What is IV Prostacyclin (Epoprostenol)?
IV prostacyclin (epoprostenol) is a synthetic prostacyclin administered as a continuous intravenous infusion for treating pulmonary arterial hypertension (PAH), and it is the only PAH therapy proven in randomized controlled trials to improve survival in idiopathic PAH. 1
Drug Characteristics and Mechanism
Epoprostenol is a synthetic salt of prostacyclin, a naturally occurring metabolite of arachidonic acid that functions as a potent vasodilator affecting both pulmonary and systemic circulations, while also inhibiting platelet aggregation. 1, 2
Pharmacokinetic Properties
The drug has an extremely short half-life of 3-5 minutes in circulation, requiring continuous IV administration without interruption. 1
Epoprostenol is stable at room temperature for only 8 hours after reconstitution, necessitating careful handling with cold packs and daily infusion changes. 1
The medication is rapidly converted to stable breakdown products or metabolites once in the bloodstream. 1
Administration Requirements
Epoprostenol must be administered via continuous IV infusion through a permanent tunnelized central venous catheter (such as a Hickman catheter) using specialized infusion pumps (e.g., CADD pump). 1, 2
Preparation and Delivery System
The drug comes as a stable, freeze-dried preparation that must be dissolved with an alkaline buffer (glycine) to allow for IV infusion. 1
Reconstitution must only be performed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP—do not mix with any other parenteral medications or solutions. 2
Subcutaneous catheters with reservoirs and transcutaneous needles are discouraged for epoprostenol administration. 1
The infusion pump must be accurate to ±6% of programmed rate, have occlusion and low-battery alarms, and allow dose adjustments in 2 ng/kg/min increments. 2
Dosing Strategy
Long-term treatment is initiated at 2-4 ng/kg/min and increased at a rate limited by side effects (flushing, headache, diarrhea, leg pain). 1, 2
Titration Protocol
The target dose for the first 2-4 weeks is usually around 10-15 ng/kg/min, with periodic dose increases required to maximize efficacy and maintain results due to possible drug tolerance. 1
Optimal dose varies between individual patients, ranging in the majority between 20-40 ng/kg/min, though the strategy for dose increases differs among centers. 1
Dose increases should occur in 1-2 ng/kg/min increments at intervals of at least 15 minutes, allowing sufficient time to assess clinical response. 2
In clinical trials, mean doses increased from 2.2 ng/kg/min at baseline to 4.1 ng/kg/min on day 7, reaching 11.2 ng/kg/min by week 12, with mean incremental increases of 2-3 ng/kg/min every 3 weeks. 2
Clinical Efficacy and Survival Data
Epoprostenol is the only treatment shown in randomized controlled trials to improve survival in idiopathic PAH (IPAH), making it the gold standard for severe disease. 1
Evidence from Clinical Trials
In a 12-week randomized controlled trial of 81 patients with severe IPAH (NYHA class III or IV), epoprostenol improved median 6-minute walk distance from 315m to 362m, while the control group decreased from 270m to 204m (p=0.002). 1
Eight patients died during the study, all in the conventional therapy group (p=0.003), demonstrating a survival benefit. 1
Hemodynamic improvements included an 8% reduction in mean pulmonary artery pressure and 21% reduction in pulmonary vascular resistance in the epoprostenol group. 1
Long-term survival data shows approximately 65% survival at 3 years, with outcomes related to baseline severity and 3-month response to therapy. 1
Epoprostenol also improved exercise capacity and hemodynamics in PAH associated with scleroderma spectrum disease. 1
Adverse Effects Profile
Common adverse effects include flushing, jaw pain, diarrhea, headache, backache, foot and leg pain, abdominal cramping, nausea, and rarely hypotension. 1
Side Effect Management
The incidence of side effects relates to how aggressively the dose is initially up-titrated, and dose reduction is required only if intensity is moderate to severe. 1
Side effects may recur after dose increases but are usually mild and self-limiting over time without dose changes. 1
Ascites has been reported in some cases, possibly related to increased permeability of the peritoneal membrane induced by epoprostenol. 1
Serious Delivery System Complications
Adverse events related to the delivery system are more serious and include pump malfunction, local site infection, catheter obstruction, and sepsis. 1
Catheter-related sepsis occurs at a rate of 0.14-0.19 episodes per patient, representing a significant risk of this therapy. 1
Four episodes of catheter-related sepsis and one thrombotic event occurred in the pivotal trial. 1
Critical Safety Considerations
Abrupt withdrawal of epoprostenol or sudden large reductions in infusion rates must be avoided except in life-threatening situations (unconsciousness, collapse). 2
Infusion rates should only be adjusted under physician direction, as interruptions can lead to rapid clinical deterioration. 2
Patients should have access to a backup infusion pump and IV infusion sets to avoid potential interruptions in drug delivery. 2
A multi-lumen catheter should be considered if other IV therapies are routinely administered. 2
Clinical Positioning
According to European Society of Cardiology guidelines, continuous IV epoprostenol may be considered as first-line therapy for IPAH patients in NYHA functional class IV due to demonstrated survival benefit, worldwide experience, and rapidity of action. 1
Most experts consider IV epoprostenol the preferred treatment for NYHA class IV patients in unstable condition, given its proven mortality benefit. 1
Due to the complexity of therapy, it is strongly recommended that patients be referred to specialized centers of excellence for initiation and management. 1
Lung transplantation should be considered for patients who remain in NYHA class III or IV or cannot achieve significant hemodynamic improvement after 3 months of epoprostenol therapy. 1