BOTOX 100 Units Allergan, Powder for Injectable Solution

Introduction

Package Leaflet: Information for the User

BOTOX 50 Units Allergan, Powder for Solution for Injection

BOTOX 100 Units Allergan, Powder for Solution for Injection

BOTOX 200 Units Allergan, 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is BOTOX and what is it used for
2. What you need to know before you use BOTOX
3. How to use BOTOX
4. Possible side effects
5. Storing BOTOX
6. Contents of the pack and other information

1. What is BOTOX and what is it used for

BOTOX is a muscle relaxant used to treat various conditions in the body. It contains the active substance botulinum toxin type A and is injected into the muscles, the bladder wall, or into the skin. It works by partially blocking the nerve impulses to the injected muscles and reducing excessive contractions of these muscles.

When injected into the skin, BOTOX acts on the sweat glands to reduce the amount of sweat produced.

When injected into the bladder wall, BOTOX acts on the bladder muscle to reduce urine loss (urinary incontinence). In the case of chronic migraine, it is believed that BOTOX may block pain signals, indirectly blocking the onset of a migraine. However, the exact way BOTOX works in chronic migraine is not fully understood.

1. BOTOX can be injected directly into the muscles and can be used to treat the following conditions:
   • Persistent muscle spasmsin the ankle and footin childrenaged 2 years or older with cerebral palsy, who can walk. BOTOX is used as support for rehabilitation therapy;
   • Persistent muscle spasmsin the wrist and handof adult patientswho have had a stroke;
   • Persistent muscle spasmsin the ankle and footof adult patientswho have had a stroke;
   • Persistent muscle spasmsin the eyelidand faceof adult patients;
   • Persistent muscle spasmsin the neck and shouldersof adult patients;

1. BOTOX is used to reducethe symptoms of chronic migrainein adultswho have headaches on 15 or more days per month, of which at least 8 days have migraine, and who have not responded adequately or are intolerant to migraine prophylactic medications.

Chronic migraine is a condition that affects the nervous system. Patients usually experience headache pain, which is often accompanied by excessive sensitivity to light, noise, or smells, as well as nausea, vomiting, or both. These headaches occur on 15 or more daysper month.

1. When injected into the bladder wall, BOTOX works on the bladder muscle to reduce urine loss (urinary incontinence) and control the following conditions in adults:
   • Overactive bladder with urine loss,the urgent need to empty the bladder and to go to the bathroom more often than usual, when another medication (known as an anticholinergic) has not been helpful;
   • Urine lossdue to bladder disorders associated with spinal cord injury or multiple sclerosis.

1. In adults, BOTOX can be injected deeply into the skin and can work on the sweat glands to reduce excessive sweatingof the armpitsthat affect daily activities, when other 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 at the proposed ;
• when you are being treated for urine loss and you have a urinary tract infection or are unable to empty your bladder suddenly (and do not use a catheter on a regular basis);
• if you are being treated for urine loss and do not want to start using a catheter if needed.

Warnings and precautions

Tell your doctor or pharmacist before using BOTOX:

• if you have ever had problems swallowingor if food or liquid has accidentally entered your lungs, especially if you are going to be treated for persistent muscle spasms in the neck and shoulders;
• if you are 65 years of ageor older and have other serious illnesses;
• if you have any other or chronic diseases that affect your muscles (such as myasthenia gravis or Lambert-Eaton syndrome);
• if you have certain diseasesthat affect the nervous system(such as amyotrophic lateral sclerosis or motor neuropathy);
• if you have weaknessor wastingof the muscles into which the medicine is to be injected;
• if you have had any or that may have changed the muscle to be injected in any way;
• if you have ever had any (such as fainting);
• if you have or skinat the injection site;
• if you have any heart or blood vessel disease;
• if you have had ;
• if you have a called angle-closure glaucoma(high pressure in the eye) or have been told you are at high risk of developing this type of glaucoma;
• if you are going to be treated for overactive bladder with urine loss and you are a male with signs and symptoms of urinary obstruction, such as difficulty urinating or a weak or interrupted urine flow.

After being injected with BOTOX

You or your caregiver should go to your doctorand seek medical attention immediately if you experience any of the following symptoms:

• difficulty breathing, swallowing, or speaking;
• , including inflammation of the face or throat, , feeling , and (possible symptoms of a severe allergic reaction).

General precautions

As with any injection, it is possible that after the procedure you may experience infection, pain, inflammation, abnormal skin sensations (such as tingling or numbness), reduced skin sensation, pain when touching, redness, bleeding/bruising at the injection site, and a drop in blood pressure or fainting: this may be a consequence of the pain and/or anxiety associated with the injection.

Adverse reactions possibly related to the spread of botulinum toxin from the site of administration (such as muscle weakness, difficulty swallowing, or unintended passage of food or liquid into the airways) have been reported with botulinum toxin. These side effects can be mild to severe, may require treatment, and in some cases, can be fatal. This risk is more pronounced for patients with underlying conditions that make them more susceptible to these symptoms.

Severe and/or immediate allergic reactions have been reported, whose symptoms may include hives, inflammation of the face or throat, shortness of breath, wheezing, or fainting. Delayed allergic reactions (serum sickness) have also been reported, which may include symptoms such as fever, joint pain, and skin rash.

Cardiovascular system-related adverse effects, including irregular heartbeat and heart attack, have been reported in patients treated with BOTOX, sometimes with a fatal outcome. However, some of these patients had a history of cardiac risk factors.

Seizures have been reported in adults and children treated with BOTOX, mostly in patients with a predisposition to seizures. It is not known whether BOTOX can cause these seizures. The seizures reported in children occurred mostly in patients with cerebral palsy being treated for persistent muscle spasms.

If you are given BOTOX too frequently or in high doses, you may experience muscle weakness and adverse reactions related to the spread of the toxin, or your body may start producing some antibodies that can reduce the effect of BOTOX.

When BOTOX is used to treat a condition that is not included in this leaflet, it may lead to serious reactions, especially in patients who have difficulty swallowing or significant weakness.

If you have not exercised much for a long time before receiving treatment with BOTOX, you should start some activity gradually after the injections.

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 to treat persistent muscle spasms of the ankle due to stroke in adults if it is not expected to improve function (e.g., walking) or symptoms (e.g., pain), or facilitate patient care. If you had a stroke more than 2 years ago or if the muscle spasm in the ankle is less severe, the improvement related to activities such as walking may be limited. Also, your doctor will determine if this treatment is suitable for patients who are more likely to fall.

BOTOX should only be used to treat muscle spasms in the ankle and foot due to stroke after evaluation by healthcare professionals with experience in the management of post-stroke rehabilitation patients.

When BOTOX is used to treat severe muscle spasms in the eyelid, it may cause you to blink less often, which can damage the surface of your eyes. To prevent this, you may need treatment with eye drops, ointments, soft contact lenses, or even a protective cover that closes your eyes. Your doctor will tell you if this is necessary.

When BOTOX is used to control urine loss, your doctor will give you antibiotics before and after treatment to prevent urinary tract infections.

You will have an appointment with your doctor about 2 weeks after the injection, if you did not use a catheter before the injection. You will be asked to urinate and then the amount of urine left in your bladder will be measured by ultrasound. Your doctor will decide if you need to come back for a repeat of this test during the following 12 weeks. You should contact your doctor if at any time you are unable to urinate, as you may need a catheter. In patients with urine loss due to bladder problems associated with spinal cord injury or multiple sclerosis, about one-third of patients who did not use a catheter before treatment may need one after treatment. In patients with urine loss due to overactive bladder, about 6 out of 100 patients may need to use a catheter after treatment.

Using BOTOX with other medicines:

Tell your doctoror pharmacist if:

? you are taking any antibiotic(used to treat infections), anticholinesterases, or . Some of these medicines may increase the effect of BOTOX;

? you have recently been injected with a medicine that contains a botulinum toxin(the active ingredient of BOTOX), as this may greatly increase the effect of BOTOX;

? you are taking any antiplatelet agent (medicines like aspirin) and/or anticoagulants (medicines that make the blood more fluid).

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy and Breastfeeding

The use of BOTOX is not recommended during pregnancy or in women of childbearing age who are not using contraception unless it is absolutely necessary. BOTOX is not recommended in breastfeeding women.

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and Using Machines

BOTOX may cause dizziness, drowsiness, fatigue, or vision problems. If you experience any of these effects, do not drive or use machines. If you are unsure, ask your doctor for advice.

BOTOX contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

3. How to use BOTOX

BOTOX should only be injected by doctors with specific skills and experience in using this medication.

BOTOX should only be prescribed for your chronic migraine if you have been diagnosed by a neurologist who is a specialist in this field. BOTOX must be administered under the supervision of a neurologist. BOTOX is not used for acute migraine, chronic tension-type headaches, or for patients with headache due to excessive use of medications.

Method and route of administration

BOTOX is injected into the muscles (intramuscularly), into the bladder wall using a specific instrument (cystoscope) for injection into the bladder, or into the skin (intradermally). It is injected directly into the affected area of your body; your doctor will normally inject BOTOX into several sites within each affected area.

General dosing information

• 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) you will be administered BOTOX. It is recommended that your doctor use the lowest effective dose.
• The doses for elderly patients are the same as for other adults.

The dose of BOTOX and the duration of its effect will vary depending on the disease for which it is being treated. The following details are specific to each disease.

The safety and efficacy of BOTOX have been established in children/adolescents over 2 years of age for the treatment of persistent muscle spasms in 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 ages listed in the following table. No dosage recommendation can be made for these indications.

Dosage

The dosing of BOTOX and the duration of its effect will vary depending on the condition for which you are being treated. The following details are specific to each condition.

• Your doctor may select a dose that makes the treatment last up to 6 months.

Time to Improvement and Duration of Effect

For persistent muscle spasms in ankle and foot in children 2 years of age or older,improvement will normally appear during the first 2 weeks following injection

For persistent muscle spasms in the wrist and hand of adult patients who have had a stroke,you will normally notice improvement during the 2 weeks following injection. The maximum effect is generally observed 4 to 6 weeks after treatment.

For persistent muscle spasms in the ankle and foot of adult patients who have had a stroke, you may receive treatment again if necessary when the effect starts to disappear, although no more frequently than every 12 weeks.

For persistent muscle spasms in eyelids and face,you will normally see improvement within 3 days after injection and the maximum effect is normally seen after 1 or 2 weeks.

For muscle spasms in neck and shoulders,you will generally notice improvement during the 2 weeks following injection. The maximum effect is normally seen 6 weeks after treatment.

For urinary incontinence due to overactive bladder,you will normally observe improvement in the first 2 weeks after injection. The effect usually lasts approximately 6-7 months after injection.

For urinary incontinence due to bladder problems associated with spinal cord injury or multiple sclerosis,you will normally observe improvement in the first 2 weeks after injection. The effect usually lasts approximately 8-9 months after injection.

For excessive sweating of the armpits, you will normally notice improvement during the first week after injection. The effect normally lasts, on average, 7.5 months after the first injection, and approximately 1 in 4 patients still show the effect after 1 year.

If you have received more BOTOX than you should

Signs of excess BOTOX may not appear immediately after injection. If you ingest BOTOX or it is accidentally injected, you should consult your doctor, who should keep you under observation for several weeks.

If you have received too much BOTOX, you may experience some of the following symptoms and should contact your doctor immediately. He/she will decide if you should go to the hospital:

• Muscle weakness that can be local or distant from the injection site;
• difficulty breathing, swallowing, or speaking due to muscle paralysis;
• some food or liquid has accidentally passed into your lungs, which can cause pneumonia (lung infection) due to muscle paralysis;
• drooping eyelids, double vision;
• generalized weakness.

If you have any additional questions about the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

In general, adverse effects occur during the first few days following injection. They usually last for a short time, but can last for several months, and in rare cases, even longer.

IF YOU EXPERIENCE ANY DIFFICULTY BREATHING, SWALLOWING, OR SPEAKING AFTER RECEIVING TREATMENT WITH BOTOX, CONTACT YOUR DOCTOR IMMEDIATELY.

If you experiencehives, inflammationincluding inflammation of the face or throat, wheezing, feeling of faintingor shortness of breath, contact your doctor immediately.

Adverse effects are classified into the following categories, depending on the frequency with which they occur:

The following are adverse effects that vary depending on the part of the body where BOTOX is injected. If any of the adverse effects worsen, or if you experience any adverse effect that does not appear in this leaflet, please inform your doctor or pharmacist.

Injections in children with persistent muscle spasms in the ankle and foot

Some rare cases of death have been spontaneously reported, sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with BOTOX.

Injections in the wrist and hand of adult patients who have had a stroke

Injections in the ankle and foot of adult patients who have had a stroke

Injections in the eyelid and face

Injections in the neck and shoulders

Injections in the head and neck for the treatment of headache in patients with chronic migraine

Injections in the bladder wall for urinary incontinence due to overactive bladder

• This adverse effect may also be related to the injection procedure.

* This adverse effect is related solely to the injection procedure.

Injections in the bladder wall for urinary incontinence due to overactive bladder in pediatric patients

• This adverse effect is related solely to the injection procedure.

Injections in the bladder wall of adult patients with urinary incontinence due to bladder problems associated with spinal cord injury or multiple sclerosis

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

Injections in the bladder wall of pediatric patients with urinary incontinence due to bladder problems associated with spina bifida, spinal cord injury, or transverse myelitis

*This adverse effect is related solely to the injection procedure.

Injections for excessive sweating in the armpits

The following list describes additional adverse effectsreported for BOTOX, in some disease, since it has been marketed:

• allergic reaction, including reactions to injection of proteins or serum
• inflammation of deep layers of the skin;
• hives;
• eating disorders, loss of appetite;
• nerve damage (brachial plexopathy),
• voice and speech problems;
• drooping of the muscles on one side of the face;
• facial muscle weakness;
• decreased skin sensation;
• muscle weakness;
• chronic disease that affects the muscles (myasthenia gravis);
• difficulty moving the arm and shoulder;
• numbness;
• pain/numbness/weakness that starts in the spine;
• seizures and fainting;
• increased eye pressure:
• strabismus;
• blurred vision;
• difficulty seeing clearly;
• decreased hearing;
• ringing in the ears;
• feeling of dizziness or vertigo;
• heart problems including heart attack
• aspiration pneumonia (inflammation of the lungs caused by accidental passage to the lungs of food, drink, saliva, or vomit);
• breathing problems, respiratory depression and/or respiratory failure;
• abdominal pain;
• diarrhea, constipation;
• dry mouth;
• difficulty swallowing;
• nausea, vomiting;
• hair loss;
• itching;
• different types of skin rashes with red spots;
• excessive sweating;
• loss of eyelashes/eyebrows
• muscle pain;
• problems with nerve conduction to the muscle/muscle contraction;
• general malaise;
• fever;
• dry eye (associated with injections around the eyes);
• localized muscle spasms/muscle contractions.
• swelling of the eyelid

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of BOTOX

Keep out of sight and reach of children.

Your doctor should not use BOTOX after the expiration date that appears on the packaging after "EXP". The expiration date is the last day of the month indicated.

Store in the refrigerator (2°C to 8°C) or store in the freezer (-5°C to -20°C).

After preparing the solution, it is recommended to use it immediately; however, it can be stored for up to 24 hours in the refrigerator (2°C to 8°C).

6. Container Content and Additional Information

Composition of BOTOX

• The active ingredient is: Botulinum Toxin* type A of Clostridium botulinum. Each vial contains 50, 100, or 200 Allergan Units of botulinum toxin type A.
• The other components are human albumin and sodium chloride.

Appearance of the Product and Container Content

BOTOX is presented as a fine white powder that may be difficult to see at the bottom of a transparent glass vial. Before injection, the product must be dissolved in a normal saline solution without preservatives (sodium chloride 0.9% injectable solution). Each container contains 1, 2, 3, or 6 vials. Additionally, the 50 and 100 Allergan Units of botulinum toxin type A formats may also be presented in containers of 10 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

AbbVie Spain, S.L.U.

Avenida de Burgos 91,

28050 Madrid, Spain

Manufacturer:

Allergan Pharmaceuticals Ireland

Castlebar Road

County Mayo

Ireland

Or

AbbVie Deutschland GmbH & Co. KG

Knollstrasse

67061 Ludwigshafen

Germany

Date of the Last Revision of this Prospectus:April 2024

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

The following information is exclusively for medical and healthcare personnel:

Please refer to the Technical Sheet for complete prescription information for BOTOX.

The Units of botulinum toxinare not interchangeable from one product to another. The recommended doses in Allergan Units are different from other products with botulinum toxin.

BOTOX should only be administered by doctors with the appropriate qualification and experience in treatment and the use of the required instrumentation.

Chronic migraine should be diagnosed and BOTOX should be administered exclusively under the supervision of neurologists who are experts in the treatment of chronic migraine.

BOTOX is indicated for the treatment of: focal spasticity of the ankle and foot in pediatric patients, two years of age or older; focal spasticity of the wrist and hand secondary to a stroke in adults; focal spasticity of the ankle and foot secondary to a stroke in adults; blepharospasm, hemifacial spasm, and associated focal dystonias; cervical dystonia (spasmodic torticollis); relief of symptoms in adults who meet the criteria for chronic migraine (headaches on ≥ 15 days per month, of which at least eight days correspond to migraine), in patients who have not responded adequately or are intolerant to migraine prophylactic medications; idiopathic overactive bladder with symptoms of urinary incontinence, urgency, and frequency in adult patients who have not responded adequately or are intolerant to anticholinergic medications; urinary incontinence in adults with neurogenic detrusor overactivity due to subcervical spinal cord injury or multiple sclerosis and severe and persistent primary axillary hyperhidrosis that interferes with daily activities and is resistant to topical treatment.

The safety and efficacy of BOTOX have not been established in indications for the pediatric population other than those described in section 4.1 of the Technical Sheet. No dosage recommendation can be made for indications other than infantile focal spasticity associated with cerebral palsy. The available data per indication are described in sections 4.2, 4.4, 4.8, and 5.1 of the Technical Sheet, as shown in the following table.

No specific dose adjustment is required for elderly patients. The initial dosage should start with the lowest recommended dose for each indication. For repeated injections, the lowest effective dose with the longest clinically indicated interval between injections is recommended. Patients of advanced age with significant medical history and concomitant medication should be treated with caution.

Generally, optimal dose levels and the number of injection points per muscle have not been established for all indications. In these cases, the doctor should establish an individual treatment regimen. The optimal dose levels should be determined by individual adjustment, but the maximum recommended dose should not be exceeded. As with any pharmacological treatment, the initial dose in a new patient should be the minimum effective dose.

Dosage and Method of Administration (please refer to sections 4.2 and 4.4 of the Technical Sheet for more information).

Focal Spasticity of the Lower Limb in Pediatric Patients

The recommended dose for treating infantile lower limb spasticity is 4 Units/kg to 8 Units/kg of body weight or 300U, whichever is lower, divided among the affected muscles. When treating both lower limbs, the total dose should not exceed 10 Units/kg of body weight or 340 Units, in an interval of 12 weeks.

• did not exceed a total dose of 150 Units

** did not exceed a total dose of 300 Units

Focal Spasticity of the Upper and Lower Limb Secondary to a Stroke:

BOTOX is a treatment for focal spasticity that has only been studied in association with usual treatment regimens and is not indicated as a substitute for these therapeutic modalities. It is likely that BOTOX will not be effective in improving the range of motion in a joint affected by a fixed contracture.

Focal Spasticity of the Upper Limb Secondary to a Stroke:

*When injecting the lumbricals and/or interosseous, the maximum recommended dose is 50 U per hand.

The recommended dose for the treatment of upper limb spasticity in adults is up to 240 Units divided among the affected muscles as indicated in the table above. The maximum dose in a treatment is 240 Units.

The exact dose and number of injection points must be individualized based on the size, number, and location of the affected muscles, the severity of the spasticity, the presence of muscle weakness, and the patient's previous response to treatment.

Focal Spasticity of the Lower Limb Secondary to a Stroke:

The recommended dose for the treatment of lower limb spasticity in adults affecting the ankle and foot is 300 Units to 400 Units divided among up to 6 muscles.

Blepharospasm/Hemifacial Spasm:

A reduction in blinking after injection of botulinum toxin in the orbicularis muscle may cause corneal pathology. Corneal sensitivity should be carefully evaluated in previously operated eyes, avoiding injection in the lower eyelid area to avoid ectropion, and using vigorous treatment of any epithelial defect. This may require protective drops, ointments, soft contact lenses, or eye closure with a patch or other means.

Cervical Dystonia:

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

Chronic Migraine

The recommended dose of reconstituted BOTOX for the treatment of chronic migraine is 155 Units to 195 Units, administered intramuscularly (IM), with a 30-gauge needle and 1.25 cm in length, with injections of 0.1 ml (5 Units), in 31 to 39 points. The injections should be divided into seven specific muscle zones of the head and neck, as specified in the following table. A 2.5 cm needle may be necessary in the neck region for patients with extremely thick neck muscles. With the exception of the procerus muscle, which should be injected at one point (midline), all muscles should be injected on both sides, administering half of the number of injections on the left side of the head and neck, and the other half on the right. If there is one or more predominant locations of pain, more injections can be administered on one or both sides, up to three specific muscle groups (occipital, temporal, and trapezius), up to the maximum dose per muscle indicated in the following table.

aOne IM injection point = 0.1 ml = 5 Units of BOTOX

bDose distributed on both sides.

Urinary Incontinence due to Overactive Bladder

The recommended dose is 100 Units of BOTOX in injections of 0.5 ml (5 Units) administered in 20 points of the detrusor, avoiding the trigone and base.

Urinary Incontinence due to Neurogenic Detrusor Overactivity:

The recommended dose is 200 Units of BOTOX in injections of 1 ml (approximately 6.7 Units) administered in 30 points of the detrusor, avoiding the trigone and base.

Primary Axillary Hyperhidrosis:

A medical history and physical examination, along with any additional specific complementary tests that may be required, should be performed to exclude potential causes of secondary hyperhidrosis (e.g., hyperthyroidism, pheochromocytoma). This will avoid symptomatic treatment of hyperhidrosis without diagnosis and/or treatment of the underlying disease.

For all Indications:

Adverse effects related to the distant spread of the toxin from the site of administration have been reported, which sometimes caused death, and in some cases were associated with dysphagia, pneumonia, and/or significant weakness. The symptoms are consistent with the mechanism of action of the botulinum toxin and have been reported from hours to weeks after injection. The risk of symptoms is probably greater in patients with underlying conditions and comorbidities that may predispose them to these symptoms, including children and adults treated for spasticity, and those being treated with high doses.

Patients treated with therapeutic doses may also experience excessive muscle weakness.

Pneumothorax associated with the injection procedure has been reported after administration of BOTOX near the thorax. Caution is needed when injecting near the lung, particularly the apices or other vulnerable anatomical structures.

Severe adverse reactions, including fatal outcomes, have been reported in patients who received BOTOX injections off-label, directly into the salivary glands, oropharyngeal region, and lingual, esophagus, and stomach. Some patients had dysphagia or significant weakness prior to treatment.

Rarely, cases of death have been reported, sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with botulinum toxin, including off-label use (e.g., in the neck area). Extreme caution should be exercised when treating pediatric patients with significant neurological weakness, dysphagia, or a recent history of aspiration pneumonia or pulmonary disease. Treatment should be administered to patients with underlying poor health only if the potential benefit to the individual patient outweighs the risks.

Exceptionally, an anaphylactic reaction may occur after injection of botulinum toxin. Therefore, epinephrine (adrenaline) and other anti-anaphylactic measures should be available.

Consult the BOTOX Technical Sheet for complete information.

In case of treatment failure after the first treatment session, for example, absence of significant clinical improvement one month after injection, the following actions should be taken:

• Clinical verification, which may include electromyographic examination by a specialist, of the action of the toxin in the injected muscle(s);
• Analysis of the cause of failure, for example, poor selection of muscles to inject, insufficient dose, poor injection technique, appearance of fixed contracture, antagonist muscles too weak, formation of neutralizing antibodies to the toxin;
• Re-evaluation of the suitability of treatment with botulinum toxin type A;
• In the absence of any undesirable side effects in the first treatment session, a second treatment should be performed as follows: a) adjust the dose, taking into account the analysis of the failure;

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• a) review of previous treatment, b) use of EMG, and c) maintaining a 3-month interval between two treatment sessions.

In the event of treatment failure or diminished effect after repeated injections, alternative treatment methods should be used.

Reconstitution of the drug:

If different sizes of BOTOX vials are used as part of an 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 Units Allergan, BOTOX 100 Units Allergan, and BOTOX 200 Units Allergan. Each syringe should be labeled appropriately.

It is good practice to carry out the reconstitution of the vial and the preparation of the syringe on plastic-coated paper towels to collect any possible spilled material.

BOTOX should be reconstituted only with sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution). Aspirate the appropriate amount of diluent (see instructions or dilution table below) with a syringe.

Dilution instructions for the treatment of urinary incontinence due to overactive bladder:

It is recommended to use a vial of 100 Units or two vials of 50 Units as they are more convenient for reconstitution.

If you need to use a vial of 200 Units, reconstitute a vial of 200 Unitsof BOTOX with 8 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix the vial. Withdraw 4 ml from the vial into a 10 ml syringe. Complete the reconstitution by adding 6 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) to the 10 ml syringe, and gently mix. This will yield a 10 ml syringe containing a total of 100 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

Reconstitute a vial of 100 Unitsof BOTOX with 10 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix. Withdraw the 10 ml from the vial into a 10 ml syringe. This will yield a 10 ml syringe containing a total of 100 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

Reconstitute two vials of 50 Unitsof BOTOX, each with 5 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix each vial. Withdraw the 5 ml from each vial into a single 10 ml syringe. This will yield a single 10 ml syringe containing a total of 100 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

This product is for single use, and any unused reconstituted product should be discarded.

Dilution instructions for the treatment of urinary incontinence due to neurogenic detrusor overactivity:

It is recommended to use a vial of 200 Units or two vials of 100 Units as they are more convenient for reconstitution.

Reconstitute a vial of 200 Unitsof BOTOX with 6 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix the vial. Withdraw 2 ml from the vial into each of three 10 ml syringes. Complete the reconstitution by adding 8 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) to each of the 10 ml syringes, and gently mix. This will yield three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

Reconstitute two vials of 100 Unitsof BOTOX, each with 6 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix the vials. Withdraw 4 ml from each vial into each of two 10 ml syringes. Withdraw the remaining 2 ml from each vial into a third 10 ml syringe. Complete the reconstitution by adding 6 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) to each of the 10 ml syringes, and gently mix. This will yield three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

If you need to use vials of 50 Units, reconstitute four vials of 50 Unitsof BOTOX, each with 3 ml of sterile normal saline solution without preservatives (0.9% sodium chloride injectable solution) and gently mix the vials. Withdraw 3 ml from the first vial and 1 ml from the second into a 10 ml syringe. Withdraw 3 ml from the third vial and 1 ml from the fourth into a second 10 ml syringe. Withdraw 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 normal saline solution without preservatives (0.9% sodium chloride injectable solution) to each of the 10 ml syringes, and gently mix. This will yield three 10 ml syringes containing a total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Discard unused saline solution.

Dilution table for BOTOX 50, 100, and 200 Units Allergan vials for the remaining indications:

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

Since BOTOX is denatured by violent agitation or bubble formation, the solvent should be injected into the vial gently. Discard the vial if the vacuum does not draw the solvent into the vial. Reconstituted BOTOX is a clear, colorless to slightly yellowish solution, free of particles. Before use, it will be visually checked that the reconstituted solution is clear and free of particles. Once reconstituted in the vial, BOTOX can be stored in the refrigerator (2°C-8°C) for up to 24 hours before use. If it is further diluted in a syringe for intradetrusor injection, it should be used immediately.

Potency studies have shown that the product can be stored for up to 5 days at 2°C-8°C after reconstitution.

From a microbiological point of view, the product should be used immediately. If it is not used immediately, the storage conditions after reconstitution and prior to use are the responsibility of the user and should not exceed 24 hours at 2°C-8°C, unless the reconstitution, dilution, etc. have taken place in controlled and validated aseptic conditions. The date and time of reconstitution should be noted on the space provided on the label.

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

Medicines should not be disposed of via wastewater or household waste. For safe disposal, unused vials should be reconstituted with a small amount of water and then autoclaved. All used vials and syringes and spilled material, etc. should be autoclaved, or the residual BOTOX can be inactivated with a diluted solution of hypochlorite (0.5%) for 5 minutes.

Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

Product identification

In order to verify that the BOTOX product is from Allergan, please look for two transparent warranty seals containing the Allergan silver and translucent logo, which are located on the top and bottom of the BOTOX box flaps, and a holographic film on the vial label. To view this film, examine the vial under a desk lamp or a fluorescent light source. By rotating the vial back and forth between your fingers, look for the horizontal lines of rainbow color on the label and confirm that the name "Allergan" appears within the rainbow lines.

Do not use the product and contact your local AbbVie office if:

• The horizontal lines of rainbow color or the word "Allergan" are not present on the vial label;
• The warranty seals are not intact and present on both flaps of the box;
• The Allergan translucent logo on the warranty seals is not clearly visible or has a black circle with a diagonal line (prohibited sign).

Additionally, two removable stickers have been added to the label of the BOTOX vial, which include the batch number and expiration date of the product. These stickers can be removed and attached to the patient's record for traceability purposes. Note that once the stickers are removed from the label of the BOTOX vial, the word "Used" will appear, ensuring that the product is authentic BOTOX manufactured by Allergan.