BOTOX 100 Units

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 or pharmacist.
• 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 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

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), or if you have bladder stones;
• if you are being treated for leakage of urine and are not willing to begin using a catheter if required.

Warnings and precautions

Talk to your doctor or pharmacist before using BOTOX:

• 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 Eaton Lambert Syndrome);
• 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 doctor plans to inject;
• if you have had any surgery that may have in some way changed the muscle to be injected;
• 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 doctor plans to inject;
• if you have had problems in the past with previous botulinum toxin injections;
• if you suffer from cardiovascular disease (disease of the heart or blood vessels);
• if you suffer of 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 will have an operation soon;
• if you are taking any blood thinning medicine.

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).

If you have been treated for vertical and/or fan-shaped lines, please inform your doctor if you see no significant improvement of your lines 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.

Side effects 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.

If you are given BOTOX too often or the dose is too high, you may experience muscle weakness and side effects 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 two or 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.

When treating adults with post-stroke ankle muscle spasms, BOTOX should only be used if it is expected to result in improvement in function (e.g. walking) or symptoms (e.g. spasms or pain) or to help with patient care. Furthermore, for patients who may be more likely to fall, your doctor will judge if this treatment is suitable.

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.

When BOTOX is used in the treatment of vertical lines and fan-shaped lines drooping of eyelid may occur after treatment.

Other medicines with BOTOX

Tell your doctor or pharmacist if:

• you are using any antibiotics (used to treat infections), or any medicines that affect the nerves that control muscles (for example 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 anticoagulants (blood thinners).

Tell your doctor or pharmacist if you are taking or 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. 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 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.

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 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 not been established in children/adolescents under the following ages;

• The safety and effectiveness of BOTOX in the treatment of cerebral palsy has not been established in children/adolescents under 2 years.
• The safety and effectiveness of BOTOX in the treatment of persistent muscle spasms in the wrist, hand or ankle of patients who have suffered a stroke has not been established in children/adolescents under 18 years.
• The safety and effectiveness of BOTOX in the treatment of persistent muscle spasms of the eyelid, face has not been established in children/adolescents under 12 years.
• The safety and effectiveness of BOTOX in the treatment of neck and shoulder has not been established in children/adolescents under 12 years.
• The safety and effectiveness of BOTOX in the treatment of chronic migraine has not been established in children/adolescents under 18 years.
• The safety and effectiveness of BOTOX in the treatment of leakage of urine has not been established in children/adolescents under 18 years.
• The safety and effectiveness of BOTOX in the treatment of excessive sweating of the armpits has not been established in children/adolescents under 12 years. There is limited experience in adolescents between age of 12 and 17 years. Speak to your doctor for further information.
• The safety and effectiveness of BOTOX in the treatment of vertical lines between the eyebrows and/or fan-shaped lines from the corner of the eyes has not been established in children/adolescents under 18 years.

In addition, there is limited experience of using BOTOX in the treatment of vertical and/or fan-shaped lines in patients older than 65 years.

Dosage

For persistent muscle spasms in the legs of children who have cerebral palsy the maximum dose (Units per affected area) in the first treatment is 4 Units/kg (hemiplegia)/6 Units/kg (diplegia) and also 4 Units/kg (hemiplegia)/6 Units/kg (diplegia) for the following treatments. The minimal time between treatments is 3 months*.

For persistent muscle spasms in the wrist and hand of patients who have had a stroke the maximum dose (Units per affected area) in the first treatment the exact dosage and number of injection sites per hand/wrist is tailored to individual needs, up to a maximum of 240 Units. In the following treatments the exact dosage and number of injection sites is tailored to individual needs, up to a maximum of 240 Units. The minimal time between treatments is 12 weeks.

For persistent muscle spasms in the ankle of patients who have had a stroke the maximum dose in the first treatment your doctor may give multiple injections in the affected muscles. The total dose is 300 Units divided among 3 muscles. The total dose is also 300 Units divided among 3 muscles in the following treatments. The minimal time between treatments is 12 weeks.

For persistent muscle spasms of the eyelid and face the maximum dose in the first treatment is 25 Units per eye. It is up to 100 Units in the following treatments. The minimal time between treatments is 3 months.

For persistent muscle spasms of the neck and shoulders the maximum dose in the first treatment is 200 Units. It is up to 300 Units for the following treatments. The minimal time between treatments is 10 weeks.

For headache in adults who have chronic migraine the maximum dose in the first treatment is 155 to 195 Units. It is also 155 to 195 Units in the following treatments. The minimal time between treatments is 12 weeks.

For overactive bladder with leakage of urine the maximum dose in the first treatment is 100 Units. It is also 100 Units in the following treatments. The minimal time between treatments is 3 months.

For leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis the maximum dose in the first treatment is 200 Units. It is also 200 Units for the following treatments. The minimal time between treatments is 3 months. The effects of more than two treatment sessions have not been evaluated.

For excessive sweating of the armpits the maximum dose in the first treatment is 50 Units per armpit. It is also 50 units per armpit for the following treatments. The minimal time between treatments is 16 weeks.

For Vertical lines between the eyebrows seen at maximum frown the maximum dose in the first treatment is 20 Units**. It is up to 50 Units for the following treatments. The minimal time between treatments is 3 months. The effects of more than four treatment sessions have not been evaluated.

For Fan-shaped lines from the corner of the eyes seen at maximum smile the maximum dose in the first treatment is 24 Units**. It is also 24 Units for the following treatments. The minimal time between treatments is 3 months.

* The doctor may select a dose that would mean the treatment may be up to 6 months apart.

** If you are treated for fan-shaped lines from the corner of the eyes seen at maximum smile at the same time as vertical lines between the eyebrows seen at maximum frown, you will receive a total dose of 44 Units.

Information for patients treated for leakage of urine

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.

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.

For overactive bladder with leakage of urine

You may be given a local anaesthetic before the injections (your bladder would be filled with anaesthetic solution for a while and then drained). You may also be given a sedative.

You will be observed for at least 30 minutes after the injection before you can leave to see if you can pass urine spontaneously.

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 6 out of 100 patients not using a catheter before treatment may need to use a catheter after treatment.

For leakage of urine due to bladder problems associated with spinal cord injury or multiple sclerosis

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 injection is 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).

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.

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 of the eyelid and face, you will usually see an improvement within 3 days after the injection and the 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 patients find 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 patients find the effect lasts approximately 9-10 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 4-7 months after the first injection.

For vertical lines between the eyebrows seen at maximum frown, 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 seen at maximum smile you will usually see an improvement within 1 week after treatment. The treatment effect has been demonstrated for an average of 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.

Injections in the legs of children with cerebral palsy

Very Common

• Viral infection, ear infection

Common

• Sleepiness, problems with walking, numbness
• Muscle pain, muscle weakness, pain of the extremities
• Urinary incontinence (leakage of urine)
• Feeling generally unwell or weak
• Pain where the injection was given
• Fall
• Rash

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

• Muscle weakness, increased muscle tension
• Pain in the hand and fingers
• Bruising and bleeding under the skin causing red patches (ecchymosis or purpura)
• Bleeding, burning, pain where the injection was given
• Fever, flu manifestations

Uncommon

• Depression, difficulty in sleeping (insomnia)
• 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, decreased skin sensation, numbness, headache
• General weakness, feeling generally unwell
• Feeling sick, numbness around the mouth
• Pain, swelling of the extremities such as the hands and feet
• Joint pain or inflammation
• Inflammation of the skin (dermatitis), rash, itching, increased sensitivity where the injection was given

Some of these uncommon side effects may also be related to your disease.

Injections in the legs of patients who have had a stroke

Common

• Rash
• Joint pain or inflammation, stiff or sore muscles
• Swelling of the extremities such as the hands and feet

Injections in the eyelid and face for muscle spasms

Very Common

• Drooping of the eyelid

Common

• 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, dry eyes, eye irritation and sensitivity to light
• Bruising under the skin
• Irritation

Uncommon

• Dizziness, weakness of the face muscles, drooping of the muscles on one side of the face
• Visual disturbance, blurred vision, double vision, inflammation of the cornea (transparent surface covering the front of the eye), abnormal turning of the eyelids outwards or inwards
• Rash
• Tiredness

Rare

• Swelling of the eyelid

Very rare

• Damage to the cornea (transparent surface covering the front of the eye) including ulcer and perforation

Injections in the neck and shoulder

Very Common

• Difficulty in swallowing
• Pain
• Muscle weakness

Common

• Dizziness, sleepiness, headache
• Feeling of weakness or generally unwell, flu manifestations
• Feeling sick, dry mouth
• Muscle cramps, stiff or sore muscles, increased muscle tension
• Decreased skin sensation
• Swelling and irritation inside the nose (rhinitis), signs of infection of the nose or throat (blocked or runny nose, cough, sore throat)

Uncommon

• Shortness of breath, changes in voice
• Double vision, drooping of the eyelid
• Fever

Injections in the head and neck to prevent headache in patients who suffer from chronic migraine

Common

• Increase in headache or migraine
• Weakness of the face muscles
• Drooping of the eyelid
• Rash, itching
• Pain where the injection was given
• Muscle weakness, neck pain, muscle pain or cramp, muscle stiffness or tightness

Uncommon

• Difficulty in swallowing
• Swollen eyelid
• Skin pain
• Jaw pain

Injections in the bladder wall for overactive bladder with leakage of urine

Very common

• Urinary tract infection, painful urination after the injection*

Common

• Inability to empty the bladder (urinary retention), incomplete emptying of the bladder, frequent daytime urination
• Bacteria or white blood cells in the urine

*This side effect is 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 (in about half the patients)
• Inability to empty the bladder (urinary retention; see section 3)

Common

• Muscle spasm
• Bulge in the bladder wall (bladder diverticulum)

The following side effects have only be reported in multiple sclerosis:

• Difficulty in sleeping (insomnia)
• Tiredness, problems with walking (gait disturbance)
• Constipation
• Muscle weakness, fall

The following side effects are related to the injection procedure:

• Blood in the urine after the injection
• Uncontrolled reflex reaction of the body (profuse sweating, throbbing headache or increase in pulse rate) around the time of the injection (autonomic dysreflexia; see section 3)

Injections for excessive sweating of the armpits

Very common

• Pain where the injection was given

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, reaction where the injection was given such as swelling, bleeding, burning or increased sensitivity

Uncommon

• Muscle weakness, muscle pain, problem with the joints
• Feeling weak
• Feeling sick

Injections in the forehead for vertical lines

Common

• Headache
• Drooping of the eyelid
• Localised muscle weakness
• Face pain
• Skin redness

Uncommon

• Infection
• Anxiety
• Numbness, dizziness
• Inflammation of the eyelid, eye pain, visual disturbance
• Swelling (face, eyelid, around the eyes), skin tightness, skin sensitivity to light, dry skin, itching
• Feeling sick, dry mouth
• Muscle twitching
• Fever, flu manifestations, feeling weak

Injections in the fan-shaped lines from the corner of the eyes

Common

• Swelling of the eyelid
• Injection site bleeding*, injection site bruising*

Uncommon

• Injection site pain*, injection site tingling or numbness

*Side effects related to the injection procedure.

Injections in the fan-shaped lines from the corner of the eyes, when treated at the same time as injections in the forehead for vertical lines

Common

• Injection site bruising*

Uncommon

• Injection site bleeding*, injection site pain*

*Side effects related to the injection procedure.

General information about other side effects

The following list describes additional side effects reported for BOTOX, in any disease, since it has been marketed:

Affecting the immune system

• sudden allergic reactions, which can be serious (swelling of the face or throat, difficulty in breathing, feeling faint)
• delayed reaction which may include fever, skin reaction, joint pain (serum sickness)
• hives

Affecting metabolism

• loss of appetite

Affecting the nervous system

• nerve damage (brachial plexopathy)
• slurred speech, speech problems
• weakness or drooping of the muscles on one side of the face
• decreased skin sensation
• muscle weakness
• chronic disease affecting the muscles (myasthenia gravis)
• difficulty moving the arm and shoulder
• numbness, tingling and pain in hands and feet
• pain/numbness/or weakness starting from the spine
• seizures, fainting

Affecting the eyes

• increase in eye pressure
• difficulty in completely closing the eye
• strabismus (squint)
• blurred vision
• visual disturbance
• dry eye

Affecting the ears

• decreased hearing
• noises in the ear
• feeling of dizziness or “spinning” (vertigo)

Affecting the cardiovascular system

• heart problems including heart attack

Affecting the respiratory system

• aspiration pneumonia (lung inflammation caused by accidentally breathing in food, drink, saliva or vomit)
• breathing problems, respiratory depression and/or respiratory failure

Affecting the gastrointestinal system

• abdominal pain
• diarrhoea, constipation
• dry mouth
• difficulty swallowing
• feeling sick, vomiting

Affecting the skin

• hair loss, loss of eyebrows
• different types of red blotchy skin rashes
• excessive sweating
• itching
• rash

Affecting muscles

• muscles pain, loss of nerve supply to/shrinkage of injected muscle
• localised muscle twitching/involuntary muscle contractions

Affecting the body

• feeling generally unwell
• fever

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

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 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 (0.9% sodium chloride for injection).

Each vial contains either 50, 100 or 200 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:

Manufacturer: