Subcutaneous treprostinil in pulmonary arterial hypertension: Practical considerations

Mathier, Michael A.; McDevitt, Susanne; Saggar, Rajan

doi:10.1016/j.healun.2010.06.013

Cited by 44 publications

(59 citation statements)

References 42 publications

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“…Eighteen patients (8%) discontinued treprostinil because of injection site pain (compared with one receiving placebo); local infusion site pain was considered dose-limiting and resulted in a low dose of treprostinil achieved by week 12 in most patients. Subsequent studies have shown that these local adverse events considered dose-limiting in this pivotal trial (of pooled data) can be transient and are not dose-related, suggesting that the trial resulted in less efficacy than would have been expected if higher doses were used (Mathier et al, 2010). Indeed, the protocols of the two pivotal studies did not allow dosing above 22.5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 over the 12-week period; compared with later trials that evaluated doses greater than 40 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 (Lang et al, 2006), patients in these trials were exposed to low doses of drug.…”

Section: B Clinical Studies (Subcutaneous Infusion)mentioning

confidence: 86%

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Frumkin

2012

Pharmacol Rev

106

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Section: B Clinical Studies (Subcutaneous Infusion)mentioning

confidence: 86%

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Frumkin

2012

Pharmacol Rev

106

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“…Within the first 6 months, 50% of the patients who discontinued due to site pain had already stopped treatment and had a comparable dropout rate to our cohort after 16 weeks of treatment [6] . Different pain treatments, including local/topical options and systemic analgesics, are available and may be used for different intensities of infusion site pain [10] . In our cohort, mostly non-opioid an- a Four subjects were WHO-FC II at baseline and remained WHO-FC II at week 16, b Three subjects had a baseline walk greater than 400 m, all increased by more than 30 m at week 16, c Two subjects had a TAPSE of greater than 2 cm at baseline and retained a value of greater than 2 cm at week 16. algesics were used.…”

Section: Discussionmentioning

confidence: 99%

“…Treprostinil dose rate has also been found to be an independent prognostic on-treatment predictor of survival in a retrospective analysis of 811 patients treated with SC treprostinil [9] . A slow dose titration is therefore a potential cause of sub-therapeutic dosages [10] , which may provoke premature discontinuation of treatment. A thorough medical management of SC treprostinil therapy, including multidisciplinary patient support and proactive infusion site pain management, is necessary to achieve a clinically effective dosing regimen [10] .…”

Section: Introductionmentioning

confidence: 99%

“…A slow dose titration is therefore a potential cause of sub-therapeutic dosages [10] , which may provoke premature discontinuation of treatment. A thorough medical management of SC treprostinil therapy, including multidisciplinary patient support and proactive infusion site pain management, is necessary to achieve a clinically effective dosing regimen [10] . Importantly, infusion site pain can be minimised by avoidance of infusion site replacement until clinically indicated.…”

Section: Introductionmentioning

confidence: 99%

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Safety, tolerability and clinical effects of a rapid dose titration of subcutaneous treprostinil therapy in pulmonary arterial hypertension: a prospective multi-centre trial.

et al. 2016

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arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. Conclusions: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome. © 2016 S. Karger AG, Basel Key Words Treprostinil · Pulmonary arterial hypertension · Subcutaneous infusionAbstract Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. Results: Thirty-nine patients with idiopathic or heritable pulmonary

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“…5 Typically this is managed with the use of a preferred site, frequent site changes, oral and topical analgesics, and rapid increases in dosage to goal. 11 Levy et al reported on 8 children (ages 1.5 to 10 years, median 4 years) who were started on SCTre after failure of oral medications. 12 A total of 5/8 patients had congenital heart defects and 3 had idiopathic PAH.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Treprostinil for Pulmonary Hypertension in Chronic Lung Disease of Infancy

et al. 2014

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Pulmonary arterial hypertension (PAH) associated with chronic lung disease of infancy can be a life-threatening disease affecting an increasing number of former premature infants. There is a need for improved delivery of targeted PAH therapies for this subgroup of patients who have severe and persistent PAH despite standard respiratory care for chronic lung disease. Currently infants who have severe PAH despite oral or inhaled therapy receive continuous intravenous prostanoid therapy (mostly epoprostenol), which is complicated because of the need for central venous access and associated catheter-related complications. We present a series of 5 infants who were successfully treated with a continuous infusion of subcutaneous treprostinil, which is a longeracting prostanoid with similar hemodynamic effects. There were improvements in echocardiographic assessment of right ventricular function and estimated pulmonary hypertension, and in respiratory support required within weeks of therapy. Unlike commonly in adults, these 5 infants had no instances of severe site erythema, bleeding, bruising, or infection. In our experience with 5 former extremely preterm infants who had PAH associated with chronic lung disease, subcutaneous treprostinil was safe, efficacious, and well tolerated. We believe that subcutaneous treprostinil can be beneficial in a select group of former premature infants who have chronic lung disease and severe pulmonary arterial hypertension who have not responded adequately to conservative therapies. Pediatrics 2014;134:e274-e278 AUTHORS:

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Subcutaneous treprostinil in pulmonary arterial hypertension: Practical considerations

Cited by 44 publications

References 42 publications

The Pharmacological Treatment of Pulmonary Arterial Hypertension

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Safety, tolerability and clinical effects of a rapid dose titration of subcutaneous treprostinil therapy in pulmonary arterial hypertension: a prospective multi-centre trial.

Subcutaneous Treprostinil for Pulmonary Hypertension in Chronic Lung Disease of Infancy

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