Epoprostenol parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
All formulations of epoprostenol.
Drugs List
Therapeutic Indications
Uses
Inhibition of platelet aggregation during renal dialysis
Primary pulmonary hypertension: functional grades III + IV
Pulmonary hypertension 2ry to autoimmune disease NYHA class III and IV
Dosage
Adults
Renal dialysis
Suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.
Prior to dialysis: 4 nanograms/kg/minute intravenously for 15 minutes.
During dialysis: 4 nanograms/kg/minute into the arterial inlet of the dialyser.
The infusion should be stopped at the end of dialysis.
The above dose should be exceeded only with careful monitoring of patient blood pressure.
Primary and Secondary pulmonary hypertension
Short term (acute) dose ranging
2 nanograms/kg/minute, increased by increments of 2 nanograms/kg/minute every 15 minutes or longer. If the initial infusion rate of 2 nanograms/kg/minute is not tolerated, a lower dose should be identified.
Administered via peripheral or central venous line to determine the long term infusion rate.
Long term continuous infusion
4 nanograms/kg/minute less than the maximum tolerated infusion rate determined during short term dose ranging. If the maximum tolerated infusion rate is 5 nanograms/kg/minute or less, the long term infusion should be started at 1 nanogram/kg/minute or at one half the maximum tolerated infusion rate (see product literature).
Long term continuous infusion of epoprostenol should be administered through a central venous catheter. Temporary peripheral intravenous infusions may be used until central access is established.
Dosage adjustments
Changes in the long term infusion rate should be based on persistence, recurrence or worsening of the patient's symptoms of pulmonary arterial hypertension (PAH) or the occurrence of adverse events due to excessive doses of epoprostenol.
Increases in dose should be considered if symptoms of PAH persist, or recur after improving. The infusion rates should be increased by 1 to 2 nanogram/kg/minute increments at intervals sufficient to allow assessment of clinical response. These intervals should be at least 15 minutes. Following new infusion rate, the patient should be observed, and standing and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.
During long term infusion, the occurrence of dose related pharmacological events similar to those observed during the dose ranging period may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2 nanogram/kg/minute decrements every 15 minutes or longer until the dose-limiting effects resolve. Abrupt withdrawal or sudden large reductions in infusion rates should be avoided. Except in life-threatening (e.g. unconsciousness, collapse, etc.) infusion rates should be adjusted only under the direction of a physician.
Children
Idiopathic pulmonary arterial hypertension (unlicensed)
Children aged 1 month to 18 years
2 nanograms/kg/minute, titrated up to 40 nanograms/kg/minute, via continuous intravenous infusion.
Neonates
Persistent pulmonary hypertension (unlicensed)
2 nanograms/kg/minute titrated to response, titrated up to a maximum of 20 nanograms/kg/minute, via continuous intravenous infusion. Rarely doses up to 40 nanograms/kg/minute are needed.
Administration
Epoprostenol is only for continuous infusion either as IV or into the blood supplying the dialyser.
Primary and secondary pulmonary hypertension
Epoprostenol is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Sterile technique must be adhered to in preparing the drug and in the care of the catheter. Even brief interruptions in the delivery may result in rapid symptomatic deterioration.
Contraindications
Breastfeeding
Chronic use if pulmonary oedema develops during dose-ranging
Pulmonary hypertension secondary to venous occlusive disorder
Severe left ventricular failure
Precautions and Warnings
Children under 18 years
Elderly
Haemorrhagic diathesis
Restricted sodium intake
Ischaemic heart disease
Pregnancy
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Not all presentations are licensed for all indications
Avoid abrupt withdrawal & large reductions in infusion rates
Dilute and use as an infusion
Do not use if solution is discoloured or particulates are apparent
If extravasation occurs follow local policy & seek expert help immediately
Incompatible with polyethylene terephthalate
Incompatible with polyethylene terephthalate glycol
Resuscitation facilities must be immediately available
Treatment to be administered under the supervision of a specialist
Monitor heart rate and blood pressure regularly
Reduce dose or discontinue if excessive hypotension occurs
Consider veno-occlusive disease if pulmonary oedema occurs
Discontinue if pulmonary oedema occurs
Not licensed for all indications in all age groups
Advise patient not to take NSAIDs unless advised by clinician
Blood pressure and heart rate should be monitored during administration. Tachycardia, bradycardia and hypotension may occur during infusion. These cardiovascular effects disappear within 30 minutes of the end of administration. The effect on heart rate may be masked by concomitant use of drugs which affect cardiovascular reflexes.
Renal dialysis:
The hypotensive effect of epoprostenol may be enhanced by the use of acetate buffer in the dialysis bath during renal dialysis.
Epoprostenol is not a conventional anticoagulant and although it has been successfully used instead of heparin in renal dialysis, in a small proportion of dialyses clotting has developed in the dialysis circuit, requiring termination of dialysis.
Primary and secondary pulmonary hypertension:
Short-term dose-ranging must be performed in a hospital setting with adequate personnel and equipment for haemodynamic monitoring and emergency care.
The decision to receive epoprostenol for primary and secondary pulmonary hypertension should be based upon the understanding that there is a high likelihood that therapy will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent intravenous catheter and infusion pump should be carefully considered.
Pregnancy and Lactation
Pregnancy
Epoprostenol should be used with caution in pregnancy.
The manufacturer advises epoprostenol may be used during pregnancy, despite the known risk of pulmonary arterial hypertension during pregnancy. At the time of writing there is limited published information regarding the use of epoprostenol during pregnancy. Potential risks are unknown.
Lactation
Epoprostenol is contraindicated during breastfeeding.
Use of epoprostenol when breastfeeding is contraindicated by the manufacturer. The presence of epoprostenol in human breast milk and the effects on exposed infants are unknown.
Side Effects
Abdominal discomfort
Agitation
Anxiety
Arthralgia
Ascites
Bleeding (surgical site)
Bradycardia
Chest pain
Chest tightness
Colic
Diarrhoea
Dry mouth
Epistaxis
Facial flushing
Gastro-intestinal haemorrhage
Headache
High output cardiac failure
Hyperglycaemia
Hyperthyroidism
Hypotension
Intracranial bleeding
Jaw pain
Lassitude
Local infection
Local pain (injection site)
Local reaction at injection site
Nausea
Nervousness
Orthostatic hypotension
Pain
Pallor
Pulmonary haemorrhage
Pulmonary oedema
Rash
Reduced platelet count
Retroperitoneal bleeding
Sepsis
Septicaemia
Splenomegaly
Sweating
Tachycardia
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2019
Reference Sources
Summary of Product Characteristics: Epoprostenol 0.5mg powder and solvent for solution for infusion. Advanz Pharma. Revised April 2018.
Summary of Product Characteristics: Epoprostenol 1.5mg powder and solvent for solution for infusion. Advanz Pharma. Revised April 2018.
Summary of Product Characteristics: Flolan 0.5mg powder and solvent for solution for infusion (with pH 12 solvent). GlaxoSmithKline UK. Revised September 2018.
Summary of Product Characteristics: Flolan 1.5mg powder and solvent for solution for infusion (with pH 12 solvent). GlaxoSmithKline UK. Revised September 2018.
Summary of Product Characteristics: Veletri 0.5mg, powder for solution for infusion. Actelion Pharmaceuticals UK Ltd. Revised April 2018.
Summary of Product Characteristics: Veletri 1.5mg, powder for solution for infusion. Actelion Pharmaceuticals UK Ltd. Revised April 2018.
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 04 September 2019
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