Package leaflet Botox®

PACKAGE LEAFLET: INFORMATION FOR THE USER
BOTOX® - 50 Allergan units,
Powder for solution for injection Botulinum toxin type A. Read all of this leaflet carefully before you start using this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• 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.

In this leaflet:

  1. What BOTOX is and what it is used for
  2. Before you use BOTOX
  3. How to use BOTOX
  4. Possible side effects
  5. How to store BOTOX
  6. Further information

1. WHAT BOTOX IS AND WHAT IT IS USED FOR

What BOTOX is
BOTOX is a muscle relaxant that is injected into the muscles 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. In the case of chronic migraine, it is thought that BOTOX blocks pain signals, which indirectly block the development of a migraine.
When injected into the skin, BOTOX works on sweat glands to reduce the amount of sweat produced.
When injected into the bladder wall, BOTOX works on the bladder muscle to prevent leakage of urine (urinary incontinence) due to uncontrolled contractions of the bladder muscle.
What BOTOX is used for
In adults, BOTOX is used to control:
• persistent muscle spasms in the eyelid and face;
• persistent muscle spasms in the neck and shoulders;
• persistent muscle spasms in the wrist and hand of patients who have suffered a
stroke;

  • excessive sweating of the armpits that affects the activities of daily living, when other local treatments do not help;
  • leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis.
    In patients who have not managed to control leakage of urine with medicines called anticholinergics, BOTOX has been shown to reduce leakage of urine, from an average of about 30 episodes per week down to 10 after 6 weeks. 37% of patients had no leakage of urine at all.
    In adults, BOTOX is used to prevent:

• headaches in patients with chronic migraine
Chronic migraine is a disease affecting the nervous system. To be diagnosed with chronic migraine, you must have headaches 15 days or more a month. In addition, on 8 or more days a month, your headaches must have at least two of the following characteristics:
• affect only one side of the head
• cause a pulsating pain
• cause moderate to severe pain
• are aggravated by routine physical activity
and they must cause at least one of the following:

  • nausea, vomiting, or both
  • sensitivity to light and sound.
    BOTOX has been shown to significantly reduce the frequency of days with headache and to improve the quality of life of patients suffering from chronic migraine. After two treatment sessions, approximately 47% of patients had a 50% or greater reduction from baseline in the number of days with headache they experienced.
    In adults less than 65 years of age, BOTOX is used for the temporary improvement of vertical lines between the eyebrows seen at frown, when the severity of these lines has an important psychological impact for the patient.
    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. BOTOX
relieves the persistent muscle spasms in the leg.

2. 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 BOTOX;
  • if you have an infection at the proposed site of injection;
  • if you are being treated for leakage of urine and have either a sudden onset of
    urinary tract infection or a sudden inability to empty your bladder (and are not regularly using a catheter) or if you have bladder stones.
    Take special care with BOTOX
    Before using BOTOX
    Tell your doctor if you:
  • have had any problems with injections (such as fainting) in the past;
  • have had problems in the past with previous botulinum toxin injections;
  • have inflammation in the muscles or skin area where your doctor plans to
    inject;
  • have significant weakness or wasting of the muscles which your doctor plans
    to inject;
  • 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;
  • suffer from any other muscle problems or chronic diseases affecting your
    muscles (such as myasthenia gravis or Eaton Lambert Syndrome);
  • suffer from certain diseases affecting your nervous system (such as
    amyotrophic lateral sclerosis or motor neuropathy);
  • 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;
  • have had any surgery that may have in some way changed the muscle to be
    injected;
  • will have an operation soon;
  • are taking any blood thinning medicine.
    After you have been given BOTOX
    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).
    If you have been treated for vertical lines, please inform your doctor if you see no
    significant improvement of your lines one month after your first course of treatment.
    General precautions
If you are given BOTOX too often or the dose is too high, 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 two or three months depending on the indication.
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.
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.
BOTOX does not prevent headaches in patients with episodic migraine, which occur less than 15 days a month.
Taking other medicines
Tell your doctor or pharmacist if:
  • you are using any antibiotics (used to treat infections), anticholinesterase
    medicines, medicines to control your heart rhythm, or muscle relaxants. Some
    of these medicines may increase the effect of BOTOX.
  • you have recently been injected with a medicine containing 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 anticoagulants
    (blood thinners).
    Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
    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. Contact your doctor if you are pregnant, plan pregnancy or become pregnant whilst being treated. Your doctor will discuss with you whether you should continue with your treatment.
    BOTOX is not recommended in breast-feeding women.
    Ask your doctor or pharmacist for advice before taking any medicine. Driving and using machines
BOTOX may cause 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 doctors with specific skills on how to use the medicine.
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 doctor 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 doctor will decide how much, how often, and in which muscle(s) BOTOX will be given to you. It is recommended that your doctor uses the lowest effective dose;
  • Dosages for the elderly 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 in the treatment of persistent muscles spasms of the eyelid, face, neck and shoulder in children (under 12 years) have not been demonstrated;
  • The safety and effectiveness of BOTOX in the treatment of chronic migraine have not been studied in children (under 18 years);
  • The safety and effectiveness of BOTOX in the treatment of vertical lines between the eyebrows in individuals under 18 years of age have not been demonstrated and such use is not recommended;
  • The safety and effectiveness of BOTOX in the treatment of excessive sweating of the armpits have not been investigated in children under 12 years. There is limited experience with BOTOX in the treatment of excessive sweating of the armpits in adolescents between age of 12 and 17 using BOTOX. The effectiveness of BOTOX in this population has not been confirmed. Speak to your doctor for further information;
  • The safety and effectiveness of BOTOX in the treatment of upper limb spasticity associated with stroke has not been established in children and adolescents under 18 years of age;
  • There is limited clinical data with BOTOX in the treatment of vertical lines between the eyebrows in patients older than 65 years and until more studies have been performed, BOTOX is not recommended in this age group.
    For persistent muscle spasms of the eyelid and face
    Dosage
    In the first treatment session, your doctor may give multiple injections in the affected muscles with 1.25 to 2.5 Units of BOTOX into each injection site.
    The maximum dose for the first treatment session is 25 Units per affected area (for example per eye). For the following treatment sessions, the total maximum dose can be increased up to 100 Units, if needed.
    Duration of treatment effect
    You will usually see an improvement within 3 days after the injection.
    The maximum effect is usually seen 1 to 2 weeks after treatment.
    When the effect starts to wear off, you can have the treatment again if needed, but not more often than every 3 months.
    For persistent muscle spasms of the neck and shoulders
    Dosage
    Your doctor may give multiple injections in the affected muscles with up to 50 Units of BOTOX into each injection site.
    The maximum dose for the first treatment session is 200 Units.
    Duration of treatment effect
    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 in the wrist and hand of patients who have had a stroke
    Dosage
    Your doctor may give multiple injections in the affected muscles. The dose and number of injections will vary depending on a number of factors, including your needs, the muscles to be injected, the size of the muscles, severity of spasms, etc.
    Duration of treatment effect
    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.
When the effect starts to wear off, you can have the treatment again if needed, but not more often than every 12 weeks.
For excessive sweating of the armpits
Dosage
Your doctor will give multiple injections with a total of 50 Units of BOTOX in each armpit.
Duration of treatment effect
You will usually see an improvement within the first week after injection.
On average the effect usually lasts 4-7 months after the first injection.
When the effect starts to wear off, you can have the treatment again if needed.
For persistent muscle spasms in the legs of children who have cerebral palsy
Dosage
The doctor may give multiple injections in the affected muscles. The dose will depend on the weight of your child.
Duration of treatment effect
The improvement usually appears within the first 2 weeks after the injection. When the effect starts to wear off, further treatment is possible, but not more often than every 2 months.
For the prevention of headache in adults who have chronic migraine
Dosage
Your doctor may give you multiple injections (between 31 and 39) in 7 muscular groups of the face, head, neck and shoulders, with up to 5 Units of BOTOX into each injection site. Injections are divided across muscles in your forehead, your temples on the side of your head, the back of your head, your upper neck area, and your shoulders. The injections are given to both the left, and right side of these head and neck muscles, except for one injection given to the muscle that is between your eyebrows
The total dose range is between 155 Units and 195 Units per treatment session.
Duration of treatment effect
When the effect starts to wear off, further treatment is possible, but not more often than every 12 weeks.
For leakage of urine due to neurogenic bladder
Dosage
Your doctor will give multiple injections into the bladder wall. The total dose is 200 Units of BOTOX.
Your doctor will give you antibiotics around the time of the injection to help prevent urinary tract infection. The injection will be administered by a procedure called cystoscopy. An instrument with a light source at the end will be introduced into your bladder through the opening by which you let out the urine (called urethra). This enables the doctor to see the inside of the bladder and place the injections into the bladder wall. Please ask your doctor to explain further details of the procedure to you. You may be given a local or general anaesthetic before the procedure.
You will be observed for at least 30 minutes after the injection before you can leave. At the time of the injection, due to the procedure by which the injections are delivered into your bladder, you may experience possible uncontrolled reflex reaction of your body (e.g. profuse sweating, throbbing headache or increase in pulse rate).
If you were not using a catheter (a soft, hollow tube that is inserted into your urethra to help empty urine from the bladder) before treatment with BOTOX, you should be seen by your doctor approximately 2 weeks after the injection. You will be asked to pass urine and will then have the volume of urine left in your bladder measured. If your doctor assesses you have too much urine left in your bladder you will be instructed to use a catheter to empty your bladder. Your doctor will decide if and when you need to return for the same test.
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 clinical trials, approximately one fifth of patients reported an inability to completely empty their bladder after BOTOX treatment. At least one third of patients not using a catheter before treatment may need to use a catheter after treatment.
Duration of treatment effect
You will usually see an improvement within 2 weeks after the injection.
Typically the effect lasts approximately 10 months after the injection.
When the effects start to wear off, you can have the treatment again if needed, but not more often than every 3 months.
For vertical lines between your eyebrows
The usual dose is 20U (units). You will be injected with the recommended volume of 0.1 millilitre (ml) (4 units) of BOTOX into each of 5 injection sites.
Improvement of severity of the lines located between the eyebrows generally occurs within one 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.
The interval between two treatments must not be less than three months.
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:
• 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
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.
Like all medicines, BOTOX 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.
As expected for any injection procedure, pain/burning/stinging, swelling and/or bruising may be associated with the injection.
The side effects are classified into the following categories, depending on how often they occur:



Very common
occur in more than 1 out of 10 people who use the medicine
Common
occur in less than 1 out of 10 people but more than 1 out of 100 people who use the medicine
Uncommon
occur in less than 1 out of 100 people but more than 1 out of 1,000 people who use the medicine
Rare
occur in less than 1 out of 1,000 people but more than 1 out of 10,000 people who use the medicine
Very rare
occur in less than 1 out of 10,000 people who use the medicine
Below are lists of side effects which vary depending on the part of the body where BOTOX is injected:
Injections in the eyelid and face for muscle spasms
Very common side effect:
• drooping of the eyelid.
Common side effects:
• swelling of the face;
• pinpoint damage of the cornea (transparent surface covering the front of the
eye);
• difficulty in completely closing the eye;
• overflow of tears;
• irritation;
• dry eyes, eye irritation and sensitivity to light; • bruising under the skin.
Uncommon side effects:
• dizziness;
• difficulties in seeing clearly;
• blurred vision;
• double vision;
• tiredness;
• inflammation of the cornea (transparent surface covering the front of the eye); • weakness of the face muscles;
• droop of the muscles on one side of the face;
• rash;
• abnormal turning of the eyelids outwards or inwards.
Rare side effect:
• swelling of the eyelid.
Very rare side effect:
• ulcer, damage to the cornea (transparent surface covering the front of the eye).
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 neck and shoulder
Very common side effects:
• difficulty in swallowing; • pain;
• muscle weakness.
Common side effects: • dizziness;
• flu syndrome;
• sleepiness;
• muscle cramps;
  • decreased skin sensation;
  • feeling of weakness;
  • feeling generally unwell;
  • feeling sick;
  • headache;
  • stiff or sore muscles;
  • swelling and irritation inside the nose (rhinitis);
  • blocked or runny nose, cough, sore throat, tickle or irritation in the throat;
  • dry mouth.
    Uncommon side effects:
    • shortness of breath;
    • double vision;
    • fever;
    • drooping of the eyelid;
    • changes in your voice.
      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 wrist and hand of patients who have had a stroke
      Common side effects:
      • muscle weakness;
      • increased muscle tension;
      • bruising and bleeding under the skin causing red patches (ecchymosis or
      purpura);
      • bleeding or burning where the injection was given; • pain in the hand and fingers.
      • pain where the injection was given;
      • fever;
      • flu syndrome.
      Uncommon side effects:
      • depression;
      • a fall in blood pressure on standing up which causes dizziness, light headedness
      or fainting;
      • feeling of dizziness or “spinning” (vertigo);
      • lack of coordination of movements;
      • loss of memory;
      • general weakness;
      • pain;
      • joint pain or inflammation;
      • decreased skin sensation;
      • numbness;
      • swelling of the extremities such as the hands and feet; • inflammation of the skin (dermatitis);
      • headache;
  • feeling generally unwell;
  • feeling sick;
  • increased sensitivity where the injection was given;
  • rash;
  • numbness around the mouth;
  • difficulty in sleeping (insomnia);
  • itching.
    Some of these uncommon side effects may also be related to your disease.
    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 for excessive sweating of the armpits
    Very common side effects:

• Injection site pain.
Common side effects:
• pain where the injection was given;
• headache;
• numbness;
• hot flushes;
• increased sweating at sites other than the armpit;
• abnormal skin odour;
• itching;
• hair loss;
• lump under the skin;
• pain in the extremities, such as the hands and fingers;
• pain;
• reactions and swelling, bleeding or burning and increased sensitivity pain where
the injection was given.
Uncommon side effects:
• muscle weakness;
• feeling of weakness;
• muscle pain;
• problem with the joints; • feeling sick.
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
Very common side effects: • viral infection;

• ear infection.
Common side effects:
• sleepiness;
• muscle weakness;
• problems with walking;
• numbness;
• muscle pain;
• urinary incontinence (leakage of urine); • feeling generally unwell;
• fall;
• rash;
• pain where the injection was given;
• feeling of weakness.
There have been rare spontaneous reports of death sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with BOTOX.
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 head and neck to prevent headache in patients who suffer from chronic migraine
Common side effects:
• headache, migraine;
• rash, itching;
• pain where the injection was given; • drooping of the eyelid;
• muscle weakness;
• neck pain;
• muscle pain, cramp;
• muscle stiffness, tightness.
Uncommon side effects:
• difficulty in swallowing; • skin pain;
• jaw pain;
• swollen eyelid.
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 bladder wall
Very common side effects:
• urinary tract infection (in about half the patients);
• inability to empty your bladder (urinary retention; see section 3);
Common side effects: † • difficulty in sleeping (insomnia) ; • tiredness†; †
• constipation ; †
• muscle weakness
• blood in the urine after the injection*;
• bulge in the bladder wall (bladder diverticulum);
• 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; see section 3)*; • fall†.
*some of these common side effects may also be related to the injection procedure †only in multiple sclerosis
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 forehead for vertical lines
Common side effects are: • headaches;
• drooping eye lid; • skin redness;
• localised muscle weakness; • face pain.
Uncommon side effects are:
  • infection;
  • anxiety;
  • numbness;
  • dizziness
  • inflammation of the eyelid;
  • eye pain;
  • visual disturbance;
  • nausea (feeling sick);
  • dry mouth;
  • skin tightness;
  • swelling (face, eyelid, around the eyes);
  • sensitivity to light;
  • itching;
  • dry skin;
  • muscle twitching;
  • flu syndrome;
  • lack of strength;
or spasm;
• fever.
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.
General information about other side effects
Side effects related to the spread of BOTOX far away from the site of injection have been reported very rarely and include
• muscle weakness;
• constipation;
• difficulty in swallowing;
• food or liquid accidentally going into the lungs which in some cases may lead to
pneumonia.
The difficulty in swallowing may range from mild to severe and in some cases you may need treatment. In rare cases, people have died because of swallowing difficulties.
Side effects affecting the heart have been rarely reported: • irregular heartbeat;
• heart attacks.
Some of these people have died. However, some of these patients were already suffering from heart complaints.
Serious or immediate allergic reactions have been rarely reported, including • hives;
• swelling including swelling of the face or throat;
• wheezing;
• feeling faint;
• shortness of breath.
There have been very rare reports of
• glaucoma (high pressure in the eye).
There have been reports of
• seizures or convulsions after treatment with BOTOX, particularly in patients
who have previously experienced these symptoms. These effects occurred mainly when BOTOX was used for the treatment of persistent muscle spasms in the legs of children with cerebral palsy.
As with any injection, you may suffer from injection related side effects: • pain, bruising, bleeding or infection where the injection is given;
• numbness;
• decreased skin sensation;
• tenderness;
• swelling/puffiness;
  • redness;
  • a drop in blood pressure or fainting may be caused by needle-related pain and/or
    anxiety.

After injection of BOTOX patients have also suffered
• fever and flu-like symptoms.
The following list describes additional side effects reported for BOTOX, in any disease, since it has been marketed:

  • allergic reactions, which can be serious (swelling of the face and airways,
    difficulty in breathing);
  • loss of nerve supply to/shrinkage of injected muscle;
  • respiratory depression and/or respiratory failure;
  • aspiration pneumonia (lung inflammation caused by accidentally breathing in
    food, drink, saliva or vomit);
  • chronic disease affecting the muscles (myasthenia gravis);
  • blurred vision;
  • difficulties in seeing clearly;
  • slurred speech
  • strabismus (squint);
  • numbness, tingling and pain in hands and feet;
  • fainting;
  • pain/numbness/or weakness starting from the spine;
  • drooping of the muscles on one side of the face;
  • weakness of the face muscles;
  • difficulty moving the arm and shoulder;
  • decreased skin sensation;
  • muscles pain;
  • abdominal pain;
  • diarrhoea, vomiting, loss of appetite;
  • fever;
  • different types of red blotchy skin rashes;
  • feeling generally unwell;
  • speech problems;
  • itching;
  • excessive sweating;
  • hair loss;
  • loss of eyebrows;
  • decreased hearing
  • noises in the ear;
  • feeling of dizziness or “spinning” (vertigo);
  • numbness.
    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.

5. HOW TO STORE BOTOX

Keep out of the reach and sight of children.
Store in a refrigerator (2°C – 8°C), or store in a freezer (at or below -5°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).
Your doctor 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.

6. FURTHER INFORMATION What BOTOX contains

  • The active substance is: Botulinum toxin type A from Clostridium botulinum.
  • The other ingredients are human albumin and sodium chloride.
    What BOTOX looks like and content of the pack
    BOTOX is presented as a white powder in a transparent glass vial. Prior to injection, the product must be dissolved in a sterile saline solution.
    Each vial contains 50 Allergan Units of botulinum toxin type A.
    Each pack contains 1, 2, 3 or 6 vials. Not all pack sizes may be marketed.
    Marketing Authorisation Holder and Manufacturer
    Marketing Authorisation Holder: Allergan Ltd.,
    Marlow International,
    The Parkway, Marlow,
    Bucks SL7 1YL UK
    Manufacturer:
    Allergan Pharmaceuticals Ireland Castlebar Road
    Westport
    County Mayo
    Ireland
    This medicinal product is authorised in the Member States of the EEA under the following name: BOTOX
    Austria, Belgium, Czech Republic, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxemburg, Malta, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Slovak Republic, United Kingdom
    This leaflet was last revised in November 2012
    --------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
Please refer to the Summary of Product Characteristics for complete prescribing information for BOTOX.
For all indications:
Side effects related to spread of toxin distant from the site of administration have been reported, sometimes resulting in death, which in some cases was associated with dysphagia, pneumonia and/or significant debility.
Patients treated with therapeutic doses may experience exaggerated muscle weakness. Patients with underlying neurological disorders including swallowing difficulties are at increased risk of these side effects. The botulinum toxin product should be used under specialist supervision in these patients and should only be used if the benefit of treatment is considered to outweigh the risk. Patients with a history of dysphagia and aspiration should be treated with extreme caution.
Serious adverse events including fatal outcomes have been reported in patients who had received BOTOX injected directly into salivary glands, the oro-lingual- pharyngeal region, oesophagus and stomach. Some patients had pre-existing dysphagia or significant debility.
Pneumothorax associated with injection procedure has been reported following the administration of BOTOX near the thorax. Caution is warranted when injecting in proximity to the lung, particularly the apices.
Reconstitution of the medicinal product:
It is good practice to perform vial reconstitution and syringe preparation over plastic- lined paper towels to catch any spillage.
Reconstitute BOTOX only with sterile unpreserved normal saline (0.9% sodium chloride for injection). Draw up an appropriate amount of diluent (see dilution table below) into a syringe.
Dilution table for BOTOX 50, 100 and 200 Allergan Units vial size:




 
50 unit vial
100 unit vial
200 unit vial
Resulting dose (Units per
0.1 ml)
Amount of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection) added in a 50 unit vial
Amount of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection) added in a 100 unit vial
Amount of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection) added in a 200 unit vial
20 Units
0.25 ml
0.5 ml
1 ml
10 Units
0.5 ml
1 ml
2 ml
5 Units
1 ml
2 ml
4 ml
4 Units
1.25 ml
2.5 ml
5 ml
2.5 Units
2 ml
4 ml
8 ml
1.25 Units
4 ml
8 ml
N/A
Since BOTOX is denatured by bubbling or similar vigorous agitation, inject the diluent gently into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Reconstituted BOTOX is a clear colourless to slightly yellow solution free of particulate matter. The reconstituted solution should be visually inspected for clarity and absence of particles prior to use. When reconstituted in the vial, BOTOX may be stored in a refrigerator (2°C - 8°C) for up to 24 hours prior to use.
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 - 8°C.
Dilution instructions for treatment of Urinary incontinence due to neurogenic detrusor overactivity:
It is recommended that 200U or 100U vials are used for convenience of reconstitution
Reconstitute a 200 Unit vial of BOTOX with 6 ml of 9 mg/ml (0.9%) preservative- free sodium chloride solution for injection and mix the vials gently. Draw 2 ml from the vial into each of three 10 ml syringes. Complete the reconstitution by adding 8 ml of 9 mg/ml (0.9%) preservative-free sodium chloride solution for injection into each of the 10 ml syringes, and mix gently. This will result in three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Dispose of any unused saline.
Or, reconstitute two 100 Unit vials of BOTOX, each with 6 ml of 9 mg/ml (0.9%) preservative-free sodium chloride solution for injection and mix the vials gently. Draw 4 ml from each vial into each of two 10 ml syringes. Draw the remaining 2 ml from each vial into a third 10 ml syringe. Complete the reconstitution by adding 6 ml of 9 mg/ml (0.9%) preservative-free sodium chloride solution for injection into each of the 10 ml syringes, and mix gently. This will result in three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Dispose of any unused saline.
Or, reconstitute four 50 Unit vials of BOTOX, each with 3 ml of 9 mg/ml (0.9%) preservative-free sodium chloride solution for injection and mix the vials gently. Draw 3 ml from the first vial and 1 ml from the second vial into one 10 ml syringe. Draw 3 ml from the third vial and 1 ml from the fourth vial into a second 10 ml syringe. Draw the remaining 2 ml from the second and fourth vials into a third 10 ml syringe. Complete the reconstitution by adding 6 ml of 9 mg/ml (0.9%) preservative- free sodium chloride solution for injection into each of the three 10 ml syringes, and mix gently. This will result in three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Dispose of any unused saline.
This product is for single use only and any unused solution should be discarded.
Procedure to follow for safe disposal of vials, syringes and materials used
For safe disposal, unused vials should be reconstituted with a small amount of water and then autoclaved. Any used vials, syringes, and spillages etc. should be
autoclaved, or the residual BOTOX inactivated using dilute hypochlorite solution (0.5%) for 5 minutes.
Identification of the product
In order to verify receipt of actual BOTOX product from Allergan, look for a holographic film on the vial label. In order to see this film, examine the vial under a desk lamp or fluorescent light source. Rotating the vial back and forth between your fingers, look for horizontal lines of rainbow colour on the label and confirm that the name “Allergan” appears within the rainbow lines. (Note that the film on the label is absent in the Expiry/Lot Number area.) If you do not see the rainbow lines or the name ”Allergan” does not appear, do not use the product and contact your local Allergan office for additional information.