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UPTRAVI® should be added at the first sign of intermediate risk for patients with pulmonary arterial hypertension (PAH).[1][2]

When to initiate UPTRAVI®

According to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, the overall treatment goal in patients with pulmonary arterial hypertension (PAH) is to achieve or maintain a low-risk status, which is associated with good exercise capacity, good quality of life, good right ventricular function and a low mortality risk. Regular multiparameter risk assessment is recommended to evaluate patient risk status.[1]

The addition of UPTRAVI® is recommended when patients are insufficiently controlled and not reaching the goal of low-risk status with double combination therapy or monotherapy.[1][2]

UPTRAVI® is the only drug with a class I recommendation for early sequential combination with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type-5 inhibitor (PDE-5i).[1]

2015 ESC/ERS guideline for sequential combination therapy with UPTRAVI®[1]
Table 5

Adapted from Galiè et al. 2016[1]

Dosing_A
Expert consensus opinion on early UPTRAVI® initiation

Learn about the patient profiles identified as benefiting from early UPTRAVI® initiation.[3]

Dosing and titration

The importance of individualised dosing

UPTRAVI® relaxes and widens the blood vessels by acting as an agonist at the prostacyclin (IP) receptors on the cellular surface. The density of these IP receptors is different amongst patients:[4]

• Patients with low IP receptor density require high IP receptor occupancy and are likely to require a higher dose of UPTRAVI®[4]
• Patients with high IP receptor density require low IP receptor occupancy and are likely to require a lower dose of UPTRAVI®[4]

These differences in physiology help explain the importance of an individualised maintenance dose for each patient. Over the course of weeks, the dose of UPTRAVI® is gradually titrated, allowing the patient’s body to adjust to the new medication.[5]

Reaching the individualised maintenance dose

The recommended starting dose is 200 mcg twice daily. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose, up to 1,600 mcg twice daily. If the dose is not tolerated, reduce to the previous tolerated dose.[6]

With individualised maintenance dosing, each patient can reach the dose that is best for them
Uptravi_dosing_graph22

If a dose of UPTRAVI® is missed, patients should take the missed dose as soon as possible unless the next dose is within the next 6 hours. If treatment is missed for 3 days or more, restart UPTRAVI® at a lower dose and then retitrate.[6]

The goal for every patient is not to reach the maximum dose of 1,600 mcg, but to reach the right dose for that individual

UPTRAVI® patient guide

The My UPTRAVI® Treatment Guide explains the dosing process and supports patients along their UPTRAVI® journey.

UPTRAVI® offers consistent efficacy, regardless of individualised maintenance dose

In the GRIPHON trial, UPTRAVI® delivered consistent efficacy across individualised maintenance dose groups, reducing the risk of a morbidity-mortality event* vs placebo in patients with pulmonary arterial hypertension (PAH) receiving twice-daily (BID) low, medium and high-dose treatment.[7]

Uptravi_dosing_graph23

Adapted from Sitbon et al. 2015[7]

*As measured by a composite primary endpoint. Results do not apply to mortality on its own.[8]
Low-dose group (HR 0.60; 95% CI: 0.41–0.88), medium-dose group (HR 0.53; 95% CI: 0.38–0.72), high-dose group (HR 0.64; 95% CI: 0.49–0.82).[7]

Managing side effects during the titration period

Side effects are an indirect sign of efficacious activation of the IP receptors and help determine each patient’s personalised dose of UPTRAVI®.[5]

Side effects during titration can be managed with over-the-counter remedies and minimised by taking the first dose of a new titration step in the evening. Side effects often level off once the patient reaches their personalised maintenance dose.[5][6]

Continue reading

Safety and tolerability

UPTRAVI® has a well-characterised and generally manageable safety profile.[6][8]

Expert consensus opinion

Learn about the patient profiles identified as benefiting from early UPTRAVI® initiation.[3]

UPTRAVI® titration guide

Guidance on correctly starting your patient on their UPTRAVI® journey.

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BID, twice daily; CI, confidence interval; ERA, endothelin receptor antagonist; ERS, European Respiratory Society; ESC, European Society of Cardiology; FC, functional class; HR, hazard ratio; IP, prostacyclin; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase type-5 inhibitor; WHO, World Health Organization

UPTRAVI® PRESCRIBING INFORMATION AND ADVERSE EVENT REPORTING

CP-220222 | May 2021

References

Galiè N et al. Eur Heart J 2016; 37(1):67–119.
Galiè N et al. Eur Respir J 2019; 53(1):1801889.
McLaughlin V et al. Chest 2020; 157(4):955–965.
Gatfield J et al. Am J Respir Crit Care Med 2016; 193:A2239.
Kingman M et al. Pulmonary Circ 2017; 7(3):598–608.
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; 373:2522–2533 (supplementary appendix).
Sitbon O et al. N Engl J Med 2015; 373:2522–2533.