Clinicians agree on individualized dosing, titration of selexipag in PAH

Key takeaways:

• There are several patient factors that influence whether the speed of titration should be slower or faster.
• Clinicians advise looking at each patient’s tolerability to side effects when determining highest dose.

Health care professionals treating patients with pulmonary arterial hypertension recommend individualized dosing and titration of oral selexipag, according to a poster presented at a scientific conference.

This poster was presented during the Pulmonary Hypertension Association International PH Conference and Scientific Sessions.

“Health care professionals were inclined to seek an individualized maximum dose for each patient, and their approach to counseling and managing expected side effects reached a high level of agreement,” Sean Studer, MD, MSc, vice president of medical affairs, pulmonary hypertension at Johnson & Johnson, told Healio.

In a double-blinded Delphi panel study, Sheryl Wu, PharmD, pharmacist at University of California, San Diego Health, and colleagues evaluated responses from 17 HCPs (11 physicians, five nurse practitioners and one RN) who actively treated patients with PAH and had experience with oral selexipag (Uptravi, Johnson & Johnson) to establish dosing, titration and side effect management recommendations for the drug via two online questionnaires (n = 17) and a virtual consensus meeting (n = 11; eight physicians, two nurse practitioners, one RN).

As Healio previously reported, initiation of oral selexipag within 12 months of PAH diagnosis may reduce all-cause hospitalizations and overall medical costs.

Physicians reported treating an average of 36 patients with oral selexipag, and this was similar to the average of 35 patients reported by the nurse practitioners and the RN.

The FDA label for selexipag has a recommended starting dosage of 200 µg two times a day. Panelists reported that there are several patient factors that influence whether the speed of titration should be slower or faster. A slower titration is recommended when the patient has a severe side effect, lacks tolerability, is older and has gastroparesis, whereas a faster titration is recommended among patients with severe PAH and those who are transitioning from a prostacyclin therapy.

When asked about maximum drug dosing, the HCPs said to look to each individual patient’s tolerability to side effects when determining the highest dose. Patients who are likely to reach a higher dose are those who received parenteral prostacyclin therapy in the past.

“The degree of consistency amongst experts regarding medication use was somewhat unexpected,” Studer told Healio. “Achieving this consensus for an individualized maximum dose dispels the idea that all patients need to achieve the same treatment dose of 1,600 µg twice daily.”

The most clinically burdensome expected side effects are headache, diarrhea and nausea, according to the panel. The management approach agreed upon by the panelists for headache was acetaminophen (Tylenol, Kenvue). Additionally, loperamide (Imodium, Kenvue) was the recommended management approach for diarrhea, and ondansetron (Zofran, Novartis) or taking selexipag with food was the recommended approach for nausea.

Other expected and clinically burdensome side effects included myalgia, vomiting and pain in extremity. The management approach agreed upon for pain in extremity was screening for iron deficiency for restless legs or acetaminophen, according to the poster.

Among the six side effects linked to oral selexipag, the side effect with the longest median length was diarrhea lasting for 8 weeks, followed by headache lasting for 6 weeks, myalgia and flushing lasting for 4 weeks, nausea lasting for 3 weeks and vomiting lasting for 2 weeks. Studer noted that not all patients will experience side effects of the above timings since these are median durations.

“This [information] positively impacts the everyday clinician in helping set expectations for patients experiencing adverse events in when to anticipate improvement,” Studer told Healio.

Notably, as time progresses, the side effects outlined above “often become manageable,” according to the panelists.

“Future studies following the Uptravi Delphi study will focus more on the patient perspective related to treatment with Uptravi,” Studer told Healio. “Now having a clearer view of expert clinician recommendations, we seek to better understand the information needed to empower patients for a more active role in their decisions regarding treatment.”

Editor's note: This story was updated Aug. 27, 2024, to correct the name of the conference. The editors regret the error.