ZIFERON

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In the name of God

 

Ziferon® 250 microgram/ml

Interferon beta-1b

Lyophilized powder and solvent for solution for injection

Read all Ziferon 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 further questions, ask your doctor, pharmacist or Medical

Support Team of Zistdaru Danesh Co.

This medicine has been prescribed for you only. Do not pass it on to

others, even if their signs of illness are the same as yours.

This medicine could be prescribed by doctor for medical condition not

mentioned in this leaflet.

If you get any side effects, talk to your doctor, pharmacist or nurse. This

includes any possible side effects not listed in this leaflet.

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Contents in this leaflet:

1. About Ziferon

2. Ziferon Packaging

3. Ziferon Indication

4. General consideration before using Ziferon.

5. Pregnant & Lactating mothers

6. Precautions

7. Ziferon & other medicines

8. Dosage & Administration

9. If you forget to use Ziferon

10. How to use Ziferon

11. Proper injection guide

12. Useful tips to reduce the risk of getting injection site reactions

13. Possible side effects

14. Storage of Ziferon

1. About Ziferon

Ziferon belongs to interferon family-group beta. Interferons are proteins

produced in the body naturally to defense against the threatening

infections by immune system.

2. Ziferon Packaging

1 Ziferon vial containing 9.6 million international unit (300 micrograms)

interferon beta-1b, 1 pre-filled syringe with solvent, 1 sterile vial adapter,

2 alcohol pad and 1 short needle packed in a small box.

• After reconstitution, each milliliter contains 250 microgram (8.0 million

IU) interferon beta-1b

• 15 small boxes, 1 patient leaflet and 1 injection card packed in a large

box.

The other ingredients in the powder: mannitol and human albumin.

Each prefilled syringe contains 1.2 milliliter sodium chloride solution

0.54% w/v.

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3. Ziferon Indication

• Ziferon is used to treat relapsing forms of multiple sclerosis (MS) to

reduce the number of flare-ups and slow down the development of

physical disability associated with MS.

4. General consideration before using Ziferon

• Children

There have been no formal clinical trials undertaken in children.

Ziferon should not be used in these populations:

• Allergic people (hypersensitive) to natural or recombinant interferon

beta, human albumin or any of the other ingredients of this medicine

(mentioned in Ziferon Packaging).

• People who currently suffer from severe depression and/or

suicidal thoughts.

• People who have severe liver disease.

• Pregnant mothers: You should not start treatment with this medicine.

Tell your doctor if any of the above applies to you.

5. Pregnant & Lactating mothers

A. Pregnant mothers

• If you could get pregnant, use appropriate contraception while you are

on Ziferon.

• If you are pregnant or you think you may be, tell your doctor. Ziferon

therapy should not be started if you are pregnant.

• If you wish to become pregnant, discuss this with your doctor first.

• If you become pregnant while using Ziferon, stop your treatment and

contact your doctor immediately.

• Your doctor will decide together with you, if your Ziferon treatment will

be continued or not.

B. Lactating mothers

• It is not known whether interferon beta-1b passes into human breast

milk. Your doctor decides whether to stop breast-feeding or to stop using

the medicine.

Talk to your doctor before you start using Ziferon:

• If you have immune system problems.

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• If you have had depression or you are depressed or you have previously

had thoughts of suicide.

Your doctor will closely monitor you during treatment.

• If your depression and/or suicidal thoughts are severe, you will not be

prescribed Ziferon.

• If you have ever had seizures or if you are taking medicines to treat

epilepsy, your doctor will monitor your treatment carefully.

• If you have severe kidney problems your doctor may monitor your

kidney function during treatment. If you notice foam forming when you

urinate, swelling in ankles or eyelids, rapid weight gain; call your doctor

to follow the signs.

Call your doctor, if you experienced the followings:

• If you experience symptoms such as itching all over your body, swelling

of your face and/or your tongue or sudden shortness of breath. These may

be symptoms of a serious allergic reaction (hypersensitivity), which may

become life threatening.

• If you feel noticeably more sad or hopeless than before the treatment

with the medicine, or if you develop thoughts of suicide. If you become

depressed while you are on Ziferon, you may need special treatment and

your doctor will closely monitor you and may also consider stopping your

treatment. If you suffer from severe depression and/or suicidal thoughts,

you will not be treated with interferon family.

• If you notice any unusual bruising, excessive bleeding after injury or

if you seem to be catching a lot of infections. These may be symptoms

of a fall in your blood cell count or in the number of platelets in your

blood (cells, which help the blood to clot). Your doctor will monitor your

treatment carefully.

• If you have loss of appetite, fatigue, feeling sick, repeated vomiting,

nausea, especially, if you notice widespread itching, yellowing of the

skin or of the whites of the eyes, or easy bruising. These symptoms may

suggest problems with your liver. The most serious liver problems were

reported in patients taking other medicines or who were suffering from

diseases that can affect the liver (e.g. alcohol abuse, severe infection).

• If you experience symptoms like irregular heartbeat, swelling such as of

the ankles or legs, or shortness of breath. This may suggest a disease of

the heart muscle. If you have had history of heart problems, inform your

doctor.

• If you notice pain in your belly which is radiating to your back, and/or

you feel sick or have a fever. This may suggest an inflammation of the

pancreas (pancreatitis).

6. Precautions

1. Your doctor prescribes diagnostic laboratory tests before starting

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Ziferon and regularly during the treatment to assess your health condition.

Also, she or he monitor your blood pressure, kidney function, etc.

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

refer to the instructional centers.

3. If anyone else helps you for preparing the medicine and injection, she

or he should refer to instructional centers.

4. It is preferred to inject Ziferon at evenings.

5. It is preferred to keep out the medicine 1 hour before injection of the

refrigerator. Cool medicine can cause getting injection site reactions.

6. Do not reuse your syringe and short needle.

7. Ziferon is a Prescribed Only Medicine (POM).

8. Ziferon has no preservative and should be used immediately after

preparation. Dispose any unused portion of the medicine.

9. Keep Ziferon out of sight and reach of the children.

10. Do not store the expired medicine and the unused.

11. Ziferon may cause drowsiness. If you are especially sensitive, this might

affect your ability to drive or use machines.

7. Ziferon & other medicines

• Tell your doctor or pharmacist if you are using, have recently used or

might use any other medicines, including medicines obtained without a

prescription.

• No formal interaction studies have been carried out to find out whether

Ziferon affects other medicines or is affected by them.

• Using this medicine with other medicines that modify the immune

system response is not recommended, except anti-inflammatory medicines

called corticosteroids or the adrenocorticotropic hormone (ACTH).

• Ziferon should be used with caution with medicines which need liver

function for their removal from the body, for example medicines used to

treat epilepsy (like phenytoin) and medicines which affect the production

of blood cells.

Ziferon with food and drink

Ziferon is injected under the skin, so any food or drink you consume is not

thought to have any effect on the medicine.

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8. Dosage & Administration

Always use this medicine exactly as your doctor has told you for more

effective treatment.

The recommended dose for sub-cutaneous (under the skin)

injection in MS patients is:

• Adults – Generally, 250 microgram (1.0 milliliter) every other day. (See

the table below for dose titration).

• Efficacy and safety of the medicine has not been investigated in children

and adolescents less than 18 years of age in comparison to others.

• Important note:

When starting treatment with Ziferon even you have had history

usage of interferon beta-1b manufactured by another company,

the following table for dose titration is recommended:

week of use

Recommended

Titration

Dose

(microgram)

Volume

(milliliter)

Weeks 1-2 25% 62.5 0.25

Weeks 3-4 50% 125 0.50

Weeks 5-6 75% 187.5 0.75

Weeks 7+ 100% 250 1

9. If you forget to use Ziferon

If you have forgotten to give yourself an injection at the right time, do

it as soon as you remember and then follow on with the next one 48

hours later. It is preferred to inject Ziferon at a regular time for example

at evenings.

Note: You are not permitted to stop treatment without your doctor

order.

• Inform your doctor if you injected too much the medicine or injected

it too often.

10. How to use Ziferon

Study the procedure described below carefully and pay attention to the

notices before injection:

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• Prepare everything you may need in injection procedure.

• Wash your hands with a soap and water thoroughly. Do not touch your

hair and skin afterwards.

• Do not touch the short needle to keep it sterile during preparation

procedure.

Proper preparing procedure

1. Take out the Ziferon kit from refrigerator.

Leave it for 1 hour until reaches the room

temperature. This will decrease pain in the

injection site.

2. Remove the protective cap from

the Ziferon vial. Do not touch top

of the vial after removing the cap.

3. Use an alcohol pad to clean

the top of the vial. Move in one

direction and then leave the

alcohol pad on top of the vial until

you are ready to use it.

4. Open the pack containing the

adapter, but leave the adapter

inside. Do not remove or touch

the adapter to keep it sterile.

5. Remove the alcohol pad from

the top of the Ziferon vial. Place

the pack containing the adapter

on top of the vial. Push it down

until it snaps into place. Make

sure of snapping into place

with pushing it down again.

If you do not perform this

step properly, leakage can

occur and you may lose your

medicine.

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6. Pick up the prefilled syringe from the box and untwist it by turning the

plastic cap. (Syringe tip should not touch the surrounding).

7. Remove the package from the adapter.

8. Keep the adapter by your thumb

and forefinger and twist the syringe on

the adapter by your other hand. Make

sure that the syringe stays firmly on the

adapter.

9. Transfer the prefilled syringe

content completely (1.2 ml) into

the vial.

10. Keeping the syringe attached

to the vial, gently swirl the vial

(8 shape) until all powder has

dissolved. Avoid shaking the vial

vigorously, as this will produce

foam. Extra foam can reduce

efficacy of the medicine. After

reconstitution, there will be 250

micrograms per milliliter solution

of interferon beta-1b and can be

kept in refrigerator for 3 hours.

Note: Wait a while until the produced foam disappears. This can

prevent loss of efficacy caused by foam forming and reduce pain

in injection site.

11. After reconstitution, Ziferon is clear, colorless to light yellow. Do not

inject the vial content and discard the vial if the solution appears cloudy,

or if floating particles are visible.

12. Turn the vial- adapter- syringe upside

down. Slowly pull back the plunger rod of

the syringe to draw up the vial content.

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13. Tap the syringe gently until any air bubbles that formed rise to the top

of the barrel of the syringe. Push the plunger rod down gently to empty

the bubbles.

14. Push the plunger rod down slowly to the required volume (printed

digits on the syringe body) as directed by your doctor.

15. Open the package containing a short needle, but leave its guard in

place.

16. Keep the adapter by your thumb and forefinger and untwist the

syringe counterclockwise by other hand protecting its tip from touching

the surrounding.

17. Twist the short needle to the syringe immediately, by turning the

guard once. Make sure that short needle stays on the syringe firmly.

18. Set the syringe aside until the injection site is prepared.

11. Proper injection guide

• Select an injection site as directed by your doctor and considering

Ziferon injection card.

There are 8 zone for injection as below:

Arms (2 areas), abdomen (2 areas), buttocks (2 areas), thighs (2 areas).

Each area consists of 6 sections: upper (right & left), median (right & left),

lower (right & left). See Ziferon Injection Card for details.

Note: You may experience injection site reactions when using the

medicine. This can include swelling, discoloration, inflammation,

and pain or hypersensitivity reaction at the injection site.

12. Useful tips to reduce the risk of getting

injection site reactions

• Compliance to useful tips in the (proper preparing procedure) section

(called sterile procedure) plays an important role in reducing injection site

reaction.

• Take out the Ziferon kit from refrigerator. Leave it for 1 hour until

reaches the room temperature. This will decrease pain in the injection site.

• Change the injection site in every new injection. Do not inject in the

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same section in 2 consecutive injections.

• Fill the Ziferon Injection card after each injection and make sure for

compliance with the schedule in the card.

• Do not inject in area where you can feel lumps, bumps, firm knots,

and pain.

• Do not inject in the skin that is discolored, indented, scabbed, or broken.

Talk to your doctor about these or any other unusual conditions you may

find.

Note: Consult your doctor in case of cracks in the skin or liquid

coming out from the injection site.

• To reduce reaction at the injection site, your initial injections must be

done in the presence of specialized nurses for Ziferon who have the

necessary information and skills. (Study steps mentioned in the section

≤proper injection under the skin≥).

• Use a cold compress few minutes before and after the injection. It can

help to relieve and reduce pain at injection site.

• You must consult your doctor or specialized nurse for Ziferon, if injection

site reactions or other side effects continue.

• The following tips are necessary for proper injection under the skin:

1. Clean and disinfect the chosen site for injection with an alcohol pad in

one direction and wait until dry. Hold the syringe containing the prescribed

dose like a pencil or dart. Remove the guard from the short needle, but do

not touch the needle itself.

2. Gently pinch the skin together around the site, to lift it up a bit. This is

necessary for proper injection under the skin.

3. Stick the straight into the skin at a 90 degrees angle with a quick, firm

motion.

4. Using the slow steady push, inject the medicine by pushing the plunger

rod all the way in until the syringe is empty.

5. After injection, wait 15 seconds and remove the needle by pulling

straight out.

6. To prevent needle stick injury and spread of infection, do not try to

recap the needle.

7. Place used needles, syringes,

vials and alcohol pads in a

closeable, puncture-resistant

container such as special

containers for hospital wastes,

plastic bottles and an empty

coffee can.

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13. Adverse effects

Along with its needed effects, a medicine may cause some unwanted

effects.

Note: If you get any serious side effects, talk to your doctor, pharmacist

or nurse. This includes any possible side effects not listed in this leaflet.

At the beginning of treatment adverse reactions are common but they

usually will be tolerate with further treatment and do not need any

medical attention. Your doctor will tell you some recommendations to

minimize common adverse effects.

Flu-like symptoms and injection site reactions are both common adverse

effects at the start of Ziferon treatment but they usually decrease or go

away over time. In general, they usually do not need any medical attention

and subside with more Ziferon administration.

Some points to reduce common adverse effects (Flu-like symptoms):

• Consider injecting Ziferon at bed or use of analgesics and/or antipyretics

before or after Ziferon administration (according to your doctor

recommendations) may be helpful to diminish Flu-like symptoms.

• Gradual dose titration according to titration table at the beginning of

treatment (in Dosage & Administration section 8) may be reduced Flu-like

symptoms.

14. Storage of Ziferon

• Keep Ziferon in a refrigerator (2 to 8 degrees of centigrade).

More Common

(1 out of 10 patient)

Less Common

(10 out of 100 patient)

Rare

(1 out of 1000 patient)

• Flu-like symptom

complex including

fever, chills, arthralgia,

malaise, sweating,

headache, or myalgia.

• Injection site

reactions including

Redness, swelling,

discoloration,

inflammation, pain,

hypersensitivity and

necrosis in rare cases.

• Gastrointestinal

symptoms

• Anemia (red blood

cell count reduction)

• Thyroid function

changes

• Menstrual disorders

• Weight changes

• Urticaria

• Pruritus

• Alopecia

• Hypersensitivity

reactions

• Pancreatitis

• Blood clots in the

small blood vessels

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ZIFERON

• Do not freeze.

• After adding of solvent to Ziferon powder, you can keep the prepared

solution for use for 3 hours in a refrigerator.

• Ziferon has no preservative and should be used immediately after

preparation. (Single use only)

• After preparation, your solution is transparent (colorless to light yellow).

Do not inject and discard the vial if the solution appears cloudy, or if

floating particles are visible.

Last Revision for this package leaflet: September 2016

For more information about Ziferon, please contact your doctor,

pharmacist, or Medical Support Team of Zistdaru Danesh Co.

Zistdaru Danesh Co. Tehran, Iran.

Website: www.zistdaru.ir

E-mail: info@zistdaru.ir

Tel: 021-88520397& 021-88520399

Cell (24 hours): +98-935-2203041 & +98-935-2203042

References: 1. www.fda.gov, FDA Approved labeling Text for Interferon

beta-1b

Revised: October 2012 Reference ID: 3220464

2. www.drugs.com, interferon beta-1b