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<DOCUMENT author="perl program" datec=020199 title="leaflet" book="ABPI" edition="1996-97" section="company">
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<HEAD weight="bold" >
Betaferon
</HEAD>


<BLOCK>
Important information, please read carefully.
</BLOCK>

<DIV type=1>

<HEAD weight="bold" >
Betaferon contains the following substances (Composition)
</HEAD>

<DIV type=2>

<HEAD slant="italic" >
Active ingredients:
</HEAD>


<BLOCK>
1 ml of the prepared solution for injection contains 0.25 mg (8 million IU) of Interferon beta-1b. Betaferon is formulated to contain 0.3 mg (9.6 million IU} of Interferon beta-1b per vial at a calculated overfill of 20%. inactive ingredients: Human albumin, dextrose
</BLOCK>


</DIV>

</DIV>
<DIV type=1>

<HEAD weight="bold" >
What presentations of Betaferon are available?
</HEAD>


<BLOCK>
Each pack of Betaferon contains 15 vials of Interferon beta-1b and 15 vials of 0.54% sodium chloride solution.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
How does Betaferon work?
</HEAD>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
(Properties of the preparation)
</HEAD>


<BLOCK>
Multiple sclerosis (MS) is a disease of the central nervous system (CNS) (i.e. brain and spinal cord) and its exact cause is unknown. An abnormal response by the body’s immune system is thought to play an important part in the process which damages the CNS.
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<BLOCK>
Interferon beta-1b has been shown to modify the immune system response.
</BLOCK>


<BLOCK>
Interferons belong to the family of cytokines, which are naturally occurring proteins.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
Who is responsible for Betaferon?
</HEAD>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
(Name and address of the holder of the marketing authorisation, manufacturer)
</HEAD>


<BLOCK>
Schering AG, D-13342 Berlin.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
For what purpose is Betaferon used?
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
(Indications)
</HEAD>


<BLOCK>
Betaferon is indicated for use in ambulatory patients (patients who can walk) with relapsing-remitting multiple sclerosis (MS) characterized by at least two attacks of neurologic dysfunction over a two year period followed by complete or incomplete recovery. In this patient population Betaferon was shown to reduce the frequency and severity of clinical relapses, to reduce the number of MS related hospitalizations and to prolong the relapse-free time.
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<BLOCK>
There is no evidence of an effect of Betaferon on the length of attacks, symptoms in between attacks, or the progression of the disease. The effect of Betaferon on performance of daily activities or in the social field is not known. Betaferon has not yet been investigated in patients with progressive multiple sclerosis.
</BLOCK>


<BLOCK>
There is no evidence of an effect on disability.
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<BLOCK>
Clinical studies show that not all patients respond to treatment with Betaferon. Despite treatment worsening of the symptoms during attacks has been observed in some patients. It is not possible to foresee which patients will not respond or whose symptoms will worsen despite treatment.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
When should Betaferon not be used?
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
(Contraindications)
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<BLOCK>
You should not use Betaferon if you are pregnant or if you have a history of hypersensitivity to natural or recombinant interferon beta or human albumin.
</BLOCK>


<BLOCK>
You should not use Betaferon if you are under 18 years of age, because it has not been investigated in this age group. It has not been investigated in this age group. You should also not use Betaferon if you have a history of severe depressive illness and/or suicidal thoughts, liver failure or inadequately treated epilepsy.
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<BLOCK>
If a serious hypersensitivity reaction occurs, treatment with Betaferon should be discontinued.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
What precautions must be observed during the use of Betaferon?
</HEAD>


<BLOCK>
Depression and suicidal thoughts have been reported by patients. In rare cases this may lead to suicidal <CB n=2> attempts. If you experience such symptoms, contact your doctor promptly.
</BLOCK>


<BLOCK>
If you have a history of seizures or of depression or if you suffer from pre-existing heart disorders, Betaferon should be administered with caution. Caution should also be exercised if you are taking anti-epileptic drugs. Betaferon should also be administered with caution if you have a bone marrow disorder. If your white blood cell count decreases, your doctor should monitor you closely for the development of fever or infection.
</BLOCK>


<BLOCK>
It is not known if Betaferon has a negative effect on human fertility but based on the experience with other interferons a decrease in male or female fertility cannot be ruled out. There is no information on the use of Betaferon in patients with kidney problems. Therefore, if you have such problems, your kidney function should be monitored during treatment. During the treatment with Betaferon your body may produce substances which may reduce the effectiveness of the treatment. This is called neutralising activity and only occurs in some patients. However, it is not possible to foresee whether you belong to this group of patients with reduced efficacy or not.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
May Betaferon be used during pregnancy and lactation?
</HEAD>


<BLOCK>
Betaferon should not be used during pregnancy or if you are trying to become pregnant. If you wish to become pregnant, discuss the matter with your doctor first. While using Betaferon women of childbearing age should take appropriate contraceptive measures. If you do become pregnant you should stop your treatment and contact your doctor immediately.
</BLOCK>


<BLOCK>
It is not known whether Interferon beta-1b is excreted in human milk. However, since serious adverse reactions to Interferon beta-lb in breast-fed infants are theoretically possible, you should discuss the mater with your doctor and make a decision whether breast-feeding or Betaferon should be stopped .
</BLOCK>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
What to be aware of if you are taking any other medicine (Interactions)
</HEAD>


<BLOCK>
With the exception of corticoids or ACTH, Betaferon should not be used with substances modifying the immune system response.
</BLOCK>


<BLOCK>
Caution should be exercised when Interferon beta-1b is administered in combination with other drugs which need a certain liver enzyme system (known as cytochrome P450 system) for their metabolism. These drugs include some widely used antipyretics (drugs against fever and pain), oral contraceptives, and antiepileptics.
</BLOCK>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
How is Betaferon used?
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
(Dosage and administration)
</HEAD>


<BLOCK>
The treatment with Betaferon should be initiated under the supervision of a physician experienced in the treatment of the disease.
</BLOCK>


<BLOCK>
At the present time it is not known how long treatment with Betaferon should last. Effectiveness of this therapy for more than two years has not been established.
</BLOCK>


<BLOCK>
The duration of treatment will be decided by your doctor. Treatment is not recommended if you have had fewer than two MS attacks in the previous two years.
</BLOCK>


<BLOCK>
Before administration, the Betaferon solution for injection has to be prepared from a vial of Betaferon and 1.2 ml of liquid from a vial of diluent. 1.0 ml of the prepared Betaferon solution for injection is then injected subcutaneously (under the skin) every other day. This is equal to 0.25 mg (8 million IU).
</BLOCK>


<BLOCK>
This will either be done by your doctor or his/her assistant or by yourself after you have been carefully and sufficiently instructed and trained. To assist you in subcutaneous self-administration of Betaferon, detailed instructions for self-injection are provided with this leaflet. These instructions also tell you how the Betaferon solution for injection is prepared.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
What to do if you miss an injection
</HEAD>


<BLOCK>
If you forget to administer your injection at the correct time you should give it as soon as you remember. Your next injection should be given 48 hours later.
</BLOCK>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
What effect could an overdose of Betaferon have? (Overdosage)
</HEAD>


<BLOCK>
Administration of many times the dose of Betaferon recommended for the treatment of MS did not lead to life-threatening situations. However, in the case of accidental overdosage, please consult the doctor who has prescribed Betaferon for you. Also if by mistake you administer your injection too frequently (e.g. one injection every 24 h instead of one injection every 48 h) you should consult your doctor.
</BLOCK>


<BLOCK>

<EMPH weight="bold">
Are there any side effects during the use of Betaferon?
</EMPH>
 Injection site reactions including inflammation, pain hypersensitivity, skin cell-death (necrosis), and non-specific reactions occur frequently. The occurrence of injection site reactions usually decreases over time. Flu-like symptoms (fever, chills, muscular pain, a general feeling of being unwell, or sweating) have been seen frequently. The occurrence of the symptoms decreased over time.
</BLOCK>


<BLOCK>
Menstrual disorders may occur in premenopausal women.
</BLOCK>


<BLOCK>
Central nervous system (CNS) related adverse events including depression, anxiety, emotional instability, loss of identity or reality (depersonalization), convulsions, suicide attempts, and confusion have been observed.
</BLOCK>


<BLOCK>
Serious hypersensitivity reactions are rare. If a severe reaction occurs, consult your doctor immediately. The number of white blood cells can decrease and the activity of enzymes which are closely related to the function of the liver may increase. Therefore, a differential white blood count and determination of serum chemistry (SGOT, SGPT) should be obtained prior to treatment and repeated regularly during the therapy. If side effects are severe or if you notice any other side effects please inform your doctor.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
How should Betaferon be stored?
</HEAD>


<BLOCK>
Betaferon must be kept cold (2-8°C). Store it in a refrigerator (but not in a freezer or the freezing compartment) before reconstitution (preparing the Betaferon solution for injection). If, after reconstitution, you do not inject Betaferon at once, you can store the reconstituted solution in a refrigerator (but not in a freezer or the freezing compartment) up to 3 hours.
</BLOCK>


<BLOCK>
Please note the expiry date on the pack. Do not use after this date.
</BLOCK>


<BLOCK>
Store all drugs properly and keep them out of the reach of children.
</BLOCK>


</DIV>
<DIV type=1>

<HEAD weight="bold" >
Package insert was last updated on:
</HEAD>


<BLOCK>
July 12, 1995.
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
Annex:
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</DIV>
<DIV type=1>

<HEAD weight="bold" >
SELF-INJECTION PROCEDURE
</HEAD>


<BLOCK>
The following instructions are intended to explain how to prepare Betaferon for administration and how to proceed in injecting Betaferon yourself. Please read the instructions carefully and follow them step by step. Your doctor or his/her assistant will instruct and assist you in learning the procedure and the technique of self-administration. Do not attempt self-administration until you are sure that you understand the requirements for preparing the injection solution and giving the injection to yourself.
</BLOCK>


<BLOCK>
The instructions comprise the following main steps:
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<LIST type="ordered">

<ITEM>

<BLOCK>
Preparing for self-injection.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Drawing up the diluent (sodium chloride solution) into the syringe
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</ITEM>


<ITEM>

<BLOCK>
Injecting the required volume of diluent (1.2 ml) into the vial of Betaferon.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Drawing up the required volume of the solution for injection (1.0 ml) into the syringe.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Choosing and preparing the injection site and injecting the Betaferon solution (1.0 ml) subcutaneously (under the skin).
</BLOCK>

</ITEM>


<CB n=2>
<ITEM>

<BLOCK>

<EMPH weight="bold">
Preparing for self-injection
</EMPH>

</BLOCK>

</ITEM>


<ITEM>

<BLOCK>

<EMPH slant = "italic">
Collect
</EMPH>
 all your equipment before you begin the process.
</BLOCK>

</ITEM>

</LIST>



<BLOCK>
You will need:
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<LIST type="bulleted">

<ITEM>

<BLOCK>
vial of diluent for Betaferon(sodium chloride solution 0.54%)
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
vial of Betaferon
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</ITEM>


<ITEM>

<BLOCK>
2-ml syringe
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
21-gauge needle
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
27-gauge needle
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
alcohol wipes
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
disposal unit (a container for used syringes and needles)
</BLOCK>

</ITEM>

</LIST>



<LIST type="ordered">

<ITEM>

<BLOCK>

<EMPH slant = "italic">
Wash
</EMPH>
 your hands thoroughly with soap and water.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>

<EMPH slant = "italic">
Remove
</EMPH>
 the protective caps from both vials.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Use alcohol wipes to 
<EMPH slant = "italic">
clean
</EMPH>
 the tops of the vials move in one direction and use one wipe per vial.
</BLOCK>

</ITEM>

</LIST>



<BLOCK>
NOTE: 
<EMPH slant = "italic">
Leave
</EMPH>
 an alcohol wipe on top of each vial until you are ready to use it.
</BLOCK>

<DIV type=2>

<HEAD ltag="bullet" >
Drawing up the diluent (sodium chloride solution) into the syringe
</HEAD>




<BLOCK>
Only the vial of diluent (liquid) that comes inside your prescription package should be used to dissolve the white powder in the Betaferon vial.
</BLOCK>


<LIST type="ordered">

<ITEM>

<BLOCK>
Resting your hands on a stable surface, 
<EMPH slant = "italic">
remove
</EMPH>
 the syringe from its wrapping. Do not touch the tip (nozzle) of the syringe.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Take the 21-gauge needle out of its wrapping and place it firmly 
<EMPH slant = "italic">
onto
</EMPH>
 the tip (nozzle) of the syringe. 
<EMPH slant = "italic">
Remove
</EMPH>
 the needle guard from the needle. Do not touch the needle.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>

<EMPH slant = "italic">
Pull back
</EMPH>
 the plunger (on the syringe) to the 1.2 ml mark.
</BLOCK>

</ITEM>

</LIST>



<BLOCK>
NOTE: Read the label on the vials - find the diluent vial and throw away the alcohol wipe on top of it.
</BLOCK>


<LIST type="ordered">

<ITEM>

<BLOCK>
Holding the vial of diluent on a stable surface, slowly insert the needle straight through the rubber stopper, into the top of the vial.
</BLOCK>

</ITEM>

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<BLOCK>
NOTE: When inserting and removing needles from vials, be sure not to touch the needles or the rubber stoppers on the vials with your hands.
</BLOCK>


<BLOCK>
If you touch a stopper, clean it with a fresh alcohol b wipe. If you touch a needle or the tip (nozzle) of the  syringe, throw it away into the disposal unit and start with a new one.
</BLOCK>


<BLOCK>
If the needle touches any surface, throw it away into the disposal unit and start with a new one.
</BLOCK>


<LIST type="ordered">

<ITEM>

<BLOCK>

<EMPH slant = "italic">
Push
</EMPH>
 in the plunger all the way to gently inject air into the vial (
<EMPH slant = "italic">
leave
</EMPH>
 the needle in the vial of diluent).
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Turn the vial of diluent 
<EMPH slant = "italic">
upside down
</EMPH>
.
</BLOCK>

</ITEM>

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<BLOCK>
NOTE: Keep the needle tip in the liquid.
</BLOCK>


<LIST type="ordered">

<ITEM>

<BLOCK>
Resting your hands on a stable surface, hold the vial and syringe in one hand and slowly 
<EMPH slant = "italic">
pull back
</EMPH>
 the plunger of the syringe to the 1.2 ml mark (to draw up that amount of liquid) with your other hand. Keeping the vial upside down, gently 
<EMPH slant = "italic">
tap
</EMPH>
 the syringe until any air bubbles rise to the top of the barrel of the syringe.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Carefully 
<EMPH slant = "italic">
push
</EMPH>
 in the plunger to eject ONLY THE AIR through the needle. Make sure that the syringe contains 1.2 ml of diluent.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>

<EMPH slant = "italic">
Remove
</EMPH>
 the needle with the syringe from the vial of diluent.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>

<EMPH weight="bold">
Injecting the required volume of diluent (1.2 ml) into the vial of Betaferon
</EMPH>
 NOTE: Find the Betaferon vial and throw away the alcohol wipe on top of it.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Holding the Betaferon vial on a stable surface, slowly 
<EMPH slant = "italic">
insert
</EMPH>
 the needle of the syringe (containing 1.2 ml of liquid) all the way through the stopper of the vial.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Push the plunger down slowly, 
<EMPH slant = "italic">
directing
</EMPH>
 the needle toward the side of the vial to allow the liquid to run down the inside wall (injecting diluent directly onto the powder will cause excess foaming).
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
Make sure that the needle 
<EMPH slant = "italic">
does not come into contact
</EMPH>
 with the powder or the resulting solution.
</BLOCK>

</ITEM>


<ITEM>

<BLOCK>
After the diluent in the syringe has been completely injected into the Betaferon vial 
<EMPH slant = "italic">
hold
</EMPH>
 the vial between your thumb, forefinger and middle finger <PB n=3>
</BLOCK>

</ITEM>

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<BLOCK>
NOTE: Do not use any areas in which you feel lumps firm knots, depressions pain, or discoloration; talk to your doctor or healthcare professional about anything you find.
</BLOCK>

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