Hypotension: 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 or with resting hypotension, hypovolaemia, severe left ventricular outflow obstruction or autonomic dysfunction).
Hyperthyroidism: Hyperthyroidism has been observed with Uptravi. Thyroid function tests are recommended as clinically indicated in the presence of signs or symptoms of hyperthyroidism.
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 with Uptravi should be discontinued.
Moderate inhibitors of CYP2C8: Concomitant administration of selexipag with moderate inhibitors of CYP2C8 (e.g. clopidogrel, deferasirox, teriflunomide) may increase the exposure to selexipag and its main active metabolite. An adjustment of the dose of selexipag should be considered in case a moderate inhibitor of CYP2C8 is coadministered or discontinued.
Hepatic impairment: There is no clinical experience with selexipag in patients with severe liver impairment (Child-Pugh class C), therefore Uptravi should not be administered in these patients. The exposure to selexipag and its active metabolite is increased in subjects with moderate hepatic impairment (Child-Pugh class B; see Pharmacology: Pharmacokinetics under Actions). In patients with moderate hepatic impairment, Uptravi should be dosed once daily (see Dosage & Administration).
Renal impairment: In patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2), caution should be exercised during dose titration. There is no experience with Uptravi in patients undergoing dialysis (see Pharmacology: Pharmacokinetics under Actions), therefore Uptravi should not be used in these patients.
Effects on Ability to Drive and Use Machines: Uptravi has minor influence on the ability to drive and use machines. The clinical status of the patient and the adverse reaction profile of selexipag (such as headache or hypotension) should be kept in mind when considering the patient's ability to drive and use machines.
Women of childbearing potential: Women of childbearing potential should practise effective contraception while taking selexipag.
Impairment of Fertility: There are no clinical data available. In rat studies, selexipag at high doses caused transient disturbances in oestrus cycles that did not affect fertility (see Pharmacology: Toxicology under Actions). The relevance for humans is not known.
Use in the Elderly: There is limited clinical experience with selexipag in patients over the age of 75 years, therefore Uptravi should be used with caution in this population (see Dosage & Administration).