The safety and tolerability of UPTRAVI® were investigated in the , the largest outcomes trial conducted in pulmonary arterial hypertension (PAH). The majority of adverse events (AEs) in the trial were mild to moderate, and prostacyclin-associated AEs were less frequent after the maintenance dose was reached.
There are no data from the use of UPTRAVI® in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. UPTRAVI® and its main metabolite showed 20–80 times lower prostacyclin (IP) receptor potency in vitro for animal species used in reproductive toxicity testing compared to humans. Therefore, safety margins for potential IP receptor-mediated effects on reproduction are accordingly lower than for non-IP-related effects.
UPTRAVI® is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is unknown whether UPTRAVI® or its metabolites are excreted in human milk. In rats, UPTRAVI® or its metabolites are excreted in milk. A risk to the suckling child cannot be excluded.
UPTRAVI® should not be used during breastfeeding.
The safety and efficacy of UPTRAVI® in children <18 years old have not been established. No data are available.
Administration of UPTRAVI® in the paediatric population is not recommended.
Animal studies indicated an increased risk of intussusception, but the clinical relevance of these findings is unknown.
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).
UPTRAVI® should not be administered in patients with severe liver impairment (Child-Pugh class C).
For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI® should be 200 mcg once daily and increased at weekly intervals by increments of 200 mcg given once daily until adverse reactions, reflecting the mode of action of UPTRAVI®, that cannot be tolerated or medically managed are experienced.
No adjustment to the dose regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).
No adjustment to the dose regimen is needed in patients with mild or moderate renal impairment.
No change in starting dose is required in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2); dose titration should be done with caution in these patients.
There is no experience with UPTRAVI® in patients undergoing dialysis, therefore UPTRAVI® should not be used in these patients.
There are no clinical data available. In rat studies, UPTRAVI® at high doses caused transient disturbances in oestrus cycles that did not affect fertility. The relevance for humans is not known.
Discover how UPTRAVI® can provide long-term benefits for patients with PAH.
Adding UPTRAVI® is recommended at the first sign of intermediate risk.
Find resources such as PAH management guidelines and UPTRAVI® dosing and titration guides.