4.1. Therapeutic indications

XEOMIN is indicated for the symptomatic treatment in adults of

• blepharospasm and hemifacial spasm,

• cervical dystonia of a predominantly rotational form (spasmodic torticollis),

• focal spasticity of the upper limb,

• focal spasticity of the lower limb affecting the ankle joint,

• chronic sialorrhea due to neurological disorders.

XEOMIN is indicated for the symptomatic treatment in children and adolescents aged 2 to 17 years and weighing ≥ 12 kg of

• chronic sialorrhea due to neurological / neurodevelopmental disorders.

4.2. Posology and method of administration

Due to unit differences in the potency assay, unit doses for XEOMIN are not interchangeable with those for other preparations of Botulinum toxin type A.

For detailed information regarding clinical studies with XEOMIN in comparison to conventional Botulinum toxin type A complex (900 kD), see section 5.1.

XEOMIN should only be administered by an appropriately qualified healthcare practitioner with expertise in the treatment of the relevant indication and the use of the required equipment, in accordance with national guidelines.

The optimum dose, frequency and number of injection sites should be determined by an appropriately qualified healthcare practitioner. Optimum dose levels should be determined by titration but the recommended maximum dose should not be exceeded.

The recommended single doses of XEOMIN should not be exceeded.

Posology

Blepharospasm and hemifacial spasm

The initial recommended dose is 1.25 to 2.5 units per injection site. The initial dose should not exceed 25 units per eye. Total dosing should not exceed 50 units per eye per treatment session. Repeated treatment should generally be no more frequent than every 12 weeks. Treatment intervals should be determined based on the actual clinical need of the individual patient.

The median time to first onset of effect is observed within four days after injection. The effect of a XEOMIN treatment generally lasts approximately 3‑5 months, however, it may last significantly longer or shorter.

At repeat treatment sessions, the dose may be increased up to two-fold if the response to the initial treatment is considered insufficient. However, there appears to be no additional benefit obtainable from injecting more than 5.0 units per site.

Patients with hemifacial spasm should be treated as for unilateral blepharospasm.

Spasmodic torticollis

In the management of spasmodic torticollis, XEOMIN dosing must be tailored to the individual patient, based on the patient's head and neck position, location of possible pain, muscle hypertrophy, patient's body weight, and response to the injection.

No more than 200 units should be injected for the first course of therapy, with adjustments made in the subsequent courses depending on the response. A total dose of 300 units at any one session should not be exceeded. No more than 50 units should be administered at any one injection site.

The median first onset of effect is observed within seven days after injection. The effect of a XEOMIN treatment generally lasts approximately 3‑4 months, however, it may last significantly longer or shorter. Treatment intervals of less than 10 weeks are not recommended. Treatment intervals should be determined based on the actual clinical need of the individual patient.

Focal spasticity

Upper limb

The exact dose, frequency and number of injection sites should be tailored to the individual patient based on the size, number and location of involved muscles, the severity of spasticity, and the presence of local muscle weakness.

Recommended treatment doses per muscle:

Clinical Pattern Muscle

Units (Range)

Number of Injection Sites Per Muscle

Flexed Wrist

Flexor carpi radialis

25-100

1-2

Flexor carpi ulnaris

20-100

1-2

Clenched Fist

Flexor digitorum superficialis

25-100

2

Flexor digitorum profundus

25-100

2

Flexed Elbow

Brachioradialis

25-100

1-3

Biceps

50-200

1-4

Brachialis

25-100

1-2

Pronated Forearm

Pronator quadratus

10-50

1

Pronator teres

25-75

1-2

Thumb-in-Palm

Flexor pollicis longus

10-50

1

Adductor pollicis

5-30

1

Flexor pollicis brevis/Opponens pollicis

5-30

1

Internally Rotated/Extended/Adducted Shoulder

Deltoideus, pars clavicularis

20-150

1-3

Latissimus dorsi

25-150

1-4

Pectoralis major

20-200

1-6

Subscapularis

15-100

1-4

Teres major

20-100

1-2

The maximum total dose for the treatment of upper limb spasticity should not exceed 500 units per treatment session, and no more than 250 units should be administered to the shoulder muscles.

Patients reported the onset of action 4 days after treatment. The maximum effect as an improvement of muscle tone was perceived within 4 weeks. In general, the treatment effect lasted 12 weeks, however, it may last significantly longer or shorter.

Repeated treatment should generally be no more frequent than every 12 weeks. Treatment intervals should be determined based on the actual clinical need of the individual patient.

Lower limb, ankle joint affected

The exact dosage, frequency and number of injection sites should be tailored to the individual patient based on size, number and localisation of involved muscles, the severity of spasticity, and the presence of local muscle weakness.

Recommended treatment doses per muscle:

Clinical Pattern Muscle

Units (Range)

Number of Injection Sites

per Muscle

Pes Equinus including Flexed Toes

Gastrocnemius medial/lateral

50-200

2-6

Soleus

50-200

2-4

Tibialis posterior

50-150

2-3

Flexor digitorum longus

50-100

1-3

Flexor hallucis longus

25-75

1-2

The maximum total dose for the treatment of lower limb spasticity should not exceed 400 units per treatment session.

Repeat treatment should generally be no more frequent than every 12 weeks. Treatment intervals should be determined based on the actual clinical need of the individual patient.

Upper and lower limbs

If treatment is required in the upper and lower limbs during the same treatment session, the dose of Xeomin to be injected in each limb should be tailored to the individual's need according to the relevant posology above and without exceeding a maximum total dose of 500 units for the first treatment session.

Following the first treatment session, if well tolerated, the maximum total dose for the combined treatment of the upper and lower limbs in subsequent treatment sessions can be increased to 600 units.

Chronic sialorrhea (adults)

A reconstituted solution at a concentration of 5 units/0.1 ml should be used.

XEOMIN is injected into the parotid and submandibular glands on both sides (per treatment four injections in total). The dose is divided with a ratio of 3:2 between the parotid and submandibular glands as follows:

Glands

Units

Volume

Parotid glands

30 per side

0.6 ml per injection

Submandibular glands

20 per side

0.4 ml per injection

The injection site should be close to the centre of the gland.

The recommended dose per treatment session is 100 units. This maximum dose should not be exceeded.

Treatment intervals should be determined based on the actual clinical need of the individual patient.

Repeat treatment more frequent than every 16 weeks is not recommended.

Chronic sialorrhea (children/adolescents)

A reconstituted solution at a concentration of 2.5 units/0.1 ml should be used.

XEOMIN is injected into the parotid and submandibular glands on both sides (per treatment four injections in total). The body-weight adjusted dose is divided with a ratio of 3:2 between the parotid and submandibular glands as indicated in the table below.

No dosing recommendations can be made for children weighing less than 12 kg.

Body weight

Parotid gland, each side

Submandibular gland, each side

Total dose, both glands, both sides

Dose per gland

Volume per injection

Dose per gland

Volume per injection

[kg]

[Units]

[ml]

[Units]

[ml]

[Units]

≥ 12 and < 15

6

0.24

4

0.16

20

≥ 15 and < 19

9

0.36

6

0.24

30

≥ 19 and < 23

12

0.48

8

0.32

40

≥ 23 and < 27

15

0.60

10

0.40

50

≥ 27 and < 30

18

0.72

12

0.48

60

≥ 30

22.5

0.90

15

0.60

75

The injection site should be close to the centre of the gland.

Treatment intervals should be determined based on the actual clinical need of the individual patient. Repeat treatment should be no more frequent than every 16 weeks.

All indications

If no treatment effect occurs within one month after the initial injection, the following measures should be taken:

- Clinical verification of the neurotoxin effect on the injected muscle: e.g. an electromyographic investigation in a specialised facility

- Analysis of the reasons for non-response, e.g. poor isolation of the muscles intended to be injected, too low dose, poor injection technique, fixed contracture, too weak antagonist, possible development of antibodies

- Review of Botulinum neurotoxin type A treatment as an adequate therapy

- If no adverse reactions have occurred during the initial treatment, an additional course of treatment can be performed under the following conditions: 1) dose adjustment with regard to analysis of the most recent therapy failure, 2) localisation of the involved muscles with techniques such as electromyographic guidance, 3) the recommended minimum interval between the initial and repeat treatment is followed

Paediatric population

The safety and efficacy of XEOMIN in indications other than the one described for the paediatric population in section 4.1 have not been established. No recommendations on posology can be made for indications other than chronic sialorrhea in children and adolescents aged 2 to 17 years and weighing ≥ 12 kg.

Currently available paediatric clinical data with XEOMIN are described in section 5.1.

Method of administration

All indications

For instructions on reconstitution of the medicinal product before administration, see section 6.6. After reconstitution, XEOMIN should be used for only one injection session and for only one patient.

XEOMIN is intended for intramuscular and intraglandular (intra-salivary gland) use.

Blepharospasm and hemifacial spasm

After reconstitution, the XEOMIN solution is injected intramuscularly using a suitable sterile needle (e.g. 27‑30 gauge/0.30‑0.40 mm diameter/12.5 mm length). Electromyographic guidance is not necessary. An injection volume of approximately 0.05 to 0.1 ml is recommended.

XEOMIN is injected into the medial and lateral orbicularis oculi muscle of the upper lid and the lateral orbicularis oculi muscle of the lower lid. Additional sites in the brow area, the lateral orbicularis oculi muscle and in the upper facial area may also be injected if spasms here interfere with vision.

In cases of unilateral blepharospasm the injections should be confined to the affected eye.

Patients with hemifacial spasm should be treated as for unilateral blepharospasm.

There is no experience with injections in the lower facial area from clinical studies with XEOMIN. Muscles in the lower facial area should not be injected due to pronounced risk of local weakness as reported in literature after injections of botulinum toxin into this area in patients with hemifacial spasm.

Spasmodic torticollis

A suitable sterile needle (e.g. 25‑30 gauge/0.30‑0.50 mm diameter/37 mm length) is used for injections into superficial muscles, and an e.g. 22 gauge/0.70 mm diameter/75 mm length needle may be used for injections into deeper musculature. An injection volume of approximately 0.1 to 0.5 ml per injection site is recommended.

In the management of spasmodic torticollis, XEOMIN is injected into the sternocleidomastoid, levator scapulae, scalenus, splenius capitis, and/or the trapezius muscle(s). This list is not exhaustive as any of the muscles responsible for controlling head position may be involved and therefore require treatment. If difficulties arise isolating single muscles, injections should be performed using techniques such as electromyographic guidance or ultrasound. The muscle mass and the degree of hypertrophy or atrophy are factors to be taken into consideration when selecting the appropriate dose.

Multiple injection sites permit XEOMIN more uniform coverage of the innervated areas of the dystonic muscle and are especially useful in larger muscles. The optimum number of injection sites depends on the size of the muscle to be chemically denervated.

The sternocleidomastoid should not be injected bilaterally as there is an increased risk of adverse reactions (in particular dysphagia) when bilateral injections or doses in excess of 100 U are administered into this muscle.

Focal spasticity of the upper and lower limbs

Reconstituted XEOMIN is injected using a suitable sterile needle (e.g. 26 gauge/0.45 mm diameter/37 mm length, for superficial muscles and a longer needle, e.g. 22 gauge/0.7 mm diameter/75 mm length, for deeper musculature).

Localisation of the involved muscles with techniques such as electromyographic guidance or ultrasound is recommended in case of any difficulty in isolating the individual muscles. Multiple injection sites may allow XEOMIN to have more uniform contact with the innervation areas of the muscle and are especially useful when larger muscles are injected.

An injection volume of approximately 0.2 to 1 ml (can be exceeded to 1.5 ml in selected cases) per injection site is recommended when treating focal spasticity of the upper limb.

An injection volume of approximately 0.2 to 1 ml per injection site is recommended when treating focal spasticity of the lower limb.

Chronic sialorrhea (adults/children/adolescents)

After reconstitution the XEOMIN solution is injected intraglandularly using a suitable sterile needle (e.g. 27‑30 gauge/0.30‑0.40 mm diameter/12.5 mm length).

In adults, anatomic landmarks or ultrasound guidance are both possible for the localisation of the involved salivary glands, however the ultrasound guided method should be preferred, because it could result in a better therapeutic outcome (see section 5.1).

For the treatment of children and adolescents ultrasound guidance should be used. Local anaesthesia (such as local anaesthetic cream), sedation, or anaesthesia in combination with sedation may be offered to children and adolescents prior to injection after a careful benefit-risk evaluation and per local site practice.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Generalised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome).

• Infection or inflammation at the proposed injection site.

4.4. Special warnings and precautions for use

Traceability:

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

General:

Prior to administering XEOMIN, the healthcare practitioner must familiarise himself/herself with the patient's anatomy and any alterations to the anatomy due to prior surgical procedures.

Care should be taken to ensure that XEOMIN is not injected into a blood vessel.

XEOMIN should be used with caution:

• if bleeding disorders of any type exist

• in patients receiving anticoagulant therapy or other substances that could have an anticoagulant effect.

The clinical effects of Botulinum neurotoxin type A may increase or decrease by repeated injections. The possible reasons for changes in clinical effects are different techniques of reconstitution, the chosen injection intervals, the injection sites and marginally varying toxin activity resulting from the biological testing procedure employed or secondary non-response.

Local and distant spread of toxin effect

Undesirable effects may occur from misplaced injections of Botulinum neurotoxin type A that temporarily paralyse nearby muscle groups. Large doses may cause paralysis in muscles distant from the injection site.

There have been reports of undesirable effects that might be related to the spread of Botulinum toxin type A to sites distant from the injection site (see section 4.8). Some of these can be life threatening and there have been reports of death, which in some cases was associated with dysphagia, pneumonia and/or significant debility.

Patients treated with therapeutic doses may experience excessive muscle weakness. . Cases of iatrogenic botulism have been reported following injection of botulinum toxin products.

Patients or caregivers should be advised to seek immediate medical care if they experience any signs or symptoms consistent with the spread of botulinum toxin effect or if swallowing, speech or respiratory disorders occur (see section 4.9).

Dysphagia has also been reported following injection to sites other than the cervical musculature.

Pre-existing neuromuscular disorders

Patients with neuromuscular disorders may be at increased risk of excessive muscle weakness particular when treated intramuscularly. The Botulinum toxin type A product should be used under specialist supervision in these patients and should only be used if the benefit of treatment is considered to outweigh the risk.

Generally, patients with a history of aspiration or dysphagia should be treated with caution. Extreme caution should be exercised when treating these patients for cervical dystonia.

XEOMIN should be used with caution:

• in patients suffering from amyotrophic lateral sclerosis

• in patients with other diseases which result in peripheral neuromuscular dysfunction

• in targeted muscles which display pronounced weakness or atrophy

Hypersensitivity reactions

Hypersensitivity reactions have been reported with Botulinum neurotoxin type A products. If serious (e.g. anaphylactic reactions) and/or immediate hypersensitivity reactions occur, appropriate medical therapy should be instituted.

Antibody formation

Too frequent doses may increase the risk of antibody formation, which can result in treatment failure (see section 4.2).

The potential for antibody formation may be minimised by injecting with the lowest effective dose at the longest intervals between injections as clinically indicated.

Paediatric population

Spontaneous reports of possible distant spread of toxin have been very rarely reported for other preparations of Botulinum toxin type A in paediatric patients with comorbidities, predominantly with cerebral palsy. In general the dose used in these cases was in excess of that recommended for these products.

There have been rare spontaneous reports of death sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with botulinum toxin products, including following off label use (e.g. neck area). The risk is considered particularly high in paediatric patients with a poor underlying health status or in patients who have significant neurologic debility, dysphagia, or in patients who have a recent history of aspiration pneumonia or lung disease.

Indication-specific warnings

Blepharospasm and hemifacial spasm

Injections near the levator palpebrae superioris muscle should be avoided to reduce the occurrence of ptosis. Diplopia may develop as a result of Botulinum neurotoxin type A diffusion into the inferior oblique muscle. Avoiding medial injections into the lower lid may reduce this adverse reaction.

Because of the anticholinergic effect of Botulinum neurotoxin type A, XEOMIN should be used with caution in patients at risk of developing a narrow angle glaucoma.

In order to prevent ectropion, injections into the lower lid area should be avoided, and vigorous treatment of any epithelial defect is necessary. This may require protective drops, ointments, soft bandage contact lenses, or closure of the eye by patching or similar means.

Reduced blinking following XEOMIN injection into the orbicularis muscle can lead to corneal exposure, persistent epithelial defects and corneal ulceration, especially in patients with cranial nerve disorders (facial nerve). Careful testing of corneal sensation should be performed in patients with previous eye operations.

Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure at the injection site can limit that risk.

Spasmodic torticollis

XEOMIN should be injected carefully when injecting at sites close to sensitive structures such as the carotid artery, lung apices and oesophagus.

Previously akinetic or sedentary patients should be reminded to gradually resume activities following the injection of XEOMIN.

Patients should be informed that injections of XEOMIN for the management of spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration and dyspnoea. Medical intervention may be necessary (e.g. in the form of a gastric feeding tube) (see also section 4.8). Limiting the dose injected into the sternocleidomastoid muscle to less than 100 units may decrease the occurrence of dysphagia. Patients with smaller neck muscle mass, or patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk. The occurrence of dysphagia is attributable to the spread of the pharmacological effect of XEOMIN as the result of the neurotoxin spread into the oesophageal musculature.

Focal spasticity of the upper limb

XEOMIN should be injected carefully when injecting at sites close to sensitive structures such as the carotid artery, lung apices and oesophagus.

Focal spasticity of the upper and lower limbs

Previously akinetic or sedentary patients should be reminded to gradually resume activities following the injection of XEOMIN.

XEOMIN as a treatment for focal spasticity has been studied in association with usual standard care regimens, and is not intended as a replacement for these treatment modalities. XEOMIN is not likely to be effective in improving range of motion at a joint affected by a fixed muscle contracture.

New onset or recurrent seizures have been reported, typically in patients who are predisposed to experiencing these events. The exact relationship of these events to Botulinum toxin injection has not been established.

Caution should be exercised when treating adult patients especially the elderly, with focal spasticity affecting the lower limbs, who may be at increased risk of fall.

Chronic sialorrhea (adults/children/adolescents)

In cases of medication-induced sialorrhea (e.g. by aripiprazole, clozapine, pyridostigmine) first of all the possibility of replacement, reduction or even termination of the inducing medication should be considered before using XEOMIN for the treatment of sialorrhea.

Efficacy and safety of XEOMIN in patients with medication-induced sialorrhea were not investigated.

If cases of “dry mouth” develop in association with the administration of XEOMIN reduction of the dose should be considered.

A dental visit at the beginning of treatment is recommended. The dentist should be informed about sialorrhea treatment with XEOMIN to be able to decide about appropriate measures for caries prophylaxis.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Theoretically, the effect of Botulinum neurotoxin may be potentiated by aminoglycoside antibiotics or other medicinal products that interfere with neuromuscular transmission, e.g. tubocurarine-type muscle relaxants.

Therefore, the concomitant use of XEOMIN with aminoglycosides or spectinomycin requires special care. Peripheral muscle relaxants should be used with caution, if necessary reducing the starting dose of relaxant, or using an intermediate-acting substance such as vecuronium or atracurium rather than substances with longer lasting effects.

In addition, when used for the treatment of chronic sialorrhea, irradiation to the head and neck including salivary glands and/or co-administration of anticholinergics (e.g. atropine, glycopyrronium, scopolamine) may increase the effect of the toxin. The treatment of sialorrhea with XEOMIN during radiotherapy is not recommended.

4‑Aminoquinolines may reduce the effect of XEOMIN.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of Botulinum neurotoxin type A in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, XEOMIN should not be used during pregnancy unless clearly necessary and unless the potential benefit justifies the risk.

Breastfeeding

It is unknown whether Botulinum neurotoxin type A is excreted into breast milk. Therefore, XEOMIN should not be used during breast-feeding.

Fertility

There are no clinical data from the use of Botulinum neurotoxin type A. No adverse effects on male or female fertility were detected in rabbits (see section 5.3).

4.7. Effects on ability to drive and use machines

XEOMIN has a minor or moderate influence on the ability to drive and use machines. Patients should be counselled that if asthenia, muscle weakness, dizziness, vision disorders or drooping eyelids occur, they should avoid driving or engaging in other potentially hazardous activities.

4.8. Undesirable effects

Usually, undesirable effects are observed within the first week after treatment and are temporary in nature. Undesirable effects may be related to the active substance, the injection procedure, or both.

Undesirable effects independent from indication

Application related undesirable effects

Localised pain, inflammation, paraesthesia, hypoaesthesia, tenderness, swelling, oedema, erythema, itching, localised infection, haematoma, bleeding and/or bruising may be associated with the injection.

Needle related pain and/or anxiety may result in vasovagal responses, including transient symptomatic hypotension, nausea, tinnitus, and syncope.

Undesirable effects of the substance class Botulinum toxin type A

Localised muscle weakness is one expected pharmacological effect of Botulinum toxin type A.

Toxin spread

Undesirable effects related to spread of toxin distant from the site of administration have been reported very rarely to produce symptoms consistent with Botulinum toxin type A effects (excessive muscle weakness, dysphagia, and aspiration pneumonia with a fatal outcome in some cases) (see section 4.4).

Hypersensitivity reactions

Serious and/or immediate hypersensitivity reactions including anaphylaxis, serum sickness, urticaria, soft tissue oedema, and dyspnoea have been rarely reported. Some of these reactions have been reported following the use of conventional Botulinum toxin type A complex either alone or in combination with other agents known to cause similar reactions.

Undesirable effects from clinical experience

The following adverse reactions have been reported with XEOMIN. The frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Blepharospasm

System Organ Class

Adverse Reaction

Frequency

Nervous system disorders

Headache, facial paresis

Uncommon

Eye disorders

Eyelid ptosis

Very common

Dry eyes, vision blurred, visual impairment

Common

Diplopia, lacrimation increased

Uncommon

Gastrointestinal disorders

Dry mouth

Common

Dysphagia

Uncommon

Skin and subcutaneous tissue disorders

Rash

Uncommon

Musculoskeletal and connective tissue disorders

Muscular weakness

Uncommon

General disorders and administration site conditions

Injection site pain

Common

Fatigue

Uncommon

Hemifacial spasm

Similar adverse reactions as for blepharospasm can be expected with hemifacial spasm.

Spasmodic torticollis

System Organ Class

Adverse Reaction

Frequency

Infections and infestations

Upper respiratory tract infection

Common

Nervous system disorders

Headache, presyncope, dizziness

Common

Speech disorder

Uncommon

Respiratory, thoracic and mediastinal disorders

Dysphonia, dyspnoea

Uncommon

Gastrointestinal disorders

Dysphagia

Very common

Dry mouth, nausea

Common

Skin and subcutaneous tissue disorders

Hyperhidrosis

Common

Rash

Uncommon

Musculoskeletal and connective tissue disorders

Neck pain, muscular weakness, myalgia, muscle spasms, musculoskeletal stiffness

Common

General disorders and administration site conditions

Injection site pain, asthenia

Common

The management of spasmodic torticollis may cause dysphagia with varying degrees of severity with the potential for aspiration which may require medical intervention. Dysphagia may persist for two to three weeks after injection, but has been reported in one case to last five months.

Focal spasticity of the upper limb

System Organ Class

Adverse Reaction

Frequency

Nervous system disorders

Headache, hypoaesthesia

Uncommon

Gastrointestinal disorders

Dry mouth

Common

Dysphagia, nausea

Uncommon

Musculoskeletal and connective tissue disorders

Muscular weakness, pain in extremity, myalgia

Uncommon

General disorders and administration site conditions

Asthenia

Uncommon

Injection site pain

Not known

Focal spasticity of the lower limb affecting the ankle joint

System Organ Class

Adverse Reaction

Frequency

Musculoskeletal and connective tissue disorders

Muscular weakness

Common

Pain in extremity

Not known

Injury, poisoning and procedural complication

Fall

Common

Chronic sialorrhea (adults)

System Organ Class

Adverse Reaction

Frequency

Nervous system disorders

Paraesthesia

Common

Speech disorder

Uncommon

Gastrointestinal disorders

Dry mouth, dysphagia

Common

Altered (thickened) saliva, dysgeusia

Uncommon

Cases of persistent dry mouth (> 110 days) of severe intensity have been reported, which could cause further complications as gingivitis, dysphagia and caries.

Chronic sialorrhea (children/adolescents)

System Organ Class

Adverse Reaction

Frequency

Gastrointestinal disorders

Dysphagia

Uncommon

Altered (thickened) saliva, dry mouth, oral pain, dental caries

Not known

Post-Marketing Experience

The following adverse reactions were reported with unknown frequency for the use of XEOMIN since market launch independent from indication:

System Organ Class

Adverse Reaction

Immune system disorders

Hypersensitivity reactions like swelling, oedema (also distant from injection site), erythema, pruritus, rash (localised and generalised) and breathlessness

Musculoskeletal and connective tissue disorders

Muscle atrophy

General disorders and administration site conditions

Flu-like symptoms

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Please see information on risks associated with local and distant spread of toxin effect in section 4.4.

Symptoms of overdose

Increased doses of Botulinum neurotoxin type A may result in pronounced neuromuscular paralysis distant from the injection site with a variety of symptoms. Symptoms may include general weakness, ptosis, diplopia, breathing difficulties, speech difficulties, paralysis of the respiratory muscles or swallowing difficulties which may result in aspiration pneumonia.

Measures in cases of overdose

In the event of overdose or spread of toxin the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis. Symptomatic treatment may be necessary. Respiratory support may be required if paralysis of the respiratory muscles occurs.