Treprostinil for the treatment of severe digital necrosis in systemic sclerosis

Engel, Gregory; Rockson, Stanley G.

doi:10.1191/1358863x05vm579cr

Cited by 14 publications

(6 citation statements)

References 16 publications

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“…However, iloprost is commercially available in the U.S. only as an inhalation which failed to improve the frequency or severity of attacks in a previous study [4]. Epoprostenol and treprostinil offer the benefit of parenteral administration and have been associated with clinical improvement in symptoms associated with Raynaud's phenomenon [5][6][7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

Use of Continuous Infusion Epoprostenol in a Patient with Secondary Raynaud’s Phenomenon

Lemieux¹

2018

Int J Pharm Pharmacol

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To describe a unique prostacyclin dosing regimen utilized to treat a case of secondary Raynaud's phenomenon and summarize the existing literature on parenteral prostacyclin use for Raynaud's phenomenon in adult patients. Summary: A 54-year-old female was admitted for initiation of continuous intravenous infusion epoprostenol to treat secondary Raynaud's phenomenon which failed to respond to nifedipine and sildenafil. The infusion was titrated to a target dose of 9 ng/kg/min for 5 days. Upon completion of treatment, improvements in the patient's pain, range of motion, and digital perfusion were observed. Sustained improvements were noted seven weeks later. Parenteral prostacyclins may therefore be considered for Raynaud's phenomenon which fails to respond to conventional therapies. Epoprostenol has previously been used to treat Raynaud's phenomenon mainly in the form of intermittent, intravenous infusions. There are logistical concerns associated with the use of a continuous infusion prostacyclin which should be addressed before this therapy is chosen. Conclusion: This case highlights a successful outcome in a patient with secondary Raynaud's phenomenon treated with a 5-day continuous infusion of epoprostenol. It is reasonable to consider this treatment regimen in patients with secondary Raynaud's phenomenon in whom other treatments have failed.

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Section: Discussionmentioning

confidence: 99%

Use of Continuous Infusion Epoprostenol in a Patient with Secondary Raynaud’s Phenomenon

Lemieux¹

2018

Int J Pharm Pharmacol

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“…3,15,25 Likewise, treprostinil has been described in only a few published articles as a potential candidate to treat digital ulcers. 29,30 Experimental oral prostanoid analogs have been largely unsuccessful in clinical trials to date, and none are currently FDA approved to treat RP in the United States. 8 More aggressive therapies such as sympathectomy, debridement, and surgery have been utilized clinically but are often reserved for situations where symptoms persist despite attempted pharmacological treatments.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Use of Epoprostenol to Treat Raynaud’s Phenomenon With or Without Digital Ulcers

et al. 2016

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Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.

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“…Parenteral treprostinil therapy has been utilized in previous studies in SSc patients with digital ulcer disease [16–19]. Due to the delivery complexities associated with this therapy an alternative was sought to enhance patient acceptance and to improve treatment options for this population.…”

Section: Discussionmentioning

confidence: 99%

Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion

et al. 2013

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IntroductionTreprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet. The availability of a formulation permitting convenient systemic delivery might have applicability to scleroderma vascular complications. We evaluated pharmacokinetics and perfusion in scleroderma patients with digital ischemia following escalating twice-daily doses of treprostinil diethanolamine SR.MethodsScleroderma patients with digital ulcers were enrolled in this dual-center, open-label, phase I pharmacokinetic study. Drug concentrations and perfusion, quantified by laser Doppler imaging, were measured over 12 hours at the 2 mg and 4 mg (or maximally tolerated) doses. Pharmacokinetic parameters were determined from individual plasma concentration versus time profiles using non-compartmental analysis methods. Digital perfusion and skin temperature were modeled as a function of log-transformed drug concentration and other covariates by performing repeated measures analyses using random effects models.ResultsNineteen scleroderma patients (84% female, 53% limited scleroderma) received treprostinil diethanolamine SR with dose titration up to 4 mg twice daily as tolerated. Peak concentrations (mean maximum plasma concentration (Cmax) = 1,176 and 2,107 pg/mL) occurred approximately 3.6 hours after dose administration, and overall exposure (under the plasma concentration-time curve from time 0 to 12 hours post dose (AUC0-12) = 7,187 and 12,992 hr*pg/mL) was linear between the 2 mg and 4 mg doses. Perfusion and digital skin temperature were positively associated with log-transformed plasma concentration at the 4 mg dose (P = 0.015 and P = 0.013, respectively). The most frequent adverse events were similar to those seen with prostacyclin analogues.ConclusionsOral treprostinil diethanolamine was effectively absorbed in patients with scleroderma. Drug administration was temporally associated with improved cutaneous perfusion and temperature. Treprostinil diethanolamine may provide a new therapeutic option for Raynaud's phenomenon and the peripheral vascular disease of scleroderma.Trial RegistrationClinicalTrials.gov NCT00848939.Electronic supplementary materialThe online version of this article (doi:10.1186/ar4216) contains supplementary material, which is available to authorized users.

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Treprostinil for the treatment of severe digital necrosis in systemic sclerosis

Cited by 14 publications

References 16 publications

Use of Continuous Infusion Epoprostenol in a Patient with Secondary Raynaud’s Phenomenon

Use of Continuous Infusion Epoprostenol in a Patient with Secondary Raynaud’s Phenomenon

Evidence for the Use of Epoprostenol to Treat Raynaud’s Phenomenon With or Without Digital Ulcers

Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion

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