Add-On Therapy with Subcutaneous Treprostinil for Refractory Pediatric Pulmonary Hypertension (original) (raw)
Related papers
The American Journal of Cardiology, 2012
The introduction of prostanoid therapy has revolutionized the treatment of pulmonary arterial hypertension (PAH). However, continuous intravenous prostacyclin infusion poses significant risks and challenges, particularly in children. Inhaled treprostinil has been shown to be safe and efficacious in adults. This study describes the safety and efficacy of inhaled treprostinil in children with PAH. A retrospective analysis of 29 children treated with inhaled treprostinil for >6 weeks was performed. Effects of inhaled treprostinil on exercise capacity, functional class, and echocardiographic and hemodynamic data were evaluated. Adverse events were documented. Patients received 3 to 9 breaths (6 g/breath) of inhaled treprostinil 4 times/day. All were receiving background PAH therapy; 12 had previously received parenteral prostanoid. Inhaled treprostinil was discontinued in 4 patients because of symptoms including cough and bronchospasm (n ؍ 3) and progression of PAH (n ؍ 1). Mild side effects including cough (n ؍ 9) and sore throat (n ؍ 6) did not require discontinuation of therapy. World Health Organization functional class improved in 19 and was unchanged in 10; exercise capacity significantly improved with the 6-minute walk distance, improving on follow-up from 455.7 ؎ 71.5 to 498 ؎ 70 m (p ؍ 0.01) and peak oxygen consumption increasing from 25.5 ؎ 10.2 to 27.4 ؎ 10 (p ؍ 0.04). In conclusion, inhaled treprostinil was associated with improvement in exercise capacity and World Health Organization functional class when added to background targeted PAH therapy in children and had an acceptable safety profile. Based on these early data, further study of inhaled treprostinil appears warranted in pediatric patients with PAH.
Pulmonary Circulation, 2021
Pulmonary arterial hypertension is a chronic, progressive, and life-threatening disease in children with diverse causes of pulmonary arterial hypertension. The most severe cases of pulmonary arterial hypertension require aggressive treatments with systemic administration of continuous prostacyclin therapy, including treprostinil and epoprostenol. The successful use of continuous subcutaneous treprostinil therapy eliminates the need for an indwelling central venous catheter and its associated risks. However, pain at the subcutaneous infusion site, an expected side effect of this therapy, is often a deterrent to its widespread use. Effective subcutaneous treprostinil site maintenance and pain management is essential to achieve success with this therapy, but strategies surrounding site maintenance and pain control vary significantly between pediatric pulmonary hypertension treatment centers. In an attempt to standardize practice, a survey on the use of subcutaneous treprostinil and sit...
Pulmonary circulation, 2014
Guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend sequential add-on therapy for patients who deteriorate or fail to improve clinically. However, it is not known whether these patients also benefit from transitioning from inhaled prostacyclins to parenteral prostacyclins. We sought to characterize PAH patients receiving inhaled treprostinil who were transitioned to parenteral treprostinil. We conducted a multicenter retrospective study at 7 PAH centers and collected reasons, methods, safety, and outcome of patients transitioned from inhaled treprostinil to parenteral treprostinil. Twenty-six patients with pulmonary hypertension in group 1, 4, or 5 transitioned from inhaled treprostinil to parenteral treprostinil (10 intravenous, 16 subcutaneous). Twenty-four patients were also on one or two oral therapies. Reasons for transition were clinical deterioration, lack of clinical improvement, and pregnancy (19, 6, and 1 patients, respectively). Transitions occ...
Transition from parenteral to oral treprostinil in pulmonary arterial hypertension
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2016
Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. A...
Pulmonary Circulation, 2013
Treprostinil is a potent prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH, World Health Organization Group I). Previously, treprostinil was available only in subcutaneous (SC) or intravenous (IV) formulations. Availability of an inhaled formulation of treprostinil has provided clinicians with an alternative to continuous SC or IV treprostinil in appropriate patients. Stable PAH patients whose quality of life has been dramatically impacted by side effects of parenteral therapy or those who have had recurrent, life-threatening bloodstream infections but are otherwise responding well to treatment may be the candidates for continuing prostacyclin therapy with inhaled treprostinil. However, there is little clinical experience with transitioning patients from parenteral to inhaled treprostinil. We present the results of two cases that highlight important considerations in transitioning patients from parenteral to inhaled therapy, including the pharmacologic and clinical equivalence of formulations, dose titration of formulations and suggested criteria for patient selection.
The Journal of Heart and Lung Transplantation, 2012
BACKGROUND: Randomized controlled trials have resulted in improved outcomes in pulmonary arterial hypertension; however, they are biased by stringent inclusion criteria, pre-specified patient sub-sets, and study durations. In addition, common practice is to start oral therapies ahead of the more potent and titratable prostanoid therapies, despite advanced disease states at diagnosis. The objectives of our prospective registry were to evaluate long-term effects on functional class, 6-minute walking distance, hemodynamics, and survival, and also long-term tolerability of first-line sub-cutaneous treprostinil, a prostacyclin analog, in patients with severe pulmonary hypertension. METHODS: Data were collected from patients with functional class III/IV pre-capillary pulmonary hypertension (Dana Point groups 1 and 4; mean right arterial pressure Ն 10 mmHg, and/or cardiac index Յ 2.2 liters/min/m 2 ). Treprostinil dose adjustments were driven by clinical symptoms and side effects.
Inhaled treprostinil sodium for pulmonary hypertension
Introduction: Pulmonary arterial hypertension is an increasingly recognized heterogeneous disease with significant morbidity and mortality, requiring a multimodal approach to treatment. Inhalation administration of treprostinil sodium (Tyvaso Ò) permits higher local drug concentration without some of the side effects of parenteral prostanoids. Areas covered: After a broad discussion centering on available prostacyclins, a thorough literature review of treprostinil is undertaken, focusing on the time-line of clinical studies, specifically highlighting the major trials that shape current indications and usage. The literature search was undertaken via multiple search engines and strategies with review of cited and associated articles to provide a comprehensive discussion on the topic. Expert opinion: While safe and well tolerated, inhaled treprostinil sodium should be limited, based on available data, to use as add-on therapy for patients with Group I pulmonary hypertension not effectively controlled on oral therapy. Despite documented safety for the conversion from inhaled ilo-prost to inhaled treprostinil, the transition of patients stable on parenteral agents to inhaled treprostinil should be cautioned due to the potential for clinical decompensation.
Pediatric Cardiology, 2013
Acute pulmonary vasodilator testing (AVT) is essential to determining the initial therapy for children with pulmonary arterial hypertension (PAH). This study aimed to report the initial experience with inhaled treprostinil used for AVT in children with PAH and to evaluate the hemodynamic change after inhaled treprostinil compared with inhaled nitric oxide. This prospective cohort study was designed for 13 children who underwent AVT with inhaled treprostinil or oxygen plus inhaled nitric oxide (iNO) during catheterization. Inhaled treprostinil was delivered during cardiac catheterization by adapting the Optineb ultrasonic nebulizer via either a flow-inflating bag or the manual mode of the anesthesia system. The median age of the patients was 10 years (range 4-17 years). The etiologies of PAH included idiopathic PAH and associated PAH. All the patients tolerated inhaled treprostinil without marked clinical worsening and received six or nine breaths (36 or 54 lg) of treprostinil. The median of the total treprostinil doses was 1.53 lg/kg (range 0.71-2.89 lg/kg).
Current and Emerging Therapies in Pulmonary Arterial Hypertension: Focus on Treprostinil
Clinical Medicine Reviews in Vascular Health, 2011
Pulmonary arterial hypertension (PAH) is a progressive disease process with a high morbidity and mortality. Until the advent of epoprostenol, a continuous prostacyclin infusion therapy, PAH was uniformly fatal but for those few who responded to calcium channel blockers. The development of PAH specific oral therapies including endothelin antagonists and phosphodiesterase-5 inhibitors provide effective alternatives to intravenous epoprostenol for mild to moderately symptomatic persons. But while effective, a significant number of patients fail oral therapy and require combination oral therapy and progression to prostacyclins. While epoprostenol improves quality of life and average life span in PAH, a short 4 minute half life places patients at high risk for rapid decompensation with even short interruptions of the infusion. Additionally, epoprostenol requires a complicated delivery system including a large pump and an indwelling central line that carries risk of infection and sudden occlusion. The second prostanoid developed was treprostinil which has the advantage of a 4 hr half life, stability at room temperature, and the ability to be continuously administered subcutaneously with a small pump. Subsequently, treprostinil was demonstrated to be safe and effective given intravenously and by inhalation. We will review the pharmacokinetics, dosing, metabolism, and side effects of treprostinil in its various forms and overall place in the treatment of PAH.