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Fast Pass: How to Start Higher Doses of Oral Treprostinil by Using IV Epoprostenol

Michael Salinero

Tina Hyman

Margarita Pallares

Javier Jimenez

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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1071

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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

To target higher oral treprostinil doses rapidly by using IV epoprostenol preloading.

Background

IV epoprostenol is a high-risk medication with no current guidelines for rapid initiation, titration, and transition from IV to oral therapy. In the PAH patient population, successful treatment depends on individualized patient therapy. This patient presented with worsening shortness of breath, fatigue and severe pulmonary hypertension naïve to prostacyclin therapy, World Health Organization (WHO) group 1 functional class IV, who was a poor candidate for IV therapy. The preplanned IV to p.o. protocol was initiated in the ICU setting; the hemodynamics were monitored via swan-ganz catheter. IV epoprostenol was infused via a central line to a maximum tolerated dose which allowed for a higher oral dose to be tolerated; this would not have been possible with the traditional dosing schedule.

Methods

IV epoprostenol was initiated at 2ng/kg/min with the goal to increase to 4ng/kg/min during the night. PRN medications to treat side effects were ordered prior to drug administration. Day 1, the first dose of oral treprostinil 0.25mg was given at bedtime. Using TID dosing, the total daily mgs of oral treprostinil administered were as follows: day 2 – 1mg total dose, day 3 – 3.75mg total dose and IV epoprostenol was decreased to 3 ng/kg/min, day4 – 6.5 mg total dose and IV epoprostenol was decreased to 2 mg/kg/min, by day 5 -- 9.0 mg total dose was achieved and IV epoprostenol was discontinued. The patient was prepared for discharge the following day.

Results

Baseline hemodynamics showed markedly elevated pulmonary pressures, elevated pulmonary vascular resistance, right ventricular pressure 120/25, pulmonary pressure 120/40, with a mean of 65, pulmonary wedge pressure 18, cardiac output 3.35, pulmonary vascular resistance 1066, and systemic artery pressure 100/52. Hemodynamically the patient improved over the first night as evidenced by markedly decreased PA pressures and increased cardiac output. Swan-ganz was removed on day2, CVP pressure remained elevated at 21. Vitals at discharge were 120/70, heart rate 80, O2 98% on 3 liters. The patient was able to tolerate a rapid initiation, titration, and transition from IV epoprostenol to a higher dose oral treprostinil therapy within a shorter time span than the traditional titration schedule for oral prostacyclin therapy. A right heart catheterization 3 months following the IV to oral transition was completed and showed a decrease in pulmonary vascular resistance of approximately 50% when compared to previous reports, from 1066 to 535. The patient experienced mild nausea, vomiting, and flushing during the admission, but remained hemodynamically stable.

Conclusions

For the patients whose condition would best be managed by oral treprostinil rather than IV epoprostenol therapy, pre-loading the patient using IV epoprostenol and then rapidly titrating with oral treprostinil can be done safely and effectively in the hospital setting to achieve higher dosing with better side effect management.