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide). Dosing frequency of Uptravi should be reverted to twice daily when co-administration of moderate CYP2C8 inhibitor is stopped. Refer to SmPC for full details of interactions.
ABILITY TO DRIVE AND USE MACHINES: Uptravi has a minor influence on the ability to drive and use machines.
LEGAL CATEGORY: Prescription Only Medicine (POM).
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
MARKETING AUTHORISATION NUMBER(S) - Northern Ireland
MARKETING AUTHORISATION NUMBER(S) - Great Britain
|BASIC NHS COSTS|
|200 μg tablets (Titration pack)||140 tablets||EU/1/15/1083/003||PLGB 00242/0666||£7,000|
|200 μg tablets||60 tablets||EU/1/15/1083/002||PLGB 00242/0666||£3,000|
|400 μg tablets||60 tablets||EU/1/15/1083/004||PLGB 00242/0667||£3,000|
|600 μg tablets||60 tablets||EU/1/15/1083/005||
|800 μg tablets||60 tablets||EU/1/15/1083/006||PLGB 00242/0669||£3,000|
|1,000 μg tablets||60 tablets||EU/1/15/1083/007||PLGB 00242/0670||£3,000|
|1,200 μg tablets||60 tablets||
|1,400 μg tablets||60 tablets||EU/1/15/1083/009||PLGB 00242/0672||£3,000|
|1,600 μg tablets||60 tablets||EU/1/15/1083/010||PLGB 00242/0673||£3,000|
MARKETING AUTHORISATION HOLDERS:
Northern Ireland: Janssen-Cilag International NV, Turnhoutseweg 30, B 2340 Beerse, Belgium.
Great Britain: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
Prescribing information last revised: April 2021