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MONONINE 500 100 IU/ML POWDER AND SOLVENT FOR SOLUTION FOR INJECTION OR INFUSION

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pbE8750_Mononine_500_1000_28_400x270 19.07.2013 14:40 Seite 1

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• The formation of inhibitors (neutralising antibodies) to Factor IX is a known
complication of treatment and it means that the treatment stops working. If your
bleeding is not being controlled with Mononine, tell your doctor immediately.
You should be monitored carefully for the development of an inhibitor.
• There is a risk of an increased formation of blood clots in a blood vessel
(thromboembolic complications), particularly:
- in low purity preparations (For highly purified concentrates like Mononine
this risk is considered to be very low.)
- if you suffer from a liver disease
- if you have just had surgery
- in new-born infants
- if you have additional thrombotic risk factors, e.g. pregnancy, oral
contraceptives, obesity, smoking.
• There is no safety and efficacy data for continuous infusion application in
children, particularly the potential for development of inhibitors is unknown.

PATIENT INFORMATION LEAFLET

®

MONONINE 500/1000
Powder and solvent for solution for injection or infusion
Human coagulation factor IX

Read all of this leaflet carefully before you start using this
medicine.

Your doctor will consider carefully the benefit of treatment with Mononine
compared with the risk of these complications.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may
harm them, even if their symptoms are the same as yours.
• If any of the side effects gets serious, or if you notice any side effects not listed
in this leaflet, please tell your doctor or pharmacist.

Virus safety
When medicines are made from human blood or plasma, certain measures are put
in place to prevent infections being passed on to patients. These include careful
selection of blood and plasma donors to make sure those at risk of carrying
infections are excluded, and the testing of each donation and pools of plasma for
signs of virus/infections. Manufacturers of these products also include steps in the
processing of the blood or plasma that can inactivate or remove viruses. Despite
these measures, when medicines prepared from human blood or plasma are
administered, the possibility of passing on infection cannot be totally excluded. This
also applies to any unknown or emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses such as human
immunodeficiency virus (HIV, the aids virus), hepatitis B virus and hepatitis C virus
(inflammation of the liver) and for the non-enveloped viruses hepatitis A and
parvovirus B19.

In this leaflet:
1.
2.
3.
4.
5.
6.

What Mononine is and what it is used for
Before you use Mononine
How to use Mononine
Possible side effects
How to store Mononine
Further information

1. WHAT MONONINE IS AND WHAT IT IS USED FOR

Your doctor may recommend that you consider vaccination against hepatitis A and
B if you regularly/repeatedly receive human plasma-derived products (e.g. Factor IX).

What is Mononine?
Mononine is made from human plasma (this is the liquid part of the blood) and it
contains human coagulation factor IX. It is used to prevent or to stop bleeding that
is caused by the lack of Factor IX (haemophilia B) in the blood.

What Mononine is used for
Factor IX is very important for blood clotting (coagulation). Lack of Factor IX means
that blood does not clot as quickly as it should and so there is an increased tendency
to bleed. The replacement of Factor IX with Mononine will temporarily repair the
blood clotting mechanisms.

It is strongly recommended that every time Mononine is given, you should record the
date of administration, the batch number and the injected volume in your treatment
diary.

Taking other medicines:

The following sections contain information that you and your doctor should consider
before you use Mononine.

• Please tell your doctor or pharmacist if you are taking or have recently taken any
medicines, including medicines obtained without a prescription.
• Factor IX and ε-aminocaproic acid (a chemical drug that stops the breakdown
of blood clots) can be used to treat bleeding from the mouth, either if this happens
after injury or after dental surgery, such as having teeth removed. However,
there is not very much information about what happens when ε-aminocaproic
acid and Mononine are given at the same time.
• Mononine must not be mixed with other medicinal products, diluents and
solvents except for those that are recommended by the manufacturer (see section
"6. Further information ")

Do NOT use Mononine:

Mononine should not affect your ability to drive and use machines.

Treatment of Haemophilia B should be started and supervised by a physician who
is experienced in this type of disorder.

Dosage
The amount of Factor IX you need and the duration of treatment will depend on
several factors, such as your body weight, the severity of your disease, the site and
intensity of the bleeding or the need to prevent bleeding during an operation or
investigation.
If you have been prescribed Mononine to use at home, your doctor will make sure
that you are shown how to inject or infuse it and how much to use.
Follow the directions given to you by your doctor or haemophilia centre
nurse.

The made up solution is to be given by injection or infusion into a vein.

2. BEFORE YOU USE MONONINE

• As with any injection of a protein, allergic reactions are possible. The early signs
include hives, generalised skin rash, tightness of the chest, wheezing, fall in
blood pressure and anaphylaxis (a serious allergic reaction that causes severe
difficulty in breathing, or dizziness).
If these symptoms occur, you should stop using the product
immediately and contact your doctor.
• Mononine contains, as remains of a special purification step, traces of mouse
protein. While the levels of mouse protein are extremely low, infusion of these
proteins can lead to allergic reactions.

The following information is intended for medical or healthcare
professionals only

Posology
The number of units of factor IX administered is expressed in International Units
(IU), which are related to the current WHO standard for factor IX products. Factor
IX activity in plasma is expressed either as a percentage (relative to normal human
plasma) or in International Units (relative to an international standard for factor IX
in plasma).
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX
in one ml of normal human plasma. The calculation of the required dosage of factor IX
is based on the empirical finding that 1 IU factor IX per kg body weight raises the
plasma factor IX activity by 1.0 % of normal activity. The required dosage is
determined using the following formula:
Required units = body weight [kg] × desired factor IX rise [% or IU/dl] × 1.0*
* reciprocal of observed recovery

If you take more Mononine than you should
No symptoms of overdose with Factor IX have been reported.

The amount to be administered, the method as well as the frequency of
administration should always be oriented to the clinical effectiveness in the individual
case. Factor IX products rarely require to be administered more than once daily
when given by bolus injection.

Reconstitution and application
General Instructions:
• The product must be dissolved and withdrawn from the vial under aseptic
conditions.
• The made up solution should be clear or slightly opalescent, i.e. it might be
sparkling when held up to the light but must not contain any obvious particles.
After filtering or withdrawal (see below) the solution should be checked by eye
for small particles and discoloration, before it is administered. Do not use the
solution if it is visibly cloudy or if it contains flakes or particles.
• Any unused product or waste material should be disposed of in accordance with
local requirements and as instructed by your doctor.

Reconstitution:
Without opening either vial, warm the Mononine product and the solvent to room or
body temperature. This can be done either by leaving the vials at room temperature
for about an hour, or by holding them in your hands for a few minutes.
DO NOT expose the vials to direct heat. The vials must not be heated above body
temperature (37 ºC).
Carefully remove the protective caps from the vials containing the product
and the solvent, and clean the exposed rubber stoppers with an alcohol swab.
Allow the vials to dry before opening the Mix2Vial package, then follow the
instructions given below.

• If you are pregnant or breast-feeding, please ask your doctor or pharmacist for
advice before taking any medicine.
• During pregnancy and breast-feeding, Mononine should be given only if it is
clearly needed.

Take special care with Mononine:

Always use Mononine exactly as your doctor has told you. You should check with
your doctor or pharmacist if you are not sure.

Pregnancy and breast-feeding

• If you are allergic to the human coagulation factor IX or to any of the
ingredients of Mononine or to mouse protein. Please inform your doctor if you
are allergic to any medicine or food.
• If you have a high risk of forming blood clots (thrombosis) or if you are more
likely to form blood clots than normal (disseminated intravascular coagulation).

3. HOW TO USE MONONINE

1. Open the Mix2Vial package by peeling off the lid. Do not
remove the Mix2Vial from the blister package!

In the case of the following haemorrhagic events, the factor IX activity should
not fall below the given plasma activity level (in % of normal or IU/dl) in the
corresponding period. The following tables can be used to guide dosing in bleeding
episodes and surgery:
Table 1: SINGLE INTRAVENOUS INJECTION
Degree of haemorrhage/
Type of surgical
procedure

Factor IX level
required
(% or IU/dl)

Frequency of doses (hours)/
Duration of therapy (days)

Haemorrhage
Early haemarthrosis,
muscle bleeding or
oral bleeding

20 – 40

Repeat every 24 hours.
At least 1 day, until the
bleeding episode as indicated
by pain is resolved or
healing is achieved.

More extensive
haemarthrosis, muscle
bleeding or haematoma

30 – 60

Repeat infusion every
24 hours for 3 – 4 days
or more until pain and acute
disability are resolved.

Life-threatening
haemorrhages

60 – 100

Repeat infusion every
8 to 24 hours until threat
is resolved.

30 – 60

Every 24 hours, at least 1 day,
until healing is achieved.

80 – 100
(pre- and
postoperative)

Repeat infusion every
8 – 24 hours until adequate
wound healing, then therapy
for at least another 7 days
to maintain a factor IX activity
of 30 % to 60 % (IU/dl).

Surgery
Minor
including tooth
extraction

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2. Place the solvent vial on an even, clean surface and hold
the vial tight. Take the Mix2Vial together with the blister
package and push the spike of the blue adapter end
straight down through the solvent vial stopper.

Major

Driving and using machines
2

Important information about some of the ingredients in
Mononine

3. Carefully remove the blister package from the Mix2Vial
set by holding at the rim, and pulling vertically upwards.
Make sure that you only pull away the blister package and
not the Mix2Vial set.

Table 2: CONTINUOUS INFUSION IN SURGERY

1

40 – 100 % (or IU/dl)

Initial loading dose to
achieve desired level

Single bolus dose 90 IU per kg
(range 75 – 100 IU/kg) body weight or
PK-guided dosing
Continuous i.v. infusion, depending on
clearance and measured factor IX levels

Duration of treatment

E8750 G28 A

Desired levels of factor IX
for haemostasis

Frequency of dosing

Mononine contains up to 10.2 mg sodium per 500 IU (up to 20.3 mg sodium per
1000 IU). Please take this into account if you are on a controlled sodium diet.

Up to 5 days, further treatment may be
necessary depending upon nature of surgery

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2

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4. Place the product vial on an even and firm surface.
Invert the solvent vial with the Mix2Vial set attached and
push the spike of the transparent adapter end straight
down through the product vial stopper. The solvent will
automatically flow into the product vial.

During the course of treatment, appropriate determination of factor IX levels is
advised to guide the dose to be administered and the frequency of repeated infusions.
In the case of major surgical interventions in particular, precise monitoring of the
substitution therapy by means of coagulation analysis (plasma factor IX activity) is
indispensable. Individual patients may vary in their response to factor IX, achieving
different levels of in vivo recovery and demonstrating different half-lives.
For long-term prophylaxis against bleeding in patients with severe haemophilia B, the
usual doses are 20 to 40 IU of factor IX per kg body weight at intervals of 3 to 4
days. In some cases, especially in younger patients, shorter dosage intervals or higher
doses may be necessary.
Patients should be monitored for the development of factor IX inhibitors. If the
expected factor IX activity plasma levels are not attained, or if bleeding is not
controlled with an appropriate dose, an assay should be performed to determine if
a factor IX inhibitor is present. In patients with high levels of inhibitor, factor IX
therapy may not be effective and other therapeutic options should be considered.
Management of such patients should be directed by physicians with experience in
the care of patients with haemophilia.

4

5. With one hand grasp the product-side of the Mix2Vial set
and with the other hand grasp the solvent-side and
unscrew the set carefully into two pieces. Discard the
solvent vial with the blue Mix2Vial adapter attached.

5

6. Gently swirl the product vial with the transparent adapter
attached until the substance is fully dissolved. Do not
shake.

Application
Mononine 500/1000 could be administered either by single intravenous injection
(see instructions in section 3) or by continuous infusion (see instructions below).

Continuous infusion
Mononine should be reconstituted with water for injections as described in section
"Reconstitution and application". After reconstitution, Mononine can be given for
continuous infusion either undiluted or diluted using a syringe pump or an
approved infusion set.
A diluted solution is obtained as follows:
• Dilute the reconstituted, filtered solution by transferring the appropriate quantity
of Mononine to the desired volume of normal saline using aseptic technique.
• In dilutions of up to 1:10 (concentration of 10 IU factor IX/ml) activity of factor
IX remains stable for up to 24 hours.
• A reduction in factor IX activity may result at higher dilutions. Factor IX activity
should be monitored to maintain the desired blood level.

6

7. Draw air into an empty, sterile syringe. While the product
vial is upright, connect the syringe to the Mix2Vial´s Luer
Lock fitting. Inject air into the product vial.

7

Withdrawal and Application:

Example for diluting 500 IU of reconstituted Mononine:
Targeted Dilution Potency

10 IU/ml

Volume of reconstituted
Mononine
Volume of normal saline
needed
Achieved dilution

5.0 ml

5.0 ml

45.0 ml

20.0 ml

1:10

8. While keeping the syringe plunger pressed, invert the
system upside down and draw the solution into the
syringe by pulling the plunger back slowly.

20 IU/ml

1:5

4. POSSIBLE SIDE EFFECTS

What Mononine looks like and contents of the pack

Like all medicines, Mononine can cause side effects, although not everybody gets them.

Mononine is presented as a white powder and is supplied with water for injections
as solvent.

If any of the following happen, contact your doctor immediately
or go to the Emergency Department or Haemophilia Centre at
your nearest hospital:
• A sudden allergic reaction (such as skin rash or hives, itchiness, swelling of the
face, lips, tongue or other parts of the body),
• Shortness of breath, wheezing or trouble breathing,
• Fits,
• Loss of effect (continuous bleeding).

Other side effects are:
• Allergic reactions, which may include:
- burning and stinging, redness and swelling of the vein where the injection or
infusion was given
- swelling of the face throat or other parts of the body, chills, flushing, skin
rash over the whole body, wheals
- headache
- fall in blood pressure, restlessness, faster heart beat, tightness of the chest,
wheezing
- tiredness (lethargy)
- feeling/being sick
- tingling
These side effects have been observed rarely, and may in some cases progress
to severe allergic reactions (anaphylaxis) including shock (this has been closely
associated with development of factor IX inhibitors).
• Rarely, fever has been reported.
• Very rarely, a special form of inflammation of the kidneys (nephrotic syndrome)
has been reported after treatment of patients who suffer from Factor IX
inhibitors. These patients were also known to have a history of allergic reaction.
• There is a potential risk of increased formation of blood clots that can lead to
heart attack (myocardial infarction), blood clots in the leg (venous thrombosis)
and blood clots in the lungs (pulmonary embolism), after administration of
Factor IX products. The use of Mononine is rarely linked with these side effects.
• Very rarely, you may develop an inhibitor (neutralising antibody) to Factor IX,
in which case Factor IX will not work properly any more. If this happens, it is
recommended that a specialised haemophilia centre be contacted.

The made up solution should be clear to slightly opalescent, i.e. it might sparkle
when held up to the light but must not contain any obvious particles.

Presentations
One pack with 500 or 1000 IU containing:
– 1 vial with powder
– 1 vial with 5 ml or 10 ml water for injections
One device pack containing:
– 1 filter transfer device 20/20
– 1 disposable 10 ml syringe
– 1 venipuncture set
– 2 alcohol swabs
– 1 non-sterile plaster

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
This leaflet was last revised in 07/2013.

If any of the side effects occur, or if you notice any side effects
not listed in this leaflet, please tell your doctor or pharmacist.
5. HOW TO STORE MONONINE
Do not use Mononine after the expiry date, which is stated on the label and carton.

8

9. Now that the solution has been transferred into the
syringe, firmly hold on to the barrel of the syringe
(keeping the syringe plunger facing down) and disconnect
the transparent Mix2Vial adapter from the syringe.

Example for diluting 1000 IU of reconstituted Mononine:
Targeted Dilution Potency

10 IU/ml

20 IU/ml

Volume of reconstituted
Mononine
Volume of normal saline
needed
Achieved dilution

10.0 ml

10.0 ml

90.0 ml

40.0 ml

1:10

1:5

9

• The use of polyvinylchloride (PVC) IV bags and tubing is recommended.
• Mix thoroughly and check bag for leaks.
• It is recommended to replace the bags with freshly diluted Mononine every 12 – 24
hours.
The recommended rate for continuous infusion with Mononine to maintain a steady
state factor IX level of approximately 80 % is 4 IU/kg b.w./hour, but will depend
on the pharmacokinetic profile of the patient and the desired factor IX target level.
In patients where the clearance of factor IX is known, the infusion rate can be
calculated for the individual patient.
Rate (IU/kg b.w./h) = Clearance (ml/h/kg b.w.) × desired factor IX increase (IU/ml)
The safety and efficacy in children have not been studied under continuous infusion. Therefore, in children and adolescents, continuous infusion of Mononine
should only be considered if pre-surgical pharmacokinetic data (i.e. incremental
recovery and clearance) are obtained for the calculation of dosage and levels are
carefully monitored perioperatively.

8

Single intravenous injection
Use the venipuncture kit that is supplied with the product, insert the needle into a
vein. Let blood flow back to the end of the tube. Attach the syringe to the threaded,
locking end of the venipuncture kit. Inject the made up solution slowly into
the vein following the instructions given to you by your doctor. Take care not to get
any blood in the syringe containing the made up solution. The maximum rate of
administration is 2 millilitres per minute.
Continuous infusion
Mononine can also be given by a long-term (continuous) infusion over several hours
or days. This must be done and controlled by your doctor.
Check yourself for any side effects that might happen straight away. If you have any
side effects that might be related to the administration of Mononine, the injection
or infusion should be stopped (see also section "Take special care with Mononine").
If you have any further questions on the use of this product, ask your doctor or
pharmacist.

4







Keep out of the reach and sight of children.
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
Store in a refrigerator (2 °C – 8 °C).
During its shelf life the product (when kept in its outer carton) may be stored at
ambient room temperature (up to 25 °C) for up to one month without being
refrigerated again during this period. The date of transfer to room temperature
and the end of the 1-month period should be recorded on the outer carton.
At the end of the period, the product has to be used or discarded.
• The made up solution should be used immediately.
• If the made up solution is diluted (up to one part in 10), the solution must be
used immediately, however the physico-chemical stability has been demonstrated
for 24 hours.
• Your doctor will inform you how to dispose of unused product or waste material.

6. FURTHER INFORMATION
What Mononine contains
Mononine contains 500 or 1000 IU human coagulation Factor IX per vial.
Once dissolved with 5 ml (500 IU) or 10 ml (1000 IU) of the solvent, the made up
solution contains approximately 100 IU human coagulation Factor IX per ml.

Other ingredients are:
Histidine, mannitol, sodium chloride, hydrochloric acid or sodium hydroxide
(in small amounts for pH adjustment).
Solvent: Water for injections.

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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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