Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Epoprostenol sodium may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
for
What Flolan is Flolan contains the active substance epoprostenol which belongs to a group of medicines called prostaglandin, which stops blood from clotting and widens the blood vessels. What Flolan is used for •
Flolan is used to treat a lung condition called 'pulmonary arterial hypertension'. This is where the pressure is high in the blood vessels in the lungs. Flolan widens the blood vessels to lower the blood pressure in the lungs.
•
Flolan is used to prevent blood clotting during kidney dialysis in emergency situations when heparin cannot be used.
2.
e Flolan
Do not use Flolan • • •
if you are allergic to Flolan or any of the other ingredients of this medicine (listed in section 6). if you have heart failure. if you start to develop a build-up of fluid in your lungs causing breathlessness after starting this treatment.
If you think any of these apply to you, don't use Flolan until you have checked with your doctor.
1
Warnings and precautions Talk to your doctor before using Flolan:
2
Driving and using machines Your treatment may have an effect on the ability to drive or use machinery. Don't drive or use machines unless you're feeling well. Flolan contains Sodium (main component of cooking/table salt) This medicinal product contains sodium. To be taken into consideration by patients on a controlled sodium diet. Reconstituted concentrate solution: This medicinal product contains 73 mg of sodium (main component of cooking/table salt) in each vial of concentrated solution. This is equivalent to 4 % of the recommended maximum daily dietary intake of sodium for an adult. Powder for solution for infusion: This medicinal product contains 3 mg of sodium (main component of cooking/table salt) in each vial of powder for solution. This is equivalent to 0.2 % of the recommended maximum daily dietary intake of sodium for an adult. Solvent for parenteral use: This medicinal product contains 70 mg of sodium (main component of cooking/table salt) in each vial of solvent. This is equivalent to 4 % of the recommended maximum daily dietary intake of sodium for an adult. 3.
Flolan
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Your doctor will decide how much Flolan is right for you. The amount you are given is based on your body weight, and your type of illness. Your dose may be increased or decreased depending on how well you respond to treatment. Flolan is given by slow infusion (drip) into a vein. Pulmonary arterial hypertension Your first treatment will be given to you in a hospital. This is because your doctor needs to monitor you and find the best dose for you. You will start with an infusion of Flolan. The dose will be increased, until your symptoms are relieved, and any side effects are manageable. Once the best dose has been found, a permanent tube (line) will be fitted into one of your veins. You can then be treated using an infusion pump. Kidney dialysis You will be given an infusion of Flolan for the duration of your dialysis. Using Flolan at home (only for treatment of Pulmonary Arterial Hypertension) If you are treating yourself at home, your doctor or nurse will show you how to prepare and use Flolan. They will also advise you how to stop treatment if necessary. Stopping Flolan must be done gradually. It is very important that you follow all their instructions carefully. Flolan comes as a powder in a glass vial. Before use, the powder needs to be dissolved in the liquid provided. The liquid does not contain a preservative. If you have any of the liquid left over, it must be thrown away. Looking after the injection line If you have been fitted with a 'line' into a vein it is very important to keep this area clean, otherwise you could get an infection. Your doctor or nurse will show you how to clean your 'line' and the area around it. It is very important that you follow all of their instructions carefully. 3
If you use more Flolan than you should Seek urgent medical attention if you think you have used or been given too much Flolan. Symptoms of overdose may include headache, nausea, vomiting, fast heart rate, warmth or tingling, or feeling like you might pass out (feeling faint/dizziness).
If you forget to use Flolan Do not take a double dose to make up for a forgotten dose. If you stop using Flolan Stopping Flolan must be done gradually. If the treatment is stopped too quickly you may get serious side effects, including dizziness, feeling weak and breathing difficulties. If you have problems with the infusion pump or injection line that stops, or prevents treatment with Flolan, contact your doctor, nurse or hospital immediately. If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse.
4.
Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor or nurse immediately, as these may be signs of infection of the blood or low blood pressure or serious bleeding:
•
pain at the injection site
Common side effects that may show up in blood tests
Reporting of side effects If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
5.
Flolan
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label. Do not store above 25 C. Store Flolan in a dry place. Store in the original outer carton, to protect from light. Do not freeze.
5
Pulmonary arterial hypertension For solutions ≤ 150 000 ng/mL: Freshly prepared Flolan solution (either as a concentrated solution or a further diluted solution) can be administered immediately or stored for a maximum of 8 days at refrigerated conditions (2 to 8 °C), in the medication cassette and used within a maximum time of: •
48 hours at up to 25 °C or
•
36 hours at up to 30 oC or
•
24 hours at up to 35 oC or
•
12 hours at up to 40 oC
For solutions >150 000 ng/mL and ≤300 000 ng/mL: Reconstituted solutions that have been stored at 2 to 8 °C for up to 7 days can be administered for up to 24 hours at 25 °C. Freshly prepared reconstituted solutions, or solutions that have been stored at 2 to 8 °C for no longer than 5 days can be administered for up to:
Once Flolan has been dissolved and diluted, any unused solution can be stored at 25 °C and used within 12 hours. 6.
What Flolan contains The active substance is epoprostenol sodium. Flolan Injection comes in different strengths. Each vial contains either:
The other ingredients are Mannitol, Glycine, Sodium Chloride, Sodium Hydroxide and Water.
6
What Flolan looks like and contents of the pack Injection: Flolan is a solution for injection made up of powder and solution. The powder is white or off-white and the solution is clear and colourless. There are six packs of Flolan available for use in the treatment of pulmonary arterial hypertension, the contents of each pack include:
0800 198 5000 (UK Only) Please be ready to give the following information: Product name Reference number
Flolan 0.5 mg and 1.5 mg injection 10949/0310
This is a service provided by the Royal National Institute of Blind People. This leaflet was last revised in October 2023. Trade marks are owned by or licensed to the GSK group of companies. © 2023 GSK group of companies or its licensor. <GSK>
<—————————————————————————————————————————-The following information is intended for medical or healthcare professionals only: Flolan 0.5 mg powder and solvent for solution for infusion Flolan 1.5 mg powder and solvent for solution for infusion epoprostenol DOSAGE AND ADMINISTRATION INFORMATION ONLY 7
Please refer to the Summary of Product Characteristics for complete prescribing information INFORMATION FOR HEALTHCARE PROFESSIONALS Pulmonary arterial hypertension There are six packs available for use in the treatment of pulmonary arterial hypertension, as follows:
Modified Acrylic Acrylonitrile butadiene styrene (ABS) Cyclic olefin polymer Polyamide Polyethersulfone Polyethylene Polyisoprene Polyolefin Polypropylene Polytetrafluoroethylene (PTFE) Polyurethane Polyvinyl chloride (PVC) (plasticised with bis(2-ethylhexyl) phthalate [DEHP]) Polyvinylidene fluoride (PVDF) Silicone
• • •
Suitable ambulatory pumps to be used include: CADD-Legacy 1 CADD-Legacy PLUS CADD-Solis VIP (variable infusion profile) Manufactured by Smiths Medical.
• •
Pump accessories found to be compatible include: CADD disposable Medication Cassette Reservoir 50 mL and 100 mL from Smiths Medical. CADD extension set with in-line 0.2 micron filter (CADD extension set with male luer, 0.2- micron aireliminating filter, clamp, and integral anti-siphon valve with male luer) from Smiths Medical. The extension set and the in-line filter must be changed at least every 48 hours. 8
Reconstitution: 1. Use only the solvent provided for reconstitution. 2. Withdraw approximately 10 mL of the solvent into a sterile syringe, through a vial adaptor*. 3. Remove syringe from vial adaptor. Attach needle to syringe, inject the 10 mL of solvent into the vial containing Flolan powder and shake gently until the powder has dissolved. 4. Draw up the resulting Flolan solution into the syringe, remove the needle, re-inject it into the remaining volume of the solvent through the vial adaptor* and mix thoroughly. *Alternatively, a needle may be used in place of a vial adaptor. This solution is now referred to as the concentrated solution and contains either 10 000 (for the 0.5 mg strength) or 30 000 nanogram per mL Flolan (for the 1.5 mg strength). Only concentrated solutions are suitable for further dilution prior to use. Use a new vial adaptor for each additional sterile diluent vial required. When 0.5 mg or 1.5 mg Flolan powder is reconstituted with 50 mL of the solvent, the final injection has a pH of approximately 12 and a sodium ion content of approximately 73 mg. Dilution: Flolan may be used either as concentrated solution or in a diluted form for the treatment of pulmonary arterial hypertension. Only concentrated solutions are suitable for further dilution with the sterile solvent prior to use. Only the solvent provided may be used for the further dilution of reconstituted Flolan, using a new vial adaptor for each additional sterile solvent vial required.
Sodium chloride 0.9 % w/v solution must not be used when Flolan is to be used for the treatment of pulmonary arterial hypertension as the required pH is not maintained. Flolan solutions are less stable at low pH. Epoprostenol must not be administered with other parenteral solutions or medications when used for pulmonary arterial hypertension. The final solution to be administered to the patient must be filtered using a 0.22 or 0.20 micron filter. Use of an in-line filter as part of the infusion set during administration is preferable. Alternatively, where in-line filtration is not possible, the final solution (either a concentrated or further diluted solution) must be filtered with the provided sterile 0.22 micron filter prior to storage in the medication cassette using firm but not excessive pressure; the typical time taken for filtration of 50 mL of solution is 70 seconds. If an in-line filter has been used during administration, then the in-line filter should be discarded when the infusion set is exchanged. If instead a syringe filter has been used during preparation, the syringe filter unit must be used only during preparation and then discarded.
Concentrations commonly used in the treatment of pulmonary arterial hypertension are as follows: • 5 000 nanogram/mL – One vial containing 0.5 mg Flolan reconstituted and diluted to a total volume of 100 mL in solvent. •
10 000 nanogram/mL – Two vials containing 0.5 mg Flolan reconstituted and diluted to a total volume of 100 mL in solvent.
•
15 000 nanogram/mL – One vial containing 1.5 mg Flolan reconstituted and diluted to a total volume of 100 mL in solvent. 9
•
30 000 nanogram/mL – Two vials containing 1.5 mg Flolan reconstituted and diluted to a total volume of 100 mL in solvent.
Calculation of infusion rate: The infusion rate may be calculated from the following formula: Infusion rate (mL/min)
=
dosage (nanogram/kg/min) x bodyweight (kg) concentration of solution (nanogram/mL)
Infusion rate (mL/h) = Infusion rate (mL/min) x 60 Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of Flolan. Special precautions for storage Don't store above 25 °C. Keep container in the outer carton to protect from light. Keep dry. Do not freeze. For additional details of stability following reconstitution, see section 5 ('How to store Flolan'). The solvent contains no preservative; consequently a vial should be used once only and then discarded. Renal Dialysis There is only one pack available for use in renal dialysis: • One 0.5 mg powder vial and one solvent vial, one vial adaptor and a filter unit Flolan prepared with sterile diluent (pH 12) must not be used with any preparation or administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG). Based on available data from inhouse testing and published literature, preparation and administration materials likely to be compatible include: • • • • • • • • • • • • • •
Modified Acrylic Acrylonitrile butadiene styrene (ABS) Cyclic olefin polymer Polyamide Polyethersulfone Polyethylene Polyisoprene Polyolefin Polypropylene Polytetrafluoroethylene (PTFE) Polyurethane Polyvinyl chloride (PVC) (plasticised with bis(2-ethylhexyl) phthalate [DEHP]) Polyvinylidene fluoride (PVDF) Silicone
10
Reconstitution: 1. Use only the solvent provided for reconstitution 2. Withdraw approximately 10 mL of the solvent into a sterile syringe, through a vial adaptor*. 3. Remove syringe from vial adaptor. Attach needle to syringe, inject the 10 mL of solvent into the vial containing 0.5 mg freeze-dried Flolan powder and shake gently until the powder has dissolved 4. Draw up the resulting Flolan solution into the syringe, remove the needle, re-inject it into the remaining volume of the solvent through the vial adaptor* and mix thoroughly. *Alternatively, a needle may be used in place of a vial adaptor. This solution is now referred to as the concentrated solution and contains 10 000 nanogram per mL Flolan. Only this concentrated solution is suitable for further dilution prior to use. When 0.5 mg Flolan powder is reconstituted with 50 mL of the solvent, the final injection has a pH of approximately 12 and a sodium ion content of approximately 73 mg. Dilution: The concentrated solution is normally further diluted immediately prior to use. It may be diluted with sodium chloride 0.9 % w/v (saline) solution, in a ratio of 2.3 volumes of saline to 1 volume of concentrated solution, e.g. 50 mL of concentrated solution further diluted with 117 mL of saline. Other common intravenous fluids are unsatisfactory for the dilution of the concentrated solution as the required pH is not maintained. Flolan solutions are less stable at low pH. To dilute the concentrated solution, draw it up into a larger syringe and dispense the concentrated solution directly into the chosen infusion solution. Mix well. The final infusion solution (either as a concentrated solution or a further diluted solution) should be transferred into a suitable container or delivery system prior to administration. A 0.22-micron sterile syringe filter must be used during transfer using firm but not excessive pressure; the typical time taken to for filtration of 50 mL of solution is 70 seconds. The syringe filter unit must be used only during preparation and then discarded. When reconstituted and diluted as directed above, Flolan infusion solutions will retain 90 % of their initial potency for approximately 12 hours at 25 °C. Calculation of infusion rate: The infusion rate may be calculated from the following formula: Infusion rate (mL/min)
=
dosage (nanogram/kg/min) x bodyweight (kg) concentration of solution (nanogram/mL)
Infusion rate (mL/h) = Infusion rate (mL/min) x 60 For administration using a pump capable of delivering small volume constant infusions, suitable aliquots of concentrated solution may be diluted with sterile sodium chloride 0.9 % w/v solution. This leaflet was last revised in October 2023. Trade marks are owned by or licensed to the GSK group of companies. © 2023 GSK group of companies or its licensor. (GSK)
11
INSTRUCTIONS FOR USE [GSK logo]
Flolan Solution Instructions for use with a vial adaptor and ambulatory infusion pumps Please read these instructions before you start to prepare your Flolan solution, if you have any questions or concerns contact your Health Care Provider.
12
Solvent vial
Vented vial adaptor
Flolan Powder vial
Syringe filter
Your pack will contain the following:
13
Preparation 1. Remove solvent vial cap Use only the solvent provided for reconstitution.
2. Peel open vial adaptor packaging
3. Attach vial adaptor
14
4. Attach syringe without needle
NO needle
5. Draw up solvent
6. Unscrew syringe
15
Making Flolan solution 7. Attach needle
8. Inject solvent into Flolan powder vial
9. Gently mix the solution
16
10. Draw up prepared solution
11. Inject solution into solvent
Cassette preparation
17
*Orange steps are optional: only when required
*Attach syringe filter Note: An in-line filter should be provided as part of your extension set (refer to Step 15). If an in-line filter is not provided as part of your extension set, then the provided syringe filter must be used to filter the solution during preparation of the cassette.
13. Filling cassette
*Diluting solution Note: If your dose needs to be diluted, prepare additional solvent solution for injection by repeating steps 1 to 6 and 13.
18
Follow the below instructions instead of step 5 for the volume of solvent to draw up.
15. Ambulatory pump
Disposal Discard used supplies 19
Storage (Solutions with a concentration less than or equal to 150 000 ng/mL) Storing the prepared solution
‒ For up to 48 hours at up to 25 °C ‒ For up to 36 hours at up to 30 °C ‒ For up to 24 hours at up to 35 °C ‒ For up to 12 hours at up to 40 °C
20
Flolan 0.5 mg Powder and Solvent for Solution for Infusion (with pH 12 solvent & Vented Vial Adaptor) comes as infusion containing 0.5mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Flolan 0.5 mg Powder and Solvent for Solution for Infusion (with pH 12 solvent & Vented Vial Adaptor) is epoprostenol sodium.
Medicines with the same active substance, strength and form include: Veletri 0.5mg; Powder for Solution for Infusion, Epoprostenol 0.5 mg powder for solution for infusion. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Flolan 0.5 mg Powder and Solvent for Solution for Infusion (with pH 12 solvent & Vented Vial Adaptor), as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Flolan is indicated for:
Pulmonary Arterial Hypertension
Flolan is indicated for the treatment of pulmonary arterial hypertension (PAH) (idiopathic or heritable PAH and PAH associated with connective tissue diseases) in patients with WHO Functional Class III-IV symptoms to improve exercise capacity (see section 5.1).
Renal Dialysis
Flolan is indicated for use in haemodialysis in emergency situations when use of heparin carries a high risk of causing or exacerbating bleeding or when heparin is otherwise contraindicated (see section 5.1).
Posology
Pulmonary Arterial Hypertension
Epoprostenol is only indicated for continuous infusion by intravenous route.
Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.
Short-term (acute) dose ranging:
This procedure should be conducted in a hospital with adequate resuscitation equipment.
A short-term dose-ranging procedure administered via either a peripheral or central venous line is required to determine the long-term infusion rate. The infusion rate is initiated at 2 nanograms/kg/min and increased by increments of 2 nanograms/kg/min every 15 min or longer until maximum haemodynamic benefit or dose-limiting pharmacological effects are elicited.
If the initial infusion rate of 2 nanograms/kg/min is not tolerated, a lower dose which is tolerated by the patient should be identified.
Long-term continuous infusion:
Long-term continuous infusion of Flolan should be administered through a central venous catheter. Temporary peripheral i.v. infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanograms/kg/min less than the maximum tolerated infusion rate determined during short-term dose-ranging. If the maximum tolerated infusion rate is 5 nanograms/kg/min or less, then the long-term infusion should be started at 1 nanograms/kg/min.
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 or the occurrence of adverse reaction due to excessive doses of Flolan.
In general, the need for increases in dose from the initial long-term dose should be expected over time. Increases in dose should be considered if symptoms of pulmonary arterial hypertension persist, or recur after improving. The infusion rate should be increased by 1 to 2 nanograms/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be of at least 15 min. Following establishment of a new infusion rate, the patient should be observed, and erect 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 reactions may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2 nanograms/kg/min decrements every 15 min or longer until the dose-limiting effects resolve. Abrupt withdrawal of Flolan or sudden large reductions in infusion rates should be avoided due to the risk of potential fatal rebound effect (see section 4.4). Except in life-threatening situations (e.g., unconsciousness, collapse, etc) infusion rates of Flolan should be adjusted only under the direction of a physician.
Renal Dialysis
Flolan is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.
The following schedule of infusion has been found effective in adults:
Prior to dialysis: 4 nanograms/kg/min intravenously for 15 mins
During dialysis: 4 nanograms/kg/min into the arterial inlet of the dialyser
The infusion should be stopped at the end of dialysis.
The recommended dose for renal dialysis should be exceeded only with careful monitoring of patient blood pressure.
Elderly
There is no specific information on the use of Flolan in patients over 65 years for renal dialysis or pulmonary arterial hypertension. In general, dose selection for an elderly patient should be made carefully, reflecting the greater frequency of decreased hepatic, renal (in the case of pulmonary arterial hypertension) or cardiac function and of concomitant disease or other medicine therapy.
Paediatric population
The safety and efficacy of epoprostenol in children younger than 18 years have not yet been established.
Method of administration
Precautions to be taken before handling or administering the medicinal product
Pulmonary Arterial Hypertension
Freshly prepared solutions for infusion (either as a concentrated solution or a further diluted solution) can be administered immediately or stored for up to 8 days at 2 °C to 8 °C prior to administration. Following this preparation or storage, the solution for infusion should be used within 48 hours at up to 25 °C, or 36 hours at up to 30 °C, or 24 hours at up to 35 °C, or 12 hours at up to 40 °C (see section 6.3).
Renal Dialysis
Freshly prepared solutions for infusion (either as a concentrated solution or a further diluted solution) can be administered for up to 12 hours at up to 25 °C.
Epoprostenol solution prepared with solvent (pH 11.7-12.3), must not be used with any preparation or administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG; see section 6.2 and 6.6).
The reconstituted solution should be examined prior to administration. Its use is forbidden in the presence of a discoloration or particles.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
Epoprostenol must not be administered as a bolus injection.
Flolan is contraindicated in patients:
• with known hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
• with congestive heart failure arising from severe left ventricular dysfunction.
• Flolan must not be used chronically in patients who develop pulmonary oedema during dose-ranging.
Because of the high pH of the final infusion solutions, care should be taken to avoid extravasation during their administration and consequent risk of tissue damage.
Flolan is a potent pulmonary and systemic vasodilator. The cardiovascular effects during infusion disappear within 30 min of the end of administration.
Flolan is a potent inhibitor of platelet aggregation, therefore, an increased risk for haemorrhagic complications should be considered, particularly for patients with other risk factors for bleeding (see section 4.5).
If excessive hypotension occurs during administration of Flolan, the dose should be reduced or the infusion discontinued. Hypotension may be profound in overdose and may result in loss of consciousness (see section 4.9).
Blood pressure and heart rate should be monitored during administration of Flolan.
Flolan may either decrease or increase heart rate. The change is thought to depend on both the basal heart rate and the concentration of Flolan administered.
The effects of Flolan on heart rate may be masked by concomitant use of drugs which affect cardiovascular reflexes.
Extreme caution is advised in patients with coronary artery disease.
Elevated serum glucose levels have been reported (see section 4.8).
The solvent contains no preservative; consequently a vial should be used once only and then discarded.
Sodium content
This medicinal product contains sodium, which should be taken into consideration by patients on a controlled sodium diet.
The amount of sodium present in the reconstituted concentrate solution equals 73 mg approximately, equivalent to approximately 4 % of the WHO recommended maximum daily dietary intake of 2 g of sodium for an adult.
The amount of sodium present in the powder for solution for infusion equals 3 mg approximately per vial, equivalent to approximately 0.2 % of the WHO recommended maximum daily dietary intake of 2 g of sodium for an adult.
The amount of sodium present in the solvent for parenteral use equals 70 mg approximately per vial, equivalent to approximately 4 % of the WHO recommended maximum daily dietary intake of 2 g of sodium for an adult.
Pulmonary Arterial Hypertension
Some patients with pulmonary arterial hypertension have developed pulmonary oedema during dose-ranging, which may be associated with pulmonary veno-occlusive disease. Flolan must not be used chronically in patients who develop pulmonary oedema during dose initiation (see section 4.3).
Abrupt withdrawal or interruption of infusion must be avoided, except in life-threatening situations. An abrupt interruption of therapy can induce a rebound of pulmonary arterial hypertension resulting in dizziness, asthenia, increased dyspnoea, and may lead to death (see section 4.2).
Flolan is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Thus, therapy with Flolan requires commitment by the patient to sterile drug reconstitution, drug administration, care of the permanent central venous catheter, and access to intense and ongoing patient education.
Sterile technique must be adhered to in preparing the drug and in the care of the catheter. Even brief interruptions in the delivery of Flolan may result in rapid symptomatic deterioration. The decision to administer Flolan for pulmonary arterial hypertension should be based upon the patients understanding that there is a high likelihood that therapy with Flolan will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent i.v. catheter and infusion pump should be carefully considered.
Renal Dialysis
The hypotensive effect of Flolan may be enhanced by the use of acetate buffer in the dialysis bath during renal dialysis.
During renal dialysis with Flolan it should be ensured that the cardiac output increases more than minimally so that delivery of oxygen to peripheral tissue is not diminished.
Flolan is not a conventional anticoagulant. Flolan has been successfully used instead of heparin in renal dialysis but in a small proportion of dialyses clotting has developed in the dialysis circuit, requiring termination of dialysis. When Flolan is used alone, measurements such as activated whole blood clotting time may not be reliable.
When Flolan is administered to patients receiving concomitant anticoagulants standard anticoagulant monitoring is advisable.
The vasodilator effects of Flolan may augment or be augmented by concomitant use of other vasodilators.
As reported with other prostaglandin analogues, Flolan may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA.
When NSAIDS or other drugs affecting platelet aggregation are used concomitantly, there is the potential for Flolan to increase the risk of bleeding.
Patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with Flolan, which although transient, may be clinically significant in patients prone to digoxin toxicity.
Pregnancy
There is a limited amount of data from the use of epoprostenol in pregnant women.
Animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Given the absence of alternative medicines, epoprostenol can be used in those women who choose to continue their pregnancy, despite the known risk of pulmonary arterial hypertension during pregnancy.
Breast-feeding
It is unknown if epoprostenol or its metabolites are excreted in human milk. A risk to the breastfeeding child cannot be excluded. Breast-feeding should be discontinued during treatment with Flolan.
Fertility
There are no data on the effects of epoprostenol on fertility in humans. Reproductive studies in animals have shown no effects on fertility (see section 5.3).
Pulmonary arterial hypertension and its therapeutic management may affect the ability to drive and operate machinery.
There are no data regarding the effect of Flolan used in renal dialysis on the ability to drive or operate machinery.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as follows: very common ≥1/10 (≥10%); common ≥1/100 and <1/10 (≥1% and <10%); uncommon ≥1/1 000 and <1/100 (≥0.1% and <1%); rare ≥1/10 000 and <1/1 000 ( ≥0.01% and <0.1%); very rare <1/10 000 (< 0.01%) and not known (cannot be estimated from the available data).
Infections and Infestations
Common
Sepsis, septicaemia (mostly related to delivery system for Flolan)1
Blood and Lymphatic System Disorders
Common
Decreased platelet count, bleeding at various sites (e.g. pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal)
Unknown
Splenomegaly, Hypersplenism
Endocrine Disorders
Very rare
Hyperthyroidism
Psychiatric Disorders
Common
Anxiety, nervousness
Very rare
Agitation
Nervous System Disorders
Very common
Headache
Cardiac Disorders
Common
Tachycardia2, bradycardia3,
Not known
High output cardiac failure
Vascular Disorders
Very common
Facial flushing (seen even in the anaesthetised patient)
Common
Hypotension
Very rare
Pallor
Not known
Ascites
Respiratory, thoracic and mediastinal disorders
Unknown
Pulmonary oedema
Gastrointestinal Disorders
Very common
Nausea, vomiting, diarrhoea
Common
Abdominal colic, sometimes reported as abdominal discomfort
Uncommon
Dry mouth
Skin and Subcutaneous Tissue Disorders
Common
Rash
Uncommon
Sweating
Musculoskeletal and Connective Tissue Disorders
Very common
Jaw pain
Common
Arthralgia
General Disorders and Administration Site Conditions
Very common
Pain (unspecified)
Common
Pain at the injection site*, chest pain
Rare
Local infection*
Very rare
Erythema over the infusion site*, occlusion of the long i.v. catheter*, lassitude, chest tightness
Investigations
Unknown
Blood glucose increased
* Associated with the delivery system for Flolan
1 Catheter-related infections caused by organisms not always considered pathogenic (including micrococcus) have been reported.
2 Tachycardia has been reported as a response to Flolan at doses of 5 nanograms/kg/min and below.
3 Bradycardia, sometimes accompanied by orthostatic hypotension, has occurred in healthy volunteers at doses of Flolan greater than 5 nanograms/kg/min. Bradycardia associated with a considerable fall in systolic and diastolic blood pressure has followed i.v. administration of a dose of Flolan equivalent to 30 nanograms/kg/min in healthy conscious volunteers.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
The main feature of overdose is likely to be hypotension.
In general, events seen after overdose of Flolan represent exaggerated pharmacological effects of the drug (e.g., hypotension and complications of hypotension).
If overdose occurs reduce the dose or discontinue the infusion and initiate appropriate supportive measures as necessary; for example, plasma volume expansion and/or adjustment to pump flow.
Ask anything about Flolan 0.5 mg Powder and Solvent for Solution for Infusion (with pH 12 solvent & Vented Vial Adaptor). The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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