PACKAGE LEAFLET: ALLERGAN® INFORMATION FOR THE USER BOTOX 100 Allergan Units, Powder for Solution for Injection Botulinum toxin type A Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your Aesthethetics Practitioner

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your Practitioner and doctor or pharmacist . This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet: 1. What BOTOX is and what it is used for 2. What you need to know before you use BOTOX 3. How to use BOTOX 4. Possible side effects 5. How to store BOTOX 6. Contents of the pack and other information 1. What BOTOX is and what it is used for BOTOX is a muscle relaxant used to treat a number of conditions within the body. It contains the active substance botulinum toxin type A and is injected into either the muscles, the bladder wall or deep into the skin. It works by partially blocking the nerve impulses to any muscles that have been injected and reduces excessive contractions of these muscles. When injected into the skin, BOTOX works on sweat glands to reduce the amount of sweat produced, or to give a temporary improvement in the appearance of vertical lines between the eyebrows seen at maximum frown (glabellar lines) or fan-shaped lines from the corner of the eyes seen at maximum smile (crow’s feet lines) or forehead lines seen at maximum raised eyebrows. When injected into the bladder wall, BOTOX works on the bladder muscle to reduce leakage of urine (urinary incontinence). In the case of chronic migraine, it is thought that BOTOX may block pain signals which indirectly block the development of a migraine. However, the way BOTOX works in chronic migraine is not fully established. 1) BOTOX can be injected directly into the muscles, and can be used to control the following conditions: o Persistent muscle spasms in the leg in children aged two years or older with cerebral palsy, who can walk, BOTOX is used to control foot deformity caused by the persistent muscle spasms in the legs. persistent muscle spasms in the wrist and hand of adult patients who have suffered a stroke; o persistent muscle spasms in the ankle and foot of adult patients who have suffered a stroke; o persistent muscle spasms in the eyelid and face of adult patients; o persistent muscle spasms in the neck and shoulders of adult patients. 2) BOTOX is used to reduce the symptoms of chronic migraine in adults who have had headaches on 15 or more days each month of which at least 8 days are with migraine and who have not responded well to other preventative migraine medications. Chronic migraine is a disease affecting the nervous system. Patients usually suffer from head pain which is often accompanied by excessive sensitivity to light, loud sounds or smells/odours, as well as nausea and/or vomiting. These headaches occur on 15 or more days each month. 3) When injected into the bladder wall, BOTOX works on the bladder muscle to reduce leakage of urine (urinary incontinence) and control the following conditions in adults:

• overactive bladder with leakage of urine, the sudden urge to empty your bladder and needing to go to the toilet more than usual when another drug (called an anticholinergic) did not help;

•leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis. 4) In adults, BOTOX can be injected deep into the skin and can work on sweat glands to reduce excessive sweating of the armpits, which affects the activities of daily living when other local treatments do not help. 5) BOTOX is used for the temporary improvement in the appearance of:

• vertical lines between the eyebrows seen at maximum frown and/or,

• fan-shaped lines from the corner of the eyes seen at maximum smile and/or,

• forehead lines seen at maximum raised eyebrows, when the severity of the facial lines has an important psychological impact in adult patients. 2. What you need to know before you use BOTOX Do not use BOTOX

• if you are allergic (hypersensitive) to botulinum toxin type A or any of the other ingredients of this medicine (listed in section 6);

• if you have an infection at the proposed site of injection;

• when you are being treated for leakage of urine and have either a urinary tract infection or a sudden inability to empty your bladder (and are not regularly using a catheter);

• if you are being treated for leakage of urine and are not willing to begin using a catheter if required;

• if you are to be treated for facial lines and have been diagnosed with myasthenia gravis or Lambert-Eaton Syndrome (chronic diseases affecting the muscles). Warnings and precautions Talk to your Practitioner, doctor, pharmacist before using BOTOX:

• if you have had any problems in the past with previous botulinum injections;

• if you have ever had problems with swallowing or food or liquid accidentally going into your lungs, especially if you will be treated for persistent muscle spasms in the neck and shoulders;

• if you are over 65 years of age and have other serious illnesses;

• if you suffer from any other muscle problems or chronic diseases affecting your muscles (such as myasthenia gravis or Lambert-Eaton Syndrome);

• if you suffer from certain diseases affecting your nervous system (such as amyotrophic lateral sclerosis or motor neuropathy);

• if you have significant weakness or wasting of the muscles which your Practitioner, plans to inject;

• if you have had any surgery or injury that may have changed the muscle to be injected in some way;

• if you have had an operation or injured your head, neck or chest;

• if you will have an operation soon;

• if you have had any problems with injections (such as fainting) in the past;

• if you have inflammation in the muscles or skin area where your practitioner plans to inject;

• if you suffer from cardiovascular disease (disease of the heart or blood vessels);

• if you suffer or have suffered from seizures;

• if you have an eye disease called closed-angle glaucoma (high pressure in the eye) or were told you are at risk for developing this type of glaucoma;

• if you are about to be treated for overactive bladder with leakage of urine and you are a male with signs and symptoms of urinary obstruction, such as difficulty in passing urine or a weak or interrupted stream. After you have been given BOTOX You or your caregiver should contact your doctor and seek medical attention immediately if you experience any of the following:

• difficulty in breathing, swallowing, or speaking;

• hives, swelling including swelling of the face or throat, wheezing, feeling faint and shortness of breath (possible symptoms of severe allergic reaction). Very rarely, an allergic reaction can occur after the injection of botulinum toxin. Inform your doctor if you are being treated for facial lines and you see no significant improvement one month after your first course of treatment. General precautions As with any injection, it is possible for the procedure to result in infection, pain, swelling, burning and stinging, increased sensitivity, tenderness, redness, and/or bleeding/bruising at the site of injection. Adverse reactions possibly related to the spread of toxin distant from the site of administration have been reported with botulinum toxin (e.g. muscle weakness, difficulty swallowing or unwanted food or liquid in the airways). This is a particular risk for patients with an underlying illness that makes them susceptible to these symptoms. Severe and/or immediate allergic reactions have been reported, the symptoms of which may include hives, swelling of the face or throat, shortness of breath, wheezing and fainting. Delayed allergic reactions (serum sickness) have also been reported, which may include symptoms such as fever, joint pain, and skin rash. Side effects related to the cardiovascular system, including irregular heartbeat and heart attacks, have also been seen in patients treated with BOTOX, sometimes with a fatal outcome. However there was a prior history of cardiac risk factors in some of these patients. Seizures have been reported in adults and children treated with BOTOX, mostly in patients who are more prone to seizures. It is not known if BOTOX is the cause of these seizures. Seizures that were reported in children were mostly in cerebral palsy patients treated for persistent muscle spasms in the legs. If you are given BOTOX too often or the dose is too high, you may experience muscle weakness and adverse reactions related to the spread of toxin, or your body may start producing some antibodies, which can reduce the effect of BOTOX. To limit this risk, the interval between two treatments must not be less than three months depending on the indication. When BOTOX is used in the treatment of a condition that it is not listed in this leaflet, it could result in serious reactions, particularly in patients who already experience difficulty in swallowing or have significant debility. If you have not done much exercise for a long time before receiving BOTOX treatment, then after your injections you should start any activity gradually. It is unlikely that this medicine will improve the range of motion of joints where the surrounding muscle has lost its ability to stretch. BOTOX should not be used when treating persistent post-stroke ankle muscle spasms in adults if it is not expected to result in improvement in function (e.g. walking) or symptoms (e.g. pain) or to help with patient care. If your stroke was more than 2 years ago or if your ankle muscle spasm is less severe, improvements related to activities such as walking may be limited. Furthermore, for patients who may be more likely to fall, your doctor will judge if this treatment is suitable. BOTOX should only be used for the treatment of post-stroke ankle and foot muscle spasms following evaluation by health care professionals experienced in the management of the rehabilitation of post-stroke patients. When BOTOX is used in the treatment of persistent muscle spasms in the eyelid, it could make your eyes blink less often, which may harm the surface of your eyes. In order to prevent this, you may need treatment with eye drops, ointments, soft contact lenses or even protective covering which closes the eye. Your doctor will tell you if this is required. The use of BOTOX for the treatment of vertical lines between the eyebrows seen at maximum frown (glabellar lines) or fan-shaped lines from the corner of the eyes seen at maximum smile (crow’s feet lines) or forehead lines seen at maximum raised eyebrows is not recommended in individuals under 18 years. There is limited experience of using BOTOX in patients older than 65 years. Drooping of the eyelid may occur after treatment. When BOTOX is used to control the leakage of urine, your doctor will give you antibiotics before and after the treatment to help prevent urinary tract infection. You will be seen by your doctor approximately 2 weeks after the injection, if you were not using a catheter before the injection. You will be asked to pass urine and will then have the volume of urine left in your bladder measured using ultrasound. Your doctor will decide if you need to return for the same test during the next 12 weeks. You must contact your doctor if at any time you are unable to pass urine because it is possible that you may need to start using a catheter. In patients with leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis, approximately one third who were not using a catheter before treatment for leakage of urine may need to use a catheter after treatment. In patients with leakage of urine due to overactive bladder, approximately 6 out of 100 patients may need to use a catheter after treatment. Other medicines with BOTOX Tell your doctor or pharmacist if:

• you are using any antibiotics (used to treat infections) including aminoglycoside antibiotics and spectinomycin, anticholinesterase medicines, or muscle relaxants. Some of these medicines may increase the effect of BOTOX;

• you have recently been injected with a medicine containing a botulinum toxin (the active substance of BOTOX), as this may increase the effect of BOTOX too much;

• you are using any anti-platelet (aspirin-like products) and/or anti-coagulants (blood thinners). Tell your practitioner or doctor or pharmacist if you are taking, have recently taken or might take any other medicine. Pregnancy and breast-feeding The use of BOTOX is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary. BOTOX is not recommended in breast-feeding women. 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 using this medicine. Driving and using machines BOTOX may cause generalised and/or specific muscular weakness, dizziness, sleepiness, tiredness or problems with your vision. If you experience any of these effects, do not drive or use any machines. If you are not sure, ask your doctor for advice. 3. How to use BOTOX BOTOX must only be injected by skilled practitioners with specific skills and experience on how to use the medicine. BOTOX should only be prescribed for you for chronic migraine if you have been diagnosed by a neurologist who is a specialist in this area. BOTOX should be administered under the supervision of a neurologist. BOTOX is not used for acute migraine, chronic tension type headaches or patients with medication overuse headache. Method and route of administration BOTOX is injected into your muscles (intramuscularly), into the bladder wall via a specific instrument (cystoscope) to inject into the bladder, or into the skin (intradermally). It is injected directly into the affected area of your body; your practitioner will usually inject BOTOX into several sites within each affected area. General information about dosage

• The number of injections per muscle and the dose vary depending on the indications; Therefore, your practitioner will decide how much, how often, and in which muscle(s) BOTOX will be given to you. It is recommended that your practitioner uses the lowest effective dose;

• Dosages for older people are the same as for other adults. The dosage of BOTOX and the duration of its effect will vary depending on the condition for which you are treated. Below are details corresponding to each condition. The safety and effectiveness of BOTOX has been established in children/adolescents over the age of two years for the treatment of foot deformity caused by muscle spasms in the legs, associated with Cerebral Palsy. Foot deformity caused by muscle spasms in the legs of children who have Cerebral Palsy 2 years Limited information is available on the use of BOTOX in the following conditions in children/adolescents over the age of 12 years. No recommendation on dosage can be made for these indications. Persistent muscle spasms in the eyelid and, face 12 years Persistent muscle spasms in neck and shoulder 12 years Excessive sweating of the armpits 12 years (limited experience in adolescents between 12 and 17 years) Dosage Indication Maximum dose (Units per affected area) Minimal time between treatments First treatment Following treatments Persistent muscle spasms in the legs of children who have cerebral palsy 4 Units/kg (hemiplegia) 6 Units/kg (diplegia) 4 Units/kg (hemiplegia) 6 Units/kg (diplegia) 3 months* Persistent muscle spasms in the wrist and hand of patients who have had a stroke The exact dosage and number of injection sites per hand/wrist is tailored to individual needs up The exact dosage and number of injection sites is tailored to individual needs up to a maximum of 240 Units 12 weeks to a maximum of 240 Units Persistent muscle spasms in the ankle and foot of patients who have had a stroke Your practitioner may give multiple injections in the affected muscles. The total dose is 300 Units to 400 Units divided among up to 6 muscles for each treatment session The total dose is 300 Units to 400 Units divided among up to 6 muscles for each treatment session 12 weeks Persistent muscle spasms of the eyelid and face 25 Units per eye Up to 100 Units 3 months Persistent muscle spasms of the neck and shoulders 200 Units Up to 300 Units 10 weeks Headache in adults who have chronic migraine 155 to 195 Units 155 to 195 Units 12 weeks Overactive bladder with leakage of urine 100 Units 100 Units 3 months Leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis 200 Units 200 Units 3 months Excessive sweating of the armpits 50 Units per armpit 50 Units per armpit 16 weeks Vertical lines between the eyebrows seen at maximum frown (glabellar lines) 4 Units per injection site (maximum total dose of 20 Units) 4 Units per injection site (maximum total dose of 20 Units) 3 months Fan-shaped lines from the corner of the eyes seen at maximum smile (crow’s feet lines) 4 Units per injection site (maximum total dose of 24 Units) 4 Units per injection site (maximum total dose of 24 Units) 3 months Forehead lines seen at maximum raised eyebrows 4 Units per injection site (maximum total dose of 20 Units) 4 Units per injection site (maximum total dose of 20 Units) 3 months The total dose for treatment of forehead lines (20 Units) in conjunction with glabellar lines (20 Units) is 40 Units. If you are treated for all 3 facial lines at the same time (fan-shaped lines from the corner of the eyes seen at maximum smile, vertical lines between the eyebrows seen at maximum frown, and forehead lines seen at maximum raised eyebrows) you will receive a total dose of 64 Units. * The practitoner may select a dose that would mean the treatment may be up to 6 months apart. Time to Improvement and Duration of Effect For persistent muscle spasms in the legs of children who have cerebral palsy, the improvement usually appears within the first 2 weeks after the injection. For persistent muscle spasms in the wrist and hand of patients who have had a stroke, you will usually see an improvement within the first 2 weeks after the injection. The maximum effect is usually seen about 4 to 6 weeks after treatment. For persistent muscle spasms in the ankle and foot of patients who have had a stroke, when the effect starts to wear off, you can have the treatment again if needed, but not more often than every 12 weeks. For persistent muscle spasms of the eyelid and face, you will usually see an improvement within 3 days after the injection and maximum effect is usually seen after 1 to 2 weeks. For persistent muscle spasms of the neck and shoulders, you will usually see an improvement within 2 weeks after the injection. The maximum effect is usually seen about 6 weeks after treatment. For leakage of urine due to overactive bladder, you will usually see an improvement within 2 weeks after the injection. Typically the effect lasts approximately 6-7 months after the injection. For leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis, you will usually see an improvement within 2 weeks after the injection. Typically the effect lasts approximately 8-9 months after the injection. For excessive sweating of the armpits, you will usually see an improvement within the first week after injection. On average the effect usually lasts 7.5 months after the first injection with approximately 1 out of 4 patients still experiencing the effect after one year. For vertical lines between the eyebrows (glabellar lines), you will usually see an improvement within 1 week after treatment, the maximum effect being observed 5 to 6 weeks after injection. The treatment effect has been demonstrated for up to 4 months after injection. For fan-shaped lines from the corner of the eyes (crow’s feet lines), you will usually see an improvement within 1 week after treatment. The treatment effect has been demonstrated for up to 4 months after injection. For forehead lines seen at maximum raised eyebrows, you will usually see an improvement within 1 week after treatment. The treatment effect has been demonstrated for up to 4 months after injection. If you have received more BOTOX than you should The signs of too much BOTOX may not appear for several days after the injection. Should you swallow BOTOX or have it accidentally injected, you should see your doctor who might keep you under observation for several weeks. If you have received too much BOTOX, you may have any of the following symptoms and you must contact your doctor immediately. He/she will decide if you have to go to hospital:

• muscle weakness which could be local or distant from the site of injection;

• difficulty in breathing, swallowing or speaking due to muscle paralysis;

• food or liquid accidentally going into your lungs which might cause pneumonia (infection of the lungs) due to muscle paralysis;

• drooping of the eyelids, double vision;

• generalised weakness. If you have any further questions on the use of this product, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. In general, side effects occur within the first few days following injection. They usually last only for a short time, but they may last for several months and in rare cases, longer. IF YOU HAVE ANY DIFFICULTY IN BREATHING, SWALLOWING OR SPEAKING AFTER RECEIVING BOTOX, CONTACT YOUR DOCTOR IMMEDIATELY. If you experience hives, swelling including swelling of the face or throat, wheezing, feeling faint and shortness of breath, contact your doctor immediately. The side effects are classified into the following categories, depending on how often they occur: Very common may affect more than 1 in 10 people Common may affect up to 1 in 10 people Uncommon may affect up to 1 in 100 people Rare may affect up to 1 in 1,000 people Very rare may affect up to 1 in 10,000 people Below are lists of side effects which vary depending on the part of the body where BOTOX is injected. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. Injections in the legs of children with cerebral palsy There have been rare spontaneous reports of death sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with BOTOX. Injections in the wrist and hand of patients who have had a stroke Common Increased muscle tension, bruising and bleeding under the skin causing red patches (ecchymosis or purpura), pain in the hand and fingers, muscle weakness, pain where the injection was given, fever, flu syndrome, bleeding or burning where the injection was given. Uncommon Depression, difficulty in sleeping (insomnia), decreased skin sensation, headache, numbness, lack of coordination of movements, loss of memory, feeling of dizziness or “spinning” (vertigo), fall in blood pressure on standing up which causes dizziness, light headedness or fainting, nausea, numbness around the mouth, inflammation of the skin (dermatitis), itching, rash, joint pain or inflammation, general weakness, pain, increased sensitivity where the injection was given, feeling generally unwell, swelling of the extremities such as the hands and feet. Some of these uncommon side effects may also be related to your disease. Injections in the ankle and foot of patients who have had a stroke Common Rash, joint pain or inflammation, stiff or sore muscles, muscular weakness, swelling of the extremities such as the hands and feet, fall. Injections in the eyelid and face Very Common Drooping of the eyelid. Common Pinpoint damage of the cornea (transparent surface covering the front of the eye), difficulty in completely closing the eye, dry eyes, sensitivity to light, eye irritation, overflow of tears, bruising under the skin, skin irritation, swelling of the face. Uncommon Dizziness, weakness of the face muscles, droop of the muscles on one side of the face, inflammation of the cornea (transparent surface covering the front of the eye), abnormal turning of the eyelids outwards or inwards, double vision, difficulties in seeing clearly, blurred vision, rash, tiredness. Rare Swelling of the eyelid. Very Rare Ulcer, damage to the cornea (transparent surface covering the front of the eye). Very Common Viral infection, ear infection. Common Sleepiness, problems with walking, numbness, rash, muscle pain, muscle weakness, pain in the extremities such as the hands and fingers, urinary incontinence (leakage of urine), feeling generally unwell, pain where the injection was given, feeling of weakness, fall. Injections in the neck and shoulder Very Common Difficulty in swallowing, muscle weakness, pain. Common Swelling and irritation inside the nose (rhinitis), blocked or runny nose, cough, sore throat, tickle or irritation in the throat, dizziness, increased muscle tension (cramps), decreased skin sensation, sleepiness, headache, dry mouth, nausea, stiff or sore muscles, feeling of weakness, flu syndrome, feeling generally unwell. Uncommon Double vision, fever, drooping of the eyelid, shortness of breath, changes in your voice. Injections in the head and neck for the treatment of headache in patients who suffer from chronic migraine Common Headache, migraine, weakness of the face muscles, drooping of the eyelid, rash, itching, neck pain, muscle pain, muscle spasm, muscle stiffness, muscle tightness, muscle weakness, pain where the injection was given. Uncommon Difficulty in swallowing, skin pain, jaw pain. Injections in the bladder wall for leakage of urine due to overactive bladder Very Common Urinary tract infection, painful urination after the injection*. Common Bacteria in the urine, inability to empty your bladder (urinary retention), incomplete emptying of the bladder, frequent daytime urination, white blood cells in the urine, blood in the urine after the injection**. * This side effect may also be related to the injection procedure. **This side effect is only related to the injection procedure. Injections in the bladder wall for leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis Very Common Urinary tract infection, inability to empty your bladder (urinary retention). Common Difficulty in sleeping (insomnia), constipation, muscle weakness, muscle spasm, blood in the urine after the injection*, painful urination after the injection*, bulge in the bladder wall (bladder diverticulum), tiredness, problems with walking (gait disturbance), possible uncontrolled reflex reaction of your body (e.g. profuse sweating, throbbing headache or increase in pulse rate) around the time of the injection (autonomic dysreflexia)*, fall. *Some of these common side effects may also be related to the injection procedure. Injections for excessive sweating of the armpits Very Common Injection site pain. Common Headache, numbness, hot flushes, increased sweating at sites other than the armpit, abnormal skin odour, itching, lump under the skin, hair loss, pain in the extremities such as the hands and fingers, pain, reactions and swelling, bleeding or burning and increased sensitivity where the injection was given, general weakness. Uncommon Nausea, muscle weakness, feeling of weakness, muscle pain, problem with the joints. Injections for the temporary improvement of vertical lines between the eyebrows at maximum frown, also known as glabellar lines These adverse reactions may be related to treatment, injection technique or both. Injections for the temporary improvement in the fan-shaped lines from the corner of the eyes, when treated with or without vertical lines between the eyebrows seen at frown Common Injection site haematoma*. Uncommon Eyelid swelling, injection site bleeding*, injection site pain*, injection site tingling or numbness. *Some of these side effects may also be related to the injection procedure. Injections for the temporary improvement in the forehead lines and vertical lines between the eyebrows seen at frown when treated with or without the fan-shaped lines from the corner of the eyes Common Headaches, drooping eyelid1 , skin tightness, drooping eyebrow2 , injection site bruising*, injection site haematoma* Uncommon Injection site pain*. 1.The median time to onset of drooping eyelid was 9 days following treatment 2. The median time to onset of drooping eyebrow was 5 days following treatment *Some of these side effects may also be related to the injection procedure. The following list describes additional side effects reported for BOTOX, in any disease, since it has been marketed:

• allergic reaction, including reactions to injected proteins or serum;

• swelling of the deeper layers of the skin;

• hives; • eating disorders, loss of appetite; • nerve damage (brachial plexopathy);

• voice and speech problems; • droop of the muscles on one side of the face;

• weakness of the face muscles; • decreased skin sensation; • muscle weakness;

• chronic disease affecting the muscles (myasthenia gravis);

• difficulty moving the arm and shoulder; • numbness; • pain/numbness/or weakness starting from the spine;

• seizures and fainting; • increase in eye pressure; • drooping eyelid

• difficulty in completely closing the eye • strabismus (crossed eyes/squint); • blurred vision; • difficulties in seeing clearly; • decreased hearing; • noises in the ear; • feeling of dizziness or “spinning” (vertigo); • heart problems including heart attack;

Common Headaches, drooping eye lid, skin redness, localised muscle weakness, face pain, numbness, nausea (feeling sick), skin tightness, injection site swelling, injection site pain, bruising under the skin, injection site irritation. Uncommon Infection, anxiety, dizziness, inflammation of the eyelid, eye pain, visual disturbance, blurred vision, dry mouth, swelling (face, eyelid, around the eyes), sensitivity to light, itching, dry skin, muscle twitching, flu syndrome, lack of strength, fever.

• aspiration pneumonia (lung inflammation caused by accidentally breathing in food, drink, saliva or vomit);

• shortness of breath; • breathing problems, respiratory depression and/or respiratory failure; • abdominal pain; • diarrhoea, constipation; • dry mouth; • difficulty swallowing; • nausea, vomiting; • hair loss; • drooping eyebrow • itching; • rash; • different types of red blotchy skin rashes; • psoriasis-like skin patches (red, thick, dry and scaly); • excessive sweating; • loss of eyelashes/eyebrows; • muscles pain, loss of nerve supply to/shrinkage of injected muscle; • malaise; • feeling generally unwell; • fever; • dry eye (associated with injections around the eyes); • localised muscle twitching/involuntary muscle contractions; • Swelling of the eyelid 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. By reporting side effects you can help provide more information on the safety of this medicine. 5. How to store BOTOX Keep out of the sight and reach of children. Your Practitioner should not use BOTOX after the expiry date which is stated on the label after ‘EXP’. The expiry date refers to the last day of that month. Store in a refrigerator (2°C – 8°C), or store in a freezer (-5°C to -20°C). After the solution is made up, immediate use of the solution is recommended; however it can be stored for up to 24 hours in a refrigerator (2°C – 8°C). 6. Contents of the pack and other information What BOTOX contains

• The active substance is: botulinum toxin type A from Clostridium botulinum. Each vial contains 100 Allergan Units of botulinum toxin type A.

• The other ingredients are human albumin and sodium chloride. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”. What BOTOX looks like and contents of the pack BOTOX is presented as a thin white powder that may be difficult to see on the bottom of a transparent glass vial. Prior to injection, the product must be dissolved in sterile unpreserved normal saline solution (0.9% sodium chloride solution for injection). Each pack contains 1, 2, 3, 6 or 10 vials. Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer Allergan Pharmaceuticals Ireland Castlebar Road Westport County Mayo Ireland This leaflet was last revised in September 2020. (THIS IS A MEDICAMENT) - Medicament is a product which affects your health, and its consumption contrary to instructions is dangerous for you. - Do not by yourself interrupt the period of treatment prescribed. - Do not repeat the same prescription without consulting your Pharmacist. Keep medicament out of reach of children Council of Arab Health Ministers Union of Arab Pharmacists ALLERGAN® Westport, Co. Mayo, Ireland ® and ™ marks owned by Allergan, Inc. © 2014 Allergan, Inc., Irvine, CA 92612

Bocouture 50+100 units Großbritannien GA Type size: 9 pt 50 units powder for solution for injection 100 units powder for solution for injection Botulinum toxin type A (150 kD), free from complexing proteins MN XXXXX MC XXXX, GB

Package leaflet: Information for the user Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your doctor, pharmacist or practitioner

• If you get any side effects, talk to your doctor, pharmacist or healthcare professional. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet: 1. What BOCOUTURE is and what it is used for 2. What you need to know before BOCOUTURE is used 3. How to use BOCOUTURE 4. Possible side effects 5. How to store BOCOUTURE 6. Contents of the pack and other information 1. What BOCOUTURE is and what it is used for BOCOUTURE is a medicine that contains the active substance Botulinum toxin type A which relaxes the injected muscles. BOCOUTURE is used for temporary improvement of upper facial lines in adults under 65 years of age when the severity of these lines has an important psychological impact for the patient:

• moderate to severe vertical lines between the eyebrows seen at maximum frown and/or • moderate to severe lateral periorbital lines seen at maximum smile and/or • moderate to severe horizontal forehead lines seen at maximum contraction 2. What you need to know before BOCOUTURE is used

Do not use BOCOUTURE • if you are allergic to Botulinum neurotoxin type A or any of the other ingredients of this medicine (listed in section 6) • if you suffer from a generalised disorder of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome) • if you have an infection or inflammation at the proposed injection site. Warnings and precautions Side effects may occur from misplaced injections of Botulinum neurotoxin type A temporarily paralysing nearby muscle groups. There have been very rare reports of side effects that may be related to the spread of toxin distant from the injection site to produce symptoms consistent to Botulinum toxin type A effects (e.g. excessive muscle weakness, swallowing difficulties or accidental swallowing of food or drink into the airways). Patients who receive the recommended doses may experience excessive muscle weakness. Contact your doctor or healthcare professional and seek medical attention immediately if you experience any of the following:

• difficulty in breathing, swallowing or speaking

• hives, swelling including swelling of the face or throat, wheezing, feeling faint and shortness of breath (possible symptoms of severe allergic reactions) (see section 4). If the dose is too high or the injections too frequent, the risk of antibody formation may increase. Antibody formation can cause treatment with Botulinum toxin type A to fail, whatever the reason for its use.

Talk to your doctor or practitioner before BOCOUTURE is used:

• if you suffer from any type of bleeding disorder

• if you receive substances that prevent the blood from clotting (e.g. coumarin, heparin, acetylsalicylic acid, clopidogrel)

• if you suffer from pronounced weakness or decreased muscle volume in the muscle where you will receive the injection

• if you suffer from amyotrophic lateral sclerosis (ALS), which can lead to generalised muscle decrease

• if you suffer from any disease that disturbs the interaction between nerves and skeletal muscles (peripheral neuromuscular dysfunction)

• if you have or have had swallowing difficulties

• if you have had problems with injections of Botulinum toxin type A in the past

• if you are due to have surgery Repeated injections with BOCOUTURE If you have repeated injections with BOCOUTURE, the effect may increase or decrease. Possible reasons for this are:

• your doctor or healthcare professional may follow a different procedure when preparing the solution for injection

• different treatment intervals • injections into another muscle • non-response/therapy failure during the course of treatment Elderly There is limited information on the treatment of patients over 65 years of age. Therefore, BOCOUTURE should not be used in patients over the age of 65 years.

Children and adolescents Do not give this medicine to children and adolescents under the age of 18 years because the use of BOCOUTURE in children and adolescents is not recommended. Other medicines and BOCOUTURE Tell your doctor, pharmacist or healthcare professional if you are taking, have recently taken or might take any other medicines. The effect of BOCOUTURE may be increased by:

• medicines used to treat certain infectious diseases (spectinomycin or aminoglycoside antibiotics [e.g. neomycin, kanamycin, tobramycin])

• other medicines that relax the muscles (e.g. muscle relaxants of the tubocurarine type). Such medicines are used, for example, in general anaesthesia. Before you have surgery, tell your anaesthetist if you have received BOCOUTURE. In these cases, BOCOUTURE must be used carefully. The effect of BOCOUTURE may be reduced by certain medicines for malaria and rheumatism (known as aminoquinolines).

Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor pharmacist or healthcare professional for advice before this medicine is administered. BOCOUTURE should not be used during pregnancy unless your doctor or healthcare professional decides that the necessity and potential benefit of the treatment justifies the possible risk on the foetus. BOCOUTURE is not recommended if you are breastfeeding. Driving and using machines You should not drive or engage in other potentially hazardous activities if drooping eyelids, weakness (asthenia), muscle weakness, dizziness or vision disorders occur. If in doubt, ask your doctor or healthcare professional for advice. 3. How to use BOCOUTURE BOCOUTURE may only be administered by doctors or healthcare professionals with appropriate specialist knowledge of treatment with Botulinum neurotoxin type A.

Vertical Lines between the Eyebrows seen at maximum frown (Glabellar Frown Lines) When treating your vertical lines between the eyebrows seen at maximum frown (glabellar frown lines) the usual total dose is 20 units. Your doctor or healthcare professional will inject 4 units into each of the 5 injection sites. The total dose may be increased by the physician to up to 30 units if required by the individual needs of the patient, with at least ‘3-months’ interval between treatments.

A reduction in the vertical lines between the eyebrows seen at maximum frown generally occurs within 2 to 3 days with the maximum effect observed on day 30. The effect lasts for up to 4 months after the injection. Lateral Periorbital Lines seen at maximum smile (Crow’s feet lines) For the treatment of lateral periorbital lines seen at maximum smile (crow’s feet lines) your doctor or healthcare professional will inject a standard dose of 24 units (12 units per eye). 4 units will be applied bilaterally into each of the 3 injection sites. A reduction in lateral periorbital lines seen at maximum smile mostly occurs within 6 days with the maximum effect observed on day 30.

The effect lasts for up to 4 months after the injection. Horizontal Forehead Lines seen at maximum contraction When treating horizontal forehead lines seen at maximum contraction your doctor or healthcare professional will use a dose within a range of 10 to 20 units according to the individual needs of the patient. The recommended dose of totally 10 to 20 units will be injected into the five horizontally aligned injection sites (2 units, 3 units, or 4 units, per injection point respectively). A reduction in the horizontal forehead lines seen at maximum contraction usually occurs within 7 days with the maximum effect observed on day 30.

The effect lasts up to 4 months after the injection. Method of administration Dissolved BOCOUTURE is intended for injections into the muscle (intramuscular use; see information for healthcare professionals at the end of this leaflet). The interval between two treatments should not be less than 3 months. If you are given more BOCOUTURE than you require Symptoms of overdose Symptoms of overdose are not apparent immediately after the injection and may include general weakness, drooping eyelid, double vision, breathing difficulties, speech difficulties, and paralysis of the respiratory muscles or swallowing difficulties which may result in pneumonia. Measures in cases of overdose In case you feel symptoms of overdose please seek medical emergency services immediately or ask your relatives to do so, and have yourself admitted to hospital. Medical supervision for up to several days and assisted ventilation may be necessary. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or healthcare professional. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them.

An allergic reaction may occur with BOCOUTURE. Serious and/or immediate allergic reactions (anaphylaxis) or allergic reactions to the serum in the product (serum sickness), causing for example difficulty in breathing (dyspnoea), hives (urticaria) or swelling of the soft tissue (oedema), have been rarely reported. Some of these reactions have been observed following the use of conventional Botulinum toxin type A complex. They occurred when the toxin was given alone or in combination with other products known to cause similar reactions. These effects cannot be ruled out completely when using BOCOUTURE.

An allergic reaction can cause any of the following symptoms:

• difficulty with breathing, swallowing or speaking due to the swelling of the face, lips, mouth or throat

• swelling of the hands, feet or ankles. If you notice any of these side effects, please inform your doctor immediately or ask your relatives to do so and go to the accident and emergency department of your nearest hospital. Usually, side effects occur in the first week after the injection and are temporary in nature. Side effects may be related to the medicine, injection technique or both. At the injection sites, the action of Botulinum toxin type A causes localised muscle weakness. Drooping eyelids can be caused by the injection technique and the effect of the medicine.

The following reactions may occur around the injection site:

• Localised pain • Inflammation • Pins and needles • Decreased skin sensation • Tenderness • Itching • Swelling (general) • Swelling of the soft tissue (oedema) • Skin redness (erythema) • Localised infection

Bocouture 50+100 units Großbritannien GA Type size: 9 pt MN XXXXX MC XXXX, GB • Bleeding • Bruising Patients with a fear of injections or needle related pain may experience temporary generalised reactions, e.g. • Fainting • Circulatory problems • Nausea • Noises in the ears Other possible side effects The following side effects have been observed with BOCOUTURE: Vertical Lines between the Eyebrows seen at maximum frown (Glabellar Frown Lines) Common (may affect up to 1 in 10 people):

• Headache • Mephisto sign (raising of the outer eyebrows) Uncommon (may affect up to 1 in 100 people): • Nasopharyngitis • Bronchitis • Influenza like illness • Drooping eyebrow (brow ptosis) • Drooping eyelids (eyelid ptosis) • Accumulation of fluid in the eyelids (eyelid oedema) • Discomfort (heavy feeling of eyelid/eyebrow) • Blurred vision • Muscle twitching (muscle spasm) • Asymmetry of eyebrows • Feeling of tightness at the injection site • Tiredness • Pain or bruising at the injection site • Itching • Bruise • Skin nodule • Insomnia Lateral Periorbital Lines seen at maximum smile (Crow’s feet lines) Common (may affect up to 1 in 10 people): • Eyelid swelling • Dry eye • Bruising at the injection site Upper Facial Lines Very common (may affect more than 1 in 10 people): • Headache Common (may affect up to 1 in 10 people): • Numbness • Bruising at the injection site • Pain at the injection site • Skin reddening around the injection site • Discomfort (heavy feeling of frontal area) • Drooping eyelids (eyelid ptosis) • Dry eye • Drooping eyebrow (brow ptosis) • Facial asymmetry

• Mephisto sign (raising of the outer eyebrows) • Nausea Post-marketing experience The following side effects were reported with unknown frequency for the use of BOCOUTURE since market launch independent from treatment area: Flu-like symptoms, shrinkage of injected muscle, and hypersensitivity reactions, such as swelling and swelling of the soft tissue (oedema), also distant from injection site, redness, itching, rash (local and generalised) and breathlessness. The following very rare side effects have been observed during Botulinum toxin type A treatment of conditions other than upper facial lines (see section 2):

• Excessive muscle weakness

• Swallowing difficulties

• Swallowing difficulties causing inhalation of foreign bodies resulting in lung inflammation and, in some cases, death Such side effects are caused by the relaxation of muscles far from the injection site. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or healthcare professional. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of this medicine. 5. How to store BOCOUTURE 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 vial label after “EXP”. The expiry date refers to the last day of that month. Unopened vial: Do not store above 25 °C. Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C to 8 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions. Your doctor or healthcare professional should not use BOCOUTURE if the solution has a cloudy appearance or contains visible particles. Do not throw away any medicines via wastewater. For instructions on disposal, please see information for healthcare professionals at the end of this leaflet. 6. Contents of the pack and other information What BOCOUTURE contains

• The active substance is: Botulinum toxin type A (150 kD), free from complexing proteins. BOCOUTURE 50 units One vial contains 50 units Botulinum toxin type A (150 kD), free from complexing proteins. BOCOUTURE 100 units One vial contains 100 units Botulinum toxin type A (150 kD), free from complexing proteins.

• The other ingredients are: human albumin, sucrose. What BOCOUTURE looks like and contents of the pack BOCOUTURE is presented as a powder for solution for injection (powder for injection). The powder is white. Dissolving the powder produces a clear, colourless solution. Pack sizes of 1, 2, 3 or 6 vials. Not all pack sizes may be marketed. Marketing Authorisation Holder Merz Pharmaceuticals GmbH 60048 Frankfurt/Main Germany Manufacturer Merz Pharma GmbH & Co. KGaA Eckenheimer Landstraße 100 60318 Frankfurt/Main P.O. Box 11 13 53 60048 Frankfurt/Main Germany Telephone: +49-69/15 03-1 Fax: +49-69/15 03-200 This leaflet was last revised in 01/2021.