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The safety and tolerability of UPTRAVI® were investigated in the GRIPHON trial, the largest outcomes trial conducted in pulmonary arterial hypertension (PAH).[1][2] 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.[1][3][4]

Prostacyclin-associated AEs

In the GRIPHON trial, the majority of AEs were mild to moderate and manageable with symptomatic treatment.[1][3][4]

Table 2

Adapted from UPTRAVI® SmPC[3] and Sitbon et al. 2015[4]

Please refer to the SmPC for full UPTRAVI® safety and tolerability information.

Common AEs in GRIPHON

Overall, 14% of patients in the UPTRAVI® group and 7% of patients in the placebo group prematurely discontinued treatment due to an AE.[1]

Table 3

Adapted from Sitbon et al. 2015[1]

Please refer to the SmPC for full UPTRAVI® safety and tolerability information.

Drug-drug interactions

UPTRAVI® has a low potential for drug-drug interactions for drugs concomitantly used in PAH therapy.[3]

table 4

Please refer to the SmPC for full UPTRAVI® safety and tolerability information.

Use in special populations

Pregnancy and breastfeeding

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.[3]

Use in children

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.[3]

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).[3]

Hepatic impairment

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).[3]

Renal impairment

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.[3]

Fertility

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.[3]

Please refer to the SmPC for full UPTRAVI® safety and tolerability information.

Continue reading

Efficacy

Discover how UPTRAVI® can provide long-term benefits for patients with PAH.[1]

Initiation and dosing

Adding UPTRAVI® is recommended at the first sign of intermediate risk.[5][6]

Resources

Find resources such as PAH management guidelines and UPTRAVI® dosing and titration guides.

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AE, adverse event; CYP, cytochrome P450; eGFR, estimated glomerular filtration rate; ERA, endothelin receptor antagonist; IP, prostacyclin; OATP, organic-anion-transporting polypeptide; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase type-5 inhibitor

UPTRAVI® PRESCRIBING INFORMATION AND ADVERSE EVENT REPORTING

CP-220222 | May 2021

References

Sitbon O et al. N Engl J Med 2015; 373(26):2522–2533.
Panagiotidou E et al. Expert Opin Pharmacother 2021; 22(1):29–36.
UPTRAVI® SmPC, February 2021. Available at: https://www.ema.europa.eu/en/documents/product-information/uptravi-epar-product-information_en.pdf (last accessed May 2021).
Sitbon O et al. N Engl J Med 2015; 373(26):2522–2533 (supplementary appendix).
Galiè N et al. Eur Heart J 2016; 37(1):67–119.
Galiè N et al. Eur Respir J 2019; 53(1):1801889.