Botox

Package leaflet: Information for the patient

BOTOX, 100 Allergan units, powder for solution for injection
BOTOX, 200 Allergan units, powder for solution for injection
botulinum toxin type A
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Botox is and what it is used for
2. Important information before using Botox
3. How to use Botox
4. Possible side effects
5. How to store Botox
6. Contents of the pack and other information

1. What Botox is and what it is used for

Botox belongs to a group of muscle-relaxing medicines and is used in the treatment of many conditions.
It contains the active substance botulinum toxin type A and is injected into muscles, the bladder wall, or deep into the skin.
The action of Botox is based on blocking nerve impulses to the muscles into which it has been injected. This prevents excessive contractions of these muscles. When injected intradermally, Botox acts on sweat glands, reducing the amount of sweat produced. When injected into the bladder wall, Botox affects the bladder muscles, reducing urine leakage (urinary incontinence). In chronic migraine, Botox is believed to block pain signals, which indirectly inhibits the development of migraine. However, the mechanism of action of Botox in chronic migraine has not yet been fully elucidated.

1. Botox may be injected into muscles to treat the following conditions:
   • Persistent contractures of the ankle and foot in children with cerebral palsy, aged two years and older, who are able to walk; Botox is used as an adjunct to rehabilitation therapy.
   • Persistent contractures of the wrist and hand in adult patients,
   • Persistent contractures of the ankle and foot in adult patients,
   • Persistent blepharospasm and hemifacial spasm in adult patients,
   • Persistent cervical and shoulder dystonia in adult patients.
2. Botox is used for the prophylaxis of headache in adult patients suffering from chronic migraine (headaches occurring on 15 or more days per month).

Chronic migraine is a neurological disorder characterized by symptoms affecting the nervous system.
Patients typically suffer from headaches, often accompanied by sensitivity to light, noise, or odors, as well as nausea and/or vomiting. Headaches usually occur on more than 15 days per month. Botox has been shown to significantly reduce the frequency of headaches and improve the quality of life in patients with chronic migraine.

3. Botox, when injected into the bladder wall, acts on the detrusor muscle of the bladder, reducing urine leakage (urinary incontinence), and is used in the treatment of the following conditions:
   • Idiopathic overactive bladder with symptoms of urinary incontinence, urgency, or frequency in adult patients when other medications (called anticholinergics) are ineffective.
   • Urinary incontinence in patients with bladder dysfunction due to stable spinal cord injuries below the cervical level and in patients with multiple sclerosis.
4. In adult patients, Botox is injected deep into the skin for the treatment of persistent, severe axillary hyperhidrosis that interferes with daily activities and is unresponsive to topical treatment.
5. Botox is indicated for the temporary improvement in the appearance of the following wrinkles:
   • vertical frown lines between the eyebrows visible at maximum frowning, and/or
   • radiating lateral periorbital lines (crow's feet) visible at full smile, and/or
   • horizontal forehead lines visible at maximum eyebrow elevation,

in adult individuals when their severity has a psychological impact on the patient.

2. Important Information Before Using Botox

When Botox Must Not Be Used

• if the patient is allergic (hypersensitive) to botulinum toxin type A or to any of the other ingredients of this medicine (listed in section 6.)
• if there is an infection at the proposed injection site
• in patients being treated for urinary incontinence who have a urinary tract infection or sudden inability to empty the bladder (and patients are not routinely undergoing catheterization)
• in patients being treated for urinary incontinence who do not wish to start using a catheter (if this were necessary).

Warnings and Precautions
Before starting treatment with Botox, discuss the following with your doctor:

• if the patient has ever experienced swallowing difficulties or accidental aspiration of food or liquid into the lungs, particularly if injections into neck and shoulder muscles are planned for the treatment of chronic neck dystonia,
• if the patient is over 65 years of age and has other serious illnesses,
• if the patient has other muscle-related problems or chronic muscle diseases (e.g. myasthenia gravis or Lambert-Eaton syndrome),
• if the patient has certain neurological disorders (e.g. amyotrophic lateral sclerosis, motor neuropathy),
• if there is significant weakness or atrophy of the muscles selected for injection,
• if the patient has undergone any surgical procedures or injuries that may have altered the muscle to be injected,
• if the patient has ever experienced problems related to injections (e.g. fainting),
• if there is inflammation of the muscles or skin at the proposed injection site,
• if the patient has a cardiovascular disease (heart or blood vessel disease),
• if the patient has had or currently has seizures,
• if the patient has an eye condition called angle-closure glaucoma (high pressure in the eye) or is at risk of developing this type of glaucoma,
• if the patient has had head, neck, leg, or chest trauma or surgery,
• if any surgical procedure is planned in the near future,
• if the patient previously experienced an allergic reaction (hives, swelling, including of the face and/or throat, wheezing, fainting, or shortness of breath) after receiving botulinum toxin type A,
• if treatment for overactive bladder with urinary incontinence is planned, in men with objective or subjective symptoms of urinary obstruction, such as difficulty urinating, weak or interrupted urinary stream.

After Receiving Botox
Contact your doctor immediately or go to the nearest hospital if, after receiving Botox injection, the patient or caregiver observes any of the following symptoms:

• difficulty breathing, swallowing, or speaking,
• hives, swelling (including of the face and/or throat), wheezing, fainting, or shortness of breath (possible signs of a severe allergic reaction).

General Warnings
As with any injection, the procedure may cause infection, pain, swelling, abnormal skin sensations (e.g. tingling or numbness), reduced skin sensitivity, tenderness to pressure, bleeding/bruising at the injection site, and low blood pressure or fainting, which may result from pain and/or anxiety related to the injection.
Following administration of botulinum toxin, adverse effects possibly related to the spread of the toxin to sites distant from the injection site (e.g. muscle weakness, difficulty swallowing, or aspiration of food or liquid into the airways) have been reported. These adverse effects can range from mild to severe, may require medical treatment, and in some cases may be fatal. This risk is particularly significant in patients with underlying conditions that make them more susceptible to such symptoms.
The patient's response to Botox may depend greatly on the treatment regimen used, frequency of injections, the type of muscles and skin areas selected for injection, and minor variations in the potency of Botox resulting from the method used to determine the dose in each vial.
If Botox is administered too frequently or at too high a dose, the patient may experience muscle weakness and symptoms related to the spread of the toxin to distant sites. Additionally, the body may produce antibodies that could reduce the effectiveness of Botox.
Using Botox for indications not listed in this leaflet may lead to serious adverse effects, especially in patients who already have difficulty swallowing or significant muscle weakness.
If the patient has led a relatively sedentary lifestyle prior to Botox treatment, physical activity should be increased gradually after treatment.
It is unlikely that Botox will improve joint mobility in cases where the muscles surrounding the joint have lost their ability to stretch.
During treatment for blepharospasm (eyelid spasms), blink frequency may decrease, which could lead to eye surface damage. To prevent this, the doctor may recommend using eye drops, ointments, soft contact lenses, or special eye shields. The doctor will inform the patient if this is necessary.
If Botox is used to treat urinary incontinence, the doctor will prescribe antibiotics before and after treatment to prevent urinary tract infections.
The patient should schedule a follow-up visit approximately 2 weeks after injection if they were not previously using a catheter. The doctor will ask the patient to urinate and then use ultrasound to measure the volume of urine remaining in the bladder. The doctor will decide whether another visit for the same test is needed within the following 12 weeks. The patient must contact the doctor immediately if they are unable to urinate, as catheterization may be required. In patients with urinary incontinence due to bladder problems caused by spinal cord injury or multiple sclerosis, about 1 in 3 patients who did not previously use a catheter may require one. After treatment for overactive bladder-related incontinence, about 6 in 100 patients who did not previously use a catheter may require one.
If Botox is used to treat glabellar lines (vertical frown lines), "crow's feet" lines, and/or horizontal forehead lines, drooping of the eyelids may occur after injection. The patient should inform the doctor if no significant improvement is observed one month after the first Botox injection for these conditions.
Botox should not be used to treat focal spasticity of the ankle joint in adult patients unless a reduction in muscle tone is expected to improve function (e.g. walking), subjective symptoms (e.g. reduced pain), or ease patient care. If Botox treatment is initiated in patients with milder ankle spasticity, functional improvement may be limited.
Botox for the treatment of spasticity of the ankle and foot may only be administered after assessment by a specialist physician experienced in patient rehabilitation.

Botox and Other Medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, including those obtained without a prescription, as well as any medicines the patient plans to take.
Inform your doctor or pharmacist if:

• the patient is taking any antibiotics (used to treat infections), cholinesterase inhibitors, or muscle relaxants, as these may enhance the effects of Botox,
• other medicines containing botulinum toxin are currently being used or have been used recently, as these may enhance the effects of Botox,
• the patient is taking any antiplatelet drugs (medicines with effects similar to aspirin) and/or anticoagulants (blood thinners). Consult your doctor, even if the above warnings refer to past situations.

Pregnancy, Breastfeeding, and Fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Botox should not be used in pregnant women or in women of childbearing age who are not using effective contraception, unless clearly necessary.
Use of Botox during breastfeeding is not recommended.

Driving and Operating Machinery
The effect of Botox on the ability to drive and operate machinery can only be assessed after administration to the individual patient.
Botox may cause dizziness, drowsiness, fatigue, or vision problems. If any of these symptoms occur, the patient should not drive or operate machinery. In case of doubt, consult a doctor.

Botox Contains Sodium
This medicinal product contains less than 1 mmol of sodium (23 mg) per vial, meaning the medicine is considered "sodium-free."

3. How to use Botox

Botox must only be administered by physicians with appropriate experience and qualifications.
Dosage and method of administration
Botox is injected into muscles (i.e. intramuscularly), into the wall of the urinary bladder via a special device (cystoscope) used for intravesical injections, or into the skin (intradermally).
The medicine is injected directly into the affected area of the body; the physician usually injects Botox
into several sites within each affected area.
General dosage recommendations

• The number of injections per muscle and the dose size depend on the indication. The physician will decide on the appropriate dose, frequency, and the muscle to be treated. It is recommended to use the lowest effective dose.
• Doses for elderly patients are the same as for other adult patients.

The dose of Botox and its duration of effect vary depending on the therapeutic indication for which the medicine is administered. Detailed recommendations for individual indications are described below.
The safety and efficacy of Botox have been established in children and adolescents above two years of age for the treatment of persistent muscle spasms of the ankle and foot associated with cerebral palsy.
Limited data are available on the use of Botox in the following indications in children/adolescents above the age specified in the table below. Dosage recommendations cannot be provided for these indications.

There is limited experience with the use of Botox in the treatment of glabellar lines and (or) crow's feet and (or) horizontal forehead lines in patients over 65 years of age.
The total dose for the treatment of horizontal forehead lines (20 units) together with vertical glabellar lines (20 units) is 40 units.
Dosing
The dosage of Botox and its duration of effect vary depending on the indication for which the drug has been administered. Detailed recommendations for individual indications are described below.

* The physician may adjust the dose so that the intervals between administrations average 6 months.
** In the case of simultaneous treatment of glabellar lines and lateral periorbital lines,
the total administered dose is 44 units.
*** When treating all three types of wrinkles simultaneously (lateral periorbital lines—“crow’s feet”
fan-shaped lines radiating from the corners of the eyes visible during maximum smile, vertical
glabellar lines visible during maximum frowning, and horizontal forehead lines visible during
maximum eyebrow elevation), the patient receives a total dose of 64 units.

Time to onset of effect and duration of action.
In the treatment of persistent muscle contractures of the ankle and foot in children aged two years and older,
improvement usually occurs within 2 weeks after injection.

In the treatment of persistent contractures of the wrist and hand in adult patients, improvement usually
occurs within 2 weeks after injection, with maximum effect typically observed approximately 4–6 weeks
after treatment.

In the treatment of persistent contractures of the ankle and foot in adult patients, when the effect of the
medicinal product begins to diminish, the product may be re-administered if necessary, but no more
frequently than every 12 weeks.

In the treatment of persistent eyelid and facial muscle spasms, improvement usually occurs within
3 days after injection, with maximum effect typically observed after 1–2 weeks.

In the treatment of persistent cervical and shoulder dystonia, improvement usually occurs within
2 weeks after injection, with maximum effect typically observed 6 weeks after treatment.

In the treatment of urinary incontinence due to overactive bladder, improvement usually occurs
within 2 weeks after injection, and the effect lasts approximately 6 to 7 months after injection.

In the treatment of urinary incontinence in patients with spinal cord injury or multiple sclerosis,
improvement usually occurs within 2 weeks after injection, and the effect lasts approximately 8 to
9 months after injection.

In the treatment of axillary hyperhidrosis, improvement usually occurs within 1 week after
injection, and the effect lasts on average up to 7.5 months after the first injection, with approximately
1 in 4 patients still experiencing the effect of the medicinal product up to 1 year after injection.

In the treatment of glabellar lines, improvement usually occurs within 1 week after injection, with
maximum effect visible 5–6 weeks after administration. The effect lasts up to 4 months after injection.

In the treatment of lateral periorbital lines, improvement usually occurs within 1 week after injection,
with maximum effect visible 3–4 days after administration. The effect lasts up to 5 months after injection.

In the treatment of horizontal forehead lines visible during maximum eyebrow elevation,
improvement usually occurs within 1 week after treatment. The therapeutic effect lasts on average
up to 4 months after injection.

Administration of a higher than recommended dose of Botox
Signs of overdose may not be apparent for several days after injection. If Botox is accidentally injected
or swallowed, the patient should contact a physician and remain under observation for several weeks.

If a patient has received an excessive dose of Botox, the following symptoms may occur and the patient
should contact a physician immediately. The physician will decide whether hospitalization is required:
weakness of muscles adjacent to or distant from the injection site,

• breathing, swallowing, or speech difficulties due to muscle paralysis,
• accidental aspiration of food or fluids into the lungs due to paralysis of muscles, which may lead to pneumonia,
• ptosis (drooping eyelids), double vision,
• generalized muscle weakness.

In case of any further doubts, contact a physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
Adverse reactions usually occur within the first few days after injection and are
transient. In individual cases, adverse reactions may persist for several months
or longer. The expected pharmacological effect of Botox is local weakening of
muscles. However, high doses may cause weakening of other muscles, not necessarily
directly near the injection site.
You should immediately inform your doctor if:

• after administration of Botox, you experience difficulty breathing, swallowing or speaking
• you develop hives, swelling (including swelling of the face or throat), wheezing, a feeling of fainting, or shortness of breath.

As with any injection, pain and bruising may occur at the injection site.
Following botulinum toxin injections, fever and influenza-like symptoms have also been observed.
You should inform your doctor if any of the above-mentioned symptoms occur.
Adverse reactions are listed below according to the following categories, depending on their frequency of occurrence:

Below are the adverse reactions, which vary depending on the part of the body into which the Botox medicine is injected. If any of the adverse reactions worsen or if you experience any adverse reactions not listed in this leaflet, inform your doctor or pharmacist.
Injections in the lower limb in children with persistent muscle spasms of the ankle joint and foot

Rare cases of death have been reported following administration of botulinum toxin, in some cases associated with aspiration pneumonia in children with coexisting severe cerebral palsy.

Injections into the forearm and hand in adult patients

Injections into the ankle joint and foot in adult patients

Injections in the eyelid and face

The physician may apply gentle pressure immediately after injection to avoid
mild bruising of the eyelid tissues.
Injections in the neck and shoulders

Swallowing difficulties may range from mild to severe, with a risk of choking, and may require
treatment. Such adverse reactions may last from two to three weeks after injection.
Cases of persistence of the aforementioned adverse reactions for up to five months after injection have also been reported.
Rare cases of deaths caused by swallowing difficulties have been reported.
Injections into head and neck muscles for the prevention of headaches in patients
with chronic migraine

Injections into the bladder wall for patients with urinary incontinence due to
idiopathic overactive bladder

• Adverse reaction may be related to the injection procedure.
  ** Adverse reaction is related solely to the injection procedure.
  Bladder wall injections in children and adolescents with urinary incontinence due to overactive bladder

• The adverse reaction is related solely to the injection procedure.
  Injections into the bladder wall in adult patients with urinary incontinence due to neurogenic detrusor overactivity

* Some of the described common adverse reactions may be related to the injection procedure.
Intravesical injections in children and adolescents with urinary incontinence due to spinal cord injury or multiple sclerosis

• The adverse reaction is related solely to the injection procedure.
  Injections for primary axillary hyperhidrosis

Use for temporary improvement in the appearance of vertical frown lines between the eyebrows

Injections intended for temporary improvement in the appearance of "crow's feet" wrinkles
(lines radiating like a fan from the corners of the eyes), when treated either
simultaneously or without forehead glabellar lines (vertical lines between the eyebrows)
visible when frowning)

*Adverse events may be related to the injection procedure
Injection for temporary improvement of the appearance of horizontal forehead lines, visible
during maximum eyebrow elevation, and vertical glabellar lines visible when frowning, with
concomitant treatment of crow’s feet lines radiating from the outer corners of the eyes or without
such treatment.

The median time to onset of eyelid ptosis was 9 days after the end of treatment.
The median time to onset of eyebrow ptosis was 5 days after the end of treatment.
*Adverse reactions may be related to the injection procedure.

Additional information
Since the introduction of Botox onto the market, the following additional adverse reactions have been reported:

• Allergic reactions, including reactions to injected proteins or serum
• Swelling of deeper layers of skin
• Urticaria, pruritus
• Nutritional disorders, loss of appetite
• Nerve damage (brachial plexopathy)
• Speech disorders, difficulty speaking
• Facial muscle weakness, facial muscle ptosis on one side of the face
• Decreased skin sensation
• Muscle weakness
• Chronic muscle diseases (myasthenia gravis)
• Difficulty moving arm and shoulder
• Numbness
• Pain/numbness and/or weakness starting from the spine
• Seizures, fainting
• Increased intraocular pressure
• Strabismus
• Blurred vision
• Difficulty seeing clearly
• Hearing impairment, tinnitus
• Sensation of dizziness or "spinning" (vertigo)
• Cardiac disorders, including myocardial infarction
• Aspiration pneumonia (pneumonia caused by accidental inhalation of food, liquid, saliva, or vomit into the lungs)
• Breathing problems, respiratory depression and/or respiratory failure
• Abdominal pain, nausea, vomiting
• Diarrhea, constipation
• Dry mouth
• Difficulty swallowing
• Hair loss
• Various types of skin rash presenting as red spots on the skin
• Excessive sweating
• Loss of eyelashes/eyebrows
• Muscle pain, denervation, and muscle atrophy
• General malaise
• Fever
• Dry eye (associated with injections around the eye area)
• Local muscle twitching/involuntary muscle contractions
• Eyelid swelling

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warszawa
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicinal product.

5. How to store Botox

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C - 8°C) or in a freezer (-5°C to -20°C).
Use immediately after reconstitution.
The solution remains stable for up to 24 hours when stored in a refrigerator (2°C - 8°C).
Do not use this medicine after the expiry date stated on the label and carton after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Botox contains:

• The active substance is a complex of Clostridium botulinum type A neurotoxin (900 kD). One vial contains either 100 or 200 Allergan units of botulinum toxin type A.
• The other ingredients are: human serum albumin, sodium chloride.

What Botox looks like and contents of the pack:
Botox is a fine white powder, which may be almost invisible at the bottom of the vial made of colourless glass. Before injection, the medicine must be reconstituted with sterile 0.9% sodium chloride injection solution.
The pack contains one vial in a cardboard carton.

Marketing Authorisation Holder
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Telephone number of the marketing authorisation holder: +48 22 3727800

Manufacturer
Allergan Pharmaceuticals Ireland
Castlebar Road
Westport
County Mayo,
Ireland
or
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Other sources of information
To listen to or receive a copy of this leaflet,
please contact the local representative of the marketing authorisation holder.

Information intended exclusively for medical professionals:

Detailed information is provided in the Summary of Product Characteristics
BOTOX.
The botulinum toxin units of the BOTOX medicinal product are not comparable to the botulinum
toxin units of other medicinal products. Doses recommended as Allergan units are not comparable
to doses of other botulinum toxin products.
The BOTOX medicinal product should only be used by physicians with appropriate qualifications
and experience in managing therapy and using the required equipment.
Chronic migraine should be diagnosed by neurologists who are specialists in the treatment of
chronic migraine, and the medicinal product BOTOX should be administered only under their
supervision.
Children and adolescents
The safety and efficacy of the BOTOX medicinal product have not been established for indications
other than those described for the pediatric population in section 4.1 of the Summary of Product Characteristics.
There are no dosing recommendations for indications other than focal spasticity associated with cerebral palsy in children.
Current data regarding indications are presented in sections 4.2, 4.4, 4.8 and 5.1 of the Summary of Product Characteristics, as shown in the table below.

In elderly patients, no specific dose adjustment is required.
Initially, the lowest recommended dose for the given indication should be used. When administering subsequent doses, it is recommended to use the lowest effective dose of the medicinal product, maintaining as long intervals as possible between injections based on clinical indications. Caution should be exercised in elderly patients with atypical medical histories and in those receiving concomitant medications.
Generally, the optimal dose level and the maximum number of injection sites into a single muscle have not been established for all indications. In such cases, the physician should develop individualized dosing regimens. The optimal dose level should be determined through trials using different concentrations of the product, but the recommended maximum dose must not be exceeded. As with any administration of a medicinal product, initial doses in patients receiving the product for the first time should be the lowest effective doses.
Dosage and method of administration (more information can be found in sections 4.2 and 4.4 of the SmPC):
Lower limb focal spasticity in children:
The recommended dose for treatment of lower limb spasticity in children is 4 units/kg to 8 units/kg body weight or 300 units, whichever is lower, divided among the affected muscles. When treating both lower limbs, the total dose should not exceed the lower of 10 units/kg body weight or 340 units within a 12-week interval.

The use of the medicinal product BOTOX in the treatment of focal spasticity has been investigated
only in combination with standard therapy regimens and replacing these procedures is not recommended.
BOTOX is unlikely to be effective in improving the range of joint motion impaired due to fixed contracture.
Focal spasticity of the upper limb in adult patients:

The recommended dose for the treatment of upper limb spasticity in adults is up to 240 units
divided among selected muscles according to the table above. The maximum dose administered
during a single procedure is 240 units.
The exact dosage and number of injection sites should be adjusted individually based on the size, number, and location of affected muscles, severity of spasticity, presence of local muscle weakness, and the patient's response to previous treatment.
Focal lower limb spasticity in adult patients:

The recommended dose for the treatment of lower limb spasticity in adults, involving the ankle joint and foot, is from 300 to 400 units divided among up to a maximum of 6 muscles.
Blepharospasm/hemifacial spasm:

Reduced blink rate following botulinum toxin injection into the orbicularis oculi muscle may lead to pathological changes. Corneal sensitivity of the previously operated eye should be carefully assessed, and injections into the lower eyelid should be avoided to prevent eyelid ectropion. In the event of corneal epithelial defects, intensive treatment is required. Therapy may involve administration of protective eye drops, ointments, therapeutic soft contact lenses, eye closure with a patch, or other procedures.

Cervical dystonia:

This list is not exhaustive, as each of the muscles responsible for controlling head positioning may be affected by the disease process and require treatment.

Chronic migraine:
The recommended dose of reconstituted BOTOX medicinal product for the treatment of chronic migraine is 155 to 195 units, administered intramuscularly (im.) using a 30 gauge, 0.5 inch needle as 0.1 mL (5 units) injections into 31 to 39 sites. Injections should be divided among 7 specified head/neck muscle areas, as indicated in the table below. In patients with very thick neck muscles, a 1-inch needle may be required. Except for the longissimus muscle, into which the medicinal product should be injected at a single site (in the midline of the muscle), all muscles should be injected bilaterally. Half of the injections should be administered into muscles on the left side and the other half into muscles on the right side of the head and neck. If pain is predominant in a specific area(s), additional injections may be performed on one or both sides into up to 3 specified muscle groups (occipital, temporal, and trapezius); the maximum dose indicated in the table below may be injected into each muscle.

1 injection im. = 0.1 mL = 5 units of BOTOX medicinal product
Injected dose bilaterally

Urinary incontinence due to detrusor overactivity:
The recommended dose is 100 units of BOTOX medicinal product, injected as 0.5 mL (5 units) at 20 sites within the detrusor muscle, avoiding the trigone and bladder base.

Urinary incontinence due to neurogenic detrusor overactivity:
The recommended dose is 200 units of BOTOX medicinal product, injected as 1.0 mL (approximately 6.7 units) at 30 sites within the detrusor muscle, avoiding the trigone and bladder base.

Primary axillary hyperhidrosis:

It is recommended to conduct an interview and clinical examination, as well as additional specific tests, to exclude potential secondary causes of hyperhidrosis (e.g. hyperthyroidism, pheochromocytoma). This will help avoid symptomatic treatment of hyperhidrosis without diagnosing and (or) treating the underlying disease.

All indications:

Adverse reactions related to the spread of toxin to sites distant from the injection site have been reported. In some cases, these led to patient death, including cases associated with swallowing difficulties (dysphagia), pneumonia, and (or) severe weakness. These symptoms are consistent with the mechanism of action of botulinum toxin, and their occurrence has been observed from several hours to several weeks after administration. The risk of these adverse events is likely higher in patients with concomitant diseases and disorders that may predispose them to such events, including children and adults treated for spasticity, as well as in patients receiving high doses of the drug.

Excessive muscle weakness may also occur in patients treated with therapeutic doses of the medicinal product BOTOX. Cases of pneumothorax associated with the injection procedure have been observed following administration of the medicinal product BOTOX near the thoracic cavity. Caution should be exercised when injecting near the lungs, especially close to the lung apices.

Severe adverse reactions, including fatal cases, have been observed in patients who received BOTOX injections into the salivary glands, oropharyngeal region, esophagus, or stomach. Some of the reported patients had pre-existing swallowing disorders or severe weakness.

Rare cases of death due to aspiration pneumonia have been reported in children with severe cerebral palsy following off-label use of botulinum toxin (e.g. injections in the neck area). Particular caution should be exercised when treating children and adolescents with significant neurological weakness, swallowing difficulties (dysphagia), or recent history of aspiration pneumonia or other lung diseases.

Treatment of patients in poor general health is possible only if it has been assessed that, for the individual patient, potential benefits outweigh the risks.

In rare cases, anaphylactic reactions may occur after botulinum toxin injection. In such cases, epinephrine (adrenaline) and other anti-anaphylactic medications should be administered.

If therapeutic failure occurs after the first procedure, defined as lack of significant improvement one month after drug administration compared to baseline, the following management strategies should be considered:

• Clinical verification, which may include electromyographic examination, to assess the effect of the toxin on the injected muscle(s).
• Analysis of reasons for failure, which may include inappropriate muscle selection for injection, insufficient drug dose, incorrect injection technique, presence of fixed contracture, weak antagonist muscles, or development of neutralizing antibodies against the toxin.
• Re-evaluation of the indication for treatment with botulinum toxin type A.
• If no adverse reactions occurred, consider repeating treatment, paying attention to the following: a) appropriate dose selection based on analysis of the previous therapeutic failure, b) use of EMG guidance, c) maintaining a three-month interval between subsequent procedures.

If there is no response or inadequate therapeutic effect after the second treatment cycle, alternative management approaches should be considered.

For detailed information, please refer to the Summary of Product Characteristics for BOTOX.

Reconstitution of the medicinal product:

If different vial sizes of the medicinal product BOTOX are used during a single procedure,
care must be taken to use the correct amount of diluent to achieve the appropriate number of units per 0.1 ml. The amount of diluent required for reconstitution of BOTOX 100 units Allergan and BOTOX 200 units Allergan differs according to the respective strengths. Each syringe should be appropriately labeled.

Good practice includes performing vial reconstitution and syringe preparation on plastic-laminated paper towels to prevent accidental spillage.

Reconstitution of BOTOX medicinal product should only be performed by adding sterile 0.9% sodium chloride injection solution without preservatives.

Idiopathic overactive bladder

For this indication, vials containing 100 units of BOTOX are recommended due to easier reconstitution.

This results in a total of 100 units of BOTOX in a 10 ml syringe. Use immediately after reconstitution.
Any unused residue of sodium chloride solution should be discarded.
The product is intended for single use only. Any unused portion of the product should be discarded.
Urinary incontinence due to neurogenic detrusor overactivity
For this indication, vials containing 100 or 200 units of BOTOX are recommended due to easier reconstitution.

Thus, a total of 200 units of BOTOX medicinal product is obtained after reconstitution,
in 3 syringes of 10 ml each. Use immediately after reconstitution. Any unused
sodium chloride solution must be discarded.
Instructions for dilution of BOTOX medicinal product in vials of 100 and 200 units for
all indications, except for the treatment of bladder disorders:

sterile, preservative-free 0.9% sodium chloride solution for injection
The medicinal product BOTOX is intended for single use only; any unused solution remaining after reconstitution must be destroyed.
The medicinal product BOTOX may denature due to bubble formation or vigorous movements during reconstitution of the powder; therefore, the diluent should be slowly injected into the vial.
If, after piercing the stopper, the saline is not drawn into the vial by vacuum, the vial should be discarded.
The reconstituted medicinal product BOTOX is a clear or slightly yellowish solution free from particulate matter. Before administration, the solution should be visually inspected to confirm clarity and absence of particulates. After reconstitution, the product may be stored for up to 24 hours in a refrigerator (2 °C – 8 °C). If further dilution of the medicinal product BOTOX is required for injection into the extensor digitorum muscle, it should be used immediately.

Chemical and physical stability of BOTOX after reconstitution has been demonstrated for up to 5 days at 2 °C – 8 °C. From a microbiological standpoint, immediate use of the reconstituted solution is recommended, and vials containing unused solution should be destroyed. If the product is not used immediately after reconstitution, the medical personnel are responsible for the storage time and conditions, which should not exceed 24 hours at 2 °C – 8 °C, unless reconstitution/dilution (etc.) was performed under controlled and validated aseptic conditions.

Procedure required for safe disposal of vials, syringes, and used materials:
Medicinal products must not be disposed of via wastewater or household waste. For safe disposal, unused vials should be reconstituted by adding a small amount of water and then autoclaved. All used vials, syringes, etc., should also be autoclaved, or the residual medicinal product BOTOX should be inactivated by adding a 0.5% sodium hypochlorite solution for 5 minutes. Ask your pharmacist how to dispose of medicines you no longer need. These measures will help protect the environment.

Medicinal product identification
To confirm receipt of authentic BOTOX medicinal product manufactured and supplied by Allergan, check the security seal consisting of a semi-transparent silver Allergan logo foil located on the top and bottom of the carton, and the presence of a holographic coating on the vial label. The hologram on the vial should be verified by viewing the vial under the light of a desk or fluorescent lamp. Rotate the vial and look for rainbow-colored horizontal lines on the label containing the word "Allergan." (The hologram is not visible in the area printed with the expiration date and batch number.)

Do not use the product and contact your local Allergan office for further information if:

• rainbow-colored horizontal lines with the word "Allergan" are missing from the label
• the security foil is damaged or missing from the top or bottom of the carton
• the semi-transparent silver Allergan logo on the security foil is unclear or displays a black circle crossed by a diagonal line (e.g., a prohibition symbol).

Additionally, the label contains stickers with the product name, expiration date, and batch number. These stickers can be peeled off and affixed to the patient's record for identification purposes.
After removing the sticker from the label, the word "USED" will become visible, further confirming the authenticity of the BOTOX product manufactured and supplied by Allergan.