Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study

Frost, Adaani E.; Janmohamed, Munir; Fritz, J.S.; McConnell, John W.; Poch, David; Fortin, Terry; Miller, Chad E.; Chin, Kelly; Fisher, Micah R.; Eggert, Michael; McEvoy, Colleen; Benza, Raymond L.; Farber, Harrison W.; Kim, Nick H.; Pfister, Thomas D.; Shiraga, Yoko; McLaughlin, Vallerie V.

doi:10.1016/j.healun.2018.09.003

Cited by 31 publications

(38 citation statements)

References 13 publications

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“…The cases presented here are small in number and come from a single center. Other reports have described more standardized protocols, with larger sample sizes and with some homogeneity between cases (7,13).…”

Section: Limitationsmentioning

confidence: 99%

“…Established guidance on transitions between various formulations within this drug class have not been standardized. A number of case reports and case series have been published describing such transitions but lack consistent processes (6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…In the TRANSIT-1 study, 34 PAH patients on inhaled treprostinil were transitioned to selexipag over 8 weeks with a 94.1% success rate. The mean dose of inhaled treprostinil at baseline was 59.3 mcg four times daily (13). In a case series of 4 patients on parenteral treprostinil, the highest dose upon initiation of the transition was 46.5 ng/kg/min, which was successfully transitioned to selexipag 1,600 mcg twice daily (11).…”

Section: Introductionmentioning

confidence: 99%

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Transitioning Between Prostanoid Therapies in Pulmonary Arterial Hypertension

et al. 2020

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Background: New oral prostacyclin therapies and prostacyclin agonists have become available for the treatment of pulmonary arterial hypertension (PAH). However, methods for transitioning between oral, inhaled, and parenteral formulations are not well-established, except in the form of case reports and case series. Collectively, these emphasize the lack of a standardized process and approach in transitioning patients between PAH prostanoid therapies. In this case series, we report our experience at an accredited Pulmonary Hypertension center in transitioning between various oral, inhaled, and parenteral prostanoids to offer additional guidance on safe transitions in therapy. Methods: All cases of prostanoid transitions at an accredited Pulmonary Hypertension center from March 2018 to September 2019 were included in this report. The transition approach for each case was developed through a review of the literature, extrapolation of available pharmacokinetic data, and collaboration between pharmacists and clinicians. Results: This case series describes the transition of 3 patients from selexipag to parenteral treprostinil; 1 patient transitioning from parenteral treprostinil to selexipag; 1 patient transitioning from oral treprostinil to parenteral treprostinil; and 1 patient transitioning from inhaled treprostinil to selexipag. Four of the 6 patients presented here were transitioned to an alternate prostanoid on account of clinical worsening, while the remaining 2 patients transitioned due to intolerance of parenteral therapy and poor medication adherence. This case series includes patients with various etiologies of PAH including idiopathic PAH, methamphetamine-associated PAH, and scleroderma-associated PAH. All patients successfully completed each transition without serious adverse events. Conclusions: With the increasing utilization and availability of prostanoids, there is a critical need for a standardized approach in transitioning safely between different formulations without compromising treatment efficacy. In this case series, we present our clinical experiences, guided by available pharmacokinetic data, in transitioning between various prostanoid formulations.

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Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transitioning Between Prostanoid Therapies in Pulmonary Arterial Hypertension

et al. 2020

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“…Bioavailability of selexipag after oral administration was demonstrated to be approximately 50%. 5,6,[9][10][11][12][13][14][15][16] The first report of a pediatric patient treated with selexipag was a 12-year-old girl with WHO functional class III, right ventricular failure, recurrent syncope, dizziness, and progressive fatigue. 7 The patient had been previously treated with bosentan and sildenafil with no improvement for 9 months.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic and clinical effects of selexipag in children with pulmonary hypertension

et al. 2020

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Selexipag is an oral prostacyclin receptor agonist; it was recently approved for use in adults with pulmonary arterial hypertension. The safety and efficacy of selexipag has not yet been determined in the pediatric population. We describe short-term hemodynamic and clinical data with selexipag therapy in four pediatric patients with pulmonary hypertension. We reviewed clinical, echocardiographic, and hemodynamic data. One patient was transitioned from subcutaneous treprostinil to selexipag, and in three patients, selexipag was added as a third agent. Drug dosing was attained empirically based on patient body size. A follow-up catheterization was performed 12–18 months after initiation of selexipag therapy. All four patients tolerated selexipag well, without significant side effects. One patient transitioned successfully from subcutaneous treprostinil to selexipag. None of the four patients had clinical deterioration. In three patients who were able to perform a 6-minute walk test, pre and post selexipag distances were 350 and 400, 409 and 390, and 300 and 360 m, respectively. Echocardiograms showed no significant changes. Catheterization showed a variable change in pulmonary vascular resistance (small decrease in three patients and increase in one patient). Brain natriuretic peptide levels before and after selexipag in the four patients were 38 and 49, 33 and 54, 29 and 25, and 12 and 14 pg/mL, respectively. Selexipag use for 16–28 months was safe in four pediatric patients; none of them had clinical deterioration. Larger number of patients and longer follow-up intervals are necessary before further recommendations can be made.

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“…• Switch PDE-5 inhibitor to riociguat 12 • Add selexipag 13,14 or inhaled treprostinil 14 (note that this study added treprostinil to monotherapy; there are no randomized, controlled data of triple-combination therapy with inhaled treprostinil, PDE-5 inhibitor, and ERA, but clinical experience suggests that it can be effective) • Add oral treprostinil (there are no conclusive randomized data to support this approach; thus far the only positive randomized, controlled trial is as monotherapy) • For stable patients receiving inhaled treprostinil who wish to convert to an all-oral program, there is preliminary short-term evidence that switching to selexipag is successful with some but not all of them 15 ; direct long-term comparative efficacy data are not available • For patients not tolerating selexipag or oral treprostinil, switching to inhaled treprostinil can largely avoid systemic prostanoid side effects…”

Section: Step 7: Adjust Treatment Approach Based On Clear Metrics Of mentioning

confidence: 99%

Treatment Considerations for Pulmonary Arterial Hypertension and Assessment of Treatment Response

Frantz

2018

Advances in Pulmonary Hypertension

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The process of considering initial treatment options for a patient with pulmonary arterial hypertension (PAH), implementing that treatment, and reassessing response can be conceived as a 7-step process. A patient-centered approach, conducted in the context of a pulmonary hypertension care team, implements these steps in a thoughtful and well-organized fashion.Step 1: Perform a thorough diagnostic evaluationStep 2: Consider patient PAH classification and comorbiditiesStep 3: Assess risk profileStep 4: Develop a nuanced understanding of patient goals and preferencesStep 5: Create an initial treatment strategyStep 6: Implement a proactive longitudinal follow-up care planStep 7: Adjust treatment approach based on clear metrics of effectiveness and tolerability The burgeoning array of treatment options for PAH provides the opportunity to tailor therapy to the needs of individual patients, but also demands that the clinician develop a cogent strategy for initiating therapy, monitoring therapeutic response, and addressing side effects of therapy. In this review, we seek to provide a practical framework for approaching this challenge.

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Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study

Cited by 31 publications

References 13 publications

Transitioning Between Prostanoid Therapies in Pulmonary Arterial Hypertension

Transitioning Between Prostanoid Therapies in Pulmonary Arterial Hypertension

Hemodynamic and clinical effects of selexipag in children with pulmonary hypertension

Treatment Considerations for Pulmonary Arterial Hypertension and Assessment of Treatment Response

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