250 micrograms/ml powder and solvent for injection, solution 
interferon beta-1b

1. What Extavia is and what it is used for

What Extavia is

Extavia is a type of medicine called interferon  Interferons are proteins produced in the body that help fight attacks on the immune system, e.g. viral infections.

How Extavia works

Multiple sclerosis (MS) is a long-term condition that affects the central nervous system ( CNS ), especially the function of the brain and spinal cord. In MS, inflammation destroys the protective sheath (called myelin) around the nerves in the CNS and prevents the nerves from functioning properly. This is called demyelination.

The exact cause of MS is unknown. It is believed that an abnormal reaction in the body’s immune system plays an important role in the CNS- damaging process.

CNS damage can occur in an MS attack ( relapse ). It can cause temporary disabilities, such as difficulty walking. The symptoms may disappear completely or partially.

Interferon beta-1b has been shown to alter the immune system’s response and help reduce disease activity.

How Extavia helps you fight the disease:

Isolated clinical events indicating a high risk of developing multiple sclerosis: Extavia has been shown to delay the development of definitive multiple sclerosis.

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

Secondary progressive multiple sclerosis: In some cases, people with relapsing-remitting MS notice that their symptoms worsen and that they develop another form of MS called secondary progressive MS. With this, they notice that they are getting worse, regardless of whether they get a relapse or not. Extavia can reduce the number of attacks and the severity of the attacks, as well as delay the progression of the disability.

What Extavia is used for

Extavia is for use in patients

  • who for the first time have had symptoms that indicate that they are at high risk of developing multiple sclerosis. Before any treatment is given, doctors will rule out any other conditions that may explain the symptoms.
  • who has relapsing-remitting MS  with at least two relapses during the last two years?
  • with secondary progressive MS with active disease, manifested by relapse.

What you need to know before using Extavia

Do not use Extavia

  • if you are allergic to natural or recombinant interferon beta-1b, human albumin, or any of the other ingredients of this medicine (listed in section 6).
  • if you are currently suffering from severe depression and/or have suicidal ideation (see “Warnings and Precautions” and Section 4, “Possible Side Effects”).
  • if you have 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 apply to you.

Warnings and cautions

Talk to your doctor before using Extavia:

  • If you have monoclonal gammopathy. This is  disorder of the immune system in which there are abnormal proteins in the blood. Problems with the thin blood vessels ( capillaries ) can occur ( systemic capillary leakage syndrome) when using medicines such as Extavia. This can lead to a state of shock (collapse), and can even be life-threatening.
  • If you have had depression or have depression or have previously had suicidal thoughts. Your doctor will monitor you closely during the treatment. If your depression and/or suicidal ideation are severe, you will not be prescribed Extavia (see also “Do not use Extavia”).
    If you have ever had a seizure or if you are taking medicines to treat epilepsy ( antiepileptic drugs ). Your doctor will then monitor your treatment closely (see also section “Other medicines and Extavia” and section 4 “Possible side effects”).
  • If you have severe kidney problems, your doctor will check your kidney function during treatment.
  • If you have ever had an allergic reaction to latex. The cover on top of the pre-filled syringe contains a derivative of natural rubber latex. Therefore, the protection may contain natural rubber latex.

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

  • If you experience symptoms such as itching all over your body, swollen face and/or swollen tongue, or sudden shortness of breath. This can be a symptom of a severe allergic reaction (hypersensitivity) that can be life-threatening.
  • If you feel significantly more sad or despairing than you did before you started treatment or if you have suicidal thoughts. If you become depressed while taking Extavia, you may need special treatment and your doctor will monitor you closely and may also consider stopping your treatment. If you suffer from severe depression and/or suicidal ideation, you will not be treated with Extavia (see also section “Do not use Extavia”).
  • If you notice that you get bruises more easily, bleed more than usual after an injury or if it seems like you get a lot of infection. This may be a symptom of a decrease in the number of blood cells or platelets (cells that help the blood to coagulate). You may need extra monitoring by your doctor.
  • If you suffer from loss of appetite, fatigue, nausea, repeated vomiting, and especially if you notice widespread itching, yellowing of the skin or whites of the eyes, or bruising easily. These symptoms may indicate liver problems. Altered liver function values ​​were observed in patients treated with Extavia in clinical trials. As with other beta- interferons, severe liver damage, including cases of liver failure, has been reported rarely in patients taking Extavia. The most severe cases were reported in patients taking other medicines or suffering from liver diseases (eg alcohol abuse, severe infection ).
  • If you get symptoms e.g. irregular heartbeat, swelling e.g. in ankles or legs,  or shortness of breath. This may indicate a heart muscle disease ( cardiomyopathy ), which has been reported in patients taking Extavia.
  • If you experience abdominal pain that radiates to the back and/or you feel unwell or have a fever. This may indicate an inflammation of the pancreas ( pancreatitis ), which has been reported with the use of Extavia. This is often associated with an increase in certain blood fats ( triglycerides ).
  • Stop using Extavia and tell your doctor immediately if any of these happen to you.

Other things to consider when using Extavia:

  • You will need blood tests for blood cell counts, blood chemistry tests, and liver enzymes. This will be done before you start using Extavia, regularly after starting treatment with Extavia, and then at regular intervals during treatment, even if you have no specific symptoms. These blood tests will be taken in addition to the tests that are normally performed to check your MS.
  • If you have heart disease, the flu-like symptoms that often occur at the beginning of treatment can prove to be stressful for you. Extavia must be used with caution and your doctor will monitor you for any worsening of your heart disease, especially at the beginning of treatment. Extavia itself does not affect the heart directly.
  • The function of your thyroid gland will be checked regularly or when your doctor deems it necessary for other reasons.
  • Extavia contains human albumin and therefore there is a  potential risk of transmitting viral diseases. The risk of transmission of Creutzfeldt-Jakob disease (CJD) cannot be ruled out.
  • While taking the medicine, the body produces substances known as neutralizing antibodies, which can react with Extavia (neutralizing activity). It is not yet known whether these neutralizing antibodies reduce the effect of the treatment. Neutralizing antibodies are not produced in all patients. It is currently not possible to predict which patients belong to this group.
  • During treatment with Extavia, kidney problems, including scarring (glomerulosclerosis), may occur, which may reduce your kidney function. Your doctor may perform tests to check your kidney function.
  • During treatment, blood clots may form in the small blood vessels. Blood clots can affect your kidneys. This can happen several weeks or up to several years after you started taking Extavia. Your doctor may want to check your blood pressure, blood count ( platelet count ), and kidney function.
  • Pale or yellow skin or dark-colored urine, possibly associated with unusual dizziness, fatigue, or shortness of breath may occur during your treatment. This may be a symptom of red blood cell breakdown. This can happen several weeks or up to several years after you started taking Extavia. Your doctor may take blood samples. Tell your doctor about other medicines you are taking at the same time as Extavia.

Injection site reactions

During treatment with Extavia, you are likely to experience reactions at the injection site. Symptoms include redness, swelling, discoloration, inflammation, pain, and hypersensitivity. Skin and tissue damage ( necrosis ) around the injection site is not as common. Over time, the reactions at the injection site tend to become less common.

Skin and tissue degradation at the injection site may cause scarring. If this is severe, a doctor may need to remove foreign matter and dead tissue (debridement), and in rare cases, skin grafts are required. Healing can take up to 6 months.

To reduce the risk of injection site reactions, you should :

  • use a sterile (aseptic) injection technique
  • change injection site for each injection (see appendix “Self-injection procedure”)

The use of an auto-injector may reduce the frequency of injection site reactions. Your doctor or nurse can tell you more about this.

If you get stretch marks in the skin, associated with swelling or fluid leaking from the injection site :

  • Discontinue injection of Extavia and talk to your doctor.
  • If you only have a sore injection site ( lesion ) and the tissue damage ( necrosis ) is not too extensive, you can continue to use Extavia.
  • If you have more than one sore injection site (multiple lesions ), you must stop using Extavia until the skin has healed.

Your doctor will regularly check your injection technique, especially if you get reactions at the injection site.

Children and young people

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

However, there are data from the treatment of adolescents between 12 and 17 years of age, which indicate that the safety of Extavia for this group is similar to that for adults. Extavia should not be used in children under 12 years of age, as no information is available for this age group.

Other medicines and Extavia

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

No formal interaction studies have been performed to investigate whether Extavia affects or is affected by other medicines.

The use of Extavia in combination with other medicines that affect the immune system is not recommended, except for anti-inflammatory medicines called corticosteroids or adrenocorticotropic hormone (ACTH).

Extavia should be used with caution along with:

  • drugs that need a certain enzyme system in the liver (the so-called cytochrome P450 system) to be removed from the body, e.g. medicines used to treat epilepsy (eg phenytoin ).
  • medicines that affect the production of blood cells s.

Extavia with food and drink

Extavia is injected under the skin. Therefore, it is not believed that food and drink have any effect on Extavia.

Pregnancy and breastfeeding

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

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

Driving and using machines

Extavia can cause side effects in the central nervous system (see section 4 “Possible side effects”). If you are particularly sensitive, this may affect your ability to drive or use machines.

Extavia contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per ml, ie essentially ‘sodium-free’.

3. How to use Extavia

Extavia treatment should always be started under the supervision of a doctor who has experience in the treatment of multiple sclerosis.

Always use this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.

The recommended dose is to inject 1.0 ml of the reconstituted Extavia solution for injection under the skin ( subcutaneously ) every other day (once every other day) (see appendix “Self-injection procedure” in the second part of this leaflet). 1.0 ml is equivalent to a dose of 250 micrograms (8.0 million IU) of interferon beta-1b.

Generally, treatment should be started with a low dose of 0.25 ml (62.5 micrograms). Dose one will then be gradually increased to a full dose of 1.0 ml (250 micrograms).

Dose one 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 with you to change the time intervals for dose escalation depending on the side effects you may experience at the beginning of treatment. Your doctor will decide this in consultation with you.

Preparation for injection

Before injection, a ready-to-use Extavia solution must be prepared from a vial of Extavia powder and 1.2 ml of liquid from the pre-filled syringe of diluent. Either your doctor or nurse does it or you do it yourself after you have first received careful instructions and practiced.

Detailed instructions on how to inject Extavia under the skin can be found in the appendix at the end of this leaflet. These instructions also tell you how to prepare the Extavia solution for injection.

Change the injection site at regular intervals. See section 2 “Warnings and Precautions” and follow the instructions under “Switching the Injection Site” in the appendix at the end of this leaflet.

Length of treatment

It is not known how long treatment with Extavia should last. Your doctor will decide with you how long the treatment should last.

If you use more Extavia than you should

No life-threatening symptoms occurred even when a dose was given that was many times higher than that recommended for the treatment of MS.

  • Contact your doctor if you have injected too much Extavia or injected too often.

If you forget to use Extavia

If you forget to give yourself an injection at the right time, do so as soon as you can. The next injection should be taken 48 hours later.

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

If you stop using Extavia

Discuss with your doctor if you stop or want to stop treatment. Extavia is not known to cause acute withdrawal symptoms at the end of treatment.

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

4. Possible side effects

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

Extavia can cause serious side effects. If any of the side effects gets 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 get symptoms such as itching all over your body, swollen face and/or swollen tongue, or sudden shortness of breath.
  • if you feel significantly more sad or despairing than you did before you started treatment or if you have suicidal thoughts.
  • if you notice unusual bruises bleed more than usual after injury or if it seems like you are getting a lot of infection.
  • if you suffer from loss of appetite, fatigue, nausea, repeated vomiting, especially if you notice widespread itching, yellowing of the skin or whites of the eyes, or bruising easily.
  • if you get symptoms such as irregular heartbeat, swelling e.g. in ankles or legs, or shortness of breath.
  • if you experience abdominal pain radiating to the back and/or you feel unwell or have a fever
  • Tell your doctor immediately :
    • if you get any or all of these symptoms: frothy urine, fatigue, swelling, especially in the ankles and eyelids, and weight gain, as they may be signs of a possible kidney problem.

Side effects are common at the beginning of treatment, but generally, they decrease during the course of treatment.

The most common side effects are:

  • flu-like symptoms such as fever, chills, joint pain, general malaise, sweating, headache, and muscle aches. These symptoms can be relieved with paracetamol or non-steroidal anti-inflammatory drugs such as ibuprofen.
  • injection site reactions. Symptoms such as redness, swelling, discoloration, inflammation, pain, hypersensitivity, tissue damage ( necrosis ). See “Warnings and Precautions” in section 2 for more information and what to do if you get reactions at the injection site. These can be reduced if an auto-injector is used. Talk to your doctor, pharmacist, or nurse for more information.

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

The following list of adverse reactions is based on reports from clinical trials with Extavia (List 1) and reported side effects of the marketed medicine (List 2).

List 1: Very common side effects that have occurred in clinical trials with Extavia (may affect more than 1 in 10 people) and that were more common than those who received placebo. The list also includes side effects that have occurred as usual (may affect up to 1 in 10 people) but that was significantly related to treatment.

  • infection  boils
  • decreased white blood cell count, swollen lymph nodes ( lymphadenopathy )
  • decreased amount of sugar in the blood ( hypoglycemia )
  • depression, anxiety
  • headache, dizziness, insomnia, migraine, numbness, or tingling ( paresthesia )
  • eye inflammation ( conjunctivitis ), visual disturbances
  • earache
  • irregular, rapid heartbeat or palpitations ( palpitation )
  • redness and/or facial redness due to dilation of the blood vessels (vasodilation), high blood pressure ( hypertension )
  • runny nose, cough, hoarseness due to infection of the upper airways, sinusitis, cough (increased), shortness of breath ( dyspnea )
  • diarrhea, constipation nausea, vomiting, abdominal pain
  • elevated levels of liver enzymes in the blood (manifested in blood tests)
  • skin effects, rash
  • muscle stiffness ( hypertension ), muscle aches ( myalgia ), muscle weakness ( myasthenia ), back pain, pain in the extremities you like fingers and toes
  • retention of urine in the bladder ( urinary retention ), protein in the urine (manifested in urine samples), frequent urination, inability to restrain urination (urinary incontinence), urinary incontinence
  • menstrual cramps ( dysmenorrhea ), menstrual disorders, heavy uterine bleeding ( metrorrhagia ) especially between menstruations, impotence
  • injection site reactions (including redness, swelling, discoloration, inflammation, pain, allergic reaction; see section 2 “Warnings and precautions”), skin and tissue damage ( necrosis ) at the injection site (see section 2 “Warnings and precautions”)
  • flu-like symptoms, fever, aches, chest pain, fluid accumulation in arms, legs, or face (peripheral edema ), lack energy or weakness ( asthenia ), chills, sweating, general malaise

Also, the following side effects have been identified during post-authorization use.

List 2: Adverse reactions reported for the marketed medicinal product (frequencies (if known) based on clinical trials ):

  • Very common (may affect more than 1 in 10 people) :
    • joint pain ( arthralgia )
  • Common (may affect up to 1 in 10 people) :
  • the number of red blood cells in the blood can drop ( anemia )
  • thyroid dysfunction (it produces too little hormone ) ( hypothyroidism )
  • weight gain or loss
  • confusion
  • abnormally fast heart rhythm ( tachycardia ),
  • a reddish-yellow pigment ( bilirubin ), produced by the liver, may increase (this is shown in blood tests)
  • swollen and usually itchy spots on the skin or mucous membranes ( urticaria )
  • itching ( pruritus )
  • hair loss on the head ( alopecia )
  • menstrual disorders ( menorrhagia )
  • Uncommon (may affect up to 1 in 100 people) :
  • the number of platelets (which help the blood to clot) may decrease ( thrombocytopenia )
  • a certain type of blood fat ( triglycerides ) may increase (shows up in blood tests), see section 2 “Warnings and Precautions”
  • suicide attempt
  • Mood swings
  • seizures
  • a special liver enzyme (gamma GT) produced by the liver may increase (this is shown in blood tests)
  • inflammation of the liver ( hepatitis )
  • discoloration of the skin
  • Rare (may affect up to 1 in 1,000 people) :
  • severe allergic (anaphylactic) reactions
  • disorder of thyroid function (thyroid disease), it produces too much hormone ( hyperthyroidism )
  • inflammation of the pancreas ( pancreatitis ), see section 2 “Warnings and precautions”
  • blood clots in the small blood vessels, which can affect the kidneys (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome ). Symptoms may include bruising, bleeding, fever, extreme weakness, headache, dizziness, or fainting. Your doctor may notice changes in your blood and kidney function

Side effects that occur only during the sales period :

  • degradation of red blood cells (hemolytic anemia ), (no known frequency).
  • kidney problems including scarring (glomerulosclerosis), which may reduce your kidney function, (less common).
  • severe loss of appetite leading to weight loss, (rare).
  • heart muscle disease ( cardiomyopathy ), (rare).
  • sudden shortness of breath ( bronchospasm ), (rare).
  • the liver does not work (liver damage [including hepatitis], liver failure), (rare).
  • problems with the thin blood vessels ( capillaries ) can occur when using drugs such as Extavia ( systemic capillary leakage syndrome ), (no known frequency).
  • rash, flushing of the face, joint pain, fever, weakness, and others caused by the drug (drug-induced lupus erythematosus), no known frequency.
  • a disease with severe narrowing of the blood vessels of the lungs leading to high blood pressure in the blood vessels that carry blood from the heart to the lungs ( pulmonary arterial hypertension ), (no known frequency). Pulmonary arterialhypertension has been observed at different times during treatment, even up to several years after starting treatment with Extavia

5. How to store Extavia

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 carton. The expiration date is the last day of the specified month.

Do not store above 25 ° C. Do not freeze.

You should use the solution immediately after reconstitution. If you can not do it, it is useful for 3 hours if stored in a refrigerator 2 ° C – 8 ° C.

Do not use this medicine if it contains particles or is discolored.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the packaging and other information

Content declaration

  • The active substance is interferon beta-1b. 1 vial contains 300 micrograms (9.6 million IU) of interferon beta-1b per vial. After reconstitution, each milliliter contains 250 micrograms (8.0 million IU) of interferon beta-1b.
  • Other ingredients are
    • in the powder: mannitol and human albumin
    • in the diluent: sodium chloride, water for injections

The cover on top of the pre-filled syringe contains a derivative of natural rubber latex. Therefore, the protection may contain natural rubber latex.

What the medicine looks like and the contents of the pack

Extavia consists of a powder and diluent for solution for injection.

The powder is white to off-white in color.

The Extavia powder is supplied in a 3-milliliter vial.

The diluent is a clear/colorless solution.

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

Extavia is available in pack sizes:

  • 5 vials of interferon beta-1b and 5 pre-filled syringes of diluent.
  • 14 vials of interferon beta-1b and 14 pre-filled syringes of diluent.
  • 15 vials of interferon beta-1b and 15 pre-filled syringes of diluent.
  • 14 vials of interferon beta-1b and 15 pre-filled syringes of diluent.
  • 3-month multipack with 42 (3×14) vials of interferon beta-1b and 42 (3×14) pre-filled syringes of diluent.
  • 3-month multipack of 45 (3×15) vials of interferon beta-1b and 45 (3×15) pre-filled syringes of diluent.
  • 3-month multipack with 42 (3×14) vials of interferon beta-1b and 45 (3×15) pre-filled syringes of diluent 

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 25

D-90429 Nuremberg

Germany

Contact the representative of the marketing authorization holder to find out more about this medicine:

Belgium / Belgique / BelgienNovartis Pharma NVTel: +32 2 246 16 11 LithuaniaSIA Novartis Baltics Lithuanian branchesTel: +370 5 269 16 50
BulgariaNovartis Bulgaria EOODTel .: +359 2 489 98 28 Luxembourg / LuxemburgNovartis Pharma NVTel: +32 2 246 16 11
Czech RepublicNovartis sroTel: +420 225 775 111 HungaryNovartis Hungary Kft.Tel .: +36 1 457 65 00
DenmarkNovartis Healthcare A / STel: +45 39 16 84 00 MaltaNovartis Pharma Services Inc.Tel: +356 2122 2872
GermanyNovartis Pharma GmbHTel: +49 911 273 0 The NetherlandsNovartis Pharma BVTel: +31 88 04 52 111
EestiSIA Novartis Baltics Eesti subsidiaryTel: +372 66 30 810 NorwayNovartis Norge ASTel: +47 23 05 20 00
GreeceNovartis (Hellas) AEBE:Ηλ: +30 210 281 17 12 AustriaNovartis Pharma GmbHTel: +43 1 86 6570
SpainNovartis Pharmacéutica, SATel: +34 93 306 42 00 PolandNovartis Poland Sp. z ooTel .: +48 22 375 4888
FranceNovartis Pharma SASTel: +33 1 55 47 66 00 PortugalNovartis Farma – Pharmaceutical Products, SATel: +351 21 000 8600
CroatiaNovartis Hrvatska dooTel. +385 1 6274 220 RomaniaNovartis Pharma Services Romania SRLTel: +40 21 31299 01
IrelandNovartis Ireland LimitedTel: +353 1 260 12 55 SloveniaNovartis Pharma Services Inc.Tel: +386 1 300 75 50
IcelandVistor hf.Phone: +354 535 7000 Slovak RepublicNovartis Slovakia sroTel: +421 2 5542 5439
ItalyNovartis Farma SpATel: +39 02 96 54 1 Finland / FinlandNovartis Finland OyPuh / Tel: +358 (0) 10 6133 200
LatviaSIA Novartis BalticsTel: +371 67 887 070 United KingdomNovartis Pharmaceuticals UK Ltd.Tel: +44 1276 698370

Muhammad Nadeem

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