Flolan

Package leaflet: Information for the user

Flolan 0.5 mg powder and solvent for solution for infusion, 1.5 mg powder and solvent for solution for infusion, 0.5 mg powder for solution for infusion

epoprostenol
Please read all of this leaflet carefully before you start using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Flolan is and what it is used for
2. What you need to know before using Flolan
3. How to use Flolan
4. Possible side effects
5. How to store Flolan
6. Contents of the pack and other information

1. What Flolan is and what it is used for

What Flolan is
Flolan contains the active substance epoprostenol, which belongs to a group of medicines called
prostaglandins. These medicines work by preventing blood from clotting and by widening blood vessels.
What Flolan is used for

• Flolan is used to treat a condition called "pulmonary arterial hypertension". This occurs when there is increased pressure in the blood vessels of the lungs.
• Flolan is used to prevent blood from clotting during emergency renal dialysis when heparin cannot be used.

2. What you need to know before using Flolan

Do not use Flolan

• If you are allergic to Flolan or to any of the other ingredients of this medicine (listed in section 6),
• if you have had a heart attack,
• if, after starting this treatment, fluid accumulation in your lungs has begun to develop, causing shortness of breath.

If you think any of these situations apply to you, do not use Flolan until you have checked with your
doctor.
Warnings and precautions
Talk to your doctor before using Flolan:

• if you have had any bleeding problems,
• if you are on a diet with controlled sodium intake.

Tissue damage at the injection site
Flolan is injected into a vein. It is important that this medicine does not leak out of the vein into the
surrounding tissues. If this happens, the skin may become damaged.
Symptoms of this include:

• tenderness
• burning
• sensation like pinpricks
• sweating
• redness.

This may be followed by the appearance of blisters and skin peeling. During treatment with
Flolan, it is important to monitor the injection site.
Contact the hospital immediately for medical advice if the area becomes irritated, painful or swollen, or
if you notice blisters or skin peeling.
Effect of Flolan on blood pressure and heart rate
Flolan may cause your heartbeat to speed up or slow down. Your blood pressure may also
become too low. During treatment with Flolan, your heart rate and blood pressure should
be monitored. Symptoms of low blood pressure include dizziness and fatigue.
Inform your doctor if you experience these symptoms. It may be necessary to reduce your prescribed
dose or stop the infusion.
Other medicines and Flolan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any
other medicines.
Some medicines may interfere with how Flolan works, or may increase the likelihood of
side effects. Flolan may also interfere with the action of other medicines if taken
concurrently.
These medicines include:

• medicines used to treat high blood pressure
• medicines used to prevent the formation of blood clots
• medicines used to dissolve blood clots
• medicines used to treat inflammation or pain (also called “NSAIDs”)
• digoxin (used to treat heart disease). Inform your doctor or pharmacist if you are taking any of these medicines.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding,
please consult your doctor or pharmacist before using this medicine, as your symptoms may
worsen during pregnancy.
It is not known whether the components of Flolan pass into breast milk. Breastfeeding must be discontinued
during treatment with Flolan.
Driving and using machines
This treatment may affect your ability to drive or operate machinery.
Do not drive or operate machinery unless you feel well.
Flolan contains sodium (the main component of table/cooking salt).
This medicine contains sodium. This should be taken into account by patients who are on a
diet with controlled sodium intake.
Reconstituted concentrate solution: This medicine contains 73 mg of sodium (main component of
table/cooking salt) in each vial of concentrated solution. This corresponds to 4% of the
maximum recommended daily dietary intake of sodium for an adult.
Powder for infusion solution: This medicine contains 3 mg of sodium (main component of
table/cooking salt) in each vial of powder for solution. This corresponds to approximately 0.2%
of the maximum recommended daily dietary intake of sodium for an adult.
Solvent for parenteral use: This medicine contains 70 mg of sodium (main component of table
salt) in each vial of solvent. This corresponds to 4% of the maximum recommended daily
dietary intake of sodium for an adult.

3. How to use Flolan

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate amount of Flolan for you. The dose administered is based on body weight and the type of disease. The dose may be increased or decreased depending on your response to treatment.
Flolan is administered as a slow intravenous infusion (by drip).

Pulmonary arterial hypertension
Initial treatment will be given in hospital. This is because your doctor needs to monitor you and determine the appropriate dose.
You will start with an infusion of Flolan. The dose will be gradually increased until symptoms are relieved and any side effects become manageable. Once the optimal dose has been identified, a permanent intravenous line (catheter) will be inserted. Treatment can then be continued using an infusion pump.

Renal dialysis
Flolan is administered by infusion during dialysis.

Use of Flolan at home (only for the treatment of Pulmonary Arterial Hypertension)
If treatment is to be continued at home, your doctor or nurse will show you how to prepare and use Flolan. They will also advise you on how to stop treatment if necessary. It is very important to follow their instructions carefully.
Flolan comes as a powder in a glass vial. Before use, the powder must be dissolved in the liquid provided. The liquid does not contain preservatives. Any unused liquid must be discarded.

Care of the infusion line
If an intravenous line has been inserted, it is very important to keep the area clean, otherwise infection may occur. Your doctor or nurse will show you how to clean the line and the surrounding area. It is very important to follow their instructions carefully.

If you use more Flolan than you should
Contact your doctor immediately if you think you or someone else has used or been given too much Flolan. Symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, warmth or tingling, or feeling faint (fatigue/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 treatment must be done gradually. If treatment is stopped too quickly, serious side effects may occur, including dizziness, feeling weak, and difficulty breathing. If you experience any problems with the infusion pump or the infusion line that interrupt or prevent Flolan treatment, contact your doctor, nurse, or hospital immediately.

If you have any questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediately if you experience any of the following, as they could be signs of a blood infection, low blood pressure, or severe bleeding:

• if you feel your heart beating too fast, or have chest pain or shortness of breath
• if you feel dizzy or weak, especially when standing up
• if you have fever or chills
• if you have more frequent or longer bleeding episodes.

If you get any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.

Very common side effects
May affect more than 1 in 10 people:

• headache
• jaw pain
• pain
• vomiting
• nausea
• diarrhoea
• facial flushing (hot flushes)

Common side effects
May affect up to 1 in 10 people:

• blood infection (septicaemia)
• increased heart rate
• slowed heart rate
• low blood pressure
• bleeding at various sites, for example from the nose or gums, and easier bruising than normal
• stomach discomfort or pain
• chest pain
• joint pain
• feeling anxious, feeling nervous
• rash
• pain at injection site.

Side effects that may be seen in blood tests:

• decrease in blood cell count (cells that help blood to clot).

Uncommon side effects
May affect up to 1 in 100 people:

• sweating
• dry mouth.

Rare side effects
May affect up to 1 in 1,000 people:

• infection at injection site.

Very rare side effects
May affect up to 1 in 10,000 people:

• chest tightness
• feeling tired, weak
• feeling restless
• pale skin
• redness at injection site
• overactive thyroid
• catheter blockage.

Other side effects
Frequency unknown (cannot be estimated from the available data):

• enlarged or overactive spleen
• fluid buildup in the lungs (pulmonary edema)
• increased blood sugar (glucose)
• swelling due to fluid accumulation around the stomach
• excessive pumping of blood from the heart leading to breathlessness, tiredness, fatigue, swelling of the legs and abdomen due to fluid retention, and persistent cough.

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor, nurse, or pharmacist. You can also report side effects directly via avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Flolan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label.
Do not store above 25°C.
Store Flolan in a dry place.
Keep in the original packaging.
Do not freeze.

Pulmonary arterial hypertension
For solutions ≤150,000 ng/mL:
The freshly prepared Flolan solution (either as a concentrated solution or subsequently diluted solution) may be administered immediately or stored for up to 8 days under 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°C, or
• 24 hours at up to 35°C, or
• 12 hours at up to 40°C.

For solutions >150,000 and ≤300,000 ng/mL:
Reconstituted solutions must be stored at a temperature between 2 and 8°C for up to 7 days and may be administered for up to 24 hours at 25°C.
Freshly prepared reconstituted solutions, or solutions that have been stored at a temperature between 2 and 8°C for no more than 5 days, may be administered for up to:

• 48 hours at up to 25°C,
• 24 hours at up to 35°C.

After this time, any unused solution must be discarded.

Renal dialysis
Once Flolan has been dissolved and diluted, unused solution may be stored at 25°C and used within 12 hours.

6. Pack contents and other information

What Flolan contains
The active substance is sodium epoprostenol. Injectable Flolan is available in different strengths.
Each vial contains:

• 0.5 mg of sodium epoprostenol or
• 1.5 mg of sodium epoprostenol

See section 2 for further important information on sodium.
The other ingredients (excipients) are mannitol, glycine, sodium chloride, sodium hydroxide and water.

Description of the appearance of Flolan and pack contents
Injection:
Flolan is an injectable solution composed of powder and solvent. The powder is white or almost white, and the solution is clear or colourless.
Flolan is available in 6 pack sizes for use in the treatment of pulmonary arterial hypertension; the contents of each pack include:

• one 0.5 mg powder vial and one solvent vial, one vial adapter and one filter;
• one 0.5 mg powder vial and two solvent vials, two vial adapters and one filter;
• one 1.5 mg powder vial and one solvent vial, one vial adapter and one filter;
• one 1.5 mg powder vial and two solvent vials, two vial adapters and one filter;
• one 0.5 mg powder vial;
• one 1.5 mg powder vial.

There is one Flolan pack available for use in renal dialysis; the pack contents include:

• one 0.5 mg powder vial and one solvent vial, one vial adapter and one filter.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
GlaxoSmithKline Trading Services Limited
12 Riverwalk,
Citywest Business Campus
Dublin 24,
Ireland
D24 YK11
Local representative: GlaxoSmithKline S.p.A. – Viale dell’Agricoltura, 7 – 37135 Verona - Italy

Manufacturer
GlaxoSmithKline Manufacturing S.p.A. – Strada provinciale Asolana, 90 - San Polo di Torrile - Parma

This medicinal product is authorised in the European Economic Area countries under the following names:

For the 0.5 mg strength:
Austria – Flolan 0.5 mg - Trockensubstanz zur Infusionsbereitung mit Lösungsmittel
Belgium – Flolan 0.5 mg powder and solvent for solution for infusion
Czech Republic – Flolan 0.5 mg, powder and solvent for solution for infusion
Denmark – Epoprostenol 500 micrograms
Estonia – Flolan
France – Flolan 0.5 mg, powder and solvent for solution for injection
Ireland – Flolan 500 micrograms Powder and Solvent for Solution for Infusion
Luxembourg – Flolan 0.5 mg powder and solvent for solution for infusion
Malta – Flolan 0.5 mg Injection Powder and solvent for solution for Infusion 0.5mg
Netherlands – Flolan 500 microgram, powder for solution for infusion
Netherlands – Flolan 500 microgram, powder and solvent for solution for infusion
Norway – Flolan
Spain – Flolan
United Kingdom – Flolan 0.5mg Injection

For the 1.5 mg strength:
Austria – Flolan 1.5 mg - Trockensubstanz zur Infusionsbereitung mit Lösungsmittel
Belgium – Flolan 1.5 mg powder and solvent for solution for infusion
Belgium – Flolan 1.5 mg powder for solution for infusion
Czech Republic – Flolan 1.5 mg, powder and solvent for solution for infusion
Denmark – Epoprostenol 1.5 mg
France – Flolan 1.5 mg, powder and solvent for solution for injection
Ireland – Flolan 1.5mg Infusion, powder and solvent for solution for infusion
Luxembourg – Flolan 1.5 mg powder and solvent for solution for infusion
Netherlands – Flolan 1500 microgram, powder and solvent for solution for infusion
Netherlands – Flolan 1500 microgram, powder for solution for infusion
Norway – Flolan
United Kingdom – Flolan 1.5mg Injection

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The following information is intended for healthcare professionals only:

7. INFORMATION FOR HEALTHCARE PROFESSIONALS

Pulmonary arterial hypertension
Six pack sizes are available for use in the treatment of pulmonary arterial hypertension, as follows:

• One vial containing 0.5 mg powder, one vial of solvent, one vial adapter, and one filter.
• One vial containing 0.5 mg powder, two vials of solvent, two vial adapters, and one filter.
• One vial containing 1.5 mg powder, one vial of solvent, one vial adapter, and one filter.
• One vial containing 1.5 mg powder, two vials of solvent, two vial adapters, and one filter.
• One vial containing 0.5 mg powder.
• One vial containing 1.5 mg powder.

Not all pack sizes may be marketed.
Initially, a pack containing solvent for parenteral use must be used. During chronic therapy with Flolan, solutions of higher concentration may be required. The final concentration of the solution can be increased by adding further vials of lyophilized Flolan powder (0.5 mg or 1.5 mg).
Only vials with the same lyophilized Flolan powder content as those included in the initial starter pack may be used to increase the final concentration of the solution.
The epoprostenol solution prepared with solvent (pH 11.7 – 12.3) must not be used with any preparation or administration material containing polyethylene terephthalate (PET) or glycol-modified polyethylene terephthalate (PETG).
Based on available data from internal testing and published literature, materials likely to be compatible for preparation and administration include:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Polyamide
• Polyethersulfone
• Polyethylene
• Polyisoprene
• Polyolefin
• Polypropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Plasticized polyvinyl chloride (PVC) with bis(2-ethylhexyl) phthalate [DEHP]
• Polyvinylidene fluoride (PVDF)
• Silicone

Suitable ambulatory infusion pumps include:

• CADD-Legacy 1
• CADD-Legacy PLUS
• CADD Solis VIP (variable infusion profile), manufactured by Smiths Medical.

Compatible pump accessories include:

• Medication Cassette disposable reservoirs for CADD pumps (50 mL and 100 mL) from Smiths Medical.
• CADD extension set with in-line 0.2 micron filter (CADD extension set with male luer adapter, 0.2 micron air-eliminating filter, clamp, and integral anti-siphon valve with male luer adapter) from Smiths Medical. The extension set and in-line filter must be replaced at least every 48 hours.

Reconstitution:

1. Use only the solvent provided for reconstitution.
2. Draw approximately 10 mL of sterile buffer solution into a sterile syringe via a vial adapter*.
3. Remove the syringe from the vial adapter. Attach a needle to the syringe, inject the 10 mL of solvent into the vial containing Flolan powder, and gently swirl until complete dissolution is achieved.
4. Draw the resulting Flolan solution into the syringe, remove the needle, re-inject it into the remaining volume of sterile buffer solution via the vial adapter*, and mix thoroughly.

* Alternatively, a needle may be used instead of a vial adapter.
This results in a concentrated solution containing 10,000 nanograms/mL (for the 0.5 mg dose) or 30,000 nanograms/mL of Flolan (for the 1.5 mg dose).
Only these concentrated solutions are suitable for further dilution prior to use. Use a new vial adapter for each sterile solvent vial.
When 0.5 mg or 1.5 mg of Flolan powder is reconstituted with 50 mL of 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 a concentrated solution or in diluted form for the treatment of pulmonary arterial hypertension. Only the concentrated solutions are suitable for further dilution with sterile diluent prior to use.
Only the sterile solvent supplied may be used for further dilution of the reconstituted Flolan solution, using a new vial adapter for each sterile solvent vial.
Sodium chloride solution (0.9% w/v) must not be used when Flolan is used for the treatment of pulmonary arterial hypertension, as the required pH cannot be maintained. Flolan solutions are less stable at low pH values.
Flolan must not be administered with other solutions or parenteral drugs when used in pulmonary arterial hypertension.
The final solution for administration 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 preferred. Alternatively, where in-line filtration is not possible, the final solution (either concentrated or further diluted) must be filtered through the provided 0.22 micron sterile filter before storing the medication in the pump reservoir, applying firm but not excessive pressure; typically, the time required to filter 50 mL of solution is 70 seconds.
If an in-line filter is used during administration, the in-line filter must be discarded when the infusion set is changed.
If a syringe filter is used during preparation, the syringe filter unit must be used only during preparation and then discarded.

Commonly used concentrations in the treatment of pulmonary arterial hypertension are as follows:

• 5,000 nanograms/mL – one vial of 0.5 mg Flolan reconstituted and diluted with solvent to a total volume of 100 mL.
• 10,000 nanograms/mL – two vials of 0.5 mg Flolan reconstituted and diluted to a total volume of 100 mL.
• 15,000 nanograms/mL – one vial of 1.5 mg Flolan reconstituted and diluted with sterile solvent to a total volume of 100 mL.
• 30,000 nanograms/mL – two vials of 1.5 mg Flolan reconstituted and diluted with sterile solvent to a total volume of 100 mL.

Infusion rate calculation
The infusion rate can be calculated using the following formula:
Infusion rate = dose (ng/kg/min) × body weight (kg)
(mL/min)  concentration of solution (ng/mL)
Infusion rate (mL/hour) = infusion rate (mL/min) × 60
Long-term administration of Flolan may require higher infusion rates, and therefore more concentrated solutions.

Special storage precautions
Do not store above 25°C.
Keep contents in the original packaging to protect from light.
Keep dry.
Do not freeze.
For further details on stability after reconstitution, see section 5 ("How to store Flolan").
The solvent does not contain preservatives; therefore each vial must be used immediately and then discarded.

Renal dialysis
The only pack size available for use in renal dialysis is:

• One vial containing 0.5 mg powder, one vial of solvent, one vial adapter, and one filter.

Flolan prepared with sterile solvent (pH 12) must not be used with any preparation or administration material containing polyethylene terephthalate (PET) or glycol-modified polyethylene terephthalate (PETG).
Based on available data from internal testing and published literature, materials likely to be compatible for preparation and administration include:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Polyamide
• Polyethersulfone
• Polyethylene
• Polyisoprene
• Polyolefin
• Polypropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Plasticized polyvinyl chloride (PVC) with bis(2-ethylhexyl) phthalate [DEHP]
• Polyvinylidene fluoride (PVDF)
• Silicone

Reconstitution:

1. Use only the solvent provided for reconstitution.
2. Draw approximately 10 mL of sterile buffer solution into a sterile syringe via a vial adapter*.
3. Remove the syringe from the vial adapter. Attach a needle to the syringe, inject the 10 mL of solvent into the vial containing 0.5 mg of Flolan powder, and gently mix until complete dissolution is achieved.
4. Draw the resulting Flolan solution into the syringe, remove the needle, re-inject it into the remaining volume of sterile buffer solution via the vial adapter*, and mix thoroughly.

* Alternatively, a needle may be used instead of a vial adapter.
This results in a concentrated solution containing 10,000 nanograms/mL of Flolan.
Only this concentrated solution is suitable for further dilution prior to use.
When 0.5 mg of Flolan intravenous powder for infusion is reconstituted with 50 mL of solvent, the final injection has a pH of approximately 12 and a sodium ion content of approximately 73 mg.

Dilution:
The concentrated solution is usually further diluted before use.
It may be diluted with sodium chloride solution (0.9% w/v), provided that the ratio does not exceed 2.3 volumes of saline to 1 volume of concentrated solution; for example, 50 mL of concentrated solution further diluted with a maximum of 117 mL of sodium chloride solution (0.9% w/v).
Other common intravenous solutions are unsuitable for diluting the concentrated solution as the required pH cannot be maintained. Flolan solutions are less stable at low pH values.
To dilute the concentrated solution, draw it into a larger syringe and inject the concentrated solution directly into the chosen infusion solution. Mix well.
The final solution (either concentrated or further diluted) must be transferred into a suitable container or delivery system prior to administration. A 0.22 micron sterile filter must be used during transfer, applying firm but not excessive pressure; typically, the time required to filter 50 mL of solution is 70 seconds.
The syringe-filter unit must be used only during preparation and then discarded.
The filter must be used once only and then disposed of.
The reconstituted and diluted Flolan infusion solution will retain 90% of its initial pharmacological activity for approximately 12 hours at 25°C.

Infusion rate calculation
The infusion rate can be calculated using the following formula:
Infusion rate = dose (nanograms/kg/min) × body weight (kg)
(mL/min)  concentration of solution (nanograms/mL)
Infusion rate (mL/hour) = infusion rate (mL/min) × 60

Appropriate amounts of concentrated solution may be diluted with a sterile sodium chloride solution (0.9% w/v) when administered via a pump capable of delivering constant small-volume infusions.

INSTRUCTIONS FOR USE

Flolan Solution
Instructions for use with a vial adapter and ambulatory infusion pumps
Please read these instructions carefully before beginning to prepare the Flolan solution. If you have any questions or doubts, contact your healthcare professional.

• Wash hands thoroughly before gathering supplies.
• Wear gloves before (Step 1) "Preparation" of Flolan.
• Keep the work area and Flolan supplies clean and dry to ensure hygienic preparation of Flolan.
• Always follow your healthcare professional's instructions exactly; the information in these instructions is intended as a reminder of the process.

Storage information

• Keep out of the reach and sight of children.
• Store Flolan in a cool, dry place.
• Protect from light by keeping Flolan in its carton until use.

Do not use Flolan after the expiry date stated on the label.
Do not freeze.

The pack contains the following:

• 1 vial of powder, 1 vial of solvent, 1 vial adapter, and one filter, or
• 1 vial of powder, 2 vials of solvent, 2 vial adapters, and one filter, or
• 1 vial of powder

You may also need (not included):

• 1 x 60 mL syringe
• 1 needle
• 1 reservoir
• 1 pump
• 1 infusion set
• Gloves
• Alcohol wipes

Preparation

1. Remove the cap from the solvent vial

Use only the solvent provided for reconstitution.

• Remove the cap from the solvent vial and clean the rubber stopper by wiping it with an alcohol-impregnated wipe

2. Open the vial adapter package

• Peel back the paper carrier from the vial adapter package. Note: Keep the adapter in place within its packaging for the next step. Do not use the vial adapter if the package is damaged. For further information, contact your doctor or pharmacist. Do not use the vial adapter if it falls out of the package.

3. Insert the vial adapter

• Take the vial adapter package and insert the inner spike vertically into the rubber stopper of the solvent vial until the adapter clicks into place.
• Ensure the adapter is securely in place before removing the packaging.
• Clean the tip of the vial adapter with an alcohol wipe. Do not touch the tip of the adapter or the syringe.

4. Attach the needle-free syringe

NO • Attach the syringe directly to the adapter
needle without needle.

• While attaching the syringe, hold the base of the adapter.
• Push and turn the syringe 180° clockwise onto the adapter. Do not attach a needle to the syringe.

5. Withdraw the solvent

• Hold the vial securely above the syringe.
• Draw 10 mL of sterile solvent solution into the syringe through the vial adapter.

6. Unscrew the syringe

• Point the syringe tip upward and, while holding the bottom of the adapter firmly, remove the adapter from the syringe. Unscrew the syringe counterclockwise to detach it from the vial adapter.
  Note: When preparing a solution, proceed to step 7. When injecting the solvent directly, proceed to step 13.

Preparing Flolan solutions

7. Attach the needle

• Remove the needle packaging.
• Attach the needle to the syringe.
• Remove the needle cap. Note: Check that the needle is securely attached before removing the needle cap. Be careful not to touch the needle tip.

8. Inject the solvent into the Flolan powder vial

• Remove the cap from the Flolan powder vial and clean the rubber stopper with an alcohol wipe.
• Insert the syringe needle vertically through the center of the rubber stopper and inject the 10 mL of solvent into the vial containing the powder.

9. Gently mix the solution

• With the needle still in the vial, gently swirl the mixture until all the powder is dissolved and the solution is clear.
  1. Do not use if the solution has any color or if the powder is not completely dissolved.

10. Withdraw the solution

• When the solution is clear, invert the vial and, with the syringe pointing upwards, withdraw the Flolan solution into the syringe.
• Keep the needle below the surface of the solution to prevent air from entering the syringe.
• Remove the needle from the vial.

11. Inject the solution into the diluent

• Remove the needle from the syringe and dispose of it in a sharps container.
• Reattach the syringe to the vial adapter of the diluent vial.
• Inject the Flolan solution into the remaining volume of diluent through the vial adapter. Do not use the needle together with the vial adapter.

12. Mix thoroughly

• Mix carefully. This solution is now referred to as the concentrated solution.
• Withdraw the entire volume of concentrated solution from the vial.
• Disconnect the syringe from the vial adapter as shown in step 6. Note: only this concentrated solution is suitable for further dilution prior to use.

Cartridge preparation
*Orange steps are optional: only if required
*Attach the syringe filter

Note: an in-line filter must be provided as part of the extension set (refer to step 15).
If an in-line filter is not provided as part of the extension set, the syringe filter must be used to filter the solution during cartridge preparation.

• Attach the sterile syringe filter included in the Flolan package to the syringe.
• Connect the syringe-filter unit to the cartridge with the tubing.

13. Filling the loader

• Attach the syringe to the loader tube.
• Slowly inject the contents of the syringe into the loader.
• Use the syringe to remove excess air from the loader. Note: ensure the sliding clamp is open.

* Dilution of the solution
Note: If the dose needs to be diluted, prepare an additional amount of solvent for injection by repeating steps 1 to 6 and 13.
Follow the instructions below instead of step 5 for the volume of solvent to be withdrawn.

• Firmly hold the vial above the syringe.
• Withdraw the required volume of solvent (or solution) from the vial.

14. Gently mix the loader

• Secure the sliding clamp.
• Mix thoroughly by gently rotating or inverting the loader. Do not shake the loader.

15. Pump

Refer to the instructions for use of the
pump.
Disposal
Dispose of used components

• Dispose of the sterile filter after preparing the Flolan solution, together with any other used components. Any residual solvent at pH 12 should also be discarded, as it contains no preservatives.
  Storage (solutions with a concentration less than or equal to 150,000 ng/mL)
  Storage of the prepared solution

• After completing preparation of the Flolan solution, it may be used immediately or stored for up to eight days in the refrigerator at 2–8°C.

• The diluted solution must be protected from light. Flolan solution may only be stored after it has been fully diluted; the reconstituted solution must never be stored prior to dilution.

• Store the Flolan cartridge in the top compartment of the refrigerator inside a container with a tightly sealed lid, ensuring it is separated from food.

• The freshly prepared Flolan solution, or solution refrigerated for up to eight days, may be used:

  • For up to 48 hours at temperatures up to 25°C
  • For up to 36 hours at temperatures up to 30°C
  • For up to 24 hours at temperatures up to 35°C
  • For up to 12 hours at temperatures up to 40°C

• Discard any unused solution after these time periods.