Lemtrada Concentrate for 12 mg/1,2 ml Solution

LEMTRADA contains the active substance alemtuzumab, which is used to treat relapsing forms of multiple sclerosis (MS) in adults. LEMTRADA does not cure MS but it can decrease the number of MS relapses. It can also help to slow down or reverse some of the signs and symptoms of MS. LEMTRADA is used if your MS is highly active despite that you have been treated with at least one other medicine for MS or if your MS is rapidly evolving.

Do not receive LEMTRADA:

• If you are allergic to alemtuzumab or any of the other ingredients of LEMTRADA (see section 6).
• If you are infected with the human immunodeficiency virus (HIV).
• If you are suffering from a serious infection.
• If you have any of the following conditions:
• uncontrolled high blood pressure
• history of tears in blood vessels supplying the brain
• history of stroke
• history of heart attack or chest pain
• history of bleeding disorder.

Warnings and precautions: Talk to your doctor before LEMTRADA is given. After having a course of treatment with LEMTRADA you may be at greater risk of developing other autoimmune conditions or experiencing serious infections. It is important you understand these risks and how to monitor for them. You will be given a Patient Alert Card and a Patient Guide with further information. It is important that you keep the Patient Alert Card with you during treatment and for 4 years after your last infusion with LEMTRADA, because side effects may occur many years after treatment. When you have medical treatment, even if it is not for your MS, show the Patient Alert Card to the doctor.

Your doctor will perform blood tests before you start treatment with LEMTRADA. These tests are done to see whether you may take LEMTRADA. Your doctor will also want to make sure that you do not have certain medical conditions or disorders before you start your treatment with LEMTRADA.

LEMTRADA will be administered to you by a person who is qualified to do so. LEMTRADA will be administered to you as an infusion into a vein. Each infusion will take approximately 4 hours.

First treatment course: You will receive one infusion per day for 5 days (course 1).

Second treatment course: One year later you will receive one infusion per day for 3 days (course 2). There is no LEMTRADA treatment between the two courses. Some patients, if they have symptoms or signs of MS disease after the initial two courses, may receive additional treatment courses consisting of one infusion per day for 3 days. These additional treatment courses may be administered twelve months or more after the prior treatments. The maximum daily dose is one infusion.

Duration of effects: Monitoring for side effects must continue for 4 years after the last infusion.

Follow-up after treatment with LEMTRADA: Once you have received LEMTRADA, you will need to undergo regular tests to ensure that any potential side effects can be diagnosed and treated quickly.

If you are given more LEMTRADA than you should receive: Patients who accidentally were given too much LEMTRADA in one infusion have experienced serious reactions, such as headache, rash, low blood pressure or increased heart rate. Doses higher than the recommended dose may result in more serious or longer lasting infusion reactions (see section 4) or a stronger negative effect on the immune system. The treatment consists of stopping LEMTRADA administration and treatment of the symptoms of the overdosage.

Missed LEMTRADA doses: It is unlikely that your dose would be missed since it is administered by a health care provider. In case of a missed dose, this should not be given on the same day as a scheduled dose.

LEMTRADA can have side effects. Not all side effects reported for LEMTRADA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while you are receiving LEMTRADA, please consult your doctor, pharmacist or other health care provider for advice.

If any of the following happens, stop receiving LEMTRADA and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of your hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing.
• Rash or itching.
• Fainting.
• Yellowing of your skin and eyes (also called jaundice).

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to LEMTRADA. You may need urgent medical attention or hospitalisation.

The most important side effects are the autoimmune conditions described in section 2 which include:

• Acquired haemophilia A (a type of bleeding disorder), (occurs less frequently): may show as spontaneous bruising, nose bleeds, painful or swollen joints, other types of bleeding, or bleeding from a cut that may take longer than usual to stop.
• ITP (bleeding disorders), (occurs frequently): may show as small scattered red, pink or purple spots on your skin; easy bruising; bleeding from a cut that is harder to stop; heavier, longer or more frequent menstrual periods than normal; bleeding between menstrual periods; bleeding from your gums or nose that is new or takes longer than usual to stop; or coughing up blood.
• TTP (blood disorder), (occurs less frequently): may show as bruising under the skin, or bruising in the mouth, that may appear as red pinpoint dots, with or without unexplained extreme tiredness, fever, confusion, speech changes, yellowing of the skin or eyes (jaundice), low amount of urine, dark coloured urine.
• Kidney disorders, (occurs less frequently): may show as blood in the urine (your urine may be red or tea-coloured), or as swelling in your legs or feet. It can also lead to damage of your lungs, which can result in coughing up blood.
• If you notice any of these signs or symptoms for bleeding or kidney disorders, call your doctor immediately to report the symptoms. If you cannot reach your doctor, you must seek immediate medical attention.
• Thyroid disorders (occurs frequently): may show as excessive sweating, unexplained weight-loss or gain, eye swelling, nervousness, fast heartbeat, feeling cold, worsening tiredness or newly occurring constipation.
• Red and white blood cells disorders (occurs less frequently): diagnosed from your blood tests.
• Sarcoidosis (occurs less frequently): symptoms can include persistent dry cough, shortness of breath, chest pain, fever, lymph swelling, weight loss, skin rashes, blurred vision.
• Autoimmune encephalitis (frequency unknown): may include symptoms such as behaviour and psychiatric changes, movement disorders, short term memory loss or seizures as well as other symptoms resembling an MS relapse.

All of these serious side effects can start many years after you have received LEMTRADA. If you notice any of these signs or symptoms, call your doctor right away to report them. You will also have regular blood and urine tests to ensure that if you develop any of these conditions, they are treated promptly.

Summary of tests you will have for autoimmune conditions:

After this time, if you have symptoms of blood, liver, kidney or thyroid disorders, your doctor will perform more tests. You should also continue looking for signs and symptoms of side effects beyond four years as detailed in your Patient Guide, and you should continue carrying the Patient Alert Card with you.

Another side effect is an increased risk of infections (see below for information on how often patients experience infections). In most cases, these are mild but serious infections can occur.

Tell your doctor right away if you have any of these signs of infection:

• fever and /or chills
• swollen glands.

To help reduce the risk of some infections, your doctor may consider giving you a vaccination against chickenpox and/or other vaccinations that they think are necessary for you (see section 2: What you need to know before you receive LEMTRADA – Vaccines). Your doctor can also prescribe a medicine for cold sores (see section 2: What you need to know before you receive LEMTRADA – Infections).

The most frequent side effects are infusion reactions (see below for information on how often patients experience these), which can happen at the time of the infusion or within 24 hours after the infusion. In most cases these are mild, but some serious reactions are possible. Occasionally allergic reactions could occur. To try to reduce infusion reactions, your doctor will give you medicine (corticosteroids) before each of the first 3 infusions of a LEMTRADA course. Other treatments to limit these reactions can also be given before the infusion or when you experience symptoms. In addition, you will be monitored during the infusion and for 2 hours after the infusion has been completed. In case of serious reactions, the infusion may be slowed down or even stopped.

Tell your doctor if you notice any of the following: Frequently occurring side effects may include:

• Infusion reactions that can happen at the time of the infusion or within 24 hours after the infusion: headache, rash, fever, feeling sick, hives, itching, reddening of the face and neck, feeling tired, nausea, increased heart rate, indigestion, chills, chest discomfort, pain, dizziness, altered taste, difficulty sleeping, difficulty breathing or shortness of breath, rash over your body, low blood pressure.
• Infections: airway infections such as colds and sinus infections, urinary tract infections (cystitis), herpes infections, cough, ear infection, flu-like illness, bronchitis, pneumonia, oral thrush or vaginal thrush, shingles, chickenpox, cold sore, swollen or enlarged glands, influenza, tooth infection.
• A decrease in the number of white blood cells (e.g. lymphocytes, leukocytes, neutrophils).
• An increase in white blood cells counts such as neutrophils, eosinophils (different types of white blood cells), anaemia, decrease in percentage of red blood cells, easy or excessive bruising or bleeding, swelling of lymph nodes.
• Exaggerated immune response.
• Pain at the site of the infusion, pain in the back, the neck, or in arms or legs, muscle pain, muscle spasms, joint pain.
• Inflammation of the mouth/gums/tongue, painful mouth or throat.
• General discomfort, weakness, vomiting, diarrhoea, abdominal pain, gastric flu (most common symptoms of diarrhoea).
• Abnormal liver test.
• Heartburn.
• Abnormalities that can be found during examinations: blood or protein in urine, decreased heart rate, irregular or abnormal heartbeat, high blood pressure, impaired kidney function, white blood cells in urine.
• Contusion.
• MS relapse.
• Trembling, loss of sensation, burning or prickling sensation.
• Overactive or underactive thyroid gland, or goitre (swelling of the thyroid gland in the neck).
• Swelling of arms and/or legs.
• Vision problems, conjunctivitis, eye disease associated with thyroid disease.
• Sensation of spinning or loss of balance.
• Feelings of anxiety, depression.
• Abnormally heavy, prolonged or irregular menstruation.
• Acne, redness of the skin, excessive sweating.
• Nose bleeds, bruises.
• Hair loss.

• Infections: genital herpes, eye infection, inflammation of the lung tissue (pneumonitis), cytomegalovirus infection.
• Problems with blood clotting.
• Athlete’s foot.
• Abnormal cervical Pap smear.
• Tuberculosis (TB).
• Inflammation of the gallbladder.
• Autoimmune disease characterised by bleeding (acquired haemophilia A).
• Excessive activation of white blood cells associated with inflammation (haemophagocytic lymphohistiocytosis).

• Listeriosis/listeria meningitis.
• Bleeding in lungs.
• Heart attack.
• Stroke.
• Tears in carotid or vertebral arteries (blood vessels supplying the brain).
• Infection due to a virus known as Epstein-Barr virus.
• Sarcoidosis (an immune disorder that can cause inflammation of one or more organs including lungs, lymph nodes, skin or heart).
• Autoimmune encephalitis (an autoimmune brain disorder).
• Adult-onset Still’s Disease (AOSD) (an inflammatory condition that affects multiple organs).
• Vitiligo (patches of skin that have lost colour).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects: If you get side effects, talk to your doctor or pharmacist. You can also report side effects to:

• The Pharmacovigilance Unit at Sanofi: [email protected] (email) or 011 256 3700 (tel), or
• SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8

By reporting side effects, you can help provide more information on the safety of LEMTRADA.

Vials: Store at 2 °C to 8 °C, protected from light. Do not freeze or shake. Keep the vial in the outer carton until required for use.

Infusion solution: LEMTRADA diluted medicine may be stored at room temperature (15 °C to 25 °C) or refrigerated (2 °C to 8 °C) for up to 8 hours. Protect from light. Partially used, unused or damaged medicine vials should be discarded appropriately. For the reconstituted medicine, from a microbiological point of view, the medicine should be used immediately. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and would normally be 2 – 8 °C, unless reconstitution/dilution has taken place in controlled and validated conditions.

STORE ALL MEDICINES OUT OF REACH OF CHILDREN.