Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - extavia

Document Subject

Generated Narrative: MedicinalProductDefinition mpaf957cdad64de8277859b4d268fc6099

identifier: http://ema.europa.eu/identifier/EU/1/08/454/008-014

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Extavia 250 microgram/ml powder and solvent for solution for injection.

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-af957cdad64de8277859b4d268fc6099

identifier: http://ema.europa.eu/identifier/EU/1/08/454/008-014

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - extavia

Attesters

Annex self-injection procedure

What is in this leaflet

1. What Extavia is and what it is used for
2. What you need to know before you use Extavia
3. How to use Extavia
4. Possible side effects
5. How to store Extavia
6. Contents of the pack and other information

What Extavia is Extavia is a type of medicine known as interferon used to treat multiple sclerosis. Interferons are proteins produced by the body that help it fight against attacks on the immune system such as viral infections.

How Extavia works Multiple sclerosis (MS) is a long-term condition that affects the central nervous system (CNS), particularly the functioning of the brain and spinal cord. In MS, inflammation destroys the protective sheath (called myelin) around the nerves of the CNS and stops the nerves from working properly. This is called demyelination.

The exact cause of MS 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.

The damage to the CNS can occur within an MS attack (relapse). It can cause temporary disability, such as difficulty walking. Symptoms may disappear completely or partly.

Interferon beta-1b has been shown to change the response of the immune system and to help to reduce disease activity.

How Extavia helps fight your disease Single clinical event indicating a high risk of developing multiple sclerosis: Extavia has been shown to delay progression to definite multiple sclerosis.

Relapsing-remitting multiple sclerosis: People with relapsing-remitting MS have occasional attacks or relapses during which symptoms become noticeably worse. Extavia has been shown to cut down the number of attacks and make them less severe. It reduces the number of hospital stays due to the disease and prolongs the time without relapses.

Secondary progressive multiple sclerosis: In some cases people with relapsing-remitting MS find that their symptoms increase and they progress to another form of MS called secondary progressive MS. With this, people find themselves becoming increasingly impaired, whether or not they have relapses. Extavia can reduce the number and severity of the attacks, and slow the progression of disability.

What Extavia is used for Extavia is for use in patients

who have experienced for the first time symptoms which indicate a high risk of developing multiple sclerosis. Your doctor will rule out any other reasons which could explain these symptoms before you are treated.

who suffer from relapsing-remitting multiple sclerosis, with at least two relapses within the last two years.

who suffer from secondary progressive multiple sclerosis with active disease shown by relapses.

Do not use Extavia

• if you are allergic to natural or recombinant interferon beta, human albumin or any of the other ingredients of this medicine (listed in section 6).
• if you currently suffer from severe depression and/or suicidal thoughts (see Warnings and precautions and section 4, Possible side effects ).
• if you have a severe liver disease (see Warnings and precautions , Other medicines and Extavia and section 4, Possible side effects ).

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

Warnings and precautions

Talk to your doctor before using Extavia:

• If you have monoclonal gammopathy. This is a disorder of the immune system where an abnormal protein is found in the blood. Problems with your small blood vessels (capillaries) may develop (systemic capillary leak syndrome) when using medicines like Extavia. This can lead to shock (collapse) and even be fatal.

• If you have had depression or are depressed or 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 Extavia (see also Do not use Extavia ).

• If you have ever had seizures or if you are taking medicines to treat epilepsy (anti- epileptics), you doctor will monitor your treatment carefully (see also Other medicines and Extavia and section 4, Possible side effects ).

• If you have severe kidney problems, your doctor may monitor your kidney function during treatment.

• If you have ever had an allergic reaction to latex. The tip cap of the pre-filled syringe contains a derivative of natural rubber latex. Therefore, the tip cap may contain natural rubber latex.

Your doctor also needs to know the following whilst you are using Extavia:

• 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, which may become life threatening.

• If you feel noticeably more sad or hopeless than before the treatment with Extavia, or if you develop thoughts of suicide. If you become depressed while you are on Extavia, 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 Extavia (see also Do not use Extavia ).

• 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). You may need extra monitoring by your doctor.

• If you experience loss of appetite, tiredness, feeling sick (nausea), repeated vomiting, and 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. Changes to liver function values occurred in patients treated with Extavia during clinical studies. As for other beta interferons, severe liver damage, including cases of liver failure, have been reported rarely in patients taking Extavia. The most serious 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 such as irregular heartbeat, swelling such as of the ankles or legs, or shortness of breath. This may suggest a disease of the heart muscle (cardiomyopathy) which has been reported in patients using Extavia.

• 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), which has been reported with Extavia use. This is often associated with an increase in certain blood fats (triglycerides).

Stop using Extavia and tell your doctor immediately if any of these happens to you.

Other things to consider when using Extavia:

• You will need blood tests to determine your blood cell count, blood chemistry and your liver enzymes. These will be performed before you start using Extavia, regularly after treatment with Extavia has been initiated and then periodically during treatment, even if you have no particular symptoms. These blood tests will be in addition to the tests which are normally done to monitor your MS.

• If you have a heart disease, the flu-like symptoms which often occur at the start of treatment may prove stressful to you. Extavia must be used with caution, and your doctor will monitor you for worsening of your heart condition, particularly at the start of treatment. Extavia itself does not affect the heart directly.

• The functioning of your thyroid gland will be checked regularly or whenever thought necessary by your doctor for other reasons.

• Extavia contains human albumin and therefore carries a potential risk for transmission of viral diseases. A risk of transmission of Creutzfeld-Jacob disease (CJD) cannot be ruled out.

• During treatment with Extavia your body may produce substances called neutralising antibodies, which may react with Extavia. It is not yet clear whether these neutralising antibodies reduce the effectiveness of the treatment. Neutralising antibodies are not produced in all patients. Currently it is not possible to predict which patients belong to this group.

• During treatment with Extavia, kidney problems that may reduce your kidney function, including scarring (glomerulosclerosis), may occur. Your doctor may perform tests to check your kidney function.

• Blood clots in the small blood vessels may occur during your treatment. These blood clots could affect your kidneys. This might happen several weeks to several years after starting Extavia. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidneys.

• Pale or yellow skin or dark-coloured urine, possibly accompanied by unusual dizziness, tiredness or shortness of breath may occur during your treatment. These may be symptoms of a breakdown of red blood cells. This might happen several weeks to several years after starting Extavia. Your doctor may perform blood tests. Inform your doctor about other medicines that you are taking at the same time as Extavia.

Injection site reactions During Extavia treatment you are likely to experience injection site reactions. Symptoms include redness, swelling, change in skin colour, inflammation, pain, and hypersensitivity. Infection around the injection site and skin breakdown and tissue damage (necrosis) are reported less frequently. Injection site reactions usually become less frequent over time.

Injection site skin and tissue breakdown can result in scars forming. If this is severe a doctor may have to remove foreign matter and dead tissue (debridement) and, less often, skin grafting is required and healing may take up to 6 months.

To reduce the risk of getting injection site reactions, such as an infection or necrosis, you must:

use a sterile (aseptic) injection technique,

rotate the injection sites with each injection (see Annex Self-Injection procedure).

Injection site reactions may occur less frequently if you use an auto-injector device and by rotating injection sites. Your doctor or nurse can tell you more about this.

If you experience any break in the skin, associated with swelling or fluid leaking out from the injection site:

Stop injecting Extavia and talk to your doctor.

If you have only one sore injection site (lesion) and the tissue damage (necrosis) is not too extensive you may continue using Extavia.

If you have more than one sore injection sites (multiple lesions) you must stop using Extavia until your skin has healed.

Your doctor will regularly check the way you inject yourself, particularly if you have experienced injection site reactions.

Children and adolescents There have been no formal clinical trials undertaken in children or adolescents. However, there are some data available in adolescents aged from 12 to 17 years which suggest that the safety of Extavia in this group is the same as in adults. Extavia should not be used in children under 12 years of age as there is no information available for this age group.

Other medicines and Extavia Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

No formal interaction studies have been carried out to find out whether Extavia affects other medicines or is affected by them.

Using Extavia with other medicines that modify the immune system response is not recommended, except anti-inflammatory medicines called corticosteroids or the adrenocorticotropic hormone (ACTH).

Extavia should be used with caution with:

• medicines which need a certain liver enzyme system (known as cytochrome P450 system) for their removal from the body, for example medicines used to treat epilepsy (such as phenytoin).
• medicines which affect the production of blood cells.

Extavia with food and drink Extavia is injected under the skin so any food or drink you consume is not thought to have any effect on Extavia.

Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

No harmful effects on the breastfed newborn/infant are anticipated. Extavia can be used during breast-feeding.

Driving and using machines Extavia may cause side effects in the central nervous system (see section 4 Possible side effects ). If you are especially sensitive, this might influence your ability to drive or use machines.

Extavia contains sodium This medicinal product contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially 'sodium- free'.

Treatment with Extavia should be started under the supervision of a doctor who is experienced in the treatment of multiple sclerosis.

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is every other day (once every two days), 1.0 ml of the prepared Extavia solution (see Annex Self-injection procedure in the second part of this leaflet) injected under the skin (subcutaneously). This equals 250 microgram (8.0 million IU) interferon beta-1b.

In general, treatment should be started at a low dose of 0.25 ml (62.5 microgram). Your doses will then be increased gradually to the full dose of 1.0 ml (250 microgram). The dose should be increased at every fourth injection in four steps (0.25 ml, 0.5 ml, 0.75 ml, 1.0 ml). Your doctor may decide together with you to change the time intervals for dose increase depending on side effects you may experience at the start of treatment.

Preparing the injection Before injection, the Extavia solution has to be prepared from a vial of Extavia powder and 1.2 ml of liquid from the pre-filled solvent syringe. This will either be done by your doctor or nurse or by yourself after you have been carefully trained.

Detailed instructions for self-injection of Extavia under the skin are provided in the Annex at the back of this leaflet. These instructions also tell you how to prepare the Extavia solution for injection.

The injection site must be changed regularly. See section 2 Warnings and precautions and follow the instructions under Rotating injection sites in the Annex at the back of this leaflet.

Duration of treatment At present it is not known how long treatment with Extavia should last. The length of treatment will be decided by your doctor together with you.

If you use more Extavia than you should Giving many times the dose of Extavia recommended for the treatment of multiple sclerosis has not led to life-threatening situations.

Talk to your doctor if you inject too much Extavia or injected too often.

If you forget to use Extavia 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.

Do not inject a double dose to make up for a forgotten individual dose.

If you stop using Extavia Talk to your doctor if you stop or wish to stop treatment. Stopping Extavia is not known to cause acute withdrawal symptoms.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

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

Extavia may cause serious side effects. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, pharmacist or nurse.

Tell your doctor immediately and stop using Extavia:

• if you experience symptoms such as itching all over your body, swelling of your face and/or your tongue or sudden shortness of breath.

• if you feel noticeably more sad or hopeless than before the treatment with Extavia, or if you develop thoughts of suicide.

• if you notice any unusual bruising, excessive bleeding after injury or if you seem to be catching a lot of infections.

• if you experience loss of appetite, tiredness, feeling sick (nausea), repeated vomiting, especially if you notice widespread itching, yellowing of the skin, or of the whites of the eyes or easy bruising.

• if you experience symptoms like irregular heart beat, swelling such as of the ankles or legs, or shortness of breath.

• if you notice pain in your belly which is radiating to your back , and/or you feel sick or have a fever.

Tell your doctor immediately:

• if you get some or all of these symptoms: foamy urine, fatigue, swelling, particularly and the ankles and eyelids, and weight gain, as they may be signs of a possible kidney problem.

At the beginning of treatment side effects are common but in general they decrease with further treatment.

The most common side effects are:

Flu-like symptoms such as fever, chills, painful joints, malaise, sweating, headache, or muscular pain. These symptoms may be reduced by taking paracetamol or non-steroidal anti- inflammatory medicines such as ibuprofen.

Injection site reactions. Symptoms can be redness, swelling, discolouration, inflammation, infection, pain, hypersensitivity, tissue damage (necrosis). See Warnings and precautions in section 2 for more information and what to do if you experience an injection site reaction. These may be reduced by the use of an auto-injector device and by rotating injection sites. Talk to your doctor, pharmacist or nurse for further information.

To reduce the risk of side effects at the start of treatment, your doctor should start you on a low dose of Extavia and increase it gradually (see section 3, How to use Extavia ).

The following side effects listing is based on reports from clinical trials with Extavia and from side effects reported on the marketed product.

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

• reduced number of white blood cells,
• headache,
• sleep disorder (insomnia),
• abdominal pain,
• a specific liver enzyme (alanine aminotransferase or ALAT) may rise (this will show up in blood tests),
• rash,
• skin disorder,
• painful muscles (myalgia),
• muscle stiffness (hypertonia),
• painful joints (arthralgia),
• urinary urgency,
• injection site reaction (including redness, swelling, discolouration, inflammation, pain, infection, allergic reactions (hypersensitivity)),
• flu-like symptoms, pain, fever, chills, accumulation of fluid in arm or leg (peripheral oedema), lack/loss of strength (asthenia).

Common (may affect up to 1 in 10 people):

• swollen lymph glands (lymphadenopathy),
• the number of red cells in the blood may fall (anaemia),
• the thyroid gland does not work properly (too little hormone is produced) (hypothyroidism),
• weight increase or decrease,
• confusion,
• abnormally rapid heartbeat (tachycardia),
• increased blood pressure (hypertension),
• a specific liver enzyme (aspartate aminotransferase or ASAT) may rise (this will show up in blood tests),
• shortness of breath (dyspnoea),
• a reddish yellow pigment (bilirubin), which is produced by your liver, may rise (this will show up in blood tests),
• swollen and usually itchy patches of skin or mucous membranes (urticaria),
• itching (pruritus),
• loss of scalp hair (alopecia),
• menstrual disorders (menorrhagia),
• heavy uterine bleeding (metrorrhagia) especially between menstrual periods,
• impotence,
• skin breakdown and tissue damage (necrosis) at the injection site (see section 2 Warnings and precautions ),
• chest pain,
• malaise.

Uncommon (may affect up to 1 in 100 people):

• the number of platelets (which help the blood to clot) may fall (thrombocytopenia),
• a certain type of blood fats (triglycerides) may increase (will show up in blood tests), see section 2 Warnings and precautions ,
• suicide attempt,
• mood swings,
• convulsion,
• a specific liver enzyme (gamma GT) which is produced by your liver, may rise (this will show up in blood tests),
• inflammation of the liver (hepatitis),
• skin discolouration,
• kidney problems, including scarring (glomerulosclerosis) that may reduce your kidney function.

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

• blood clots in the small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome). Symptoms may include increased bruising, bleeding, fever, extreme weakness, dizziness or light-headedness. Your doctor may find changes in your blood and the function of your kidneys,
• serious allergic (anaphylactic) reactions,
• the thyroid gland does not work properly (thyroid disorders), too much hormone is produced (hyperthyroidism),
• severe loss of appetite leading to weight loss (anorexia),
• disease of the heart muscle (cardiomyopathy),
• sudden shortness of breath (bronchospasm),
• inflammation of the pancreas (pancreatitis), see section 2 Warnings and precautions ,
• the liver does not work properly (hepatic injury including hepatitis, hepatic failure).

Not known (frequency cannot be estimated from the available data)

• breakdown of red blood cells (haemolytic anaemia),
• problems with your small blood vessels may develop when using medicines like Extavia (systemic capillary leak syndrome),
• depression, anxiety,
• dizziness,
• irregular, rapid beating or pulsation of the heart (palpitation),
• redness and/or facial flushing due to widening of blood vessels (vasodilation),
• severe narrowing of the blood vessels in the lungs resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary arterial hypertension). Pulmonary arterial hypertension has been seen at various time points during treatment, including several years after starting treatment with Extavia,
• nausea,
• vomiting,
• diarrhoea,
• rash, redness of the skin in the face, joint pain, fever, weakness and others caused by the medicine (drug-induced lupus erythematosus),
• menstrual disorder,
• sweating.

Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.

Do not store above 25 C. Do not freeze.

After preparing the solution you should use it immediately. However, if you are not able to do so, it will remain usable for a period of 3 hours, if kept in a refrigerator (2 C - 8 C).

Do not use this medicine if you notice it contains particles or is discoloured.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Extavia contains

The active substance is interferon beta-1b. Each vial contains 300 microgram (9.6 million IU) interferon beta-1b per vial. After reconstitution, each millilitre contains 250 microgram (8.0 million IU) interferon beta-1b.

The other ingredients are

in the powder: mannitol and human albumin.

in the solvent: sodium chloride, water for injection.

The tip cap of the pre-filled syringe contains a derivative of natural rubber latex. Therefore, the tip cap may contain natural rubber latex.

What Extavia looks like and contents of the pack Extavia is a powder and solvent for solution for injection.

The powder is white to off-white in colour. The Extavia powder is provided in a 3-millilitre vial. The solvent is a clear/colourless solution. The solvent for Extavia is provided in a 2.25 ml pre-filled syringe and contains 1.2 ml sodium chloride 5.4 mg/ml (0.54% w/v) solution for injection.

Extavia is available in pack sizes of:

5 vials of interferon beta-1b and 5 pre-filled syringes containing solvent.

14 vials of interferon beta-1b and 14 pre-filled syringes containing solvent.

15 vials of interferon beta-1b and 15 pre-filled syringes containing solvent.

14 vials of interferon beta-1b and 15 pre-filled syringes containing solvent.

3-month multipack containing 42 (3x14) vials of interferon beta-1b and 42 (3x14) pre-filled syringes containing solvent.

3-month multipack containing 45 (3x15) vials of interferon beta-1b and 45 (3x15) pre-filled syringes containing solvent.

3-month multipack containing 42 (3x14) vials of interferon beta-1b and 45 (3x15) pre-filled syringes containing solvent.

Not all pack sizes may be marketed.

Marketing Authorisation Holder Novartis Europharm Limited Vista Building Elm Park, Merrion Road Dublin 4 Ireland

Manufacturer Novartis Pharma GmbH Roonstrasse D-90429 Nuremberg Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien Novartis Pharma N.V. T l/Tel: +32 2 246 16 Lietuva SIA Novartis Baltics Lietuvos filialas Tel: +370 5 269 16
Novartis Bulgaria EOOD .: +359 2 489 98 Luxembourg/Luxemburg Novartis Pharma N.V. T l/Tel: +32 2 246 16 esk republika Novartis s.r.o. Tel: +420 225 775 Magyarorsz g Novartis Hung ria Kft. Tel.: +36 1 457 65 Danmark Novartis Healthcare A/S Tlf: +45 39 16 84 Malta Novartis Pharma Services Inc. Tel: +356 2122 2Deutschland Novartis Pharma GmbH Tel: +49 911 273 0

Nederland Novartis Pharma B.V. Tel: +31 88 04 52 Eesti SIA Novartis Baltics Eesti filiaal Tel: +372 66 30 Norge Novartis Norge AS Tlf: +47 23 05 20
Novartis (Hellas) A.E.B.E. : +30 210 281 17 sterreich Novartis Pharma GmbH Tel: +43 1 86 6Espa a Novartis Farmac utica, S.A. Tel: +34 93 306 42 Polska Novartis Poland Sp. z o.o. Tel.: +48 22 375 4France Novartis Pharma S.A.S. T l: +33 1 55 47 66 Portugal Novartis Farma - Produtos Farmac uticos, S.A. Tel: +351 21 000 8Hrvatska Novartis Hrvatska d.o.o. Tel. +385 1 6274 Rom nia Novartis Pharma Services Romania SRL Tel: +40 21 31299 Ireland Novartis Ireland Limited Tel: +353 1 260 12 Slovenija Novartis Pharma Services Inc. Tel: +386 1 300 75 sland Vistor hf. S mi: +354 535 7Slovensk republika Novartis Slovakia s.r.o. Tel: +421 2 5542 5Italia Novartis Farma S.p.A. Tel: +39 02 96 54 1 Suomi/Finland Novartis Finland Oy Puh/Tel: +358 (0)10 6133
Novartis Pharma Services Inc. : +357 22 690 Sverige Novartis Sverige AB Tel: +46 8 732 32 Latvija SIA Novartis Baltics Tel: +371 67 887 United Kingdom (Northern Ireland) Novartis Ireland Limited Tel: +44 1276 698This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: