VELETRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VELETRI (VELETRI).
Epoprostenol is a direct vasodilator of pulmonary and systemic arterial vascular beds and an inhibitor of platelet aggregation. It works by binding to prostacyclin receptors, activating adenylate cyclase, increasing intracellular cAMP levels, leading to smooth muscle relaxation and vasodilation.
| Metabolism | Epoprostenol is rapidly metabolized via hydrolysis to 6-keto-prostaglandin F1α and other metabolites. Metabolism occurs primarily in the liver and also in the kidneys and lungs. |
| Excretion | Primarily renal excretion of inactive metabolites (68% of dose); 12% fecal. |
| Half-life | Terminal elimination half-life approximately 6 minutes; clinically irrelevant due to rapid redistribution and metabolism. |
| Protein binding | Approximately 58% bound to human plasma proteins. |
| Volume of Distribution | 0.37 L/kg (range 0.19-0.56 L/kg); suggests distribution into total body water. |
| Bioavailability | Oral: <1% due to extensive first-pass metabolism. |
| Onset of Action | Continuous IV infusion: immediate hemodynamic effects within 5 minutes. |
| Duration of Action | Effects persist only during continuous IV infusion; short-lived after cessation due to rapid redistribution (half-life ~2-3 minutes). |
Continuous intravenous infusion via central line, initiated at 1.25 ng/kg/min and titrated in increments of 1.25 ng/kg/min every 15 minutes or more based on clinical response. Maintenance dose typically ranges from 20-40 ng/kg/min, but may vary individually.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; drug is not renally eliminated. |
| Liver impairment | No specific dose adjustment guidelines for hepatic impairment; use with caution as metabolism may be affected. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; initiate at lower end of dosing range due to potential for decreased organ function and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VELETRI (VELETRI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Consider developmental and health benefits of breastfeeding along with mother's clinical need for Veletri and potential adverse effects on the infant. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal studies, epoprostenol (the active ingredient) has been shown to be teratogenic in rats at doses approximately 2.5 times the recommended human dose (on a mg/m² basis), causing skeletal and visceral anomalies. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. First trimester: unknown risk; second and third trimesters: may cause uterine relaxation and potentially premature cervical dilation. |
■ FDA Black Box Warning
VELETRI must not be abruptly discontinued. Abrupt withdrawal may lead to worsening of pulmonary hypertension symptoms, including symptomatic deterioration and death. In clinical trials, abrupt discontinuation was associated with severe rebound pulmonary hypertension and death.
| Serious Effects |
Chronic use in patients who develop pulmonary edema during initial dose ranging. Absolute contraindication: Known hypersensitivity to epoprostenol or structurally related compounds. Relative contraindications: Severe left ventricular systolic dysfunction, severe coronary artery disease, or severe cardiac arrhythmias; caution in patients with bleeding risk factors.
| Precautions | Abrupt discontinuation or sudden large dose reductions may lead to rebound pulmonary hypertension and death. Use caution in patients with concurrent conditions that increase bleeding risk (e.g., peptic ulcer, trauma, surgery). May cause pulmonary edema if used in patients with pulmonary veno-occlusive disease. Prolonged infusion may lead to tachyphylaxis requiring dose escalation. Monitor for signs of sepsis due to chronic indwelling catheter. |
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| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate), continuous pulse oximetry, signs of pulmonary edema, bleeding complications (due to antiplatelet effects), and uterine activity. Fetal monitoring: non-stress test and biophysical profile as clinically indicated. Assess maternal renal and hepatic function periodically. |
| Fertility Effects | No human data on fertility. In animal studies, epoprostenol did not impair fertility in male or female rats at doses up to 30 mg/kg/day (approximately 30 times the recommended human dose on a mg/m² basis). Potential for antiplatelet effects to affect implantation. No known permanent effects on fertility. |