Adult: For the treatment of cases (idiopathic or heritable pulmonary arterial hypertension associated with connective tissue diseases) in patients with NYHA Class III or IV symptoms to improve exercise capacity: Short-term (acute) dose-ranging: Initially, 2 ng/kg/min via peripheral or central venous line. May increase by increments of 2 ng/kg/min every 15 minutes or longer until Max haemodynamic benefit or dose-limiting pharmacological effects occur. Use a lower dose if the initial infusion rate is not tolerated. Long-term continuous infusion: Initially, 4 ng/kg/min less than the Max tolerated infusion rate via a central venous catheter (temporary peripheral line may be used until central access is established). If the Max tolerated infusion rate is ≤5 ng/kg/min, initiate the long-term infusion at 1 ng/kg/min. Generally, the infusion rate may be increased by increments of 1-2 ng/kg/min at adequate intervals (at least 15 minutes) that will allow clinical response evaluation. If dose-related pharmacological events occur, doses may be decreased gradually by increments of 2 ng/kg/min every 15 minutes or longer until the dose-limiting effects resolve. Child: There is limited information regarding the use of this drug in this population, treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Parenteral Prophylaxis of platelet aggregation
Adult: For emergency cases during haemodialysis when the use of heparin carries a high risk of causing or worsening bleeding, or when heparin is contraindicated: 4 ng/kg/min via IV infusion for 15 minutes prior to dialysis, then 4 ng/kg/min into the arterial inlet of the dialyser during dialysis. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Reconstitution
Reconstitute vials labelled as 0.5 mg or 1.5 mg with 5 mL of sterile water for inj or NaCl 0.9%. Using a sufficient volume of the same diluent, the reconstituted solution should be immediately further diluted to a desired final concentration that is compatible with the infusion pump and within the capacity of the drug delivery reservoir. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).
Contraindications
Hypersensitivity. CHF due to severe left ventricular systolic dysfunction. Not for chronic use in patients who develop pulmonary oedema during dose-ranging.
Special Precautions
Patient with CAD, pulmonary veno-occlusive disease. Patients at risk for bleeding or pulmonary oedema. Avoid sudden large dose reduction, abrupt withdrawal, or interruptions (excluding life-threatening situations). Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Rebound pulmonary hypertension, vasodilation (e.g. hypotension); pulmonary oedema, pulmonary embolism; increased risk of haemorrhagic complications. Blood and lymphatic system disorders: Splenomegaly, hypersplenism, bleeding at various sites (e.g. pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal). Cardiac disorders: Bradycardia, tachycardia. Endocrine disorders: Rarely, hyperthyroidism. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, dry mouth. General disorders and administration site conditions: Flu-like symptoms, chills, inj site pain. Hepatobiliary disorders: Hepatic failure. Infections and infestations: Sepsis, septicaemia (delivery system-related). Investigations: Increased blood glucose, decreased platelet count. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Back pain, neck pain, non-specific musculoskeletal pain, arthralgia, myalgia, jaw pain. Nervous system disorders: Dizziness, headache, hyperaesthesia, hypoaesthesia, paresthesia. Psychiatric disorders: Anxiety, nervousness. Rarely, agitation. Respiratory, thoracic and mediastinal disorders: Dyspnoea, chest pain. Skin and subcutaneous tissue disorders: Rash, urticaria, sweating, dermal ulcer, eczema. Vascular disorders: Facial flushing. Potentially Fatal: Anaphylactic reactions.
Monitor vital signs daily; arterial pressure, bleeding. After establishing a new chronic infusion rate, monitor the blood pressure (standing and supine) and heart rate for several hours to ensure tolerance to new infusion rate. Monitor for improvements in pulmonary function (fatigue, chest pain, syncope, decreased exertional dyspnoea) and quality of life. Check the pump device and catheters frequently to prevent system-related malfunctions. Assess for signs and symptoms of overdose.
Overdosage
Symptoms: Headache, nausea, vomiting, diarrhoea, flushing, hypotension (may lead to loss of consciousness), tachycardia, hypoxaemia, and respiratory arrest. Management: Symptomatic and supportive treatment. Consider plasma volume expansion and/or pump flow modification.
Drug Interactions
Increased risk of bleeding with other antiplatelet agents or anticoagulants, and NSAIDs. Enhanced hypotensive effect with other vasodilators, antihypertensives, and diuretics. May increase the serum concentration of digoxin. May decrease the thrombolytic effect of tissue plasminogen activator (e.g. alteplase).
Action
Description: Mechanism of Action: Epoprostenol, a metabolite of arachidonic acid, is a naturally occurring prostaglandin and the most potent platelet aggregation inhibitor. It activates the intracellular adenylate cyclase which results in the elevation of intracellular levels of cyclic adenosine monophosphate (cAMP) within the platelets. The increase in cAMP levels regulates intracellular Ca concentration through Ca removal stimulation, thus inhibiting platelet aggregation due to the decrease of cytoplasmic Ca which is vital for platelet shape alteration, aggregation, and release reaction. Pharmacokinetics: Distribution: Rapidly distributed from blood to tissue. Metabolism: Rapidly hydrolysed into 6-keto-prostaglandin F1α (more stable but less active metabolite); undergoes enzymatic degradation into 6,15-diketo-13,14-dihydro-prostaglandin F1α (2nd metabolite). Excretion: Via urine (82%); faeces (4%). Elimination half-life (≤6 minutes).
Chemical Structure
Epoprostenol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5282411, Epoprostenol. https://pubchem.ncbi.nlm.nih.gov/compound/Epoprostenol. Accessed Jan. 25, 2024.
Storage
Intact vial: Store between 20-25°C. Diluted solution: Stable between 2-8°C for up to 8 days. Stable at room temperature for 24, 48, or 72 hours depending on the final concentration of the solution or timing of administration. Do not freeze. Protect from light. Storage and stability recommendations may vary among individual products and between countries (refer to specific product guidelines).
B01AC09 - epoprostenol ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.
References
Anon. Epoprostenol. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 07/09/2023.Anon. Epoprostenol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/09/2023.Buckingham R (ed). Epoprostenol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/09/2023.Epoprostenol 0.5 mg Powder for Solution for Infusion (Sun Pharmaceutical Industries Europe B.V). MHRA. https://products.mhra.gov.uk. Accessed 07/09/2023.Janssen-Cilag (New Zealand) Ltd. Veletri 500 micrograms, 1.5 mg Powder for Injection data sheet 29 June 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 07/09/2023.Joint Formulary Committee. Epoprostenol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/09/2023.Veletri 0.5mg, 1.5 mg Powder for Solution for Infusion (Actelion Pharmaceuticals Ltd.). MIMS Hongkong. http://www.mims.com/hongkong. Accessed 07/09/2023.Veletri Injection, Powder, Lyophilized, for Solution (Actelion Pharmaceuticals US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/09/2023.
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