BOTOX50 Allergan Units Powder for solution for injection

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Botulinum toxin type a
Available from:
Allergan Pharmaceuticals Ireland
ATC code:
M03AX; M03AX01
INN (International Name):
Botulinum toxin type a
Dosage:
50 Allergan Units
Pharmaceutical form:
Powder for solution for injection
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Other muscle relaxants, peripherally acting agents; botulinum toxin
Authorization status:
Marketed
Authorization number:
PA0148/060/002
Authorization date:
2008-01-18

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Package leaflet: Information for the user

BOTOX,

50 Allergan Units, Powder for Solution for Injection

BOTOX,

100 Allergan Units, Powder for Solution for Injection

BOTOX,

200 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 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:

What BOTOX is and what it is used for

What you need to know before you use BOTOX

How to use BOTOX

Possible side effects

How to store BOTOX

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.

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.

BOTOX can be injected directly into the muscles, and can be used to control the following

conditions:

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;

persistent muscle spasms in the ankle and foot of adult patients who have suffered a

stroke;

persistent muscle spasms in the eyelid and face of adult patients;

persistent muscle spasms in the neck and shoulders of adult patients;

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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.

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.

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.

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.

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);

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 doctor 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 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 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;

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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).

General precautions

As with any injection, it is possible for the procedure to result in infection, pain, swelling, abnormal

skin sensations (e.g. tingling or numbness), decreased skin sensation, tenderness, redness,

bleeding/bruising at the site of injection and a drop in blood pressure or fainting; this may be the

consequence of pain and/or anxiety associated with 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). These side effects can be mild to severe, may require treatment and in some

cases may be fatal. 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.

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

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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.

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 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), 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 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 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 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.

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3.

How to use BOTOX

BOTOX must only be injected by doctors 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 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 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 exact dosage and

The exact dosage and

12 weeks

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the wrist and hand of

patients who have had a

stroke

number of injection

sites per hand/wrist

is tailored to

individual needs up

to a maximum of 240

Units

number of injection

sites is tailored to

individual needs up to

a maximum of 240

Units

Persistent muscle spasms in

the ankle and foot of patients

who have had a stroke

Your doctor 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

1.25-2.5 Units per

injection site.

Up to 25 Units per

eye for eye spasms.

Up to 100 Units for

spasms of the eye.

3 months for

spasms of the eye.

Persistent muscle spasms of

the neck and shoulders

200 Units

No more than

50 Units should be

given at any one site

Up to 300 Units

10 weeks

Headache in adults who have

chronic migraine

155 to 195 Units

No more than 5 Units

should be given at

any one site

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

* The doctor 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.

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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.

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.

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Injections in the legs of children with cerebral palsy

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.

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).

Injections in the neck and shoulder

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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.

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;

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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;

strabismus (crossed-eyes);

blurred vision;

difficulties in seeing clearly;

decreased hearing;

noises in the ear;

feeling of dizziness or “spinning” (vertigo);

heart problems including heart attack;

aspiration pneumonia (lung inflammation caused by accidentally breathing in food, drink, saliva

or vomit);

breathing problems, respiratory depression and/or respiratory failure;

abdominal pain;

diarrhoea, constipation;

dry mouth;

difficulty swallowing;

nausea, vomiting;

hair loss;

itching;

different types of red blotchy skin rashes;

excessive sweating;

loss of eyelashes/eyebrows;

muscles pain, loss of nerve supply to/shrinkage of injected muscle;

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. This includes any possible side effects not listed in this

leaflet.

You can also report side effects directly via:

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

Health Products Regulatory Authority

13 July 2020

CRN009FKR

Page 1 of 29

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

BOTOX50 Allergan Units Powder for solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Botulinum toxin

type A, 50 Allergan Units/vial.

from Clostridium botulinum

Botulinum toxin units are not interchangeable from one product to another.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for solution for injection.

White powder.

BOTOX product appears as a thin white deposit that may be difficult to see on the base of the vial.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

BOTOX is indicated for the management of:

Neurologic disorders:

-Focal spasticity

associated with dynamic equinus foot deformity due to spasticity in ambulant

paediatric cerebral palsy

patients, two years of age or older.

-Focal spasticity of the wrist and hand in adult post stroke patients.

-Focal spasticity of the ankle and foot in adult post stroke patients (see section 4.4).

-Blepharospasm, hemifacial spasm and associated focal dystonias.

-Cervical dystonia (spasmodic torticollis).

-Symptom relief in adults fulfilling criteria for

chronic migraine

(headaches on ≥15 days per month of which at least 8 days

with migraine) in patients who have responded inadequately or are intolerant of prophylactic migraine medications (see

section 4.4).

Bladder disorders:

-Idiopathic overactive bladder

with symptoms of urinary incontinence, urgency and frequency in adult patients who have an

inadequate response to, or are intolerant of, anticholinergic medication.

-Urinary incontinence in adults with

neurogenic detrusor overactivity

resulting from neurogenic bladder due to stable

sub-cervical spinal cord injury, or multiple sclerosis.

Skin and skin appendage disorder:

-Persistent severe primary hyperhidrosis of the axillae, which interferes with the activities of daily living and is resistant to

topical treatment.

4.2 Posology and method of administration

Posology

Health Products Regulatory Authority

13 July 2020

CRN009FKR

Page 2 of 29

Botulinum toxin units are not interchangeable from one product to another. Doses recommended in Allergan Units are

different from other botulinum toxin preparations.

Chronic migraine should be diagnosed by, and BOTOX should be exclusively administered under the supervision of

neurologists who are experts in the treatment of chronic migraine.

Elderly patients

No specific dose adjustment is required for use in the elderly. Initial dosing should begin at the lowest recommended dose for

the specific indication. For repeat injections the lowest effective dose with the longest clinically indicated interval between

injections is recommended. Elderly patients with significant medical history and concomitant medications should be treated

with caution. See sections 4.4, 4.8 and 5.1 for further information.

Paediatric population

The safety and efficacy of BOTOX in the treatment of individual indications have not been established in children and

adolescents under the ages listed in the table below. No data are available.

· Blepharospasm/Hemifacial spasm

· Cervical dystonia

· Focal spasticity associated with paediatric cerebral palsy

· Upper and lower limb spasticity associated with stroke

· Chronic migraine (CM)

· Overactive Bladder (OAB) and Neurogenic Detrusor Overactivity (NDO)

· Primary hyperhidrosis of the axillae

12 years

12 years

2 years

18 years

18 years

18 years

12 years

(limited experience in adolescents between 12 and 17 years)

The following information is important:

If different vial sizes of BOTOX are being used as part of one injection procedure, care should be taken to use the

correct amount of diluent when reconstituting a particular number of units per 0.1 ml. The amount of diluent varies

between BOTOX 50 Allergan Units, BOTOX 100 Allergan Units and BOTOX 200 Allergan Units. Each syringe should be

labelled accordingly.

BOTOX must only be reconstituted with sterile unpreserved normal saline (0.9% sodium chloride for injection). The appropriate

amount of diluent (see dilution table below) should be drawn up into a syringe.

This product is for single use only and any unused solution should be discarded.

For instructions on use, handling and disposal of vials please refer to section 6.6.

Dilution table for BOTOX50, 100and 200 Allergan Units vial size for all indications except bladder disorders:

Resulting dose

(Units per 0.1 ml)

20 Units

10 Units

5 Units

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2.5 Units

1.25 Units

50 Unit vial

100 Unit vial

200 Unit vial

Amount of diluent (sterile unpreserved

normal saline (0.9% sodium chloride

for injection) added in a 50 Unit vial

Amount of diluent (sterile unpreserved

normal saline (0.9% sodium chloride for

injection) added in a 100 Unit vial

Amount of diluent (sterile unpreserved

normal saline (0.9% sodium chloride for

injection)) added in a 200 Unit vial

0.25 ml

0.5 ml

1 ml

0.5 ml

1 ml

2 ml

1 ml

2 ml

4 ml

2 ml

4 ml

8 ml

4 ml

8 ml

Overactive bladder:

It is recommended that a 100 Unit or two 50 Unit vials are used for convenience of reconstitution.

Dilution instructions using two 50 Unit vials:

Reconstitute two 50 Unit vials of BOTOX each with 5 ml of sterile unpreserved normal saline (0.9% sodium

chloride for injection) and mix the vials gently.

Draw the 5 ml from each of the vials into a single 10 ml syringe.

This will result in a 10 ml syringe containing a total of 100 Units of reconstituted BOTOX. Use immediately after

reconstitution in the syringe. Dispose of any unused saline.

Dilution instructions using a 100 Unit vial:

Reconstitute a 100 Unit vial of BOTOX with 10 ml of sterile unpreserved normal saline (0.9% sodium chloride for

injection) and mix gently.

Draw the 10 ml from the vial into a 10 ml syringe.

This will result in a 10 ml syringe containing a total of 100 Units of reconstituted BOTOX. Use immediately after reconstitution

in the syringe. Dispose of any unused saline.

Dilution instructions using a 200 Unit vial:

Reconstitute a 200 Unit vial of BOTOX with 8 ml of sterile unpreserved normal saline (0.9% sodium chloride for

injection) and mix gently.

Draw 4 ml from the vial into a 10 ml syringe.

Complete the reconstitution by adding 6 ml of sterile unpreserved normal saline (0.9% sodium chloride for

injection) into the 10 ml syringe and mix gently.

This will result in a 10 ml syringe containing a total of 100 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 reconstituted product should be disposed of.

Urinary incontinence due to neurogenic detrusor overactivity:

It is recommended that a 200 Unit vial or two 100 Unit vials are used for convenience of reconstitution.

Dilution instructions using four 50 Unit vials:

Reconstitute four 50 Unit vials of BOTOX, each with 3 ml of sterile unpreserved normal saline (0.9% sodium

chloride 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.

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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 sterile unpreserved normal saline (0.9% sodium chloride 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.

Dilution instructions using two 100 Unit vials:

Reconstitute two 100 Unit vials of BOTOX, each with 6 ml of sterile unpreserved normal saline (0.9% sodium

chloride 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 sterile unpreserved normal saline (0.9% sodium chloride 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.

Dilution instructions using a 200 Unit vial:

Reconstitute a 200 Unit vial of BOTOX with 6 ml of sterile unpreserved normal saline (0.9% sodium chloride for

injection) and mix the vial gently.

Draw 2 ml from the vial into each of three 10 ml syringes.

Complete the reconstitution by adding 8 ml of sterile unpreserved normal saline (0.9% sodium chloride 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.

Method of Administration

Refer to specific guidance for each indication described below.

BOTOX should only be given by physicians with appropriate qualifications, and expertise in the treatment and the use of the

required equipment.

Generally valid optimum dose levels and number of injection sites per muscle have not been established for all indications. In

these cases, individual treatment regimens should therefore be drawn up by the physician. Optimum dose levels should be

determined by titration but the recommended maximum dose should not be exceeded.

NEUROLOGIC DISORDERS:

Focal spasticity associated with paediatric cerebral palsy

Recommended needle: Sterile 23-26 gauge/0.60–0.45 mm needle

Administration guidance: To be

administered as a divided dose through single injections into the medial and lateral heads of

the affected gastrocnemius muscle.

Recommended dose:

Hemiplegia: The initial recommended dose is 4 Units/kg body weight in the affected limb.

Diplegia: The initial recommended dose is 6 Units/kg body weight divided between the affected limbs.

Maximum total dose: 200 Units.

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Additional information:

Clinical improvement generally occurs within the first two weeks after injection. Repeat doses should

be administered when the clinical effect of a previous injection diminishes but not more frequently than every three months. It

may be possible to adapt the dosage regimen to obtain an interval of at least six months between treatment sessions.

Focal upper limb spasticity associated with stroke

Recommended needle:

Sterile 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and

depth.

Administration guidance:

Localisation of the involved muscles with electromyographic guidance or nerve stimulation

techniques may be useful. Multiple injection sites may allow BOTOX to have more uniform contact with the innervation areas

of the muscle and are especially useful in larger muscles.

Recommended dose:

The exact dosage and number of injection sites should be tailored to the individual based on the size,

number and location of muscles involved, the severity of spasticity, presence of local muscle weakness, and the patient

response to previous treatment.

In controlled clinical trials the following doses were administered:

Muscle

Flexor digitorum profundus

Flexor digitorum sublimis

Flexor carpi radialis

Flexor carpi ulnaris

Adductor Pollicis

Flexor Pollicis Longus

Total Dosage; Number of Sites

15 – 50 Units; 1-2 sites

15 – 50 Units; 1-2 sites

15 – 60 Units; 1-2 sites

10 – 50 Units; 1-2 sites

20 Units; 1-2 sites

20 Units; 1-2 sites

Maximum total dose:

In controlled and open non-controlled clinical trials doses between 200 and 240 Units divided among

selected muscles have been used at a given treatment session. Re-injections should not occur before 12 weeks.

Additional information:

In controlled clinical trials patients were followed for 12 weeks after single treatment. Improvement

in muscle tone occurred within two weeks with the peak effect generally seen within four to six weeks.

In an open,

non-controlled continuation study, most of the patients were re-injected after an interval of 12 to 16 weeks, when the effect on

muscle tone had diminished.

These patients received up to four injections with a maximal cumulative dose of 960 Units over 54

weeks. If it is deemed appropriate by the treating physician, repeat doses may be administered, when the effect of a previous

injection has diminished.

The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in

the dose of BOTOX and muscles to be injected. The lowest effective dose should be used.

Focal lower limb spasticity associated with stroke

Recommended needle:

Sterile 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and

depth.

Administration guidance:

Localisation of the involved muscles with electromyographic guidance or nerve stimulation

techniques may be useful. Multiple injection sites may allow BOTOX to have more uniform contact with the innervation areas

of the muscle and are especially useful in larger muscles.

The following diagram indicates the injection sites for adult lower limb spasticity:

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Recommended dose: The recommended dose for treating adult lower limb spasticity involving the ankle is 300 Units divided

among 3 muscles.

BOTOX Dosing by Muscle for Adult Lower Limb Spasticity:

Muscle

Gastrocnemius

Medial head

Lateral head

Soleus

Tibialis Posterior

Recommended Dose

Total Dosage; Number of Sites

75 Units; 3 sites

75 Units; 3 sites

75 Units; 3 sites

75 Units; 3 sites

Additional information: If it is deemed appropriate by the treating physician, the patient should be considered for

re-injection when the clinical effect of the previous injection has diminished, but generally no sooner than 12 weeks after the

previous injection.

Blepharospasm/hemifacial spasm

Recommended needle: Sterile, 27-30 gauge/0.40–0.30 mm needle.

Administration guidance: Electromyographic guidance is not necessary.

Recommended dose: The initial recommended dose is 1.25-2.5 Units injected into the medial and lateral orbicularis oculi of

the upper lid and the lateral orbicularis oculi of the lower lid. Additional sites in the brow area, the lateral orbicularis and in the

upper facial area may also be injected if spasms here interfere with vision.

Maximum total dose: The initial dose should not exceed 25 Units per eye. In the management of blepharospasm total

dosing should not exceed 100 Units every 12 weeks.

Additional information: Avoiding injection near levator palpebrae superioris may reduce the complication of ptosis. Avoiding

medial lower lid injections, and thereby reducing diffusion into the inferior oblique, may reduce the complication of diplopia.

The following diagrams indicate the possible injection sites:

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In general, the initial effect of the injections is seen within three days and reaches a peak at one to two weeks post-treatment.

Each treatment lasts approximately three months, following which the procedure can be repeated as needed. At repeat

treatment sessions, the dose may be increased up to two-fold if the response from the initial treatment is considered

insufficient. However, there appears to be little benefit obtainable from injecting more than 5 Units per site. Normally no

additional benefit is conferred by treating more frequently than every three months.

Patients with hemifacial spasm or VIIth nerve disorders should be treated as for unilateral blepharospasm, with other affected

facial muscles (e.g. zygomaticus major, orbicularis oris) being injected as needed

Cervical dystonia

Recommended needle: Appropriately sized needle (usually 25-30 gauge/0.50–0.30 mm).

Administration guidance: In clinical trials the treatment of cervical dystonia has typically included injection of BOTOXinto the

sternocleidomastoid, levator scapulae, scalene, splenius capitis, semispinalis, longissimus and/or the trapezius muscle(s). This

list is not exhaustive as any of the muscles responsible for controlling head position may be involved and therefore require

treatment.

The muscle mass and the degree of hypertrophy or atrophy are factors to be taken into consideration when selecting the

appropriate dose. Muscle activation patterns can change spontaneously in cervical dystonia without a change in the clinical

presentation of dystonia.

In case of any difficulty in isolating the individual muscles, injections should be made under electromyographic assistance.

Recommended dose:No more than 200 Units total should be injected for the first course of therapy, with adjustments made

in subsequent courses dependent on the initial response.

In initial controlled clinical trials to establish safety and efficacy for cervical dystonia, doses of reconstituted BOTOX ranged

from 140 to 280 Units. In more recent studies, the doses have ranged from 95 to 360 Units (with an approximate mean of

240 Units). As with any drug treatment, initial dosing in a naïve patient should begin at the lowest effective dose. No more

than 50 Units should be given at any one site. No more than 100 Units should be given to the sternomastoid. To minimise the

incidence of dysphagia, the sternomastoid should not be injected bilaterally.

Maximum total dose: A total dose of 300 Units at any one sitting should not be exceeded. The optimal number of injection

sites is dependent upon the size of the muscle. Treatment intervals of less than 10 weeks are not recommended.

Additional information: Clinical improvement generally occurs within the first two weeks after injection. The maximum

clinical benefit generally occurs approximately six weeks post-injection. The duration of beneficial effect reported in clinical

trials showed substantial variation (from 2 to 33 weeks) with a typical duration of approximately 12 weeks.

Chronic Migraine

Recommended needle: Sterile 30-gauge, 0.5 inch needle

Administration guidance:

Injections should be divided across 7 specific head/neck muscle areas as specified in the table below. A 1‑inch needle may be

needed in the neck region for patients with extremely thick neck muscles. With the exception of the procerus muscle, which

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should be injected at 1 site (midline), all muscles should be injected bilaterally with half the number of injections sites

administered to the left, and half to the right side of the head and neck. If there is a predominant pain location(s), additional

injections to one or both sides may be administered in up to 3 specific muscle groups (occipitalis, temporalis, and trapezius),

up to the maximum dose per muscle as indicated in the table below.

The following diagrams indicate the injection sites:

The following diagrams indicate recommended muscle groups for optional additional injections.

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Recommended dose: 155 Units to 195 Units administered intramuscularly as 0.1 ml (5 Units) injections to 31 and up to 39

sites.

BOTOX Dosing By Muscle for Chronic Migraine:

Head/Neck Area

Corrugator

Procerus

Frontalis

Temporalis

Occipitalis

Cervical Paraspinal Muscle Group

Trapezius

Total Dose Range:

Recommended Dose

Total Dosage (number of sites

a

)

10 Units (2 sites)

5 Units (1 site)

20 Units (4 sites)

40 Units (8 sites) up to 50 Units (up to 10 sites)

30 Units (6 sites) up to 40 Units (up to 8 sites)

20 Units (4 sites)

30 Units (6 sites) up to 50 Units (up to 10 sites)

155 Units to 195 Units

31 to 39 sites

1 IM injection site = 0.1 ml = 5 Units BOTOX

Dose distributed bilaterally

Additional information: The recommended retreatment schedule is every 12 weeks.

BLADDER DISORDERS:

Patients should not have a urinary tract infection at the time of treatment.

Prophylactic antibiotics should be administered 1-3 days pre-treatment, on the treatment day, and 1-3 days post-treatment.

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It is recommended that patients discontinue anti-platelet therapy at least 3 days before the injection procedure. Patients on

anti-coagulant therapy need to be managed appropriately to decrease the risk of bleeding.

For the management of urinary incontinence, BOTOX should be administered by physicians who are experienced in the

assessment and treatment of bladder dysfunction (eg, urologists and urogynaecologists).

Overactive bladder

Recommended needle: A flexible or rigid cystoscope can be used. The injection needle should be filled (primed) with

approximately 1 ml of the reconstituted BOTOX prior to the start of the injections (depending on the needle length) to remove

any air.

Administration guidance: Prior to injection an intravesical instillation of diluted local anaesthetic, with or without sedation,

may be used, per local site practice. If a local anaesthetic instillation is performed, the bladder should be drained and irrigated

with sterile saline before the next steps of the procedure.

Reconstituted BOTOX (100 Units/10 ml) is injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the

trigone and base. The bladder should be instilled with enough saline to achieve adequate visualisation for the injections, but

over-distension should be avoided.

The needle should be inserted approximately 2 mm into the detrusor, and 20 injections of 0.5 ml each (total volume 10 ml)

should be spaced approximately 1 cm apart (see figure below). For the final injection, approximately 1 ml of sterile normal

saline should be injected so the full dose is delivered. After the injections are given, the saline used for bladder wall

visualisation should not be drained so that patients can demonstrate their ability to void prior to leaving the clinic. The patient

should be observed for at least 30 minutes post-injection and until a spontaneous void has occurred.

Recommended dose:The recommended dose is 100 Units of BOTOX, as 0.5 ml (5 Units) injections across 20 sites in the

detrusor.

Additional information: Clinical improvement may occur within 2 weeks. Patients should be considered for reinjection when

the clinical effect of the previous injection has diminished (median duration in phase 3 clinical studies was 166 days [~24

weeks], based on patient request for re-treatment), but no sooner than 3 months from the prior bladder injection.

Urinary incontinence due to neurogenic detrusor overactivity

Recommended needle: A flexible or rigid cystoscope can be used. The injection needle should be filled (primed) with

approximately 1 ml prior to the start of the injections (depending on the needle length) to remove any air.

Administration guidance: Prior to injection, either an intravesical instillation of diluted anaesthetic (with or without sedation)

or general anaesthesia may be used, per local site practice. If a local anaesthetic instillation is performed, the bladder should be

drained and rinsed with sterile saline before the next steps of the injection procedure.

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