Betaferon 250 microgramos/ml, polvo y disolvente para solucion inyectable

Prospecto: information for the user

Betaferon 250 micrograms/ml, powder and solvent for injectable solution

interferon beta-1b

Read this prospect carefully before starting to use this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse,even if they are not listed in this prospect. See section4.

Appendix – procedure for self-injection

What is Betaferon

Betaferon is a type of medication known as an interferon, used in the treatment of multiple sclerosis. Interferons areproteins produced by the body that help fight off attacks on the immune system, such as viral infections.

How Betaferon works

Multiple sclerosis (MS)is a chronic disorder that affects the central nervous system (CNS), particularly the functioning of the brain and spinal cord. In MS, inflammation destroys the protective covering (calledmyelin) that surrounds the nerves of the CNS and prevents nerves from functioning properly. This is calleddemylination.

The exact cause of MS is unknown. It is thought that in the process that damages the CNS, an abnormal response by the immune system plays an important role.

Damage to the CNScan occur during an MS attack(relapse). It can cause temporary disability, such as difficulty walking. Symptoms may disappear completely or partially.

It has been shown that interferon beta-1b changes the immune system's response and contributes to reducing disease activity.

How Betaferon helps combat your disease

Single clinical episode suggestive of a high risk of developing multiple sclerosis:Betaferon has been shown to delay progression to defined multiple sclerosis.

Relapsing-remitting multiple sclerosis:People with RRMShave occasional or relapsing attacks, during which symptoms worsen significantly. Betaferon has been shown to reduce the number of attacks and make them less severe, reduce the number of hospital stays due to the disease, and prolong the time without relapses.

Secondary and progressive multiple sclerosis:In some cases, people with RRMS notice that their symptoms increase and progress to another form of MS, called secondary progressive MS. With this, people feel increasingly disabled, with or without relapses. Betaferon can reduce the number and severity of attacks, and delay the progression of disability.

What is Betaferon used for

Betaferon is for use in patients

?Who have experienced symptoms for the first time that indicate a high risk of developing multiple sclerosis. Your doctor will rule out other causes that could explain these symptoms before administering treatment.

?Who suffer from relapsing-remitting multiple sclerosis, with the appearanceof at least two relapses in the two years prior.

?Who suffer from secondary progressive multiple sclerosis, with active disease demonstrated by the appearance of relapses.

Do not use Betaferon

• If you are allergic(hypersensitive)to interferon beta natural or recombinant, human albumin, or any of the other components of this medication (listed in section6).
• If you currently have severe depression and/or suicidal thoughts(see also “Warnings and precautions” and section4. “Possible side effects”).

–If you have a severe liver disease(see “Warnings and precautions”, “Use of Betaferon with other medications” and section4.“Possible side effects”).

?Inform your doctorif any of the above situations apply to you.

Warnings and precautions

Consult your doctor before starting to use Betaferon:

• If you havemonoclonal gammopathy. This is a disease of the immune system or in which there is an abnormal protein in the blood.Problems with smaller blood vessels (capillaries)may occur when using medications like Betaferon(systemic capillary leak syndrome). This can lead to shock(collapse)and even be fatal.

–If you have had or have depression, or have previously had suicidal thoughts.Your doctor will closely monitor you during treatment. If your depression and/or suicidal thoughts are severe, you will not be prescribed Betaferon (see also “Do not use Betaferon”).

• Ifyou have ever had seizures or are using medications to treat epilepsy(antiepileptics), your doctor will closely monitor your treatment (see also “Use of Betaferon with other medications” and section4. “Possible side effects”).

• If you haveserious kidney problems, your doctor may monitor your renal function during treatment.

Your doctor should also be aware of the following circumstanceswhile using Betaferon:

• If you experience symptoms such as itching all over your body, swelling of the face and/or tongue, or sudden difficulty breathing.This may be a sign of a severe allergic reaction(hypersensitivity), which could be fatal.

• If you feel significantly more sad or hopeless than before starting treatment with Betaferon, or if you have suicidal thoughts.If you become depressed while on Betaferon treatment, you may need special treatment, and your doctor will closely monitor you and may also consider interrupting your treatment. If you have severe depression and/or suicidal thoughts, you will not be treated with Betaferon (see also “Do not use Betaferon”).

• If you notice that you bruise easily, bleed excessively when you have cuts, or contract many infections.This may be a sign of a decrease in blood cell count or platelet count.

• If you experience loss of appetite, fatigue, dizziness(nausea), repeated vomiting, especially if you experience diffuse itching, the appearance of a yellowish color on your skin or in the white part of your eyes, or if you bruise easily.This may indicate liver problems. In some clinical studies, changes in liver function values have been observed in patients treated with Betaferon. As with other interferon betas, rare cases of severe liver damage, including liver failure, have been reported in patients treated with Betaferon. The most severe cases were reported in patients taking other medications or having diseases that can affect the liver (e.g., alcohol abuse, severe infection).

• If you experience symptoms such as irregular heartbeats or swelling in your ankles or legs, or difficulty breathing.This may indicate heart muscle disease(myocarditis), which has been reported in rare cases in patients using Betaferon.

• Ifyou experience abdominal pain radiating to your back, and/or if you feel dizzy or have a fever.This may indicate pancreatitis(pancreatitis), which has been reported with the use of Betaferon. This is often associated with an increase in certain fats in the blood(triglycerides).

?Stop using Betaferon and inform your doctor immediatelyif any of these occur.

Other things to consider when using Betaferon

• You will need a blood testto measure your blood cell count, blood biochemistry, and liver enzymes. This will be donebefore starting Betaferon treatment, regularly after starting treatment with Betaferon, and periodically while continuing with it,even if you do not have specific symptoms.These blood tests will be done in addition to the blood tests that are normally done to monitor your EM.

• If you have heart disease,the flu-like symptoms that often occur at the start of treatment may be a strain on you.Betaferon should be used with caution, and your doctor will monitor any possible worsening of your heart condition, especially at the start of treatment. Betaferondoes not directly affect the heart.

• You will have a thyroid function check,regularly or whenever your doctor considers it necessary for other reasons.

• Betaferon contains human albumin and, therefore, carries a potential risk of transmission of viral diseases.No risk of transmission of Creutzfeldt-Jakob disease (CJD) can be ruled out.

• During treatment with Betaferon, your body may produce substances calledneutralizing antibodies,which may react with Betaferon(neutralizing activity).It is not clear if these neutralizing antibodies reduce the effectiveness of treatment. Neutralizing antibodiesdo not occur in all patients. Currently, it is not possible to predict which patients belong to this group.

• During treatment with Betaferon, problems with your kidneys may occur that can affect your renal function,including scarring (glomeruloesclerosis).Your doctor may perform tests to check your renal function.

• During treatment, blood clots may form in small blood vessels.These clots may affect your kidneys. This may occur after several weeks or several years of starting Betaferon treatment.Your doctor may want to monitor your blood pressure, blood (platelet count) and renal function.

• During treatment, you may experience pallor, yellow skin, or dark urine, possibly accompanied by unusual dizziness, fatigue, or difficulty breathing.This may be a sign of a decrease in red blood cells. This may occur after several weeks or several years of starting Betaferon treatment. Your doctor may perform blood tests. Inform your doctor about any other medications you are taking at the same time as Betaferon.

Reactions at the injection site

During treatment with Betaferon, you are likely to experience reactions at the injection site.The symptoms include redness, swelling, skin color change, inflammation, pain, and hypersensitivity. Less frequently, infections around the injection site and skin lesions and tissue damage(necrosis)are observed. Reactions at the injection site usually become less frequent over time.

Skin lesions and tissue damage may result in scarring. If these are severe, a doctor may need to perform tissue removal and dead tissue removal(debridement)and, less frequently, skin grafting, which may take up to six months to heal.

To reduce the risk of having a reaction at the injection site, such as infection or necrosis, you should:

• Use a sterile injection technique(aseptic).
• Rotate the injection sites with each injection (see Appendix “Procedure for self-injection”, Part II, in the second part of this prospectus).

Reactions at the injection site may occur less frequently if you use an autoinjector and rotate the injection sites. Your doctor or nurse may inform you about this.

If you experience skin rupture, which may be associated with swelling or fluid loss at the injection site:

• Stop injecting Betaferonand inform your doctor.

?If you have a single ulcerated injection site(lesion)and tissue destruction(necrosis)is not too extensive,you can continue using Betaferon.

?If you have multiple ulcerated injection sites(multiple lesions),you should stop using Betaferon until your skin has healed.

Your doctor will regularly checkhow you self-inject, especially if you have experienced reactions at the injection site.

Children and adolescents

No formal clinical trials have been conducted in children or adolescents.

However, there are some data in children and adolescents aged 12to 16years. These data suggest that the safety profile of this age group is the same as that of adults for the administration of 8.0 million IU of Betaferon under the skin every other day. There is no information on the use of Betaferon in children under 12 years. Therefore, Betaferon should not be used in this population.

Other medications and Betaferon

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription.

No formal interaction studies have been conducted to determine if Betaferon affects other medications or is affected by them.

Betaferon should not be used with other medications that modify the immune system response, except for anti-inflammatory medications calledcorticosteroidsor adrenocorticotropic hormone (ACTH).

Betaferon should be used with caution with:

• Medications that require a specific liver enzyme systemfor their elimination from the body (known as thecitochromeP450system), for example, medications used to treat epilepsy (such as phenytoin).
• Medications that affect blood cell production.

Use of Betaferon with food and drinks

Betaferon is injected under the skin, so no food or drink you consume is expected to have any effect on Betaferon.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Noharmful effects are expected in the newborn/infant during breastfeeding.Betaferonmay be used during breastfeeding.

Driving and operating machines

Betaferon may cause central nervous system side effects (see section4. “Possible side effects”). If you are particularly sensitive, this may affect your ability to drive or operate machines.

Betaferon contains mannitol, human albumin, and sodium

Among the inactive components of Betaferon are

• small amounts of mannitol, a natural sugar, and human albumin, a protein.
• Sodium - this medication contains less than 1 mmol of sodium (23 mg) per ml; this is, essentially “sodium-free”.

If you are allergic(hypersensitive)to any of the components or become hypersensitive, you should not use Betaferon.

The treatment with Betaferon should be initiated under the supervision of a doctor with experience in the treatment of multiple sclerosis.

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

The recommended dose is:

Every other day(once every two days) 1.0ml of the prepared solution is injected under the skin(subcutaneously)(see the Annex “Procedure for self-injection” in the second part of this prospectus). This is equivalent to 250micrograms (8.0 million IU) of interferon beta-1b.

When starting treatmentwith Betaferon, it will be tolerated better if it is initiated with a dose and gradually increased, i.e. starting with only 0.25ml of the medication and then increasing, after three injections, first to0.5ml, then to0.75ml, and finally to the full dose (1ml) of Betaferon.

Your doctormay decide, with you, to change the time interval between dose increases,depending on the adverse effects you may experience when starting treatment.To easily increase dosing during the first 12 injections, you may be provideda special escalating packagecontaining four packages in different colors that include special syringes with marks and a ‘starter package for escalating dose’ with detailed instructions.

Preparation of the injection

Before the injection, the Betaferon injection solutionis prepared from a Betaferon powder vial and 1.2ml of liquid from one of the pre-loaded syringes with solvent. This will be done by your doctor or nurse, or even by yourself once you have been carefully instructed in the technique. For more information on how the Betaferon injectable solution is prepared, see Annex “Procedure for self-injection”, Part I.

Instructions for self-injecting Betaferon under the skinare included below in the skinin Part IEof the Annex “Procedure for self-injection”.

The injection site should be changed regularly.See section2. “Warnings and precautions” and follow the instructions indicated in Part II “Rotation of injection sites” and Part III (Calendar for Betaferon administration) of the Annex “Procedure for self-injection”.

Duration of treatment

At present, it is not known for how long the patient should be treated.The duration of treatment should be decided by the doctor together with you.

If you use more Betaferon than you should

The administration of very high doses of Betaferon above the recommended doses for multiple sclerosis has not led to situations that put life at risk.

?Inform your doctorif you have injected too much Betaferon or if you have injected it too frequently.

If you forget to use Betaferon

If you have forgotten to administer an injection at the scheduled time, do it as soon as possible and continue with the next one, 48hours later.

Do not inject a double dose to compensate for the missed doses.

If you interrupt the treatment with Betaferon

Talk to your doctor ifyou interrupt or want to interrupt the treatment. It is unknown if the interruption of Betaferon causes acute withdrawal symptoms.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Betaferon can cause serious side effects. If you consider that any of the side effects you experience are serious or if you notice any side effect not mentioned in this leaflet, inform your doctor, pharmacist or nurse.

• Inform your doctor immediately and stop using Betaferon:

• If you experiencesymptoms such asitching all over the body, swelling of the face and/or tongue, or sudden difficulty breathing.
• If you feelconsiderably more depressed or hopeless than before starting treatment with Betaferon, or if you have thoughts of suicide.
• If you notice that you arebruising easily, bleeding excessively when you have cuts, or getting many infections.
• If you haveloss of appetite, fatigue, nausea, repeated vomiting, especially if you notice diffuse itching, the appearance of a yellowish color on the skin or in the white part of the eyes, or if you arebruising easily.
• If you experience symptoms such asirregular heartbeats or swelling in the ankles or legs, or difficulty breathing.
• If you noticeabdominal pain that radiates to the back, and/or if you feel dizzy or have a fever.

?Inform your doctor immediately:

• If you haveany orall of these symptoms:foamy urine, fatigue, swelling, especially intheanklesand in the eyelids,andweight gain,as they may be signs of a possiblekidney problem.

When starting treatment, common side effects are usual, but they generally decrease as you continue with it.

The most frequent side effects are:

?A complex of flu-like symptoms, such as fever, chills, joint pain, discomfort, sweating, headache, or muscle pain. These symptoms can be reduced by taking paracetamol or non-steroidal anti-inflammatory drugs, such asibuprofen.

?Reactions at the injection site. The symptoms may be redness, swelling, discoloration, inflammation, infection, pain, hypersensitivity, or tissue damage(necrosis). See “Warnings and precautions” in section2for more information and what to do if you experience a reaction at the injection site. These can be reduced by using an auto-injector device and rotating the injection sites. Talk to your doctor, pharmacist, or nurse for additional information.

To reduce side effects at the start of treatment, your doctor should start with a low dose of Betaferon and gradually increase it (see section3. “How to use Betaferon”).

The list of side effects that follows is basedon communications from clinical trials with Betaferon and on side effects reported from marketed medication.

?Very common (may affect more than 1 in 10 patients):

-reduction in the number ofwhite blood cells

-headache

-sleep disturbances(insomnia)

-abdominal pain

-one specific liver enzyme (alanine aminotransferase or ALT) may increase (this will be revealed in blood tests)

-skin rash

-skin disorder

-muscle pain(mialgia)

-muscle stiffnessmuscle(hypertonia)

-joint pain(artralgia)

-urgency to urinate

-reaction at the injection site (including redness, swelling, discoloration, inflammation, pain, infection, allergic reactions(hypersensitivity)

-flu-like symptoms, pain, fever, chills, peripheral edema, lack/loss of strength(asthenia)

?Frequent (may affect up to 1 in 10patients):

• swelling of thelymph nodes(lymphadenopathy)
• may reduce the number of red blood cells in the blood(anemia)
• the thyroid gland does not function correctly (produces little hormone)(hypothyroidism)
• weight gain or loss
• confusion
• abnormally fast heartbeats(tachycardia)
• increase inblood pressure(hypertension)
• one specific liver enzyme (aspartate aminotransferase or ALT) may increase (this will be revealed in blood tests)
• difficulty breathing(dyspnea)
• may increase a yellowish-brown pigment(bilirubin)produced by the liver(this will be revealed in blood tests)

-hives or membranous, edematous, and itchy skin lesions(urticaria)

-itching(pruritus)

-hair loss(alopecia)

-menstrual disorders(menorrhagia)

-heavy uterine bleeding(metrorrhagia)especially between menstrual periods

-impotence

-skin lesions and tissue damage(necrosis)at the injection site (see section 2 “Warnings and precautions”)

-chest pain

-discomfort

?Rare (may affect up to 1 in 1,000patients):

• coagulation of blood in small blood vessels that may affect your kidneys (thrombotic thrombocytopenic purpura or uremic hemolytic syndrome). The symptoms may include increased urine production, bleeding, fever, extreme weakness, dizziness, or confusion. Your doctor may find changes in your blood and kidney function.
• severe allergic reactions(anaphylactic)
• the thyroid gland does not function correctly(thyroid disorders),produces too much hormone(hyperthyroidism)
• important loss of appetite that causes weight loss(anorexia)
• heart muscle disease(myocarditis)
• sudden difficulty breathing(bronchospasm)
• pancreatitis(pancreatitis), see section2 “Warnings and precautions”
• the liver does not function correctly (liver damage including hepatitis, liver insufficiency)

• Frequency unknown (the frequency cannot be estimated from available data)

• destruction of red blood cells(hemolytic anemia)
• may cause problems with small blood vessels when using medications such as Betaferon(systemic capillary leak syndrome)
• depression, anxiety
• dizziness
• irregular heartbeats or palpitations(palpitations)
• facial flushing and/or erythema due to vasodilation(vasodilation)
• important narrowing of the blood vessels in the lungs that causes an increase in pressure in the blood vessels that transport blood from the heart to the lungs(pulmonary hypertension). Pulmonary hypertension has been reported at different times during treatment, even several years after starting treatment with Betaferon.
• nausea
• vomiting
• diarrhea
• skin rash, facial flushing, joint pain, fever, weakness, and other symptoms caused by the medication(drug-induced lupus erythematosus)
• menstrual disorders
• sweating

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not mentioned in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25 °C. Do not freeze.

You must use the solution immediately after preparation. However, if this is not possible, it will be in good condition for use for 3 hours, if stored between 2 and 8 °C (in a refrigerator).

Do not use Betaferon if you observe that it contains particles or presents any discoloration.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Betaferon

The active ingredientis interferon beta-1b, 250 micrograms per millilitre reconstituted

The other components are

• In the powder: mannitol and human albumin.
• In the solvent: (sodium chloride solution with 5.4 mg/ml (0.54% w/v)): sodium chloride, water for injection.

The Betaferon powder is supplied in a 3millilitre vial containing 300 micrograms (9.6million IU) of interferon beta-1b per vial. After reconstitution, each millilitre contains 250 micrograms (8.0 million IU) of interferon beta-1b.

The solvent for Betaferon is supplied in a pre-filled syringe of 2.25millilitres and contains 1.2millilitres of a sodium chloride solution with 5.4 mg/ml (0.54% w/v).

Appearance of the product and contents of the pack

Betaferon is a sterile white or almost white powder for injection solution.

Betaferon is supplied in:

• multi-dose pack with 5 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• multi-dose pack with 12 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• multi-dose pack with 14 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• multi-dose pack with 15 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• packs for 2 months with 2 x 14 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• packs for 3 months with 3 x 15 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• packs for 3 months with 3 x 14 individual packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 adapter for vial with needle and 2 alcohol wipes, or
• dose escalation pack for the first 12 injections containing 4 triple packs, each containing 3 vials with powder, 3 pre-filled syringes with solvent, 3 adapters for vial with needle and 6 alcohol wipes

Only some pack sizes may be marketed.

Marketing authorisation holder and responsible manufacturer

Marketing authorisation holder

Bayer AG

51368 Leverkusen

Germany

Responsible manufacturer

Bayer AG

Müllerstraße 178

13353 Berlin

Germany

For further information on this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

Appendix: PROCEDURE FOR SELF-INJECTION

Your doctor has prescribed Betaferon to treat your MS. You will tolerate Betaferon better if you start with a low dose and gradually increase it to the standard full dose (see the first part of this leaflet, section3. “How to use Betaferon”).

To easily increase the dosage during the first 12 injections, you may be provided with a dose escalation pack, which presents four triple packs in different colours that include special needles and a “Introductory leaflet for the dose escalation pack” with detailed instructions.

The needles in this dose escalation pack are marked according to the corresponding doses (0.25; 0.5; 0.75 or 1.0ml).

The following instructions and illustrations are intended to explain how to prepare the Betaferon injection and how to administer it to yourself. Read the instructions carefully and follow them step by step. Your doctor or nurse will instruct and train you in the procedure and technique of self-administration. Do not attempt self-administration until you are sure you have understood how to prepare the injection solution and how to administer it.

Part I: STEP-BY-STEP INSTRUCTIONS

The instructions include the following main steps:

1. General advice
2. Preparing to inject
3. Step-by-step reconstitution of the solution
4. Preparing the injection
5. Administering the injection
6. Quick review of the process

A)General advice

?Start well!

You will find that in a few weeks the treatment will become part of your life. To start, the following may help:

• Have a suitable area permanently prepared at home, out of sight and reach of children, where you can easily find Betaferon and the other utensils.

Check the storage conditions in section5 of the leaflet: “Storage of Betaferon” in the first part of this leaflet.

• Try to inject yourself at the same time every day, as this will make it easier for you to remember and reserve a period of time when you will not be interrupted.

• Prepare each dose only when you are ready to inject yourself, as you must inject Betaferon immediately after reconstituting it (if you do not use it immediately, see section5 in the first part of this leaflet: “Storage of Betaferon”).

?Important advice to keep in mind

• Be consistent. Use Betaferon as described in section3, in the first part of this leaflet: “How to use Betaferon”. Always check the prepared dose twice.
• Keep the container in the place where you dispose of the needles and needles out of sight and reach of children. Close the material under lock, if possible.
• Never reuse needles or needles.
• Always use a sterile technique(aseptic), as described below.
• Always dispose of used needles in the appropriate container.
  

B)Preparing to inject

?How to choose the injection site

Before preparing the Betaferon injection, decide where you will inject it. You must inject Betaferon into the fatty layer between the skin and the muscle (i.e. into the subcutaneous tissue, between 8and 12mm below theskin). The best places for injection are those where the skin is soft and smooth, and away from joints, nerves or bones, for example, the abdomen, arm, thigh or buttocks.

Important:Do not inject into areas where you perceive lumps, haematomas, firm nodules, pain, or an area where the skin is discoloured, depressed, crusty, or has an open wound. Discuss these or any other unusual conditions you may find with your doctor or nurse.

You must rotate the injection site each time you inject. If any area is too difficult to reach, it may be possible for a family member or friend to help you administer the injections. Follow the sequence described in the diagram at the end of the Appendix (see Part II “Rotation of injection sites”) and you will return to the first site where you injected after 8 injections (16days). In that time, each injection site will have fully recovered before receiving the next injection.

See the rotation diagram at the end of this Appendix to help you choose the injection site. It is also a good idea to know where you will apply the injection before preparing the syringe. The diagram shown below will help you vary the sites appropriately. For example, administer the first injection on the right side of the abdomen, choose the left side for the second injection, then move to the right thigh for the third, and so on through the diagram until all possible areas of the body have been used. Keep a record of where and when you last injected. One way to do this is to note this information in the “Administration calendar” that is included.

Following this sequence, you will return to the initial site (i.e. the right side of the abdomen) after 8injections (16days). This is known as the “Rotation Cycle”. In our example calendar, each of the 8 body areas has been divided into 6 injection sites (adding them all up, there are 48 sites where you can administer the injections), left and right: upper, middle and lower parts of each body area. When you return to an injection site after completing a rotation cycle, choose the most distant site within that area. If any ulcer appears, consult your doctor or nurse before choosing other injection sites.

Rotation calendar:

To help you rotate the injection sites appropriately, we recommend that you fill in a record with the date and injection site. You can use the following rotation sequence.

Work each rotation cycle successively. Each cycle will be 8 injections (16days), administered from the first area to the eighth area, in turn. Following this sequence, each area will have the opportunity to recover before receiving another injection.

First rotation cycle:Upper left section of each area

Second rotation cycle:Lower right section of each area

Third rotation cycle:Central left section of each area

Fourth rotation cycle:Upper right section of each area

Fifth rotation cycle:Lower left section of each area

Sixth rotation cycle:Central right section of each area

Part II: ROTATION OF INJECTION SITES

You must choose a new site for each injection, to allow the area time to recover and help prevent infection. Guidance is provided on which areas to choose in the first part of this Appendix. It is a good idea to know where you will apply the injection before preparing the syringe. The diagram shown below will help you vary the sites appropriately. For example, administer the first injection on the right side of the abdomen, choose the left side for the second injection, then move to the right thigh for the third, and so on through the diagram until all possible areas of the body have been used. Keep a record of where and when you last injected. One way to do this is to note this information in the “Administration calendar” that is included.

Following this sequence, you will return to the initial site (i.e. the right side of the abdomen) after 8injections (16days). This is known as the “Rotation Cycle”. In our example calendar, each of the 8 body areas has been divided into 6 injection sites (adding them all up, there are 48 sites where you can administer the injections), left and right: upper, middle and lower parts of each body area. When you return to an injection site after completing a rotation cycle, choose the most distant site within that area. If any ulcer appears, consult your doctor or nurse before choosing other injection sites.

Calendar of rotation:

To help you rotate the injection sites appropriately, we recommend that you fill in a record with the date and injection site. You can use the following rotation sequence.

Work each rotation cycle successively. Each cycle will be 8 injections (16days), administered from the first area to the eighth area, in turn. Following this sequence, each area will have the opportunity to recover before receiving another injection.

First rotation cycle:Upper left section of each area

Second rotation cycle:Lower right section of each area

Third rotation cycle:Central left section of each area

Fourth rotation cycle:Upper right section of each area

Fifth rotation cycle:Lower left section of each area

Sixth rotation cycle:Central right section of each area

Part III: ADMINISTRATION CALENDAR FOR BETAFERON

Instructions for controlling injection sites and dates

-Choose an injection site for your first injection.

-Clean the injection site with an alcohol wipe and let it dry.

-After the injection, fill in the injection site and date in the “Administration calendar” (see the example below with instructions for controlling injection sites and dates).