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EPOPROSTENOL GEBRO 0.5 MG POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

Active substance(s): EPOPROSTENOL SODIUM

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PACKAGE LEAFLET: INFORMATION FOR THE USER
Epoprostenol Gebro 0.5 mg Powder and Solvent for Solution for Infusion
Epoprostenol (as sodium)
Read all of this leaflet carefully before you start using this medicine.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor, nurse or pharmacist.
In this leaflet:
1.
What Epoprostenol Gebro is and what it is used for
2.
Before you are given Epoprostenol Gebro
3.
How Epoprostenol Gebro is given
4.
Possible side effects
5.
Storing Epoprostenol Gebro
6.
Further information

1. WHAT EPOPROSTENOL GEBRO IS AND WHAT IT IS USED FOR
This medicine contains epoprostenol.
Epoprostenol Gebro has two separate uses.
It can be used during kidney dialysis (to stop your blood from clotting), or it can be used to treat
primary and secondary pulmonary hypertension – where Epoprostenol Gebro widens the blood
vessels in the lungs and so lowers the blood pressure in your lungs.

2. BEFORE YOU ARE GIVEN EPOPROSTENOL Gebro
Do not use Epoprostenol Gebro
if you are allergic (hypersensitive) to epoprostenol or any of the other ingredients of
Epoprostenol Gebro (listed in Section 6)
if you have heart failure that makes you short of breath. This may be worse when lying flat and
can also cause swollen legs or feet due to a build-up of fluid.
If you are unsure, talk to your doctor or nurse before having Epoprostenol Gebro.
Take special care with Epoprostenol Gebro
Your doctor needs to know before you are given Epoprostenol Gebro if you have a tendency to bleed
easily e.g. haemophilia. If you are unsure, talk to your doctor or nurse.
This medicine can affect your blood pressure and heart rate and therefore your doctor will monitor
these.
Taking other medicines
Please tell your doctor, nurse or pharmacist if you are taking, or have recently taken, any other
medicines, including medicines obtained without a prescription. This includes herbal medicines. This
is because epoprostenol can affect the way some medicines work. Also, some other medicines can
affect the way epoprostenol works.
In particular, tell your doctor, nurse or pharmacist if you are taking:
• Medicines to prevent blood clots, such as heparin, warfarin or aspirin.
• Medicines for high blood pressure such as doxazocin.
• Medicines for angina, such as glyceryl trinitrate or other nitrate medicines.
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Anti-inflammatory pain killers (also called 'NSAIDs') such as ibuprofen.
Medicines for heart failure or irregular heartbeats, such as digoxin.
Medicines used to treat primary pulmonary hypertension, such as sildenafil,
sitaxentan, bosentan.

Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
The effects of epoprostenol on driving and using machinery have not been studied.
Important information about some of the ingredients of Epoprostenol Gebro
This medicinal product contains 2.43 mmol (or 56 milligram) sodium (salt) per dose. To be taken into
consideration by patients on a controlled sodium (salt) diet.

3. HOW EPOPROSTENOL GEBRO IS GIVEN





Epoprostenol Gebro will not be given by quick injection; instead it will be given slowly into your
vein over a long period of time.
Your doctor will decide how much Epoprostenol Gebro is right for you and how long you should
use it for.
The amount you are given is based on your body weight.
Your dose may be increased or decreased depending on how you respond to treatment.

Dosage
Kidney dialysis:
Adults:
The usual starting dose for adults is 4 nanograms of epoprostenol for each kilogram of body weight,
for each minute it is given.
• Before your dialysis, Epoprostenol Gebro may be given as a slow injection
into your vein.
• During dialysis, Epoprostenol Gebro will be slowly injected into the blood
going into the dialysis machine.
Epoprostenol Gebro will not be given after the end of your dialysis.
Children and the elderly:
There is no specific information available on the use of Epoprostenol Gebro for kidney dialysis in
children or in elderly patients.
Primary and Secondary Pulmonary Hypertension:
Adults:



The usual starting dose for adults is 2 nanograms of epoprostenol for each kilogram of your
body weight for each minute it is given
This dose is then increased every 15 minutes until the best dose is found for you. The best
dose will relieve your symptoms but cause the fewest possible side-effects.

Once the correct dose has been found, a permanent tube or line will be fitted.
Your doctor will then continue to give you this dose through a pump.
There are only certain pumps which can be used. Your doctor will make sure you are using the right
one.

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Children:
There is limited information on the use of Epoprostenol Gebro for Primary and Secondary Pulmonary
Hypertension in children.
Elderly:
There is limited information on the use of Epoprostenol Gebro in patients over 65. In general, dose
selection for an elderly patient should be made carefully, reflecting the greater frequency of decreased
hepatic, renal or cardiac function and of concomitant disease or other drug therapy.
Method of administration
A short-term dose-ranging procedure administered via either a peripheral or central venous line is
required to determine the long-term infusion rate.
Long-term continuous infusion of Epoprostenol Gebro should be administered through a central
venous catheter.
If you are given more Epoprostenol Gebro than you need
This can cause low blood pressure which can make you feel light-headed or faint. Your doctor or
nurse will do whatever is necessary to correct this and may adjust your dose.

4. POSSIBLE SIDE EFFECTS
Like all medicines, Epoprostenol Gebro can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediately if:
• You get palpitations, chest pain, shortness of breath or sweating.
• You feel dizzy or feel faint, especially on standing
These can be symptoms of an irregular heart beat or low blood pressure. Your doctor may check you
regularly for these side effects.
Other possible side effects include:
Very common (affects more than 1 user in 10)
• Infection in the bloodstream, which may be due to the way this medicine is given.
• Flushing (redness) of the face
• Feeling sick (nausea) or being sick (vomiting)
• Headache
• Jaw pain
Common (affects 1 to 10 users in 100)
• Bleeding and/or bruising more easily than usual, for example from the nose or gums. Bleeding
can be serious therefore tell your doctor or nurse as soon as possible if you think this applies
to you.
• Feeling anxious or nervous
• Stomach pain or discomfort which usually comes in waves (colic)
Uncommon (affects 1 to 10 users in 1,000)
• Dry mouth
Rare (affects 1 to 10 users in 10,000)
Infection at the injection site

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Very rare (affects less than 1 user in 10,000)
• Pain and redness at the injection site
• Pain or tightness in the chest
• Pale skin
• Feeling tired, weak or agitated
• Sweating
If any of these side-effects gets serious or you notice any side-effects not listed in this leaflet, please
tell your doctor or nurse.

5. STORING EPOPROSTENOL GEBRO
Powder for solution for infusion:
Keep the vial in the outer carton in order to protect from light.
Keep the vial tightly closed in order to protect from moisture.
Store below 25°C
Solvent:
Keep the vial in the outer carton in order to protect from light.
Store below 25°C
Keep out of the reach and sight of children.
Do not use Epoprostenol Gebro after the expiry date which is stated on the bottle. The expiry date
refers to the last day of that month.
Shelf-life after reconstitution:
Kidney Dialysis:
When reconstituted with the Glycine Buffer Diluent and diluted with physiological saline as
instructed (see information for medical or healthcare professionals below), freshly prepared
Epoprostenol solutions should be used within a maximum time frame of 12 hours at 25°C.
Primary and Secondary Pulmonary Hypertension:
When reconstituted and diluted with the Glycine Buffer Diluent as instructed (see information for
medical or healthcare professionals below), freshly prepared Epoprostenol solutions should be infused
immediately. If not used immediately, in-use storage times are the responsibility of the user and
should not be longer than 24 hours at 2-8°C.
Where the solution is held in an ambulatory infusion pump system, a cold pouch must be used to
maintain the temperature of the solution at 2-8°C for the full administration period. Epoprostenol
Gebro solution may then be used over a 24 hour period provided that the cold pouch is changed as
necessary throughout the day.
Where an ambulatory cold pouch system cannot be used the maximum administration time at 25°C is
12 hours for freshly prepared solutions and 8 hours for solutions that have been stored prior to use.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.

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6. FURTHER INFORMATION
What Epoprostenol Gebro contains
Powder for solution for infusion
The active substance is Epoprostenol (as Sodium).
1 vial contains 0.531 milligrams Epoprostenol Sodium, corresponding to 0.5 milligrams
Epoprostenol.
-

The other ingredients are:
Powder for solution for infusion: Mannitol, Glycine, Sodium Chloride, Sodium Hydroxide (for
pH adjustment)
Solvent: Glycine, Sodium Chloride, Sodium Hydroxide (for pH adjustment), Water for
Injection
Where 1 vial with 0.5 mg epoprostenol is reconstituted with 50 ml of sterile buffer, the resultant
concentration is 10,000 nanograms per ml.
Solvent
Each vial of solvent contains 50 ml of a sterile glycine buffer solution containing approximately
55 milligram sodium.
What Epoprostenol Gebro looks like and contents of the pack
Epoprostenol Gebro is a white lyophilised powder cake packed in clear glass vials with grey lyo
stopper and aluminium caps with blue flip-off inserts. The solvent is a clear, colourless solution
packed in clear glass vials.
After reconstitution Epoprostenol Gebro is a colourless solution, practically free of particles.
Each pack unit contains
- one vial Epoprostenol Gebro 0.5 mg, containing a white freeze-dried powder cake packed in a
15 ml clear glass vial Type I with grey lyo stopper and aluminium caps with blue flip-off
inserts.
- one 50ml sterile Glycine buffer solution, pH 10.5 in a clear glass vial
- one single unit sterile filter device for aseptic preparation of infusion solution
Marketing Authorisation Holder and Manufacturer
Gebro Pharma GmbH
6391 Fieberbrunn
AUSTRIA
This medicinal product is authorised in the Member States of the EEA under the following
names:
UK:
Austria:
Hungary:
Spain:

Epoprostenol Gebro 0.5 mg Powder and Solvent for Solution for Infusion
Dynovas 0,5 mg Pulver und Lösungsmittel zur Herstellung einer Infusionslösung
Dynovas 0,5 mg Por és oldószer oldatos infúzióhoz
Dynovase 0,5 mg Polvo y disolvente para solución para perfusión

This leaflet was last approved in 08/2013

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<---------------------------------------------------------------------------------------------------------------------->
The following information is intended for medical or healthcare professionals only:

Reconstitution and dilution:
Particular care should be taken in the preparation of the infusion and in calculating the rate of
infusion. The procedure given below should be closely followed.
Reconstitution and dilution of Epoprostenol Gebro 0.5 mg must be carried out using sterile
techniques, immediately prior to clinical use.
Reconstitution time should be below 30 seconds.
After reconstitution Epoprostenol Gebro is a colourless solution, practically free of particles.
Renal dialysis
Reconstitution:
1. Use only the Glycine Buffer Diluent provided for reconstitution.
2. Withdraw approximately 10 ml of the Glycine Buffer Diluent into a sterile syringe, inject the
contents of the syringe into the vial containing 0.5 mg freeze-dried epoprostenol and shake
gently until the powder has dissolved.
3. Draw up the resulting epoprostenol solution into the syringe, re-inject it into the remaining
volume of the Glycine Buffer Diluent solution and mix thoroughly.
This solution is now referred to as the concentrated solution and contains 10,000 nanograms per ml
epoprostenol. Only this concentrated solution is suitable for further dilution prior to use.
When 0.5 mg epoprostenol powder is reconstituted with 50 ml of the Glycine Buffer Diluent, the final
injection has a pH of approximately 10.5 and a sodium ion content of approximately 56 mg.
Dilution:
For administration using a pump capable of delivering small volume constant infusions, suitable
aliquots of concentrated solution may be diluted with sterile physiological saline.
It may be diluted with physiological saline (0.9%), provided a ratio of 6 volumes of saline to 1 volume
of concentrated solution is not exceeded; e.g. 50 ml of concentrated solution further diluted with a
maximum of 300 ml saline.
Other common intravenous fluids are unsatisfactory for the dilution of the concentrated solution as
the required pH is not attained. Epoprostenol solutions are less stable at low pH.
Prior to using the concentrated solution, or the diluted form, a filtration step is needed. To filter, draw
the reconstituted product into a large syringe and then attach the sterile filter provided to the syringe.
Dispense the concentrated solution directly into the chosen infusion solution using firm but not
excessive pressure; the typical time taken for filtration of 50 ml of concentrated solution is 70
seconds. Mix well.
The filter unit must be used once only and then discarded.
When reconstituted and diluted as directed above, epoprostenol infusion solutions have a pH of
approximately 10 and will retain 90% of their initial potency for approximately 12 hours at 25°C.
CALCULATION OF INFUSION RATE:
The infusion rate may be calculated by the following formula:
Infusion rate =
(ml/min)

dosage (ng/kg/min) x bodyweight (kg)
concentration of solution (ng/ml)
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Infusion rate (ml/hr) = Infusion rate (ml/min) x 60
Infusion rate formulae - examples
When used in renal dialysis Epoprostenol Gebro 0.5 mg may be administered as the concentrated
solution (a) or in diluted form (b).
a. Using concentrated solution i.e. 10,000 ng/ml epoprostenol.
Concentration of solution = 10,000 ng/ml epoprostenol
Dosage
(ng/kg/min
)

1
2
3
4
5

Bodyweight (kilograms)
30

40

50

60

70

80

90

100

0.1
8
0.3
6
0.5
4
0.7
2
0.9
0

0.2
4
0.4
8
0.7
2
0.9
6
1.2
0

0.3
0
0.6
0
0.9
0
1.2
0
1.5
0

0.3
6
0.7
2
1.0
8
l.44

0.4
2
0.8
4
1.2
6
1.6
8
2.1
0

0.4
8
0.9
6
1.4
4
1.9
2
2.4
0

0.5
4
1.0
8
1.6
2
2.1
6
2.7
0

0.6
0
1.2
0
1.8
0
2.4
0
3.0
0

1.8
0

Flow rates in ml/hr

b. Using concentrated solution, diluted:
10ml concentrated solution + 40 ml physiological saline (0.9%). To give a final total volume of 50
ml.
Resultant concentration = 2,000 nanograms/ml epoprostenol.
Concentration of solution = 2,000 ng/ml epoprostenol
Dosage
(ng/kg/min
)

1
2
3
4
5

Bodyweight (kilograms)
30

40

50

60

0.9
0
1.8
0
2.7
0
3.6
0
4.5
0

1.2
0
2.4
0
3.6
0
4.8
0
6.0
0

1.5
0
3.0
0
4.5
0
6.0
0
7.5
0

1.8
0
3.6
0
5.4
0
7.2
0
9.0
0

70

80

90

100

2.10

2.40

2.70

3.00

4.20

4.80

5.40

6.00

6.30

7.20

8.10

9.00

8.40

9.60

10.5
0

12.0
0

10.8
0
13.5
0

12.0
0
15.0
0

Flow rates in ml/hr

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Primary and secondary Pulmonary Hypertension
The following pack unit is available for use in the treatment of primary pulmonary hypertension:
One vial containing sterile freeze-dried epoprostenol sodium equivalent to 0.5 mg epoprostenol
supplied with one 50 ml vial of sterile Glycine Buffer Diluent solution.
Initially a pack unit containing diluent buffer must be used. During chronic epoprostenol therapy the
final concentration of solution may be increased by the addition of a further 0.5 mg or 1.5 mg vial of
freeze dried epoprostenol.
Only vials of the same amount as that included in the initial starter pack may be used to increase the
final concentration of solution.
Reconstitution:
This should be carried out according to the instructions given for renal dialysis. Where a pack
containing 0.5 mg epoprostenol is reconstituted with 50 ml sterile diluent the resultant concentration
is 10,000 nanograms per ml.
Dilution:
Epoprostenol Gebro 0.5 mg may be used either as concentrated solution or in a diluted form for the
treatment of PPH/SPH. Only the Glycine Buffer Diluent provided may be used for the further dilution
of reconstituted Epoprostenol Gebro 0.5 mg. Physiological saline must not be used when
Epoprostenol Gebro 0.5 mg is to be used for the treatment of primary pulmonary hypertension.
Concentrations commonly used in the treatment of primary or secondary pulmonary hypertension are
as follows:
− 15,000 ng/ml – 3vials of 0.5mg epoprostenol or one vial of 1.5mg epoprostenol reconstituted
and diluted to a total volume of 100ml in the Glycine Buffer Diluent.
− 10,000 ng/ml – two vials containing 0.5mg epoprostenol reconstituted and diluted to a total
volume of 100ml in the Glycine Buffer Diluent.
The maximum recommended concentration for administration in primary pulmonary hypertension is
60,000ng/ml.
Epoprostenol Gebro 0.5 mg must not be administered with other parenteral solutions or medications
when used for primary or secondary pulmonary hypertension.
To dilute the concentrated solution, draw it up into a larger syringe and then attach the sterile filter
provided to the syringe.
Dispense the concentrated solution directly into the pump cassette using firm but not excessive
pressure; the typical time taken for filtration of 50 ml of concentrated solution is 70 seconds.
Remove the filter from the syringe and draw up the additional volume of the Glycine Buffer Diluent
required to achieve the desired dilution.
Refit the filter to the syringe and dispense the additional buffer through this into the concentrated
Epoprostenol Gebro 0.5 mg solution in the cassette.
Mix well.
The filter unit must be used for the dilution of one pack only and then discarded.
The ambulatory pump used to administer Epoprostenol Gebro 0.5 mg should (1) be small and
lightweight, (2) be able to adjust infusion rates in ng/kg/min increments, (3) have occlusion, end of
infusion, and low battery alarms, (4) be accurate to ± 6% of the programmed rate (5) be positive
pressure driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at

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infusion rates used to deliver Epoprostenol Gebro 0.5 mg, and (6) include a cold pouch system. The
reservoir should be made of polyvinyl chloride, polypropylene, or glass.
Protect infusion bags from light during infusion.
CALCULATION OF INFUSION RATE:
The infusion rate may be calculated from the formula given above for renal dialysis.
An example of a concentration commonly used in primary or secondary pulmonary hypertension is
shown below.
Infusion rates for a concentration of 15,000 nanograms/ml:
Concentration of solution = 15,000 ng/ml epoprostenol
Dosage
(ng/kg/min)

Bodyweight (kilograms)
30

40

50

4
6

60

70

80

90

100

1.0

1.1

1.3

1.4

1.6

1.0

1.2

1.4

1.7

1.9

2.2

2.4

8

1.0

1.3

1.6

1.9

2.2

2.6

2.9

3.2

10

1.2

1.6

2.0

2.4

2.8

3.2

3.6

4.0

12

1.4

1.9

2.4

2.9

3.4

3.8

4.3

4.8

14

1.7

2.2

2.8

3.4

3.9

4.5

5.0

5.6

16

1.9

2.6

3.2

3.8

4.5

5.1

5.8

6.4

Flow rates in ml/hr

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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