Posology : מינונים

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.

General
XEOMIN may only be administered by physicians with suitable qualifications and the requisite experience in the application of Botulinum toxin type A.
For blepharospasm, spasmodic torticollis and post-stroke spasticity of the upper limb, the optimum dose, frequency and number of injection sites in the treated muscle should be determined by the physician individually for each patient. A titration of the dose should be performed.

The recommended single doses of XEOMIN should not be exceeded.

Posology
Blepharospasm
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 100 units 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 3-4 months, however, it may last significantly longer or shorter. The treatment can be repeated if required.

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.

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.

Post-stroke Spasticity of the upper limb presenting with flexed wrist and clenched fist in adults The exact dose and number of injection sites should be tailored to the individual patient based on the size, number and location of muscles involved, the severity of spasticity, and the presence of local muscle weakness.

Recommended initial doses:

Clinical Pattern                        Units
Muscle
Flexed Wrist
Flexor carpi radialis             50
Flexor carpi ulnaris              40
Clenched Fist
Flexor digitorum                  40 superficialis
Flexor digitorum profundus        40
Flexed Elbow
Brachioradialis                   60
Biceps                            80
Brachialis                        50

Pronated Forearm
Pronator quadratus                 25
Pronator teres                     40
Thumb-in-Palm
Flexor pollicis longus             20
Adductor pollicis                  10
Flexor pollicis brevis/            10
Opponens pollicis

Recommended treatment doses for repeated treatment per muscle:

Clinical Pattern                        Units (Range) Number of
Muscle                                          injection sites per muscle
Flexed Wrist
Flexor carpi radialis             25-100           1-2
Flexor carpi ulnaris              20-100           1-2
Clenched Fist
Flexor digitorum                  40-100           2 superficialis
Flexor digitorum profundus        40-100           2
Flexed Elbow
Brachioradialis                   25-100           1-3
Biceps                            75-200           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/           5-30             1
Opponens pollicis

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

Moderate to Severe Vertical Lines between the Eyebrows seen at frown (Glabellar Frown Lines) in Adults below 65 Years When the Severity of These Lines Has an Important Psychological Impact For The Patient
After reconstitution of XEOMIN a dose of 4 units is injected into each of the 5 injection sites: two injections in each corrugator muscle and one injection in the procerus muscle, which corresponds to a standard dose of 20 units. The dose may be increased by the physician to up to 30 units if required by the individual needs of the patients, with at least ‘3-months’ interval between treatments.



An improvement in the vertical lines between the eyebrows seen at frown (glabellar frown lines) generally takes place within 2 to 3 days with the maximum effect observed on day 30. The effect lasts up to 4 months after the injection.

If no treatment effect occurs within one month after the initial injection, the following measures should be taken:
• Glabellar Frown Lines indication o Analysis of the reasons for non-response, e.g. too low dose, poor injection technique, possible development of neurotoxin-neutralising antibodies o Dose adjustment with regard to the analysis of the most recent therapy failure o Review of Botulinum neurotoxin type A treatment as an adequate therapy o If no adverse reactions have occurred during the initial treatment, an additional course of treatment can be performed in compliance with the minimum interval of 3 months between the initial and repeat treatment

• All other indications o Clinical verification of the neurotoxin effect on the injected muscle: e.g. an electromyographic investigation in a specialised facility o 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 o Review of Botulinum neurotoxin type A treatment as an adequate therapy o 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

Special populations
There are limited clinical data from phase 3 studies of XEOMIN in patients over 65 years of age for the treatment of Glabellar Frown Lines. Until further data are available in this age group, XEOMIN is not recommended for use in patients over 65 years of age for the treatment of Glabellar Frown Lines.

Paediatric population
The safety and efficacy of XEOMIN in children and adolescents younger than 18 years has not yet been established. XEOMIN is thus not recommended in the paediatric population.

Method of administration

All indications
For instructions on reconstitution of the medicinal product before administration and for instructions on disposal of the vials, see section 6.6. After reconstitution, XEOMIN should be used immediately (see section 6.3), for only one injection session and for only one patient.

Reconstituted XEOMIN is intended for intramuscular injection.

Blepharospasm
After reconstitution, the XEOMIN solution is injected 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.


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.

Post Stroke Spasticity of the upper limb presenting with flexed wrist and clenched fist in adult 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.

Glabellar frown lines
Reconstituted XEOMIN is injected using a thin sterile needle (e.g. 30-33 gauge/0.20-0.30 mm diameter/13 mm length needle). An injection volume of approximately 0.04 to 0.1 ml per injection site is recommended. The intervals between treatments should not be shorter than 3 months. If the treatment fails, or the effect lessens with repeated injections, alternative treatment methods should be used.

Before and during the injection, the thumb or index finger should be used to apply firm pressure below the edge of the eye socket in order to prevent diffusion of the solution in this region. Superior and medial alignment of the needle should be maintained during the injection. To reduce the risk of blepharoptosis, injections near the levator palpebrae superioris and into the cranial portion of the orbicularis oculi should be avoided. Injections into the corrugator muscle should be done in the medial portion of the muscle, and in the central portion of the muscle belly at least 1 cm above the bony edge of the eye socket.