Lemtrada 12 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

LEMTRADA 12 mg concentrate for solution for infusion

alemtuzumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read the entire leaflet carefully before you are administered this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to refer to it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What LEMTRADA is and what it is used for

LEMTRADA contains the active substance alemtuzumab, which is used to treat a form of multiple sclerosis (MS) in adults called relapsing-remitting multiple sclerosis (RRMS). LEMTRADA does not cure MS, but it can reduce the number of relapses. It may also slow down or reverse some of the signs and symptoms of MS. In clinical trials, patients treated with LEMTRADA had fewer relapses and were less likely to experience worsening disability compared to patients treated with an interferon beta injected several times per week.

LEMTRADA is used if your MS is highly active despite prior treatment with at least one other MS medicine, or if your MS is rapidly evolving.

What is multiple sclerosis?

MS is an autoimmune disease that affects the central nervous system (brain and spinal cord). In MS, the immune system mistakenly attacks the protective layer (myelin) that covers nerve fibers, causing inflammation. When inflammation causes symptoms, it is often referred to as an "attack" or "relapse". In relapsing-remitting MS (RRMS), patients experience relapses followed by periods of recovery.

The symptoms experienced depend on which part of the central nervous system is affected. Nerve damage caused by this inflammation may be reversible, but as the disease progresses, damage can accumulate and become permanent.

How LEMTRADA works

LEMTRADA modulates the immune system to limit its attacks on the nervous system.

2. What you need to know before you are given LEMTRADA

DO NOT use LEMTRADA:

• if you are allergic to alemtuzumab or to any of the other ingredients of this medicine (listed in section 6)

• if you are a carrier of the human immunodeficiency virus (HIV)

• if you have a serious infection

• if you have any of the following conditions:

• another autoimmune disease in addition to multiple sclerosis

• uncontrolled high blood pressure

• history of tear in the blood vessels supplying the brain

• history of stroke (cerebrovascular accident)

• history of heart attack or chest pain

• history of bleeding disorder.

Warnings and precautions

Talk to your doctor before you are given LEMTRADA. After completing a treatment cycle with LEMTRADA, you may have an increased risk of developing other autoimmune diseases or experiencing serious infections. It is important that you understand these risks and know how to recognize them. You will be provided with a Patient Card and a Patient Guide containing further information. It is important that you carry your Patient Card with you during treatment and for up to 4 years after your last LEMTRADA infusion, as adverse effects may occur years after treatment. Whenever you receive medical care, even if it is not for MS, show your Patient Card to the doctor.

Your doctor will perform blood tests before starting treatment with LEMTRADA. These tests are carried out to determine whether you can receive LEMTRADA. Your doctor will also ensure that you do not have certain medical conditions or disorders before starting treatment with LEMTRADA.

• Autoimmune diseases

Treatment with LEMTRADA may increase the risk of autoimmune diseases. These diseases occur when the immune system mistakenly attacks the body itself. Below is information about specific autoimmune diseases that have been observed in patients with MS treated with LEMTRADA.

Autoimmune diseases may occur many years after treatment with LEMTRADA. Therefore, blood and urine tests are required for up to 4 years after the last infusion. These tests are necessary even if you feel well and your MS symptoms are under control. There are certain signs and symptoms you should monitor yourself. Furthermore, these diseases may appear beyond 4 years, so you should remain vigilant for signs and symptoms even after monthly blood and urine tests are no longer required. Details about signs, symptoms, tests, and actions to take are provided in sections 2 and 4 – autoimmune diseases.

More useful information about these autoimmune diseases (and associated tests) can be found in the LEMTRADA Patient Guide.

• Acquired haemophilia A

Rarely, patients have developed a bleeding disorder caused by antibodies against factor VIII (a protein necessary for normal blood clotting), known as acquired haemophilia A. This condition must be diagnosed and treated immediately. Symptoms of acquired haemophilia A are described in section 4.

• Immune thrombocytopenic purpura (ITP)

Frequently, patients have developed a bleeding disorder caused by low platelet levels, called immune thrombocytopenic purpura (ITP). This disorder must be detected and treated quickly, as its effects can be serious or even fatal. Signs and symptoms of ITP are described in section 4.

• Kidney disease (such as anti-GBM disease)

Rarely, patients have experienced kidney problems due to autoimmune disorders, such as anti-glomerular basement membrane disease (anti-GBM disease). Signs and symptoms of kidney disease are described in section 4. If untreated, it may lead to kidney failure requiring dialysis or transplantation and could result in death.

• Thyroid disorders

Very commonly, patients have experienced an autoimmune disorder of the thyroid gland, affecting its ability to produce or regulate hormones important for metabolism.

LEMTRADA may cause different types of thyroid disorders, including:

• Overactive thyroid gland (hyperthyroidism), when the thyroid produces too much hormone
• Underactive thyroid gland (hypothyroidism), when the thyroid does not produce enough hormone

Signs and symptoms of thyroid disorders are described in section 4.

If you develop a thyroid disorder, in most cases you will require lifelong treatment with medications to control the condition, and in some cases, surgical removal of the thyroid gland may be necessary.

It is very important to continue appropriate treatment for thyroid disorders, especially if you become pregnant after using LEMTRADA. Untreated thyroid disorders may harm the fetus or newborn.

• Liver inflammation

Some patients have developed liver inflammation after receiving LEMTRADA. Liver inflammation can be detected through blood tests performed regularly after LEMTRADA treatment. Inform your doctor if you experience one or more of the following symptoms: nausea, vomiting, abdominal pain, fatigue, loss of appetite, yellowing of the skin or eyes, dark urine, or bleeding or bruising more easily than normal.

• Thrombotic thrombocytopenic purpura (TTP)

A blood clotting disorder called thrombotic thrombocytopenic purpura (TTP) may occur with LEMTRADA. Blood clots form in blood vessels and may occur throughout the body. Seek immediate medical help if you experience any of the following symptoms: skin or mouth bruising that may appear as small red spots, with or without unexplained extreme fatigue, fever, confusion, speech changes, yellowing of the skin or eyes (jaundice), low urine output, or dark urine. Urgent medical attention is recommended, as prolonged TTP can be fatal (see section 4 "Possible side effects").

• Sarcoidosis

An immune system disorder (sarcoidosis) has been reported in patients treated with LEMTRADA. Symptoms may include persistent dry cough, shortness of breath, chest pain, fever, swollen lymph nodes, weight loss, skin rashes, and blurred vision.

• Autoimmune encephalitis

Autoimmune encephalitis (an immune-mediated brain disorder) may occur after receiving LEMTRADA. This condition may include symptoms such as behavioral and/or psychiatric changes, short-term memory loss, or seizures. Symptoms may resemble an MS relapse. If you develop one or more of these symptoms, contact your doctor.

• Other autoimmune diseases

Rarely, some patients have experienced autoimmune diseases related to red blood cells or white blood cells. These diseases can be diagnosed through regular blood tests performed after LEMTRADA treatment. If you develop one of these conditions, your doctor will inform you and take appropriate measures to treat it.

• Infusion reactions

Most patients treated with LEMTRADA will experience adverse effects during or within 24 hours after the infusion. To help reduce infusion reactions, your doctor will treat you with other medications (see section 4 – infusion reactions).

• Other serious reactions occurring shortly after LEMTRADA infusion

Some patients have had serious or potentially life-threatening reactions after LEMTRADA infusion, including lung bleeding, heart attack, stroke (cerebrovascular accident), or tears in the blood vessels supplying the brain. Reactions may occur after any of the doses during the treatment cycle. In most cases, reactions occurred within days 1–3 after infusion. Your doctor will monitor vital signs, including blood pressure, before and during the infusion. Seek immediate help if you experience any of the following symptoms: difficulty breathing, coughing up blood, chest pain, facial drooping, sudden severe headache, weakness on one side of the body, difficulty speaking, or neck pain.

• Hemophagocytic lymphohistiocytosis

Treatment with LEMTRADA may increase the risk of excessive activation of white blood cells associated with inflammation (hemophagocytic lymphohistiocytosis), which can be fatal if not diagnosed and treated promptly. If you experience multiple symptoms such as fever, swollen glands, bruising, or skin rash, contact your doctor immediately.

• Adult-onset Still’s disease (AOSD)

AOSD is a rare condition that may cause inflammation in multiple organs, with symptoms including fever >39°C or 102.2°F lasting more than 1 week, joint pain and stiffness with or without swelling, and/or skin rash. If you experience a combination of these symptoms, contact your doctor immediately.

• Infections

Patients treated with LEMTRADA have an increased risk of serious infection (see section 4 – infections). In general, infections can be treated with standard medications.

To reduce the risk of infection, your doctor will check whether other medications you are taking may affect your immune system. Therefore, it is important to inform your doctor about all medications you are taking.

Also, inform your doctor if you have a serious infection before starting LEMTRADA treatment, as your doctor should delay treatment until the infection resolves.

Patients treated with LEMTRADA have a higher risk of developing herpes infections (e.g., cold sores). Generally, once a patient has had a herpes infection, they are at increased risk of developing another. It is also possible to develop a herpes infection for the first time. Your doctor is advised to prescribe appropriate treatment to reduce the risk of herpes infection, which should be taken during the days when LEMTRADA is administered and for the month following treatment.

Additionally, infections may occur that can cause cervical abnormalities. Therefore, it is recommended that all female patients undergo an annual cervical screening test (e.g., Pap smear). Your doctor will advise you on the necessary tests.

Infections with a virus called cytomegalovirus have been reported in patients treated with LEMTRADA. Most cases occurred within two months after alemtuzumab administration. Inform your doctor immediately if you have symptoms of infection, such as fever or swollen glands.

Patients treated with LEMTRADA have also experienced infections due to the Epstein-Barr virus (EBV), including cases with severe and sometimes fatal liver inflammation. Inform your doctor immediately if you have symptoms of infection such as fever, swollen glands, or fatigue.

Patients treated with LEMTRADA also have a high risk of developing listeria infection (a bacterial infection caused by consuming contaminated food). Listeria infection can cause serious illness, including meningitis, but can be treated with appropriate medications. To reduce this risk, you should avoid eating raw or undercooked meats, soft cheeses, and unpasteurized dairy products for two weeks before treatment, during treatment, and for at least one month after LEMTRADA treatment.

If you live in an area where tuberculosis is common, you may be at higher risk. Your doctor will schedule tests to screen for tuberculosis.

If you are a carrier of the hepatitis B or hepatitis C virus (which affect the liver), extra caution is needed before receiving LEMTRADA, as it is unknown whether treatment could reactivate the infection, potentially causing liver damage.

Cases of a rare brain infection called PML (progressive multifocal leukoencephalopathy) have occurred in patients receiving Lemtrada. PML has been reported in patients with other risk factors, particularly prior treatment with MS medications associated with PML.

PML can lead to severe disability over weeks or months and may be fatal.

Symptoms may resemble an MS flare and include progressive weakness or clumsiness in limbs, vision problems, difficulty speaking, or changes in thinking, memory, and orientation, leading to confusion and personality changes. It is important to inform your family members or caregivers about your treatment, as they may notice symptoms you are not aware of. Inform your doctor immediately if you experience any symptoms suggestive of PML.

• Pneumonitis and pericarditis

Pneumonitis (inflammation of lung tissue) has been reported in patients treated with LEMTRADA. Most cases occurred within the first month after treatment. Cases of pericardial effusion (fluid accumulation around the heart) and pericarditis (inflammation of the membrane surrounding the heart) have also been reported in patients treated with LEMTRADA. Inform your doctor if you experience symptoms such as difficulty breathing, cough, wheezing, chest pain or tightness, or coughing up blood, as these may be caused by pneumonitis, pericardial effusion, or pericarditis.

• Gallbladder inflammation

LEMTRADA may increase the risk of gallbladder inflammation. This may be a serious medical condition that could potentially be fatal. Inform your doctor if you experience symptoms such as stomach pain or discomfort, fever, nausea, or vomiting.

• Previous cancer diagnosis

If you have previously been diagnosed with cancer, inform your doctor.

• Vaccines

It is unknown whether LEMTRADA affects the response to vaccines. If you have not completed the necessary standard vaccinations, your doctor will consider whether you should receive them before LEMTRADA treatment. In particular, your doctor may consider vaccinating you against varicella if you have not had it. Any vaccination should be administered at least 6 weeks before starting a LEMTRADA treatment cycle.

You should NOT receive certain types of vaccines (live virus vaccines) if you have recently received LEMTRADA.

Children and adolescents

LEMTRADA must not be used in children and adolescents under 18 years of age, as it has not been studied in MS patients under this age.

Other medicines and LEMTRADA

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines (including vaccinations or herbal remedies).

Besides LEMTRADA, other treatments (including those for MS or other conditions) may affect the immune system and thus affect your ability to fight infections. If you are taking any of these medicines, your doctor may ask you to stop them before starting LEMTRADA treatment.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine.

Women of childbearing potential must use effective contraception during each treatment cycle with LEMTRADA and for 4 months after each cycle.

Special care is needed if you become pregnant after LEMTRADA treatment and develop a thyroid disorder during pregnancy. Thyroid disorders may harm the baby (see section 2 Warnings and precautions – autoimmune diseases).

Breast-feeding

It is unknown whether LEMTRADA passes into breast milk, but there is a possibility that it may. Breast-feeding is recommended to be interrupted during each treatment cycle with LEMTRADA and for 4 months after each cycle. However, breast milk may be beneficial (it may protect the baby from infections), so consult your doctor if you plan to breastfeed, and they will advise you on what is best for you and your baby.

Fertility

LEMTRADA may remain in your body during the treatment cycle and up to 4 months after. It is unknown whether LEMTRADA affects fertility during this period. Consult your doctor if you are planning to have children. There is no evidence that LEMTRADA impacts male fertility.

Driving and using machines

Many patients experience adverse effects during or within 24 hours after LEMTRADA infusion, and some of these effects, such as dizziness, may make driving or operating machinery unsafe. If this occurs, stop these activities until you feel better.

LEMTRADA contains potassium, sodium, and polysorbate

This medicine contains potassium, less than 1 mmol of potassium (39 mg) per infusion; this is essentially “potassium-free”.

This medicine contains less than 1 mmol of sodium (23 mg) per infusion; this is essentially “sodium-free”.

This medicine contains 0.12 mg of polysorbate 80 (E433) per vial with a nominal fill volume of 1.2 ml, equivalent to 0.1 mg/1.0 ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any allergies.

3. How LEMTRADA is administered

Your doctor will explain how LEMTRADA is administered. If in doubt, please ask your doctor.

The initial treatment you will receive consists of one infusion per day for 5 days (cycle 1), and one year later, one infusion per day for 3 days (cycle 2).

You will not receive LEMTRADA treatment between the two cycles. Two treatment cycles may reduce MS activity for up to 6 years.

Some patients who have symptoms or signs of MS disease activity after the initial two cycles may additionally receive one or two further treatment cycles, each consisting of one infusion per day for 3 days. These additional treatment cycles may be administered twelve months or more after the previous treatment.

The maximum daily dose is one infusion.

LEMTRADA will be administered to you by intravenous infusion. Each infusion lasts approximately 4 hours. Monitoring for adverse reactions and periodic testing must continue for 4 years after the last infusion.

To help you better understand the duration of treatment effects and the necessary follow-up period, please refer to the diagram below.

Follow-up after LEMTRADA treatment

After receiving LEMTRADA, you must undergo periodic testing so that any potential adverse effects can be diagnosed and treated promptly. These tests must continue for up to 4 years after the last infusion and are described in section 4, Most important adverse effects.

If you receive more LEMTRADA than you should

Patients who have accidentally received an excessive amount of LEMTRADA during an infusion have experienced serious reactions such as headache, rash, low blood pressure, or increased heart rate. Doses higher than recommended may cause more severe or prolonged infusion reactions (see section 4) or a greater effect on the immune system. Treatment consists of stopping the administration of LEMTRADA and managing the symptoms.

If you forget to use LEMTRADA

It is unlikely that you will miss a dose, as it is administered by a healthcare professional. However, note that if a dose is missed, it should not be administered on the same day as a scheduled dose.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

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

The most important adverse effects are autoimmune disorders described in section 2, which include:

• Acquired haemophilia A (a type of bleeding disorder), (uncommon – may affect up to 1 in 100 people): may present as spontaneous bruising, nosebleeds, pain or swelling in joints, other types of bleeding, or bleeding from cuts that takes longer than normal to stop.
• Immune thrombocytopenia (ITP) (common – may affect up to 1 in 10 people): may present as small red, pink, or purple spots scattered across the skin; tendency to bruise easily; bleeding from cuts that is harder to stop; menstrual periods that are heavier, longer, or more frequent than normal; bleeding between menstrual periods; new or prolonged bleeding from gums or nose; or coughing up blood.
• Thrombotic thrombocytopenic purpura (TTP) (rare – may affect up to 1 in 1,000 people): may present as bruising on the skin or in the mouth, which may appear as tiny red spots, with or without unexplained extreme fatigue, fever, confusion, changes in speech, yellowing of the skin or eyes (jaundice), reduced urine output, or dark-colored urine.
• Kidney disorders (rare – may affect up to 1 in 1,000 people): may present as blood in the urine (urine may appear red or tea-colored) or swelling of the legs or feet. It may also cause lung damage and lead to coughing up blood.

If you experience any of these signs or symptoms related to kidney or bleeding disorders, inform your doctor immediately. If you cannot contact your doctor, seek immediate medical attention.

• Thyroid disorders (very common – may affect more than 1 in 10 people): may present as excessive sweating; unexplained weight gain or loss; bulging eyes; nervousness; rapid heart rate; feeling cold; worsening fatigue; or new-onset constipation.
• Disorders of red and white blood cells (uncommon – may affect up to 1 in 100 people), diagnosed through blood tests.
• Sarcoidosis (uncommon – may affect 1 in 100 people): symptoms may include persistent dry cough, shortness of breath, chest pain, fever, swollen lymph nodes, weight loss, skin rashes, and blurred vision.
• Autoimmune encephalitis (uncommon – may affect 1 in 100 people): may include symptoms such as behavioral and/or psychiatric changes, short-term memory loss, or seizures. Symptoms may resemble an MS relapse.

All of these serious adverse effects may occur years after receiving LEMTRADA. If you experience any of these signs or symptoms, inform your doctor immediately. You will also undergo periodic blood and urine tests to ensure that, if you develop any of these conditions, you receive prompt treatment.

Summary of tests you will undergo to monitor for the development of autoimmune conditions:

Test	When?	Duration
Blood test (to diagnose all the serious adverse effects mentioned above)	Before starting treatment and every month after treatment	Up to 4 years after the last LEMTRADA infusion
Urine test (additional test to diagnose kidney disorders)	Before starting treatment and every month after treatment ends	Up to 4 years after the last LEMTRADA infusion

After this period, if you experience symptoms of ITP, acquired hemophilia A, PTT, or thyroid or kidney disorders, your doctor will carry out further tests. You should remain vigilant for signs and symptoms of adverse reactions beyond the four years as indicated in the Patient Guide, and you should continue to carry your Patient Card with you.

Another important adverse reaction is an increased risk of infections (see below for information on how frequently patients experience infections). In most cases, these infections are mild, but serious infections may occur.

If you experience any of these signs of infection, inform your doctor immediately fever and/or chills swelling of the glands

To help reduce your risk of certain infections, your doctor may consider giving you vaccination against varicella and/or other vaccinations that they think you may need (see section 2: What you need to know before using LEMTRADA – Vaccinations). Your doctor may also prescribe you a medication for mouth ulcers (see section 2: What you need to know before using LEMTRADA – Infections).

The most common side effects are infusion reactions (see below for information on how frequently patients experience them), which may occur during or within 24 hours after the infusion. In most cases, these reactions are mild, but serious reactions may occur. Allergic reactions may sometimes occur.

To help reduce infusion reactions, your doctor will give you medications (corticosteroids) before each of the first 3 infusions of a LEMTRADA cycle. Other treatments may also be given before the infusion or when symptoms occur to help limit these reactions. In addition, you will be monitored during the infusion and for up to 2 hours after it ends. In case of serious reactions, the infusion may be slowed down or even stopped.

Refer to the LEMTRADA patient guide for more information about these events.

These are the side effects you may experience:

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

• Infusion reactions that may occur during or within 24 hours after the infusion: changes in heart rate, headache, rash, rash over the body, fever, hives, chills, itching, redness of the face and neck, feeling of tiredness, nausea
• Infections: respiratory tract infections such as colds and sinusitis, urinary tract infections, herpes infections
• Decrease in white blood cell count (lymphocytes, leukocytes, neutrophils)
• Thyroid disorders such as overactive or underactive thyroid gland

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

• Infusion reactions that may occur during or within 24 hours after the infusion: indigestion, chest discomfort, pain, dizziness, altered taste, difficulty sleeping, difficulty breathing or shortness of breath, low blood pressure, pain at the infusion site
• Infections: cough, ear infection, flu-like illness, bronchitis, pneumonia, oral thrush or vaginal candidiasis, herpes, mouth ulcers, swollen or enlarged glands, influenza, shingles (herpes zoster infection), dental infection
• Increase in white blood cell count such as neutrophils, eosinophils (different types of white blood cells), anemia, decrease in red blood cell percentage, easy or excessive bruising or bleeding, swollen lymph nodes
• Exaggerated immune response
• Back, neck, arm, or leg pain, muscle pain, muscle spasms, joint pain, mouth or throat pain
• Inflammation of mouth/gums/tongue
• General malaise, weakness, vomiting, diarrhea, abdominal pain, stomach flu, hiccups
• Abnormal liver test results
• Heartburn
• Abnormal findings during examination: blood or proteins in urine, decreased heart rate, irregular or abnormal heartbeat, high blood pressure, altered kidney function, white blood cells in urine
• Bruising
• MS relapse
• Tremor, loss of sensation, burning or tingling sensation
• Autoimmune overactive or underactive thyroid gland, thyroid antibodies, or goiter (enlargement of the thyroid gland in the neck)
• Numbness in arms and/or legs
• Vision problems, conjunctivitis, eye disease associated with thyroid disease
• Dizziness or loss of balance, migraine
• Feeling anxious, depression
• Irregular, prolonged, or abnormally heavy menstruation
• Acne, skin redness, excessive sweating, skin discoloration, skin lesion, dermatitis
• Nosebleeds, bruising
• Hair loss
• Asthma
• Muscle and bone pain, chest discomfort

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

• Infections: stomach flu, gum inflammation, fungal nail infections, tonsillitis, acute sinusitis, bacterial skin infection, cytomegalovirus infection
• Pneumonitis
• Athlete's foot
• Abnormal vaginal smear
• Increased sensitivity, sensory disturbances such as numbness, tingling, and pain, tension headache
• Double vision
• Ear pain
• Difficulty swallowing, sore throat, productive cough
• Weight loss, weight gain, decrease in red blood cells, increased blood glucose, increased size of red blood cells
• Constipation, acid reflux, dry mouth
• Rectal bleeding
• Bleeding gums
• Decreased appetite
• Blisters, night sweats, facial swelling, eczema
• Stiffness, discomfort in arms and legs
• Kidney stones, excretion of ketone bodies in urine, kidney disease
• Decreased/weakened immune system
• Tuberculosis
• Inflammation of the gallbladder with or without gallstones
• Warts
• Autoimmune bleeding disorder (acquired hemophilia A)
• Sarcoidosis
• Autoimmune brain disorder (autoimmune encephalitis)
• Patches of skin with loss of color (vitiligo)
• Autoimmune hair loss (alopecia areata)

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

• Excessive activation of white blood cells associated with inflammation (hemophagocytic lymphohistiocytosis)
• Autoimmune blood clotting disorder (thrombotic thrombocytopenic purpura, TTP)

Frequency not known (cannot be estimated from available data):

• Listeriosis/meningitis due to Listeria
• Bleeding in the lungs
• Heart attack
• Stroke
• Tears in the vertebral or carotid arteries (blood vessels supplying blood to the brain)
• Infection with a virus known as Epstein-Barr virus
• Inflammatory disease affecting multiple organs, adult-onset Still's disease (AOSD)

Show the Patient Card and this leaflet to any physician involved in your treatment, not only to your neurologist.

You will also find this information in the Patient Card and the patient guide provided by your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor, including any possible side effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of LEMTRADA

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 and label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

Keep in the original packaging in order to protect from light.

Immediate use of the product after dilution is recommended due to the possible risk of microbial contamination. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user and must not exceed 8 hours at a temperature of 2 °C to 8 °C, protected from light.

6. Contents of the pack and other information

Composition of LEMTRADA

The active substance is alemtuzumab.

Each vial contains 12 mg of alemtuzumab in 1.2 ml.

The other components are:

• Disodium phosphate dihydrate (E339)
• Disodium edetate dihydrate
• Potassium chloride (E508)
• Potassium dihydrogen phosphate (E340)
• Polysorbate 80 (E433)
• Sodium chloride
• Water for injections

Appearance of LEMTRADA and contents of the pack

LEMTRADA is a sterile, transparent, colourless or slightly yellow concentrate for solution for infusion. It is supplied in a glass vial with a stopper.

There is 1 vial in each carton.

Marketing Authorization Holder

Sanofi Belgium
Leonardo Da Vincilaan 19
B-1831 Diegem
Belgium

Manufacturer

Genzyme Ireland Limited
IDA Industrial Park
Old Kilmeaden Road
Waterford
Ireland

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium/Luxembourg/Luxembourg Sanofi Belgium Tel/Tel: + 32 2 710 54 00	Lithuania Swixx Biopharma UAB Tel. +370 5 236 91 40
	Hungary SANOFI-AVENTIS Zrt Tel: +36 1 505 0050
Czech Republic sanofi-aventis, s.r.o. Tel: +420 233086 111	Malta Sanofi S..l. Tel: +39 02 39394275
Denmark Sanofi A/S Tlf: +45 45 16 70 00	Netherlands Sanofi B.V. Tel: +31 20 245 4000
Germany Sanofi Belgium Tel: +49 (0) 6102 3674 451	Norway sanofi-aventis Norge AS Tlf: + 47 67 10 71 00
Estonia Swixx Biopharma OÜ Tel. +372 640 10 30	Austria sanofi-aventis GmbH Tel: + 43 1 80 185 - 0
Greece Sanofi-Aventis Μονοπρόσωπη AEBE Tel: +30 210 900 16 00	Poland Sanofi Sp. z o.o. Tel.: +48 22 280 00 00
Spain sanofi-aventis, S.A. Tel: +34 93 485 94 00	Portugal Sanofi – Produtos Farmacêuticos, Lda. Tel: +351 21 35 89 400
France Sanofi Winthrop Industrie Tel: 0 800 222 555 Call from abroad: +33 1 57 63 23 23	Romania Sanofi Romania SRL Tel: +40 (0) 21 317 31 36
Croatia Swixx Biopharma d.o.o. Tel: +385 1 2078 500	Slovenia Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Iceland Vistor ehf. Tel: +354 535 7000	Slovakia Swixx Biopharma Tel.: +421 2 208 33 600
Ireland sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +44353 (0) 403 56 00	Finland Sanofi Oy Puh/Tel: + 358 201 200 300

Italy Sanofi S.r.l. Tel: 800536389	Sweden Sanofi AB Tel: +46 (0)8 634 50 00
Cyprus C.A. Papaellinas Ltd. Tel: +357 22 741741
Latvia Swixx Biopharma SIA Tel: +371 6 616 47 50CP

Date of the most recent review of this leaflet: .

Other sources of information

To help educate patients about potential adverse effects and instructions on what to do if certain adverse effects occur, the following risk minimisation materials are available:

1 Patient Card: For the patient to present to other healthcare professionals to alert them about the patient's use of LEMTRADA.

2 Patient Guide: For further information about autoimmune reactions, infections, and other information.

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

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This information is intended for healthcare professionals only:

Risk minimisation information – autoimmune conditions

• It is extremely important that the patient understands the need to undergo periodic testing (for 4 years following the last infusion) even if they are asymptomatic and their disease is well controlled.

• You need to plan and manage regular follow-up visits together with the patient.

• Patients who are non-compliant may require additional counselling to highlight the risks of missing scheduled monitoring tests.

• You should monitor test results and remain vigilant for any symptoms of adverse reactions.

• Review the package leaflet and the patient guide for LEMTRADA with your patient. Remind the patient to remain alert for any symptoms related to autoimmune conditions and to seek medical help if in doubt.

Educational materials are also available for healthcare professionals:

• LEMTRADA Healthcare Professional Guide
• LEMTRADA Training Module
• LEMTRADA Prescriber Checklist

Please read the Summary of Product Characteristics (available on the aforementioned EMA website) for further information.

Information for preparing administration of LEMTRADA and monitoring the patient

• Patients must be pre-treated with corticosteroids immediately before each LEMTRADA infusion on the first 3 days of any treatment cycle. Premedication with antihistamines and/or antipyretics may also be considered prior to administration of LEMTRADA.

• An oral antiviral agent should be administered to all patients during treatment and for 1 month after treatment. In clinical trials, 200 mg of aciclovir twice daily or equivalent was administered to patients.

• Baseline assessments and screening tests are described in section 4 of the Summary of Product Characteristics.

• The contents of the vial should be inspected visually before each administration to ensure there are no particles or discoloration. If the concentrate contains particles or shows discoloration, it must not be used. DO NOT SHAKE THE VIALS BEFORE USE.

• Use aseptic techniques to withdraw 1.2 ml of LEMTRADA from the vial and inject it into 100 ml of either a 9 mg/ml (0.9%) sodium chloride infusion solution or a 5% glucose infusion solution. The bag should be gently inverted to mix the solution. Care must be taken to ensure the sterility of the prepared solution.

• Administer the LEMTRADA infusion solution intravenously over a period of approximately 4 hours.

• Other medicinal products must not be added to the LEMTRADA infusion solution, nor should they be co-administered through the same intravenous line.

• The product should be used immediately after dilution due to the potential risk of microbial contamination. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user and must not exceed 8 hours at a temperature of 2°C to 8°C, protected from light.

• Appropriate handling and disposal procedures must be followed. Disposal of any unused product or waste material must be in accordance with local regulations.

After each infusion, the patient should be observed for 2 hours for possible infusion-associated reactions. Symptomatic treatment may be initiated if necessary – see Summary of Product Characteristics. Continue monthly laboratory testing to detect autoimmune diseases for up to 4 years after the last infusion. Refer to the LEMTRADA Healthcare Professional Guide for further information, or read the Summary of Product Characteristics available on the aforementioned EMA website.