Epoprostenol (Flolan)

Emergency & Prehospital

• Known PAH patient on a home epoprostenol pump: Keep the infusion running with no gap. Any pump, line or catheter problem is time-critical.

ED / ICU / Transport

• Pulmonary arterial hypertension (PAH, WHO Group 1): Long-term IV therapy is FDA-labeled to improve exercise capacity. For high-risk patients, IV prostacyclin is part of initial triple therapy (ESC/ERS 2022, WSPH 2024).
• Acute-on-chronic right ventricular (RV) failure in known PAH: Keep the home dose running with no gap. In decompensated, high-risk PAH, parenteral prostacyclin (IV epoprostenol) is guideline-recommended therapy. It is not a last resort. Only the pulmonary hypertension (PH) team starts it in the ICU or raises the dose.
• Refractory hypoxemia in ARDS (inhaled, off-label). This is the rescue for hypoxemia that persists despite lung-protective ventilation and prone positioning, or the bridge to ECMO or transfer. Responders get better oxygenation, but there is no proven mortality benefit. Don't let it delay proning. Proning reduces mortality in moderate-severe ARDS (PaO₂/FiO₂ below 150, ESICM 2023).
• Acute RV failure from high pulmonary vascular resistance (PVR) (inhaled, off-label): used after cardiac surgery or massive pulmonary embolism, or in other RV failure with raised PVR. It works as a bridge alongside milrinone or vasopressors.
• Interfacility transport of severe hypoxemic or RV failure (inhaled, off-label): the critical-care transport team starts it or keeps it running to protect oxygenation en route.

Other Uses

• Acute vasoreactivity testing (IV) during right heart catheterization. ESC/ERS 2022 recommends inhaled nitric oxide (iNO) or inhaled iloprost. If neither is available, IV epoprostenol can be used. Stepwise IV testing takes much longer.

Doses vary by protocol; follow local protocols and medical direction. Below are the FDA label or guideline values (see References). Inhaled dosing is off-label and protocol-based.

Available Forms

• Lyophilized powder, single-dose 10 mL vial: 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol as the sodium salt. Each Veletri vial also holds 50 mg arginine and 100 mg sucrose. Read the excipient list on the label of any generic product in your hands.
• Reconstitution: Veletri takes 5 mL Sterile Water for Injection or 0.9% NaCl only, then dilution with the identical diluent.
• Home infusion: a pump reservoir labeled in ng/mL, running from 3,000 ng/mL to 60,000 ng/mL or more. Don't expect EMS to stock epoprostenol.

Adult Dosing

Dosing weight: the label doses IV epoprostenol in ng/kg/min but never names a weight. Use the weight the PH center prescribes. Inhaled protocols commonly use ideal body weight. Say which weight you used at handoff.

Pediatric Dosing

Neonates: Epoprostenol carries no neonatal label. For term and near-term (>34 weeks) neonates with hypoxic respiratory failure and pulmonary hypertension, the FDA-approved inhaled pulmonary vasodilator is inhaled nitric oxide 20 ppm. Run weight-based dosing checks on every pediatric infusion.

Continuous Infusion

Preparation & Administration

• Dilution: reconstitute each vial with 5 mL of the labeled diluent and dilute in the pump reservoir with the identical diluent; never mix with other drugs or solutions before or during infusion.
• Line: Chronic infusion needs its own central venous catheter. During initiation, or while central access is re-established, a temporary peripheral IV is acceptable.
• Filter: infusion set with an in-line 0.22 micron filter.
• Pump requirement: The pump must adjust in 2 ng/kg/min steps and carry occlusion, end-of-infusion and low-battery alarms. The patient should have a backup pump and infusion sets.
• Never flush or bolus: A flush in the epoprostenol lumen sends the drug down the line as a bolus. Give other drugs through a separate lumen or IV.
• Inhaled setup (off-label): A syringe pump feeds the solution nonstop into a vibrating mesh nebulizer. That nebulizer sits in the ventilator, high-flow nasal cannula or noninvasive circuit. In a bench model with a heated humidifier, placement at the humidifier inlet or outlet delivered more drug than placement near the Y-piece.

Contraindications

• Chronic use in heart failure from severe left ventricular systolic dysfunction: A large trial stopped early for higher mortality on epoprostenol.
• Chronic use after pulmonary edema during dose initiation: That pattern may signal pulmonary veno-occlusive disease.
• Hypersensitivity to epoprostenol or structurally related compounds.
• Inhaled use (off-label): severe left ventricular failure with cardiogenic pulmonary edema, and active bleeding, especially intracranial (relative).

Precautions

• Hypotension: It is most likely during starts and increases, and with volume depletion.
• Bleeding: The drug blocks platelets from clumping. For chronic use, the label advises anticoagulant therapy unless it is contraindicated (section 5.2). Current PH guidelines tailor that decision to each patient.
• Patent foramen ovale or right-to-left shunt: Paradoxical embolism is the risk here. Keep air and clot out of the line.
• Central catheter: The central catheter carries infection risk. Use aseptic technique for every access.

Hold / Reassess If

• Delivery interrupted (pump alarm, occlusion, empty reservoir, line break, dislodged catheter): restart within minutes. If the central line is unusable, restart through a peripheral IV.
• MAP below target, or symptomatic hypotension (ESC/ERS 2022 aims for MAP above 60 mmHg in right heart failure. Many ICU protocols use 65 mmHg. Follow the local target): support MAP with a vasopressor (vasopressin or norepinephrine) and call the PH team. Reduce the dose in 2 ng/kg/min steps only when they direct it, or at once for collapse from a suspected bolus.
• New pulmonary edema after a start or increase: stop uptitrating and reassess for left heart failure or veno-occlusive disease.
• Inhaled, no response (PaO₂ rise under 10% at about 2 hr): wean off over several hours (see Dosing).
• Fever, rigors or catheter-site redness: draw blood cultures and start the sepsis workup. Keep the infusion running.

Common

• Flushing (58% during initiation) and headache (49%)
• Nausea and vomiting (32%); diarrhea with chronic use
• Hypotension (16%) and dizziness
• Jaw pain (54–75% with chronic use), myalgia and musculoskeletal pain
• Anxiety, chest pain, flu-like symptoms, rash

Serious / Life-Threatening

Long-term use (postmarketing reports): anemia, pancytopenia, splenomegaly or hypersplenism, and hyperthyroidism.

Overdose & Toxicity Management

• Signs: exaggerated vasodilator effects: flushing, headache, hypotension, tachycardia, nausea, vomiting, diarrhea.
• Immediate: reduce the rate; with a half-life of 6 min or less, effects fade within minutes. Support MAP with a vasopressor if needed.
• Antidote: none. Check reservoir concentration and pump programming.

Clinically Significant Interactions

IV Compatibility

• Diluent: Sterile Water for Injection or 0.9% NaCl (Veletri and current generics); the identical diluent for reconstitution and dilution.
• Do not mix: no other drug or solution in the reservoir or line, before or during infusion.
• Dedicated line or lumen: no piggybacks, pushes or flushes through the epoprostenol lumen; use another lumen or a separate IV for other therapy.
• Verify with an institutional compatibility resource.

• Pediatrics: Not FDA-established. The 2024 World Symposium pediatric task force recommends initial IV or subcutaneous prostacyclin for high-risk pediatric PAH. A pediatric PH center manages it. See the Pediatric Dosing block.
• Neonates: There is no neonatal labeling. For term and near-term neonates with hypoxic respiratory failure, the labeled inhaled pulmonary vasodilator is inhaled nitric oxide.
• Pregnancy: Limited case data have not established a drug-associated risk of birth defects, miscarriage or adverse outcomes. Untreated PAH carries risk of heart failure, stroke, preterm delivery and maternal and fetal death. ESC/ERS 2022 considers prostacyclin analogues safe in pregnancy, though the evidence is limited. Manage it at an expert PH center.
• Lactation: There are no data on transfer into milk or effects on the infant. Weigh the mother's need for therapy against the unknown infant risk.
• Older Adults: No difference in response has been identified. Start at the low end of the dose range.
• Renal Impairment: No specific renal adjustment has been set. The metabolites clear mainly in urine.
• Hepatic Impairment: No specific adjustment has been established. Hepatic failure has been reported, but causality is not established.
• Obesity / Dosing Weight: For IV dosing, use the weight the PH center prescribes. Inhaled protocols commonly use ideal body weight.
• Home-Infusion Patients: The patient and caregiver are trained to mix the drug and run the pump. They carry a backup pump, supplies and the PH center's number.

• Scope: EMT and paramedic: keep a home infusion running, never titrate, and transport with the pump. RN and critical-care transport (CCT): manage IV and inhaled epoprostenol per protocol and medical direction. It varies by state and agency protocol.
• Storage & Stability: vials at 20–25°C (68–77°F) in the carton, out of direct sunlight. A diluted reservoir lasts 24–72 hr at 25°C (77°F), depending on concentration and prior refrigeration. Above 25°C and up to 30°C (77–86°F), reservoirs under 60,000 ng/mL need changing every 24 hr. 60,000 ng/mL or more can run up to 48 hr (given immediately or after up to 8 days refrigerated). Up to 40°C (104°F), 60,000 ng/mL or more can run up to 24 hr if given immediately. Short 40°C excursions from the 25°C limits: up to 2 hr below 15,000 ng/mL, 4 hr at 15,000–60,000 ng/mL and 8 hr above 60,000 ng/mL. Hot vehicles shorten the window.
• Carried Concentration: EMS does not stock epoprostenol. Read the concentration (ng/mL), dose (ng/kg/min) and rate (mL/hr) from the patient's pump and reservoir label. Never assume a standard mix.
• Infusions in Transport: Keep the patient's own pump running. Bring the backup pump, spare reservoir, supplies and PH center number. When you switch to a hospital pump, have it primed, programmed and double-checked before you stop the home pump, so there is no gap. Keep a working peripheral IV (see IV insertion) as a backup route.
• Inhaled Epoprostenol in Transport: Set up the syringe pump and nebulizer on the transport ventilator before the move, and keep nebulization running. Every disconnect or ventilator swap stops delivery. The half-life is 6 min or less (Veletri label, section 12.3), so the effect wanes soon after delivery stops. Rebound is possible after prolonged use. Follow program guidance on filter changes. Watch for valve alarms or rising pressures.
• No Nitroglycerin by Default: Do not give nitroglycerin to a patient on IV epoprostenol or treprostinil (NASEMSO 2022 model EMS guidelines). Do not give it to anyone taking sildenafil, tadalafil or riociguat either. That is a labeled contraindication, and many of these patients take one. Check the medication list first. Give it only if the PH team directs.
• Handoff Essentials: product, concentration (ng/mL), dose (ng/kg/min), dosing weight, pump rate (mL/hr), reservoir volume and time hung, line or lumen used, any interruption and its length, PH center contact. Inhaled: dose, weight used, start time, oxygenation response, nebulizer position.

Mechanism of Action

• Prostacyclin (IP) receptor agonism: It turns on the IP receptor, which raises cAMP in vascular smooth muscle. The arteries dilate, in both the pulmonary and systemic beds. Result: lower PVR and SVR, with higher cardiac output and stroke volume.
• Platelet IP receptors: The same receptor on platelets blocks aggregation, which raises bleeding risk.
• Heart rate: Vagally mediated bradycardia at low doses. Reflex tachycardia at higher doses (animal data).
• Inhaled route: The drug reaches ventilated alveoli. Blood flow shifts to the ventilated lung, which improves V/Q matching and oxygenation with less systemic hypotension.

Pharmacokinetics

• Half-life: 6 min or less. In human blood, the in vitro half-life is about 6 min. The label expects the in vivo half-life to be no greater (Veletri label, section 12.3). No assay can reliably measure human plasma levels.
• Metabolism: The drug hydrolyzes spontaneously at neutral pH to 6-keto-PGF₁α. Enzymes break it down to 6,15-diketo-13,14-dihydro-PGF₁α. Both are far less active.
• Elimination: about 82% of a radiolabeled dose in urine and 4% in feces over 1 week.
• Chemistry: It is unstable at physiologic pH. The reconstituted solution is strongly alkaline (pH 11 to 13 per the Veletri label). It gets less stable as pH drops, and it must not be mixed with other drugs.

Generic Name

Epoprostenol sodium (prostacyclin, PGI₂); doses expressed as epoprostenol

Brand Names

Veletri (US); Flolan (GlaxoSmithKline; discontinued in the US per Drugs@FDA, NDA 020444)

Pharmacologic Class

Prostacyclin (PGI₂) vasodilator; synthetic form of endogenous prostacyclin

Therapeutic Class

Pulmonary arterial hypertension therapy; pulmonary vasodilator

Controlled Substance

Not controlled

ISMP High-Alert

Yes: ISMP high-alert medication (epoprostenol, IV)

Look-Alike / Sound-Alike

None on the ISMP confused drug names list. Do not swap with other prostacyclin pathway drugs (treprostinil, iloprost, selexipag): no established dose conversion

Error-Prone Units

ng/kg/min misread or entered as mcg/kg/min (1,000-fold); write units in full. Inhaled orders are sometimes written correctly in mcg/kg/min (0.05 mcg/kg/min = 50 ng/kg/min): convert, do not "correct"