Botox

Leaflet attached to the packaging: patient information

BOTOX, 100 units of Allergan Clostridium botulinum type A neurotoxin complex

(900kD), powder for solution for injection

BOTOX, 200 units of Allergan Clostridium botulinum type A neurotoxin complex (900kD), powder for solution for injection

Botulinum toxin type A

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Botox and what is it used for
• 2. Important information before using Botox
• 3. How to use Botox
• 4. Possible side effects
• 5. How to store Botox
• 6. Package contents and other information

1. What is Botox and what is it used for

Botox belongs to muscle relaxants and is used to treat many diseases.
It contains the active substance botulinum toxin type A and is injected into muscles, the bladder wall, or skin.
The action of Botox is based on blocking nerve impulses to the muscles into which it has been injected. This counteracts muscle spasms. After subcutaneous injection, Botox acts on sweat glands, reducing the amount of sweat produced. After injection into the bladder wall, Botox acts on the bladder muscles, reducing urine leakage (incontinence). It is believed that in the case of chronic migraine, Botox blocks pain signals, which indirectly inhibit the development of migraine. However, the mechanism of action of Botox in chronic migraine has not been finally explained.

• 1. Botox may be injected into muscles to treat the following conditions:
• in the treatment of persistent muscle spasms of the ankle and foot in childrenwith cerebral palsy, aged two and older, who are able to walk; Botox is used as an adjunct to rehabilitation therapy.
• in the treatment of persistent muscle spasms of the wrist and hand in adult patients,
• in the treatment of persistent muscle spasms of the ankle and foot in adult patients,
• in the treatment of persistent eyelid spasms and hemifacial spasms in adult patients,
• in the treatment of persistent cervical dystonia in adult patients.
• 2. Botox is used for the prophylaxis of headaches in adult patients suffering from chronic migraine(headaches occurring 15 days a month or more).

Chronic migraine is a disease characterized by neurological symptoms.
Patients usually suffer from headache, which is often accompanied by sensitivity to light, noise, or smells, as well as nausea and/or vomiting. Headaches usually occur more than 15 days a month. It has been shown that Botox significantly reduces the frequency of headaches and improves the quality of life of patients suffering from chronic migraine.

• 3. Botox injected into the bladder wall acts on the detrusor muscle, reducing urine leakage (incontinence) and is used to treat the following conditions:
• Idiopathic overactive bladder with symptoms of incontinence, urgency, or frequency, in adult patients, when other medications (called anticholinergics) are ineffective.
• Urinary incontinencein patients with neurogenic detrusor overactivity, following 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 resistant to local treatment.
• 5. Botox is indicated for temporary improvement in the appearance of the following wrinkles:
• vertical frown lines between the eyebrows visible at maximum frown and/or,
• lateral canthal lines (crow's feet lines) in the area of the lateral canthus of the eye 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 not to use Botox

• if the patient is allergic (hypersensitive) to the Clostridium botulinum type A neurotoxin complex or any of the other ingredients of this medicine (listed in section 6);
• if there is an infection at the site where the medicine is to be administered;
• in patients undergoing treatment for urinary incontinence, who have urinary tract infections or acute urinary retention (and patients are not routinely catheterized);
• in patients undergoing treatment for urinary incontinence, who do not want to start using a catheter (if necessary).

Warnings and precautions

Before starting treatment with Botox, you should discuss it with your doctor:

• if the patient has ever had problems with swallowing, breathing, or choking, especially if the patient is planned to receive injections into the muscles of the neck or shoulders,
• if the patient is over 65 years old and has other serious illnesses,
• if the patient has other muscle problemsor chronic muscle diseases (e.g., myasthenia gravisor Lambert-Eaton syndrome),
• if the patient has certain nervous system diseases(e.g., amyotrophic lateral sclerosis, motor neuropathy),
• if there is significant weakness or atrophyof the muscles selected as the injection site,
• if the patient has had any surgical operationsor injuries that may have affected the function of the muscle into which the medicine is to be injected,
• if the patient has ever had problems with injections (e.g., fainting),
• if there is inflammationat the proposed injection site,
• if the patient has cardiovascular disease (heart disease or blood vessel disease),
• if the patient has seizures,
• if the patient has glaucoma(a eye disease related to high pressure in the eye) or is at risk of developing this disease,
• if the patient has had surgery or injury to the head, neck, legs, or chest,
• if any surgery is planned in the near future,
• if the patient has had an allergic reaction to botulinum toxin type A in the past (hives, swelling, including face and/or throat, wheezing, feeling of fainting or shortness of breath),
• if the treatment of overactive bladder with incontinence is planned in men with significant obstructive symptoms of benign prostatic hyperplasia, such as difficulty urinating, weak or interrupted stream during urination.

After administration of Botox
You should contact your doctor or go to the nearest hospital immediatelyif, after injection of Botox, the patient or caregiver observes the occurrence of the following symptoms:

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

General warnings

Like other injections, administration of Botox may result in complications at the injection site. The injection may cause local infection, pain, inflammation, paresthesia, numbness, pressure tenderness, swelling, redness, and/or bleeding/bruising.
There have been reports of adverse reactions related to the spread of the toxin to sites distant from the site of administration (muscle weakness, swallowing or choking problems).
The risk of their occurrence is likely to be higher in patients with concomitant diseases and disorders that may predispose to their occurrence.
The response to Botox may depend to a large extent on the therapy used, the frequency of injections, the type of muscles and skin areas selected for injection, and the small difference in the potency of Botox, which results from the method of measuring the dose in each vial.
If injections are given too close together or the dose is too high, the patient may experience muscle weakness and symptoms related to the spread of the toxin to distant sites from the injection site, and the body may also produce antibodies that can reduce the effectiveness of Botox.
Administration of Botox for indications other than those listed in the leaflet may lead to serious adverse reactions, especially in patients who have had difficulty swallowing or significant weakness.
If the patient has been leading a less active lifestyle for a long time before Botox therapy, any activity should be increased gradually after administration of the medicine.
It is unlikely that the medicine will increase mobility in the joints if the surrounding muscles have lost their ability to stretch.
During treatment for eyelid spasms, the frequency of blinking may decrease, which can lead to eye surface damage. To prevent this, the doctor may recommend using eye drops, ointment, soft contact lenses, or special eye shields.
If Botox is used to treat frown lines between the eyebrows and/or crow's feet lines and/or horizontal forehead lines, eyelid drooping may occur after injection.
The patient should inform the doctor if they do not notice significant improvement after one month from the first injection of Botox for the treatment of frown lines between the eyebrows and/or crow's feet lines and/or horizontal forehead lines.
Botox should not be used to treat focal spasticity of the ankle in adult patients if it is not expected that the reduction of muscle tone could lead to improvement in function (e.g., improvement in gait), or improvement in subjective symptoms (e.g., reduction of pain), or facilitation of patient care. If treatment with Botox is started in patients with ankle spasticity of lesser severity, improvement in ankle function may be limited.
Botox for the treatment of ankle spasticity and foot spasticity may only be administered after assessment by a specialist doctor with experience in the rehabilitation of patients.
If Botox is used to treat urinary incontinence, the doctor will give the patient antibiotics before and after therapy to prevent urinary tract infections.
The patient will be scheduled for a follow-up visit about 2 weeks after injection, if they did not use a catheter before injection. The doctor will ask the patient to urinate and then measure the volume of urine remaining in the bladder using ultrasound. The doctor will decide whether another visit is necessary to perform the same test within the next 12 weeks. The patient must contact the doctor every time they are unable to urinate, as it may be necessary to use a catheter.
After treatment of urinary incontinence due to spinal cord injury or multiple sclerosis, a catheter may be needed in about 1 in 3 patients who did not use a catheter before treatment for urinary incontinence.
After treatment of urinary incontinence due to overactive bladder, a catheter may be needed in about 6 in 100 patients who did not use a catheter before treatment for urinary incontinence.

Botox and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those that are available without a prescription, as well as any medicines you plan to take.
Tell your doctor or pharmacist if:

• you are taking any antibiotics, acetylcholinesterase inhibitors, muscle relaxants, as they may enhance the effect of Botox,
• you are currently taking or have recently taken other medicines containing botulinum toxin, as they may enhance the effect of Botox,
• you are taking any antiplatelet medicines (medicines with a similar effect to aspirin) and/or anticoagulant medicines (blood thinners). You should consult your doctor, even if the above warnings refer to situations that occurred in the past.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.
Botox should not be used in pregnant women and women of childbearing age not using effective contraception, unless it is absolutely necessary.
Botox is not recommended for use in breastfeeding women.

Driving and using machines

Assessment of the effect of Botox on the ability to drive and use machines can only be made after its administration to the patient.
Botox may cause dizziness, drowsiness, fatigue, or vision problems. If the patient experiences any of these symptoms, they 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, i.e., the medicine is considered "sodium-free"

3. How to use Botox

Botox can only be administered by doctors with the appropriate experience and qualifications.

Dosage and administration

Botox is injected into muscles (i.e., intramuscularly), into the bladder wall through a special device (cystoscope) used for injections into the bladder, or into the skin (subcutaneously).
The medicine is injected directly into the treated area of the body; the doctor usually injects Botox into several sites in each area affected by the condition.

General dosing information

• The number of injections per muscle and the dose size depend on the indication. The doctor will decide what dose, how often, and into which muscle to administer. The smallest effective dose of the medicine should be used.
• Doses for elderly patients are the same as for other adult patients.

The dose of Botox and the duration of its action vary depending on the therapeutic indication for which the medicine was administered. Detailed recommendations for individual indications are described below.
The safety and efficacy of Botox have been established in children and adolescents over two years of age for the treatment of persistent muscle spasms of the ankle and foot associated with cerebral palsy.
There is limited information on the use of Botox for the following indications in children/adolescents over the age specified in the table below. No dosing recommendations can be made for these indications.

There is limited experience with the use of Botox for the treatment of frown lines between the eyebrows and/or crow's feet lines and/or horizontal forehead lines in patients over 65 years of age.
The total dose for the treatment of horizontal forehead lines (20 units) in combination with frown lines between the eyebrows (20 units) is 40 units.

Dosage

The dose of Botox and the duration of its action vary depending on the therapeutic indication for which the medicine was administered. Detailed recommendations for individual indications are described below.

* The doctor may adjust the dose so that the intervals between administrations are approximately 6 months.
** In the case of simultaneous treatment of frown lines between the eyebrows and crow's feet lines, the total dose administered is 44 units.
*** In the case of treatment of all three types of wrinkles simultaneously (crow's feet lines, frown lines between the eyebrows, and horizontal forehead lines), the patient receives a total dose of 64 units.

Time to improvement and duration of action

In the treatment of persistent muscle spasms of the ankle and foot in children aged two and older
with cerebral palsy, improvement usually occurs within 2 weeks after injection.
In the treatment of persistent muscle spasms of the wrist and hand in adult patients, improvement usually occurs within two weeks after injection, and maximum effect is achieved after 1-2 weeks.
In the treatment of persistent muscle spasms of the ankle and foot in adult patients, when the effect of the medicine wears off, it can be administered again if necessary, but not more frequently than every 12 weeks.
In the treatment of persistent cervical dystonia, improvement usually occurs within 2 weeks after injection, and maximum effect is achieved after 6 weeks.
In the treatment of overactive bladder with symptoms of incontinence, improvement usually occurs within 2 weeks after injection, and the effect lasts for 6 to 7 months after injection.
In the treatment of urinary incontinence in patients with spinal cord injuries or multiple sclerosis, improvement usually occurs within 2 weeks after injection, and the effect lasts for 8 to 9 months after injection.
In the treatment of axillary hyperhidrosis, improvement usually occurs within 1 week after injection, and the effect lasts for an average of 7.5 months after injection, with about 30% of patients experiencing the effect of the medicine for up to 1 year after injection.
In the treatment of frown lines between the eyebrows, improvement usually occurs within 1 week after injection, and maximum effect is visible after 5-6 weeks after administration. The effect lasts for up to 4 months after injection.
In the treatment of crow's feet lines, improvement usually occurs within 1 week after injection, and maximum effect is visible after 3-4 days after administration. The effect lasts for up to 5 months after injection.
In the treatment of horizontal forehead lines visible at maximum eyebrow elevation, improvement usually occurs within 1 week after administration. The effect of the treatment lasts for an average of up to 4 months after injection.

Overdose of Botox

Signs of overdose may not be visible for several days after injection. If accidental injection or ingestion occurs, the patient should contact their doctor and remain under observation for several weeks.
You should contact your doctor immediately if, after injection of Botox, the patient observes the occurrence of the following symptoms:

• weakness of adjacent muscles and/or muscles distant from the injection site,
• difficulty breathing, swallowing, or speaking,
• accidental aspiration of food or liquids into the lungs, caused by muscle paralysis, which can lead to pneumonia,
• eyelid drooping, double vision,
• generalized weakness.

The doctor will decide whether the patient should be hospitalized.
In case of any further doubts, you should contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, Botox can cause side effects, although not everybody gets them.

General

You should inform your doctor immediately if you experience problems with swallowing, speaking, or breathing.

You should inform your doctor immediately if you experience hives, swelling, including face and/or throat, wheezing, feeling of fainting, or shortness of breath.

Side effects usually occur within the first few days after injection and are transient. In individual cases, side effects may persist for several months or longer. The expected pharmacological effect of Botox is local muscle weakness. However, high doses may cause weakness of other muscles, not necessarily directly in the area of the injection site.
As with any injection, pain and bruising may occur at the injection site. After botulinum toxin injections, fever and flu-like symptoms have also been observed.
You should inform your doctor if you experience any of the above symptoms.
Side effects are presented according to the following categories, depending on their frequency:

Below are the side effects presented according to the site of administration of Botox.

Injections into the lower limb in children with persistent muscle spasms of the ankle and foot

There have been reports of deaths after administration of botulinum toxin, in some cases related to aspiration pneumonia in children with severe cerebral palsy.

Injections into the wrist and hand in adult patients

Injections into the ankle and foot in adult patients

Injections into the eyelid and face

The doctor may apply gentle pressure immediately after injection to prevent mild bruising of the eyelid tissue.

Injections into the neck and shoulders

Difficulty swallowing may be mild to severe with the risk of choking and may require treatment. Such side effects may last from two to three weeks after injection.
There have also been reports of persistence of the above side effects for up to five months after injection. Rare cases of death due to difficulty swallowing have been reported.

Injections into the muscles of the head and neck for the prevention of headaches in patients with chronic migraine

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

* The side effect may be related to the injection procedure.
** The side effect is related only to the injection procedure.

Injections into the bladder wall in children and adolescents with urinary incontinence due to overactive bladder

* The side effect is related only to the injection procedure.

Injections into the bladder wall in adult patients with urinary incontinence due to neurogenic detrusor overactivity

* Some of the common side effects may be related to the injection procedure.

Injections into the bladder wall in children and adolescents with urinary incontinence due to spinal cord injuries or multiple sclerosis

* The side effect is related only to the injection procedure.

Injections for primary axillary hyperhidrosis

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

Injections for temporary improvement in the appearance of crow's feet lines (lines forming a fan shape from the outer corner of the eye) when treated alone or with frown lines between the eyebrows

visible at maximum frown
* Side effects may be related to the injection procedure

Injections for temporary improvement in the appearance of horizontal forehead lines visible at maximum eyebrow elevation and frown lines between the eyebrows visible at maximum frown, with or without simultaneous treatment of crow's feet lines

extending from the outer corner of the eye

The median time to onset of eyelid drooping was 9 days after treatment ended.
The median time to onset of eyebrow drooping was 5 days after treatment ended.
* Side effects may be related to the injection procedure

Additional information

Since the marketing of Botox, the following additional side effects have been reported:

• allergic reactions that can be life-threatening (face and/or throat swelling, difficulty breathing),
• swelling of deeper skin layers,
• hives,
• loss of appetite,
• nerve damage,
• speech disorders, difficulty speaking,
• drooping of the muscles on one side of the face,
• facial muscle weakness,
• decreased skin sensation,
• excessive muscle weakness,
• chronic muscle diseases (myasthenia gravis),
• disturbances in arm mobility with the shoulder,
• numbness, tingling, and pain in the hands and feet,
• local muscle twitching/muscle spasms
• pain, numbness, or weakness radiating from the spine,
• seizures, fainting,
• eyelid drooping,
• increased intraocular pressure,
• strabismus,
• blurred vision,
• difficulty closing the eye completely,
• visual disturbances,
• dry eye,
• hearing loss,
• tinnitus,
• dizziness,
• heart rhythm disorders, including myocardial infarction,
• aspiration pneumonia (pneumonia caused by accidental inhalation of food, liquid, saliva, or vomit during inhalation),
• depression or respiratory failure,
• abdominal pain,
• diarrhea, constipation,
• dry mouth,
• difficulty swallowing,
• nausea, vomiting,
• hair loss,
• various types of skin rash,
• increased sweating,
• eyebrow loss,
• eyebrow drooping,
• itching,
• hives,
• muscle pain, nerve damage, and muscle atrophy at the injection site,
• general malaise,
• fever,
• dry eye,
• local muscle twitching/muscle spasms
• eyelid edema

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Botox

The medicine should be stored out of sight and reach of children.
Store in a refrigerator (2°C - 8°C) or freezer (-5°C to -20°C).
Use immediately after reconstitution.
The solution remains stable for 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 month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and other information

What Botox contains:

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

What Botox looks like and what the package contains:

Botox is a fine white powder that may be almost invisible at the bottom of the vial made of colorless glass. Before injection, the medicine should be diluted in sterile sodium chloride solution without preservatives (0.9% sodium chloride for injection).
The package contains one vial in a cardboard box.

Marketing authorization holder

AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Phone number of the marketing authorization holder: +48 22 3727800

Manufacturer

Allergan Pharmaceuticals Ireland
Castlebar Road
Westport
County Mayo,
Ireland

Date of last update of the leaflet: 04/2024 ---------------------------------------------------------------------------------------------------------------------------

Information intended exclusively for professional medical personnel:

Detailed information has been included in the Summary of Product Characteristics.

The Botox medicine should only be used by doctors with appropriate qualifications and documented experience in conducting therapy and using the required equipment. Generally applicable optimal dose level and the number of injection sites into one muscle have not been established. In such cases, the doctor should develop individual administration schedules for the medicine. The optimal dose level should be determined as a result of trials, using different concentrations of the medicine. The units of botulinum toxin of the Botox medicine are not comparable with the units of botulinum toxin of other medicines. The doses recommended as Allergan units are not comparable with the doses of other botulinum toxin medicines. Children and adolescents: The safety and efficacy of the Botox medicinal product have not been established in indications other than those described for the pediatric population in section 4.1 of the Summary of Product Characteristics. There are no dosage recommendations for indications other than focal spasticity associated with cerebral palsy in children. Current data on 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.

Focal spasticity of the lower limb in children:

The recommended dose for the treatment of lower limb spasticity in children is 4 units/kg to 8 units/kg of body weight, or 300 units - whichever is lower, divided among the affected muscles. In the case of treating both lower limbs, the total dose should not exceed the lower of 10 units/kg of body weight or 340 units at 12-week intervals.

Regarding cervical dystonia: No more than 100 units should be administered to the sternocleidomastoideus muscle. To minimize the risk of swallowing disorders, toxin should not be administered to both sternocleidomastoideus muscles at the same time. Regarding blepharospasm: The decrease in blink frequency after injection of botulinum toxin into the orbicularis oculi muscle may lead to pathological changes in the cornea. It is necessary to carefully check the corneal sensitivity after administration of the medicine and avoid injections into the lower eyelid to prevent ectropion, and in case of any epithelial damage, treat them intensively. Treatment may require the administration of protective drops, ointment, therapeutic soft contact lenses, eye patching, or other procedures. Regarding focal spasticity associated with cerebral palsy and focal spasticity of the wrist and hand, ankle, and foot in adult patients: The administration of Botox for the treatment of focal spasticity has been studied only in combination with standard treatment regimens and is not recommended to replace these procedures. Botox is likely not effective in improving the range of motion of joints altered by permanent contracture. Regarding focal spasticity of the upper limb in patients:

The recommended dose for the treatment of upper limb spasticity in adults is up to 240 units divided among the selected muscles according to the table above. The maximum dose during one procedure is 240 units. Regarding primary axillary hyperhidrosis: It is recommended to conduct an interview and clinical examination, as well as additional specific tests, to exclude potential causes of secondary hyperhidrosis (e.g., hyperthyroidism, pheochromocytoma). This will help avoid symptomatic treatment of hyperhidrosis without diagnosis and/or treatment of the underlying disease. Notes on all indications: There have been reports of adverse reactions related to the spread of the toxin to remote sites from the site of administration. Sometimes they caused the patient's death, in some cases related to difficulty swallowing (dysphagia), pneumonia, and/or significant weakness. These symptoms are consistent with the mechanism of action of botulinum toxin, and their occurrence has been observed within a few hours to a few weeks after administration. The risk of these symptoms is likely higher in patients with concomitant diseases and disorders that may predispose to their occurrence, including children and adults treated for spasticity and patients receiving high doses of the medicine. In patients treated with therapeutic doses of Botox, excessive muscle weakness may also occur. Cases of pneumothorax related to the injection procedure have been observed after administration of Botox near the chest. Caution should be exercised when injecting near the lungs, especially in the apical region. Severe cases of adverse reactions, including deaths, have been observed in patients who received Botox by injection into the salivary glands, mouth-throat area, esophagus, or stomach. Some of the described patients had pre-existing swallowing disorders or significant weakness. Rare cases of death due to aspiration pneumonia have been reported in children with severe cerebral palsy after the use of botulinum toxin, off-label (e.g., injection into the neck area). Particular caution should be exercised when treating children and adolescents with significant neurological weakness, difficulty swallowing (dysphagia), or recent aspiration pneumonia or other lung disease. Treatment of patients in poor general condition is possible only if it has been assessed that the potential benefits outweigh the risk. In rare cases, after injection of botulinum toxin, an anaphylactic reaction may occur. In such cases, epinephrine (adrenaline) and other anti-anaphylactic medications should be used. In the event of therapeutic failure after the first procedure, defined as the lack of significant improvement after one month from administration compared to the initial state, the following strategies should be considered:

• Clinical verification, which may include electromyographic examination, to assess the action of the toxin in the muscle(s) after injection.
• Analysis of the causes of failure, which may include:
• inappropriate selection of muscles for injection,
• too small a dose of the medicine,
• improper injection technique,
• presence of fixed contracture,
• too weak antagonist muscles,
• formation of neutralizing antibodies to the toxin.
• Reconsideration of the indication for treatment with botulinum toxin type A.
• If no adverse reactions have occurred, it is recommended to consider repeating the treatment, paying attention to the following problems: a) proper selection of the medicine dose based on the analysis of the previous therapeutic failure, b) use of EMG, c) maintaining a three-month interval between consecutive procedures.

In the event of lack of or unsatisfactory therapeutic effect after the second treatment cycle, it is recommended to consider the use of alternative treatment methods. For detailed information, please refer to the Summary of Product Characteristics of Botox.

Reconstitution of the medicine:

It is recommended to reconstitute the contents of vials and fill syringes on paper, laminated with plastic, to avoid accidental contamination of the environment. The reconstitution of Botox should be prepared only by adding sterile, preservative-free saline solution (0.9% sodium chloride for injection). If different sizes of Botox vials are used during one procedure, attention should be paid to using the correct amount of diluent to achieve the appropriate number of units in 0.1 ml. The amount of diluent required for reconstitution is different for different strengths. Each syringe should be properly labeled.

Idiopathic overactive bladder

In this indication, it is recommended to use vials containing 100 units of Botox due to easier reconstitution.

Instructions for dilution in the case of vials containing 100 units

• The Botox vial containing 100 units should be reconstituted using 10 ml of 9 mg/ml (0.9%) sterile, preservative-free saline solution (0.9% sodium chloride for injection) and gently mixed.
• Reconstitution should be completed by withdrawing 10 ml of solution from the vial into a 10 ml syringe. This will result in a total of 100 units of Botox in a 10 ml syringe. Use immediately after reconstitution. Discard any unused solution.

Instructions for dilution in the case of vials containing 200 units

• The Botox vial containing 200 units should be reconstituted using 8 ml of 9 mg/ml (0.9%) sterile, preservative-free saline solution (0.9% sodium chloride for injection) and gently mixed.
• 4 ml of solution should be withdrawn from the vial into a 10 ml syringe.
• Reconstitution should be completed by adding 6 ml of 0.9% sterile, preservative-free saline solution (0.9% sodium chloride for injection) to the syringe and gently mixed. This will result in a total of 100 units of Botox in a 10 ml syringe. Use immediately after reconstitution. Discard any unused solution.

Neurogenic detrusor overactivity

In this indication, it is recommended to use vials containing 100 or 200 units of Botox due to easier reconstitution.

Instructions for dilution in the case of vials containing 100 units for neurogenic detrusor overactivity:

• Each of the 2 Botox vials containing 100 units should be reconstituted using 6 ml of 9 mg/ml (0.9%) sterile, preservative-free saline solution (0.9% sodium chloride for injection) per vial and gently mixed.
• 4 ml should be withdrawn from each vial into two 10 ml syringes.
• 2 ml should be withdrawn from both vials into a third 10 ml syringe.
• Reconstitution should be completed by adding 6 ml of 0.9% sterile, preservative-free saline solution (0.9% sodium chloride for injection) to each syringe and gently mixed. This will result in a total of 200 units of Botox after reconstitution in 3 syringes of 10 ml each. Use immediately after reconstitution. Discard any unused solution.

Instructions for dilution in the case of vials containing 200 units

• The Botox vial containing 200 units should be reconstituted using 6 ml of 9 mg/ml (0.9%) sterile, preservative-free saline solution (0.9% sodium chloride for injection) and gently mixed.
• 2 ml should be withdrawn from the vial into each of three 10 ml syringes.
• Reconstitution should be completed by adding 8 ml of 0.9% sterile, preservative-free saline solution (0.9% sodium chloride for injection) to each syringe and gently mixed. This will result in a total of 200 units of Botox after reconstitution in 3 syringes of 10 ml each. Use immediately after reconstitution. Discard any unused solution.

Instructions for dilution for vials of 100 and 200 units in all indications, except for the treatment of urinary disorders:

Botox is intended for single use only; any remaining unused solution should be destroyed. Botox may denature as a result of bubble formation or vigorous movement during reconstitution of the powder, so the saline solution should be slowly injected into the vial. If, after piercing the stopper, the saline solution is not drawn into the vial by the vacuum, the vial should be discarded. The reconstituted Botox is a clear or slightly yellowish solution without solid particles. Before administration, the solution should be inspected and evaluated for clarity and absence of solid particles. After reconstitution, the medicine can be stored for up to 24 hours in a refrigerator (2°C - 8°C). Chemical and physical stability of Botox after reconstitution has been demonstrated for up to 5 days at 2°C - 8°C. From a microbiological point of view, it is recommended to use the solution immediately and discard the vials with unused solution. If the medicine 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.

Procedure necessary for the safe disposal of vials, syringes, and used materials:

A small amount of water should be added to the vials with unused toxin, and then they should be placed in an autoclave. All used vials, syringes, etc. should also be autoclaved. The remaining medicine can also be inactivated by adding a hypochlorite solution (0.5%) for 5 minutes.

Medicine identification:

To confirm the receipt of authentic Botox, manufactured and supplied by Allergan, check the warranty seal in the form of a foil with a semi-transparent silver Allergan logo on the cap and bottom of the carton, as well as the presence of a hologram coating on the vial label. The hologram on the vial should be checked by viewing the vial under a desk lamp or fluorescent light. By rotating the vial, look for horizontal lines in rainbow colors containing the word "Allergan" on the label. (The hologram is not visible in the area of the print of the expiration date and batch number). Do not use the medicine and contact the local Allergan office for further information if:

• the horizontal lines in rainbow colors with the word "Allergan" are not present on the label
• the protective foil is damaged or missing from the cap or bottom of the carton
• the semi-transparent, silver Allergan logo on the protective foil is unclear or has a black circle with a diagonal line (e.g., a prohibition sign).

Additionally, the label contains stickers with the medicine name, expiration date, and batch number. The stickers can be peeled off and placed in the patient's card for identification purposes. After peeling off the sticker from the label, the word "USED" will be visible, further confirming the authenticity of the Botox product, manufactured and supplied by Allergan.