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Successful Transition from Oral Selexipag to Subcutaneous Treprostinil

M. P. George

James Coons

Darlene Kim

John Buckner

Michael Mathier


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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1074

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Purpose

We describe a protocol for conversion from oral selexipag to subcutaneous (SQ) treprostinil.

Background

Despite advances in oral medications exploiting the prostacyclin pathway, pulmonary hypertension remains a progressive disease, and in some patients it may be necessary to convert to parenteral therapy. To date, there are no published protocols describing this conversion.

Methods

Our patient is a 33-year-old woman with idiopathic pulmonary arterial hypertension diagnosed in 2015, on triple drug therapy (tadalafil 40mg daily, ambrisentan 10mg daily, selexipag 1600 mcg BID) who suffered recurrent admissions for right ventricular failure and volume overload. She was admitted for conversion from selexipag to SQ treprostinil. She had been at maximum dose selexipag currently (1600mcg BID) without side effects. Our goal was to initiate and increase her medication to an initial goal of 20ng/kg/min SQ treprostinil, initiated during her inpatient admission with continued dose increases as an outpatient. Given the difference in half lives of selexipag (active metabolite, 6.2-13.5 h) and treprostinil (4 h), we developed a protocol in the interest of avoiding underdosing (leading to worsening right ventricular failure) and overdosing (leading to hypotension). Protocol: On the night of admission we reduced the patient’s evening dose of selexipag to 1000 mcg BID, and the following morning began SQ remodulin at 2.5 ng/kg/min. Over the subsequent days we decreased the evening dose of selexipag by 200 mcg every night and increased the daily dose of treprostinil as tolerated by 2.5 ng/kg/min. We monitored the patient’s vital signs and symptoms per routine, and also asked her to repeat her hall walk daily to be able to detect worsening exertional dyspnea, which would be an earlier symptom than any discomfort at rest.

Results

Our patient successfully weaned her selexipag over the next 5 days, and was able to increase her SQ treprostinil to 12.5 ng/kg/min by the time of discharge. She had mild side effects of headache and flushing, but no dose-limiting side effects. She was able to walk farther each day without stopping and reported decreased exertional dyspnea. We continued her titration over the next several weeks to a goal dose of 24 ng/kg/min, at which she had improved hemodynamics, and ultimately were dose limited by reduction in systemic vascular resistance.

Conclusions

This is the first report of successful transition from selexipag to SQ treprostinil.