UPTRAVI

What it is

UPTRAVI is a film-coated tablet containing selexipag. Each round film-coated tablet contains 200 micrograms or multiples thereof (respectively 400, 600, 800, 1000, 1200, 1400, or 1600 micrograms) selexipag.

Approved indications UPTRAVI is indicated for the treatment of:

— Idiopathic pulmonary arterial hypertension — Heritable pulmonary arterial hypertension — Pulmonary arterial hypertension associated with connective tissue disease — Pulmonary arterial hypertension associated with congenital heart disease with repaired shunts — Pulmonary arterial hypertension associated with drugs and toxins in patients with WHO functional class II, III or IV symptoms

Dosing overview

The recommended starting dose of UPTRAVI 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, until adverse pharmacological effects that cannot be tolerated or medically managed are experienced, or until a maximum dose of 1600 micrograms twice daily is reached. The highest tolerated dose reached during dose titration should be maintained. Selexipag can be used in combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE 5) inhibitor, or as monotherapy in patients who are not candidates for these therapies.

Key safety warnings

UPTRAVI has vasodilatory properties that may result in lowering of blood pressure. Before prescribing UPTRAVI, physicians should carefully consider whether patients with certain underlying conditions could be adversely affected by vasodilatory effects (e.g., patients on antihypertensive therapy, other PAH therapy or with resting hypotension, hypovolaemia, severe left ventricular outflow obstruction or autonomic dysfunction). UPTRAVI may cause a moderate increase in heart rate after each dose. Hyperthyroidism has been observed with UPTRAVI (2% patients on selexipag and 0% of placebo-treated patients) and other prostacyclin receptor agonists. Thyroid function tests are recommended as clinically indicated. Should signs of pulmonary oedema occur, consider the possibility of associated pulmonary veno-occlusive disease. If confirmed, discontinue UPTRAVI. The most commonly reported adverse drug reactions related to the pharmacological effects of UPTRAVI are headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, flushing, and arthralgia. These reactions are more frequent during the dose titration phase. The majority of these reactions are of mild to moderate intensity.

Contraindications

UPTRAVI is contraindicated in patients with: known hypersensitivity to the active substance selexipag or to any of the excipients; severe hepatic impairment (Child-Pugh class C); 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; cerebrovascular events (e.g., 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; and concomitant administration of strong inhibitors of CYP2C8 (e.g., gemfibrozil).

PBS listing

UPTRAVI is listed on the PBS in eight strengths: 200 micrograms, 400 micrograms, 600 micrograms, 800 micrograms, 1 milligram, 1.2 milligrams, 1.4 milligrams, and 1.6 milligrams. All strengths are restricted and require authority approval. The ex-manufacturer price for the 200 microgram strength is A$7647.50, and the ex-manufacturer price for all other strengths is A$3277.50.

Regulatory history

UPTRAVI was first listed on the ARTG on 24 March 2016 across all eight tablet strengths. The AusPAR approval date was 18 March 2016. The PBAC recommended UPTRAVI in July 2020 for pulmonary arterial hypertension (WHO Functional Class III or IV PAH) as triple therapy in combination with an ERA and a PDE-5 inhibitor.