ALL-40030 Unlocking the code

MD D NA Codes™

Unlocking the code to facial expression Volume 1 – An introduction to facial dynamics and the MD DYNA Codes™

Produced by Allergan – ND-BCT-1950013 | Date of preparation: October 2019

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Preface and acknowledgements Our journey together started in 2015 with the Allergan Medical Institute® (AMI) Leaders programme, where we introduced a new language in facial aesthetics – the MD Codes™ – and discovered the value of discussing patient wants versus patient needs. Following this, in 2016, the AMI Visionary programme launched a new concept that changed the way that we consult with our patients . The emotional attributes approach took a closer look at personal motivations for seeking treatment with patient feels. In 2017, the AMI Distinction programme brought everything together with the MD Codes Formulas™ to guide the holistic treatment of the emotional attributes with the MD Codes™.

I am thrilled to introduce a new programme in 2018 – AMI Expression – where the theme ‘patient expresses’ is brought to life. The need to start assessing our patients on animation both before and after treatment is the newest trend in medical aesthetics.

With this in mind we will explore two new concepts: dynamic beauty and dynamic ageing, and the importance of considering them in our treatment plans.

Ageing is a dynamic process. We can predict where aesthetic lines will appear at rest by assessing patients on animation.

Dynamic lines occur before static lines. Can we really avoid the appearance of static lines, and thus the ageing process?

Maybe not, but can we slow it down and maintain a youthful look for longer? That’s for sure.

We don’t go to bed looking young and wake up the following morning looking old.

This book presents part one of our journey into the world of facial dynamics and myomodulation. As we always should, let’s start at the beginning with the underlying principles. In this volume, I will explain the dynamic muscle relationships involved in facial expression and their impact on overall appearance. I will also introduce my new clinical tool – the MD DYNA Codes™, developed specifically for structures that move – by exploring the general principles of chemical and mechanical myomodulation.

I would like to thank Courtney Kennedy, Mark Chaplin and Maggie Liu from the AMI for their productive discussions and support. I would also like to thank Victoria Kay and the Litmus Medical Communications teams for bringing this book to life.

Dr Mauricio de Maio Plastic Surgeon, Brazil June 2018

Adverse events should be reported to your local regulatory authority and Allergan office

Produced and funded by Allergan.

All case studies are provided by Dr Mauricio de Maio with permission to use. Patient images are provided by Allergan and Dr Mauricio de Maio. The MD DYNA Codes™ have been developed by Dr Mauricio de Maio and all recommendations presented in this guide are based on his clinical experience and personal opinion. Please refer to local product licences and the ‘Directions for Use’ for each product. Responses to treatment may vary between patients.

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Contents Introduction Our clinical tools and products ����������������������������������������������������������������������������������������������� 7 Patient expresses The importance of facial expression �������������������������������������������������������������������������������������� 11 The anatomy of facial expression Understanding muscle function ������������������������������������������������������������������������������������������� 19 Introducing the MD DYNA Codes™ Underlying principles of chemical myomodulation ���������������������������������������������������������������� 29 Underlying principles of mechanical myomodulation ������������������������������������������������������������ 33 Putting principles into clinical practice Case study 1: Assessment with MD ASA™ ������������������������������������������������������������������������������� 41 Case study 1: Treatment planning with the MD DYNA Codes™ ������������������������������������������������ 66 Case study 2: Assessment with MD ASA™ ������������������������������������������������������������������������������� 79 Case study 2: Treatment planning with the MD DYNA Codes™ ���������������������������������������������� 100 References ����������������������������������������������������������������������������������������������������������������������� 113 Prescribing information �������������������������������������������������������������������������������������������������� 117

Introduction

Our clinical tools and products

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What are the MD Codes™?

The MD Codes™ are the structural codes.* They are designed to raise awareness that each aesthetic facial unit (e.g. cheek, chin, lips) comprises subunits that must be respected during injection. These subunits – the MD Codes™ – are the structural sites that aim to create or recreate the most desirable facial architecture for patients.

What are the MD DYNA Codes™?

The MD DYNA Codes™ are the dynamic codes. They are injection techniques for the precise placement of product with respect to the influence on muscle activity, designed to deliver natural facial expression and avoid or correct an abnormal facial appearance on animation.

What is MD ASA™?

MD ASA™ (Multi-Dimensional Aesthetic Scan Assessment) is a facial assessment tool.† It introduces a system of aesthetic hierarchy to organise the patient assessment process and train the brain to decipher complex and unveiled signs of the face.

MD ASA™ can be administered when the face is at rest and on animation, before and after treatment.

MD D NA Codes™

MD ASA™

• The structural codes

• The dynamic codes

• System for facial assessment

• Builds facial structure by creating foundation, contour and refinement

• Optimises expression by modulating muscle function

• Identifies and helps to decipher complex facial messages

• For facial enhancement on animation

• For assessment at rest and on animation

• For facial enhancement at rest

*For more information on the MD Codes™, please refer to the book Unlocking the code to facial revitalisation: A step-by-step approach to using injectables with the MD Codes™, † For more information on MD ASA™, please refer to the book Unlocking the unveiled signs of the face: Volume 1 – An advanced approach to facial assessment with MD ASA™.

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Linking our three clinical tools together A sophisticated approach to facial aesthetics starts with proper assessment and diagnosis. For this we can apply MD ASA™ at rest and on animation. When the face is at rest, MD ASA™ can help to identify the emotional attributes* and determine the required structural improvements (the MD Codes™) to enhance overall facial appearance. When the face is animated, MD ASA™ is applied to assess muscle function and determine the proper technique and precise placement of product to optimise facial expression (the MD DYNA Codes™).

We now have three systems to refine our approach to treatment and provide a strong foundation to showcase our scientific artistry.

Facial assessment at rest

MD ASA™

Facial assessment on animation

MD D NA Codes™ • Foundation, contour and refinement

• Muscle dynamics and modulation

• Correcting deficiencies in structure and enhancing structural features

• Correcting or avoiding abnormalities in expression

• Emotional attributes at rest

• Dynamic beauty and dynamic ageing

*For more information on the emotional attributes approach to patient consultation and treatment, please refer to the book Unlocking the messages of the face: Addressing emotional attributes with the MD Codes™ Formulas.

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Choosing the right products The MD Codes™ and MD DYNA Codes™ have been specifically developed for use with Allergan products. For more information on Allergan products and their indications, please refer to your local prescribing information or ‘Directions for Use’ documents.

VISTABEL® (botulinum toxin type A) VISTABEL® is for the temporary improvement in the appearance of specific facial lines when the severity has an important psychological impact in adult patients.1 VISTABEL® is a distinct Clostridium botulinum type A neurotoxin complex,2 consisting of an ~900 kDa complex containing a ~150 kDa neurotoxin core and a full complement of accessory proteins.3 This has been shown to produce the following effects and outcomes:

• Blocks neuromuscular transmission,4 producing partial chemical denervation of the muscle5 • Exhibits a targeted effect, demostrating limited migration from the point of injection 6

JUVÉDERM® The JUVÉDERM® range of hyaluronic acid injectables utilises two technologies: VYCROSS® and HYLACROSS®.

• VYCROSS® is JUVÉDERM®’s advanced technology, so you can apply your skill and artistry for full facial enhancement • HYLACROSS® sets the standard for facial injectables, with established results and trusted technology13,14 The VYCROSS® range comprises Juvéderm® VOLUMA with lidocaine,15 Juvéderm® VOLIFT with lidocaine,16 Juvéderm® VOLBELLA with lidocaine,17 and Juvéderm® VOLITE.18 The HYLACROSS® range comprises Juvéderm® ULTRA19 and Juvéderm® ULTRA PLUS,20 which do not contain lidocaine. Juvéderm® ULTRA XC and Juvéderm® ULTRA PLUS XC formulations are the same products respectively, but with lidocaine.

Patient expresses

The importance of facial expression

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Moving beyond facial revitalisation at rest We are used to assessing the face at rest and are skilled at optimising static features and deficiencies. The emotional attributes approach has taught us that our resting faces often portray messages or emotions that don’t reflect how we feel on the inside. The MD Codes™ and MD Codes™ Formulas have provided the tools to help us improve these emotional attributes and, consequently, outcomes for our patients. But we should not forget to consider the effect that facial expression has on our appearance and on how we portray ourselves to others.

A common fear that our patients have is that their results will look unnatural. It is not enough to improve the face at rest. The treatment impact on muscle function has to be considered so that natural results, both at rest and on animation, are achieved.

With this in mind, let’s consider a new concept – patient expresses. Give each patient a rating from 0 to 10 at rest, where 10 is the best that they could look for their age and ethnicity, and zero is the worst. Please bear in mind that no one is a 10 and no one is a zero! Then ask the patient to smile. Does the number increase (upgrade) or decrease (downgrade)? What are the favourable and unfavourable signs that are present on animation and/or at rest? How should we adapt our treatment plan to preserve the favourable signs, optimise the unfavourable signs and maintain natural expression?

We now have four concepts to help us to individualise treatment as we aim to provide the best possible outcome for each patient.

Patient wants

Patient needs

Patient feels

Patient expresses

Patient’s perceptions of their appearance

Expert's opinion of clinical priorities

Patient’s emotional motivation for seeking treatment

Patient’s fear of unnatural expression

The face speaks – Multi-Dimensional Aesthetic Scan Assessment (MD ASA™)

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Reading the face with MD ASA™ The Multi-Dimensional Aesthetic Scan Assessment (MD ASA™) is a tool to organise assessment of the face at rest and on animation. The face speaks and we must be able to read it. What our patients see in the mirror often differs from how they see themselves in photos and how they are perceived by others. MD ASA™ will help them to bridge this gap.

The aesthetic hierarchy forms the basis of MD ASA™ and defines the systematic process of facial evaluation, all the way from full facial assessment (hierarchy 1 or H1) to identification of individual distractions on the face (H5). The ideal outcome should focus on H1, where the unfavourable messages are reduced when the patient looks in the mirror, at themselves in photos and when they are observed by others. However, patients often come to us with a request that falls lower down the hierarchy and focuses on tiny distractions. MD ASA™ is a useful assessment tool to integrate all of the facial hierarchies and deliver the most favourable outcome.

We have to teach the patient to differentiate what is important from what is just annoying to them. It is very common for them to say, ‘I hate this line’; however, the treatment of this tiny, annoying distraction is unlikely to impact their overall message. So it can be considered unimportant.

At rest

Smiling H1: Full face: Analysis Patient feels: Emotional attributes

H2: Facial thirds and neck: Analysis Patient presents: Symmetry and proportion

H3: Periorbital and perioral: Analysis Patient expresses: Animation H4: Facial units: Analysis Patient needs: Key facial units or areas H5: Facial subunits: Analysis Patient wants: Distractions

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The face speaks: Dynamic beauty Do we all look better when we smile?

The answer is that we should, but it is not true for everyone. Patients who upgrade their appearance when they smile are generally easier to treat than those who do not. Assuming that we are all slightly asymmetric, key features of dynamic beauty are the absence of significant asymmetry on animation, and a balanced or co-ordinated movement of facial structures.

Please observe this patient. At age 58, she presents negative messages such as tiredness, sadness and sagginess at rest. When the face animates into a smile, all of these messages disappear. She looks more attractive and younger. Why? Because her cheeks are lifted, her jowls and marionette lines disappear and her eyebags reduce in severity. This is the concept of dynamic beauty. Please note that when she smiles there are more lines around the eyes and a deeper nasolabial fold. She looks better despite the fact that she has more lines. It is very common that patients like her visit us complaining about crow's feet lines and the nasolabial fold, though treatment here would have no impact on her appearance. This example clearly shows us the power of dynamic beauty even in mature patients. The challenge for injectors is to treat her at rest and maintain the attractiveness that she had on animation without any treatment. This is the role of the MD DYNA Codes™.

At rest

Smiling 58 years

Suboptimal appearance

Optimal appearance

When trying to upgrade a suboptimal appearance at rest, we may end up downgrading an optimal appearance on animation that was present before treatment. Understanding the concept of myomodulation will help us to overcome this challenge and avoid unnatural outcomes.

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The face speaks: Dynamic ageing The ageing process affects multiple facial layers: the bony skeleton, fat pads, mimetic muscles and skin.21–23 Volume loss at the bone and fat pad levels may impact muscle behaviour by reducing soft tissue support, reducing the facial height and altering the distance from muscle origin and insertion points.23 Over the years the impact of constant muscle activity and the repetitive trauma on the skin may produce localised fractures known as lines.24 Ageing leads to an increment of facial lines both at rest and on animation.25 Ageing is a dynamic process and its impact may be reduced if we start assessing our patients on animation.26 In youth, lines will first appear when the face is animated, but with age these same lines will gradually become visible and static at rest as skin changes become permanent.23,26 The concept of dynamic ageing will help us to understand the role of muscle activity during the ageing process and to find treatments to reduce the negative impact of muscles on the skin surface.26 Let us observe the mother and daughter below. The MD Codes™ can treat the facial lines at rest, and the MD DYNA Codes™ can treat those present on animation. For the daughter, treatment with the MD DYNA Codes™ may reduce her dynamic lines and avoid their conversion to static lines.

Mother, 41

Daughter, 19

Kissing

Mother, 41

Daughter, 19

At rest

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Facial expressions change with age Although the human face can express a multitude of positive and negative emotions, here we will focus on the most common features that we can improve with injectables. Please observe that the degree of severity of dynamic lines is linked to age.

In the daughters, we can see the early signs of what is to come, meaning that we can take action earlier.

Mother, 58

Daughter, 47

Mother, 67

Mother, 58

Daughter, 47

Mother, 67

Daughter, 25

Anger (action: Frown)

Daughter, 25

Surprise (action: Raised brows)

Daughter, 47

Mother, 67

Daughter, 47

Mother, 67

Daughter, 25

Mother, 58

Affection (action: Kiss)

Mother, 58

Daughter, 25

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Happiness (action: Smile)

Mother, 67

Daughter, 47

Mother, 58

Daughter, 25

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Disappointment (action: Baby cry)

The anatomy of facial expression

Understanding muscle function

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The mimetic muscles of the face Emotions are often revealed through the gestures of face and body rather than verbal communication,27 and may be conveyed through a range of microexpressions.28 Because of this complexity of movement, the face must be viewed as a three-dimensional moving unit, not an isolated photograph.28 Facial (mimetic) muscles are responsible for the expression and appearance of a face. Mimetic muscles work differently in comparison with other skeletal muscles because they move the skin instead of joints,27 which may play a role in bone and tissue interactions within the ageing face.30 They are thin, flat muscles that act either as elevators and depressors, or as sphincters of facial orifices.29 Generally, facial mimetic muscles have their origin in the bone, and insert on the skin or among the fibres of other muscles.30 Differences may also be seen under histological examination, where smaller fibre sizes and greater variation in fibre size may be observed in facial mimetic muscles compared with limb muscles.31,32 Facial muscles contain mostly type II muscle fibres, which typically contract quickly in brief bursts.32 These muscles are not able to sustain contraction for long periods of time.32 Finally, facial mimetic muscles appear to lack typical muscle spindles.33,34 Three key concepts affect the role of muscle action on facial appearance: muscle pulley and lever systems, length–tension relationship, and the action of synergist muscle groups and antagonist muscle pairs.30 Facial expressions are most visible in two key regions – the periorbital and perioral areas.

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MD DYNA Codes™: The muscles of expression Periorbital expression

Perioral expression

MD DYNA Codes™

Muscle

MD DYNA Codes™

Muscle

F

Frontalis

N

Nasalis

C

Corrugator supercilii

LAN

Levator labii superioris alaeque nasi

P

Procerus

LLS

Levator labii superioris

OOc

Orbicularis oculi

LAO

Levator anguli oris

ZMj

Zygomaticus major

ZMi

Zygomaticus minor

DSN

Depressor septi nasi

B

Buccinator

OO

Orbicularis oris

R

Risorius

DAO

Depressor anguli oris

DLI

Depressor labii inferioris

M

Mentalis

PL

Platysma

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MD DYNA Codes™: The muscles of periorbital expression

F

F

C

C P

OOc

Figure adapted from Holmes S, 2016.35 For illustrative purposes only.

OOc

23

F

Frontalis

C

Corrugator supercilii

P

Procerus

OOc

Orbicularis oculi

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MD DYNA Codesâ„¢: The muscles of perioral expression

N

*

LAO

N

DSN

R

LAN LLS

ZMi ZMj

OO

OO

DAO

DLI

PL

*Deep to upper lip levators.

Figure adapted from Holmes S, 2016.35 For illustrative purposes only.

M B*

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N

Nasalis

LAN

Levator labii superioris alaeque nasi

LLS

Levator labii superioris

LAO

Levator anguli oris

ZMj

Zygomaticus major

ZMi

Zygomaticus minor

DSN

Depressor septi nasi

B

Buccinator

OO

Orbicularis oris

R

Risorius

DAO

Depressor anguli oris

DLI

Depressor labii inferioris

M

Mentalis

PL

Platysma

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The superficial musculo-aponeurotic system (SMAS) The SMAS is a fibrofatty superficial fascia consisting of an envelope of collagen fibres, elastic fibres and fat cells.29 This is where the mimetic muscles and overlying dermis are enveloped and interconnected.29 Considerable variability exists in the histological appearance of the SMAS.37 It plays an important functional role in appearance and in facial expression,29 as it is responsible for connecting the facial muscles to the dermis.22,38

Epidermis Dermis

Fibrous septum

SMAS

Vessels Fascia Muscle Motor nerves Adipose tissue

Figure adapted from AO foundation; accessed December 2017.39 For illustrative purposes only.

Figure adapted from Gosain AK, 1993.37

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Muscles function in synergist/antagonist pairs The role of functional synergist and antagonist muscle groups and pairs is understood to be crucial in biomechanical efficiency of movement around joints.40,41 With mimetic muscles, consideration of this concept is largely limited in literature to the opposing actions of brow levators and depressors, which has guided clinical practice.28,42 The role of muscle synergists and antagonists in other facial areas has historically received less attention.

Muscles rarely act in total isolation.43 Antagonistic muscle action may be defined as muscles working together to allow co-ordinated movement. Synergistic muscle action holds a steady position so that the muscle-flexing action is more effective.44 Throughout the face, the actions of functional synergist and antagonist muscles contribute to facial movement and appearance.30

Contraction of the frontalis (F) muscle with its synergistic occipitalis (O) and antagonistic action of the procerus (P), corrugator supercilii (C) and orbicularis oculi (OOc) Galea aponeurotica

F O

F

F

C OOc

OOc Figure adapted from Holmes S, 2016.35 For illustrative purposes only.

C P

OOc

OOc

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Ageing can disrupt the synergist/antagonist relationship The fine balance that exists between synergistic and antagonistic mimetic muscle pairs allows for a myriad of facial expressions.30 If the action of one muscle is completely eliminated, it can cause an imbalance that significantly changes the face’s emotive ability.41 In the mimetic muscles, such an imbalance may result from facial nerve impairment, structural deficiencies or changes in muscle action due to natural ageing, and is observed in both the appearance and the expressive ability of the face.30 Understanding the complex interactions of facial muscles and the loss of stability on their action will help injectors better assess and treat each individual face. This allows the injector to personalise the treatment plan with neuromodulators and hyaluronic acid.30 In contrast, failure to fully understand the interplay between mimetic muscles can result in inadequate or inappropriate treatment that may produce an unnatural appearance. The complexity of the face and it's different expressions suggest that planning and technique are critical to achieve an optimal result.42 A clear example of the synergist–antagonist relationship during the ageing process – between the zygomaticus major and depressor anguli oris – will be discussed in more detail later on.

Introducing the MD DYNA Codes™

Underlying principles of chemical myomodulation

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Neuromodulation: Producing temporary muscle relaxation through chemical denervation45 Neuromodulators are used to reduce muscle movement in overacting muscles to diminish the appearance of dynamic lines.42 The neurotoxin botulinum toxin type A (BoNTA) undergoes a four-step process of 1) cell binding; 2) internalisation; 3) translocation and cleavage; and 4) blockage of acetylcholine release.45

1. Cell binding

2. Internalisation

A

C

BoNTA

BoNTA

Accessory proteins

A. Following injection, BoNTA dissociates from the accessory proteins;45 the precise timing of this dissociation is unknown46

B

C. The binding of BoNTA to its receptor initiates a process termed receptor-mediated endocytosis, which results in the internalisation of the neurotoxin47

D BoNTA

Receptor

B. BoNTA binds to receptors at the axon terminal of the neuron, at the neuromuscular junction45

BoNTA Vesicle

D. This internalisation results in BoNTA being packed inside vesicles47

Images developed by Allergan. For illustrative purposes only.

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3. Translocation and cleavage

4. Blockage of acetylcholine release

E

Neurotransmitter (acetylcholine)

G

Vesicle

Vesicle

Neurotoxin heavy chain

Neurotoxin light chain Axon terminal

SNAP 25

SNAP 25 Axon terminal

E. After internalisation, the light chain is released from the vesicle into the axon terminal47

F

G. The cleavage of SNAP 25 inhibits the formation of the SNARE complex45

H Neurotransmitter (acetylcholine)

SNAP 25 Neurotoxin light chain

Axon terminal

SNAP 25

Acetylcholine receptor Muscle fibre

F. In the axon terminal, the light chain cleaves SNAP 2547

H. Without the SNARE complex, the vesicle cannot release acetylcholine to initiate muscle contraction, producing flaccid muscle paralysis45 Images developed by Allergan. For illustrative purposes only.

Introducing the MD DYNA Codes™

Underlying principles of mechanical myomodulation

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Muscle mechanics change with age A lever–fulcrum mechanism supports muscle function48 In youth, normal facial structure (underlying bone and fat) creates a fulcrum that gives muscle fibres convexity and supports the powerful contraction of the levator muscles.23 The levator and depressor muscles work in balance to keep facial structures in their normal position, including the anchoring point.

Deflation of facial structure with age moves the anchoring point 49 With ageing, deflation of the fat pads and loss of bone structure reduce the underlying support for muscle function.50 The mechanical advantage provided by the lever–fulcrum mechanism is diminished49 and the levator loses lifting power to counteract gravity. Muscle fibres are stretched as skin sags.23,50 With reduced opposition, the depressor muscle increases in tone over time and pulls facial structures downward in a domino effect.

Normal/Youth

Ageing

Levator muscle Skin

Fat

Levator muscle Skin

Bone

Fat Bone

Anchoring point Anchoring point Sagging Depressor muscle

Depressor muscle Images developed by Allergan and adapted from de Maio M, 2018.30 For illustrative purposes only.

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Hyaluronic acid injectables replace lost volume Precise injection of hyaluronic acid can return structures to their correct location A hyaluronic acid bolus placed below the muscle can replace lost volume to rebuild the fulcrum, increasing the mechanical advantage of the levator muscle and strengthening its power of contraction.30 The extra volume reduces sagging, but also indirectly reduces contraction of the depressor muscle, reversing some of the changes triggered by ageing.30

Precise injection of hyaluronic acid can alter the distance between muscle origin and insertion A hyaluronic acid bolus placed under the muscle will increase convexity and bring the origin and the insertion closer together, facilitating muscle contraction. A hyaluronic acid bolus placed above the muscle adds volume that stretches the muscle fibres, extending the distance between origin and insertion.30 The longer the distance, the greater the work ‘effort’ to contract the muscle. With ageing the loss of volume (bone and fat pads) leads to a longer distance between, for example, the zygomatic arch and the oral commissure, leading to hyperextended fibres and more work to lift the oral commissure.30 As a result, there is facilitated action of the antagonist, depressor anguli oris (DAO), that pulls down the oral commissure. In this instance, a hyaluronic acid injection placed below the zygomatic major (ZMj) will facilitate its contraction, and another injection placed above the depressor anguli oris (DAO) will reduce its contraction, leading to the lifting of the oral commissure. Thus, the impact of dynamic ageing can be reduced with mechanical myomodulation with injectables.

Hyaluronic acid below muscle

Hyaluronic acid above muscle

Levator muscle (ZMj)

Levator muscle (ZMj)

Origin

Origin

Skin

Skin Hyaluronic acid injectable

Hyaluronic acid injection below the ZMj to facilitate its contraction

ZMj insertion

Lifts anchoring point (oral commissure)

ZMj insertion

DAO insertion Hyaluronic acid injection above the DAO to decrease its contraction

Lowers anchoring point (oral commissure) DAO insertion

Hyaluronic acid injectable

Depressor muscle (DAO)

Depressor muscle (DAO)

Origin

Origin Images developed by Allergan and adapted from de Maio M, 2018.30 For illustrative purposes only.

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Mechanical myomodulation: Mode of action Unlike with chemical myomodulation, where the mode of action causes a decrease in muscle function, mechanical myomodulation presents two opposing modes of action, depending on the placement of hyaluronic acid filler in relation to the muscle fibres.30

Place hyaluronic acid above the muscle

Place hyaluronic acid below the muscle

Muscle fibres stretch

Lever effect created

Reduction of muscle action

Facilitation of muscle action

Mechanical myomodulation of the upper lip levators: Smile line

Gummy smile

Asymmetic smile

Reduce upper lip levators

Facilitate left upper lip levators

Lower smile line

Balance smile line

Images developed by Allergan. For illustrative purposes only.

37

Decrease muscle action – excessive gummy show

Objective: Reduce action of upper lip elevators

Desired outcome: Lower smile line; no gummy show

Increase muscle action – asymmetrical smile with low smile line

Left side weaker Objective: Facilitate zygomaticus major (left only) and levator labii superioris (left only)

Desired outcome: Symmetrical smile with higher smile line; more teeth shown

Images developed by Allergan. For illustrative purposes only.

Putting principles into clinical practice

Treatment planning with MD ASA™ and the MD DYNA Codes™

Case study 1: Assessment with MD ASA™ H1: Full face Patient feels: Emotional attributes

42

H1: Full face

Age, 33

Assess the overall message of the face

43

H1: Full face What are the top three emotional attributes that this patient needs to improve?

Expert perspective Less tired

Patient perspective 1

Less sad

Less tired

2

Less sad

Less saggy

2

Less saggy

Less angry

3

Less angry

More attractive

More attractive

Younger

Younger

Slimmer/more contoured

Slimmer/more contoured

More feminine

More feminine

1

3

44

H1: Full face

Age, 33

Does facial appearance upgrade on animation?

Upgrades In this case the patient slightly downgrades her appearance on animation due to the asymmetry of her smile.

Equivalent Downgrades

X

45

H1: Full face Which is her best side?

She presents with moderate asymmetry at rest and it is difficult to assess which side is her best. We need a more detailed approach.

Left side

Age, 33

Right side

46

H1: Full face What about when we separate the sides?

Is there a side where she looks softer and more feminine? It is still difficult to assess.

Left side

Age, 33

Right side

47

H1: Full face Which is her best side?

Let us now create mirror images comprising two right sides and two left sides of the face. When compared with her actual image, can you now identify which side is best?

Actual

Two left sides

Her two right sides is her best image. Her facial shape is more oval, her nose is more delicate and she looks more feminine.

Her actual image presents moderate asymmetry of her jawline.

It is evident here that this is her worst image.

Her nose is too broad and her jawline too masculine.

Age, 33

Two right sides

48

H1: Full face Which is her best smile?

When compared with her actual image, can you now identify which side produces the best smile?

Actual

Two left sides

Her smile on the right side is clearly the most attractive, indicating that symmetry on animation is critical for her.

In her actual image, she presents with an asymmetric smile.

The presence of a ‘DAO (depressor anguli oris) smile’ on her left side is a negative feature.

Age, 33

Two right sides

Case study 1: Assessment with MD ASA™ H2: Facial thirds and neck Patient presents: Symmetry and proportion

50

H2: Facial thirds and neck

Age, 33

Upper third

Ideal Favourable Acceptable Unfavourable

X

There is an absence of distractions (facial lines) in the upper face, and there is good proportion between forehead width and height. Her eyebrows are in a favourable position, despite the mild asymmetry.

51

H2: Facial thirds and neck

Age, 33

Mid third

Ideal Favourable Acceptable Unfavourable

X

The infraorbital area is unfavourable as the patient presents with eyebags.

52

H2: Facial thirds and neck

Age, 33

Lower third

Ideal Favourable Acceptable Unfavourable

X

There is heaviness in the lower cheeks, but overall appearance in the lower third is acceptable.

53

H2: Facial thirds and neck

Age, 33

Neck

Ideal Favourable Acceptable Unfavourable

X

There is an absence of sagginess and submental fat, creating a favourable appearance for her age in the neck.

Case study 1: Assessment with MD ASA™ H3: Periorbital and perioral Patient expresses: Animation

56

H3: Periorbital and perioral analysis Patient expresses: Anger Frowning

Age, 33

At rest

Upgrades Glabellar lines appear when the face animates into a frown, downgrading her appearance in the periorbital area.

Equivalent Downgrades

X

57

H3: Periorbital and perioral analysis Patient expresses: Happiness Smiling

Age, 33

At rest

At rest this patient presents with eyebags, which downgrade her. When smiling she presents with asymmetry in her eyes and the presence of periorbital lines, which also downgrade her appearance.

We select equivalent whenever the distractions downgrade her appearance both at rest and on animation to the same degree. Although the issues are different, periorbital appearance is downgraded to the same degree when at rest or smiling, so we select the equivalent option.

Upgrades Equivalent Downgrades

X

58

H3: Periorbital and perioral analysis Patient expresses: Surprise Raised brows

Age, 33

At rest

Upgrades Equivalent When her brows are raised she presents with forehead lines, which downgrade her appearance.

Downgrades

X

59

H3: Periorbital and perioral analysis Patient expresses: Happiness Smiling

Age, 33

At rest

Upgrades The patient presents with an asymmetric smile that downgrades the appearance of the perioral area.

Equivalent Downgrades

X

60

H3: Periorbital and perioral analysis Patient expresses: Affection Kissing

Age, 33

At rest

Upgrades Equivalent Perioral lines appear when kissing, which downgrade her appearance.

Downgrades

X

61

H3: Periorbital and perioral analysis Patient expresses: Disappointment Baby cry

Age, 33

At rest

Upgrades When creating the ‘baby cry’ action, the patient presents with upper lip lines and lower lip eversion, which downgrade her appearance.

Equivalent Downgrades

X

Case study 1: Assessment with MD ASA™ H4: Facial units Patient needs: Key facial units or areas

63

H4: Facial units Patient needs prioritised for treatment Select the unfavourable or acceptable structural deficits, and the negative equivalents or downgrading animation deficits.

Structural deficits Ideal

Age, 33

Favourable

Unfavourable

Acceptable

X

Unfavourable

X

Acceptable

Animation deficits

Upgrades Downgrades

Equivalent

Downgrades

Downgrades

Downgrades

Downgrades

Equivalent

X

Downgrades

X

Case study 1: Assessment with MD ASA™ H5: Facial subunits Patient wants: Distractions

65

H5: Facial subunits Patient wants disclosed during initial consultation Forehead lines

Saggy cheeks

Age, 33

Crow’s feet lines

Clinical evaluation: Mild Moderate Severe

Mild X

Moderate Severe

Mild X

Moderate Severe

X

Case study 1: Treatment planning with the MD DYNA Codes™ Chemical myomodulation

67

The MD Codes™ Equations for H4 and H5

Glabellar lines

MD D NA Codes™ C+P

Age, 33

G1 + G2

Crow’s feet lines

MD D NA Codes™

Age, 33

O1 + O2 + O3

OOc

68

VISTABELÂŽ treatment: Glabellar lines

C

C

Age, 33

P

Dose: 20 U1

For illustrative purposes only.

Treatment should always be based on individual patient needs. Please refer to Summary of Product Characteristics for full product information.

69

VISTABELŽ treatment: Crow’s feet lines

Age, 33

OOc

Dose: 12 U per side1

For illustrative purposes only.

Treatment should always be based on individual patient needs. Please refer to Summary of Product Characteristics for full product information.

70

After treatment with VISTABELÂŽ

Age, 33

Treatment of the glabellar lines and crow’s feet lines has indirectly softened the angry appearance of the upper face.

Before

After 4 days

Age, 33

When smiling there are fewer periorbital lines and the eyebrows are raised, brining more energy to her eyes.

Before Ideal

X

Favourable

After 4 days Acceptable

Unfavourable

Treatment should always be based on individual patient needs. Please refer to Summary of Product Characteristics for full product information.

Case study 1: Treatment planning with the MD DYNA Codes™ Mechanical myomodulation

72

Aesthetic rehabilitation of an asymmetric smile As we determined with MD ASA™, our 33-year-old patient presents with an asymmetric smile. Observe the left side of her face – particularly the presence of a saggy and heavy cheek, downturn of the oral commissure and wrinkling in the lower chin.

Smiling

Age, 33

At rest

73

Which muscles are responsible?

This asymmetry is the result of the loss of balance between the zygomaticus major muscle and its antagonist, the depressor anguli oris (DAO) muscle. When the patient smiles, the action on her right side more effective due to contraction of the zygomaticus major. On her left side the zygomaticus major is less efficient, meaning that the DAO is able to contract and pull down the corner of the mouth.

Age, 33

To correct this, we need to facilitate the action of the zygomaticus major on her left side, converting a DAO smile into a zygomatic smile and thus reducing overall asymmetry.

Right side: Zygomatic smile

Left side: DAO smile

For illustrative purposes only.

74

What are the MD DYNA Codes™ for this patient?

Here we focus on the left side of the patient’s face to restore the lever–fulcrum balance. By placing volume below the zygomaticus major muscle we can facilitate contraction. By placing volume above the DAO muscle we can reduce contraction.

Careful placement of precise volumes of hyaluronic acid can re-balance the relationship between the zygomaticus major and DAO muscles on the left side. This will facilitate the zygomaticus major to raise the oral commissure to the same degree as observed on the right side, reducing asymmetry of the smile.

MD D NA Codes™

Age, 33

Left side Saggy and heavy cheek

Ck1 + Ck2 + Ck4

ZMj

Downturn of oral commissure

C1

DAO

Lower chin wrinkling

Jw4

DAO

75

After treatment with JUVÉDERM®: Smile After

Age, 33

Before

Ideal Favourable

X

After treatment with the MD DYNA Codes™ her smile is more symmetrical. Please note the alignment of the upper lip and teeth.

Acceptable Unfavourable

The patient received hyaluronic acid filler in the cheeks (2.6 mL), chin (1.5 mL) and jawline (0.5 mL). She also received treatment in her nasolabial folds (1.4 mL) and lips (1.0 mL). Overall the patient received 7.0 mL of product. Four days prior, the patient had received VISTABEL® as previously described.

76

After treatment with JUVÉDERM®: At rest After treatment the patient looks more contoured and better proportioned. Observe the width of her mouth and jawline. Her eyebags have also improved.

After

Age, 33

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), chin (1.5 mL) and jawline (0.5 mL). She also received treatment in her nasolabial folds (1.4 mL) and lips (1.0 mL). Overall the patient received 7.0 mL of product. Four days prior, the patient had received VISTABEL® as previously described.

77

After treatment with JUVÉDERM®: At rest Overall the patient looks younger, less tired, more attractive and less saggy. She now has fuller cheeks with better defined cheek bones and her lips look fuller.

After

Age, 33

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), chin (1.5 mL) and jawline (0.5 mL). She also received treatment in her nasolabial folds (1.4 mL) and lips (1.0 mL). Overall the patient received 7.0 mL of product. Four days prior, the patient had received VISTABEL® as previously described.

Case study 2: Assessment with MD ASA™ H1: Full face Patient feels: Emotional attributes

80

H1: Full face

Age, 37

Assess the overall message of the face

81

H1: Full face What are the top three emotional attributes that this patient needs to improve?

Expert perspective

Patient perspective

Less tired

2

Less tired

Less saggy

3

Less saggy

Less angry Less sad

1

Less angry 1

Less sad

Younger

Younger

More feminine

More feminine

More attractive

More attractive

Slimmer

Slimmer

3

2

82

H1: Full face

Age, 37

Does facial appearance upgrade on animation?

There are unfavourable features at rest, such as eyebags and chin dimpling. When smiling, there is skin excess in her lower eyelid, with multiple lines and the presence of a gummy smile and downturn of the tip of the nose. She needs improvement, both at rest and on animation.

Upgrades Equivalent Downgrades

X

83

H1: Full face Which is her best side?

She presents moderate asymmetry at rest and it is difficult to assess which side is her best. We need a more detailed approach.

Left side

Age, 37

Right side

84

H1: Full face What about when we separate the sides?

We observe practically the same distractions on both sides and the decision making continues to be challenging. Let’s go on.

Left side

Age, 37

Right side

85

H1: Full face Which is her best side?

Let us now create mirror images comprising two right sides and two left sides of the face. When compared with her actual image, can you now identify which side is best?

Actual

Two left sides

There are problems with proportion. The face is too wide and the nose too narrow.

Although not ideal, her actual image is more balanced despite the mild asymmetries.

There are problems with proportion. The face is too narrow and the nose is too broad.

Age, 37

Two right sides

Conclusion: For this patient, improving her symmetry is not important.

We should prioritise reducing the negative messages of the face.

86

H1: Full face Which is her best smile?

When compared with her actual image, can you now identify which side produces the best smile?

Actual

Two left sides

Although she presents with fewer lines in the lateral periorbital area and cheeks, her gummy smile is very distracting.

The mild asymmetry, with multiple dynamic lines and gummy smile, produce an unfavourable appearance.

She presents with an increase in lines, both in the periorbital and cheek areas.

Age, 37

Two right sides

Conclusion: Her appearance on animation is a top priority for correction.

Case study 2: Assessment with MD ASA™ H2: Facial thirds and neck Patient feels: Symmetry and proportion

88

H2: Facial thirds and neck

Age, 37

Upper third

Ideal Favourable Acceptable Unfavourable

X

Her upper third is favourable but not ideal due to the shape of the brows. At rest, it is not a priority for treatment.

89

H2: Facial thirds and neck

Age, 37

Mid third

Ideal Favourable Acceptable Unfavourable

X

The presence of eyebags and sadness in the eyes requires correction.

90

H2: Facial thirds and neck

Age, 37

Lower third

Ideal Favourable Acceptable Unfavourable

X

The small chin, as well as wrinkling and sadness in the mouth area, requires correction.

91

H2: Facial thirds and neck

Age, 37

Neck

Ideal Favourable Acceptable Unfavourable

X

The neck can be considered favourable due to the absence of distractions such as lines, skin excess or submental fat deposits. She is not ideal due to skin quality.

Case study 2: Assessment with MD ASA™ H3: Periorbital and perioral Patient expresses: Animation

93

H3: Periorbital analysis Patient expresses: Happiness Smiling

Age, 37

At rest

Upgrades Here we select ‘equivalent’ because she presents unfavourable distractions both at rest and on animation.

Equivalent Downgrades

X

94

H3: Perioral analysis Patient expresses: Happiness Smiling

Age, 37

At rest

At rest she looks sad. On animation her gummy smile and droop of the tip of the nose have a negative impact on her appearance. Thus, she needs treatment both at rest and on animation.

Upgrades Equivalent Downgrades

X

95

H3: Perioral analysis Patient expresses: Affection Smiling

Age, 37

At rest

Although she needs treatment at rest, on animation she presents more distractions with a higher degree of severity, such as hollow cheeks, perioral lines and chin wrinkling. Overall her appearance is downgraded on animation.

Upgrades Equivalent Downgrades

Conclusion: In her case, treating the kissing expression is more important than treating her gummy smile.

X

Case study 2: Assessment with MD ASA™ H4: Facial units Patient needs: Key facial units or areas

97

H4: Facial units Patient needs prioritised for treatment Select the unfavourable or acceptable structural deficits, and the negative equivalents or downgrading animation deficits.

Structural deficits Ideal

Age, 37

Favourable

Unfavourable

Acceptable

X

Unfavourable

X

Unfavourable

Animation deficits Upgrades

Downgrades

Downgrades

Downgrades

Equivalent

X

Downgrades

X

Case study 2 : Assessment with MD ASA™ H5: Facial subunits Patient wants: Distractions

99

H5: Facial subunits Patient wants disclosed during initial consultation Nasolabial folds

Glabellar lines

Age, 37

Crow’s feet lines

Clinical evaluation: Mild

Mild

Moderate

Moderate

Severe

X

Severe

Mild X

Moderate Severe

X

Case study 2: Treatment planning with the MD DYNA Codes™ Chemical myomodulation

101

The MD Codes™ and MD DYNA Codes™ Equations for H4 and H5 Chemical myomodulation Glabellar lines

MD D NA Codes™ G1 + G2

C+P

Age, 37

Total dose: 20 U of VISTABEL®

Crow’s feet lines

MD D NA Codes™ O1 + O2 + O3

OOc

Age, 37

Total dose: 24 U of VISTABEL®

102

After treatment with VISTABELÂŽ After treatment, the appearance of the glabellar area can be considered ideal with full resolution of the lines.

After three days

Age, 37 Age, 33

Before

However, we were only able to reduce the lateral periorbital lines with the chemical myomodulation approach.

After three days

Age, 37 Age, 33

Before

The patient received VISTABELÂŽ as previously described and according to the product label. Please refer to the Summary of Product Characteristics for more details.1

103

After treatment with VISTABEL® and JUVÉDERM® Three days after VISTABEL®

Immediately after JUVÉDERM®

Age, 37

Before

In her case we needed further treatment with mechanical myomodulation to indirectly reduce the lower eyelid lines on animation. Let us now look at how this was achieved.

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

Case study 2: Treatment planning with the MD DYNA Codes™ MD Codes™ for structure MD DYNA Codes™ for mechanical myomodulation

105

The MD Codes™ and MD DYNA Codes™ Equations for H4 and H5 The mechanical myomodulation approach is needed to reduce the deflation surrounding her periorbital area. With a lack of support, the orbicularis oculi muscle presents excessive over-contraction, leading to multiple lines.

Structure at rest

Ck1 + Ck2 + Ck3

Eyebags

Ck1 + Ck2 + Ck3 T1 Tt1 + Tt2 + Tt3

Age, 37

Saggy cheeks

On animation

Age, 37

MD D NA Codes™ Lateral orbital lines

Ck1 + Ck2 + Ck3 T1 O1 + O2 + O3

OOc

Lower eyelid lines

Ck1 + Ck2 + Ck3 T1 O1 + O2 + O3 Tt1 + Tt2 + Tt3

OOc

106

The MD Codes™ and MD DYNA Codes™ Equations for H4 and H5 Her gummy smile derives from the excessive action of the upper lip elevators. There is also a droop of the tip of the nose and inversion of the upper lip. The MD Codes™ can provide the structure and the MD DYNA Codes™ can reduce the muscle overactivity.

Structure at rest

Chin wrinkling

C1 + C2 + C6

Nasolabial folds

Ck1 + Ck2 + Ck3 NL1 + NL2 + NL3 Lp1 + Lp1 + Lp6

Age, 37

Deflated lips

On animation

MD D NA Codes™ Nasal flare rotation Gummy smile

Age, 37

Upper lip inversion

NL1

LAN

NL1 + NL2 + NL3 Lp1 + Lp8

LAN + LLS + ZMi OO

Lp1

OO

107

The MD Codes™ and MD DYNA Codes™ Equations for H4 and H5 Note that when she kisses, multiple structures, such as the buccal area, lips and chin, suffer deformation due to lack of structural support and muscle modulation.

Structure at rest

Chin wrinkling NLF

Ck1 + Ck2 + Ck3 NL1 + NL2 + NL3 Lp1 + Lp1 + Lp6

Age, 37

Deflated lips

C1 + C2 + C6

On animation

MD D NA Codes™ Perioral lines Chin wrinkling

Age, 37

Hollow cheeks

Lp1 + Lp1 Lp2 + Lp3 + Lp3

OO

C1 + C2 + C6

M

Ck5

B

108

After treatment with JUVÉDERM®: Smile After injecting the MD DYNA Codes™ we notice the correction of her gummy smile. Please also notice that her upper lip does not invert anymore.

After

Age, 37

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

109

After treatment with JUVÉDERM®: Kissing After treatment with the MD DYNA Codes™ there is evident better co-ordination of muscle activity with less deformation of the skin surface. Observe the change in the buccal area, perioral lines and chin.

After

Age, 37

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

110

After treatment: At rest To improve the tired and sad look, we needed a combination of VISTABEL® and JUVÉDERM®. Observe the improvement in her cheek, eyebags, chin and lips.

Three days after VISTABEL®

Immediately after JUVÉDERM®

Age, 37

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

111

After treatment: Smile With chemical myomodulation we were able to improve the lateral periorbital lines. With mechanical myomodulation we improved the lower eyelid lines and gummy smile.

Three days after VISTABEL®

Immediately after JUVÉDERM®

Age, 37

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

112

After treatment: Kiss Please observe the change in her hollow cheeks, improvement of lip fullness and correction of the perioral lines.

Three days after VISTABEL®

Immediately after JUVÉDERM®

Age, 37

Before

The patient received hyaluronic acid filler in the cheeks (2.6 mL), temples (1.4 mL), tear trough (1.0 mL), nasolabial folds (1.0 mL), chin and jawline (3.0 mL), and lips (2.0 mL). Overall the patient received 11.0 mL of product. Three days prior, the patient had received VISTABEL® as previously described.

References

114

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Prescribing information

118 DK Vistabel® (botulinumtoksin type A) Lægemiddelform: Pulver til injektionsvæske, opløsning. Indikationer: VISTABEL er indiceret til midlertidig forbedring af udseendet af: moderate til svære lodrette rynker mellem øjenbrynene (glabellalinjer), der ses ved maksimal panderynken og/eller moderate til svære rynker på ydersiden af øjnene (kragetæer/smilerynker), der ses ved maksimalt smil og/eller moderate til svære panderynker, som ses ved maksimalt hævede øjenbryn når omfanget af følgende ansigtsrynker har en væsentlig psykologisk indvirkning på voksne patienter. Dosering og indgivelsesmåde: For fuldstændige oplysninger henvises til Produktresuméet. Et præparats botulinumtoksin-enheder kan ikke erstattes med enheder af et andet præparat. De anbefalede doser i Allergan-enheder svarer ikke til enhederne i andre præparater med botulinumtoksin. Vistabel må kun indgives af læger med de rette kvalifikationer og viden om behandlingen og som har det fornødne udstyr.

Må kun anvendes til én injektionsbehandling pr. patient. Der skal træffes særlige forsigtigheds­regler under tilberedning og administration af lægemidlet samt for at inaktivere og bortskaffe rester i form af ikke anvendt lægemiddel. Rekonstitueres med en 0,9% opløsning natriumchlorid isotonisk injektionsvæske uden konserveringsmiddel. Den anbefalede injektionsmængde pr. injektionssted er 0,1 ml. Der skal drages omsorg for, at Vistabel ikke injiceres i et blodkar ved injektion.

Administrationsinstruktioner for glabellalinjer: Rekonstitueret Vistabel (50 enheder/1,25 ml eller 100 enheder/2,5 ml) injiceres ved hjælp af en 30 G-kanyle.

Der indgives 0,1 ml (4 enheder) i hvert af de 5 injektionspunkter: 2 injektioner i hver corrugator-muskel og 1 injektion i procerus-musklen for en samlet dosis på 20 enheder. Administrationsinstruktioner for kragetæer: Rekonstitueret Vistabel (50 enheder/1,25 ml eller 100 enheder/2,5 ml) injiceres ved hjælp af en steril 30 G-kanyle. Der indgives 0,1 ml (4 enheder) i hvert af de 3 injektionspunkter på hver side (i alt 6 injektionssteder) i den laterale orbicularis oculi muskel, for en samlet dosis på 24 enheder i et samlet volumen på 0,6 ml (12 enheder per side). Ved behandling samtidig med glabellalinjerne er dosen 24 enheder for kragetæer og 20 enheder for glabellalinjer for en samlet dosis på 44 enheder i et samlet volumen på 1,1 ml. Administrationsinstruktioner for panderynker, som ses ved maksimalt hævede øjenbryn: Rekonstitueret Vistabel (50 enheder/1,25 ml eller 100 enheder/2,5 ml) injiceres ved hjælp af en steril 30 G-kanyle. Der indgives 0,1 ml (4 enheder) i hvert af de 5 injektionssteder i musculus frontalis for en samlet dosis på 20 enheder i et samlet volumen på 0,5 ml. Den samlede dosis ved behandling af panderynker (20 enheder) samtidig med glabellalinjer (20 enheder) er 40 enheder/1,0 ml. Ved samtidig behandling af glabellalinjer og kragetæer er den samlede dosis 64 enheder fordelt på 20 enheder til panderynker, 20 enheder til glabellalinjer (se Administrationsinstruktioner for glabellalinjer og figur 1) og 24 enheder til kragetæer (se Administrationsinstruktioner for kragetæer og figur 2 og 3). Behandling bør ikke finde sted oftere end med 3 måneders interval.

Kontraindikationer: Kendt overfølsomhed over for botulinumtoksin type A eller over for et eller flere af hjælpestofferne. Myasthenia gravis eller Eaton-Lamberts syndrom. Infektion ved de foreslåede injektionssteder. Advarsler/ Forsigtighedsregler: Indeholder under 1 mmol natrium (23 mg) pr. dosis. Den relevante anatomi og eventuelle anatomiske ændringer, der skyldes tidligere kirurgiske indgreb, skal klarlægges før indgift af Vistabel, og det bør undgås at injicere lægemidlet i sårbare anatomiske strukturer. De anbefalede doseringer og intervaller mellem indgift af Vistabel må ikke overskrides. Adrenalin eller enhver anden behandling mod anafylaksi skal være til rådighed. Patienter med hidtil ubemærkede neuromuskulære sygdomme kan have en øget risiko for at få klinisk signifikante systemiske bivirkninger inklusive svær dysfagi og belastning af luftvejene. Injektion af Vistabel anbefales ikke til patienter, der har dysfagi og aspiration i anamnesen. Patienter eller deres omsorgspersoner skal rådes til straks at søge lægehjælp, hvis der opstår synke-, tale- eller vejrtrækningsproblemer. Hvis produktet administreres for ofte eller i for store doser, kan dette øge risikoen for dannelse af antistoffer, som kan føre til behandlingssvigt. Der skal udvises forsigtighed, når Vistabel anvendes ved tilstedeværelse af betændelsestilstand ved det/de foreslåede injektionssteder, samt når de muskler, der skal injiceres, udviser udpræget muskelslaphed eller -atrofi. Forsigtighed, når Vistabel anvendes til behandling af patienter med amyotrofisk lateral sklerose eller med perifere neuromuskulære forstyrrelser. Brug af Vistabel anbefales ikke til unge under 18 år og patienter over 65 år.

Interaktioner: Virkningen af botulinumtoksin kan forstærkes af aminoglykosidantibiotika, spectinomycin, eller af andre lægemidler, som påvirker neuromuskulær transmission. Der er ikke kendskab til virkningen af at administrere forskellige botulinum neurotoksin-serotyper samtidig eller inden for nogle måneder. Der kan opstå forværring af omfattende neuromuskulær svækkelse ved administration af et andet botulinumtoksin, før virkningen af det tidligere administrerede botulinumtoksin har fortaget sig. Fertilitet, graviditet og amning: Fertilitet: Der foreligger ikke tilstrækkelige data om virkningerne efter anvendelse af botulinumtoksin til fertile kvinder. Graviditet: Anvendelsen af Vistabel kan ikke anbefales under graviditet eller til kvinder i den fertile alder som ikke anvender sikker kontraception. Amning: Anvendelse af Vistabel under amning kan ikke anbefales. Bivirkninger: I kontrollerede kliniske studier vedrørende glabellalinjer, blev der rapporteret hændelser, som af investigatorerne

ansås for at være relateret til Vistabel, hos 23,5% (placebo: 19,2%) af patienterne.

Sådanne hændelser blev i behandlingscyklus 1 af de kontrollerede hovedstudier vedrørende kragetæer, som ses ved maksimalt smil, rapporteret hos 7,6 % (24 enheder for kragetæer alene) og 6,2 % (44 enheder: 24 enheder for kragetræer indgivet samtidig med 20 enheder for glabellalinjer) af patienter sammenlignet med 4,5 % for placebo. I behandlingscyklus 1 i de kliniske studier vedrørende panderynker, der ses ved maksimalt hævede øjenbryn, blev der rapporteret hændelser, som af investigatorerne ansås for at være relateret til VISTABEL hos 20,6 % af de patienter, der blev behandlet med 40 enheder (20 enheder i m. frontalis med 20 enheder i glabellakomplekset) og 14,3 % af de patienter, der blev behandlet med 64 enheder (20 enheder i m. frontalis med 20 enheder i glabellakomplekset og 24 enheder i området omkring de laterale canthuslinjer), sammenlignet med 8,9 % af de patienter, som fik placebo. Reaktionerne forekommer som regel i løbet af de første par dage efter injektionen, og de er forbigående. De fleste rapporterede bivirkninger var af mild til moderat sværhedsgrad. Bivirkningerne er anført efter hyppighed; almindelig (>1/100 til <1/10), ikke almindelig (≥1/1.000 til <1/100). Almindelig. Nervesystemet; hovedpine, paræstesi. Øjne; øjenlågs-ptose, øjenlågsødem. Mave-tarmsygdomme; kvalme. Hud og subkutane væv; erytem, stramhed i huden. Knogler, led, muskler og bindevæv; lokaliseret muskelsvaghed. Almene symptomer og reaktioner på administrationsstedet; ansigtssmerter, ødem på injektionsstedet, ekkymose, smerter på injektionsstedet, irritation på injektionsstedet, blødning på injektionssætning, hæmatom ved injektionsstedet. Ikke almindelig. Infektioner og parasitære sygdomme; infektion. Psykiske forstyrrelser; angst. Nervesystemet; svimmelhed. Øjne; blepharitis, øjensmerter, synsforstyrrelser (herunder uskarpt syn). Mave-tarm-sygdomme; mundtørhed. Hud og subkutane væv; ødem (i ansigt, øjenlåg, omkring munden), fotosensibilitetsreaktion, pruritus, tør hud. Knogler, led, muskler og bindevæv; muskeltrækninger. Almene symptomer og reaktioner på administrationsstedet; Blå mærker på injektionsstedethæmatom ved injektionsstedet, influenzasyndrom, asteni, feber, smerter på injektionsstedet, paræstesi på injektionsstedet, blødning på injektionsstedet. Hyppighed ukendt (rapporteret efter markedsføring): Immunsystemet; anafylaksi, angioødem, serumsyge, urticaria. Metabolisme og ernæring; anoreksi. Nervesystemet; plexus brachialis, dysfoni, dysartri, facialis-parese, hypæstesi, muskelsvaghed, myasthenia gravis, perifer neuropati, paræstesi, radikulopati, synkope, bells parese. Øjne; vinkelblokglaukom (til behandling af blefarospasme), lagophthalmus, strabismus, uskarpt syn, synsforstyrrelse, øjentørhed. Øre og labyrint; hypoacusis, tinnitus, vertigo. Luftveje, thorax og mediastinum; aspirationspneumoni, dyspnø, bronkospasme, respirationsdepression, respirationsinsufficiens. Mave-tarmkanalen; abdominalsmerter, diaré, tør mund, dysfagi, kvalme, opkastning. Hud og subkutane væv; alopeci, dermatitis psoriasiform, erythema multiforme, hyperhidrose, madarose, pruritus, udslæt. Knogler, led, muskler og bindevæv; muskelatrofi, myalgi, lokale muskeltrækninger/ufrivillige muskelsammentrækninger.

Almene symptomer og reaktioner på administrationsstedet; denerveringsatrofi, utilpashed, pyreksi.

Pakningsstørrelser og priser: Vistabel® 50 Allergan-enheder/hætteglas, Vistabel® 100 Allergan-enheder/hætteglas: Se dagsaktuel pris på www. medicinpriser.dk. Udlevering NBS. Tilskud: - Indehaver af markedsføringstilladelsen: Allergan Pharmaceuticals Ireland, Castlebar Road, Westport Co. Mayo, Irland. Yderligere oplysninger kan fås hos: Allergan Norden AB, Strandbergsgatan 61, 112 51 Stockholm, Sverige. Telefon: 80 88 45 60.

Baseret på produktresume dateret: 15. april 2019.

Produktinformationen er forkortet i forhold til det af Lægemiddelstyrelsens godkendte produktresumé. Produktresuméet kan vederlagsfrit rekvireres fra Allergan.

NO Vistabel «Allergan» Muskelrelakserende middel til lokal behandling. ATC-nr.: M03A X01 PULVER TIL INJEKSJONSVÆSKE, oppløsning: Hvert hetteglass inneh.: Botulinumtoksin type A fra Clostridium botulinum 50 enheter, humant albumin, natriumklorid. Rekonstituert opp­løsning: 4 enheter pr. 0,1 ml. Allergan-enheter tilsvarer ikke enheter for andre preparater med bo­tulinumtoksin.

Indikasjoner: Når graden av følgende furer har en viktig psykologisk betydning for voksne pasi­enter, brukes Vistabel for midlertidig bedring av utseendet: 1) Moderate til kraftige vertikale rynker mellom øyenbrynene som er synlige når man rynker pannen maksimalt (glabellalinjer). 2) Mode­rate til kraftige vifteformede rynker ved øyekroken som er synlige ved maksimal smiling (kråketær/smilerynker). 3) Moderate til kraftige pannerynker som er synlige ved maksimal heving av øyebry­nene.

Dosering: Botulinumtoksin-enheter er forskjellige fra preparat til preparat. Doser som er anbefalt i Allergan-enheter, er forskjellige fra de for andre botulinumtoksinpreparater.

119 Preparatet bør kun gis av leger med relevante kvalifikasjoner og ekspertise innen behandlingen og bruk av nødvendig utstyr. Det bør utvises forsiktighet for å unngå at preparatet injiseres i en blodåre når det injiseres inn i glabellalinjer, som er synlige når man rynker pannen maksimalt, eller i kråketær, som er syn­lige ved maksimalt smil, eller i pannerynker, som er synlige ved maksimal heving av øyebrynene. Etter rekonstituering må preparatet kun brukes til én behandling pr. pasient. Spesiell forsiktighet bør utvises ved håndtering. Det skjer vanligvis forbedring av glabellalinjene, som er synlige når pannen rynkes maksimalt, innen 1 uke etter behandling. Virkningen varer i opptil 4 måneder. Be­handling bør ikke foretas hyppigere enn hver 3. måned. Ved mislykket behandlingsresultat etter førstegangs injeksjon, dvs. ubetydelig forbedring 1 måned etter injeksjon, vurderes ev. årsaker, f.eks. injeksjon i feil muskler, injeksjonsteknikk, dannelse av toksinnøytraliserende antistoffer, utilstrekkelig dose. Hvorvidt behandlingen er hensiktsmessig, bør revurderes. Dersom ingen bi­virkninger forekommer etter den første behandlingsrunden, kan den andre behandlingsrunden på­begynnes med minst 3 måneder mellom de to behandlingsrundene. I tilfeller med utilstrekkelig dose for glabellalinjer, som er synlige når pannen rynkes maksimalt, iverksettes andregangsbe­ handling ved å justere totaldosen opp til 40 eller 50 enheter. Ta hensyn til vurdering av tidligere mislykket behandling. Effekt og sikkerhet ved gjentatte injeksjoner av preparatet utover 12 måne­der er ikke vurdert. Spesielle pasientgrupper: Barn og ungdom <18 år: Sikkerhet og effekt er ikke klarlagt og preparatet anbefales derfor ikke til denne pasientgruppen. Eldre >65 år: Begrensede da­ta. Ingen spesifikke dosejusteringer er nødvendig. Tilberedning/Håndtering: Rekonstituering bør foretas iht. regler for god praksis, spesielt mht. asepsis. Vistabel skal rekonstitueres med natrium­klorid 9 mg/ml (0,9%) injeksjonsvæske uten konserveringsmiddel. Som angitt i fortynningstabel­len under, skal nødvendig mengde oppløsningsvæske trekkes opp i en sprøyte for å oppnå en re­konstituert oppløsning med en konsentrasjon på 4 Allergan-enheter/0,1 ml.

Volum oppløsningsvæske (0,9% natriumkloridoppløsning) tilsatt et hetteglass på 50 Allergan-enheter

Resulterende dose (Allerganenheter pr. 0,1 ml)

1,25 ml

4 Allergan-enheter

Den midtre delen av gummikorken skal vaskes med alkohol. Oppløsningsvæsken injiseres lang­somt inn i hetteglasset, og glasset roteres forsiktig for å unngå bobledannelse. Hetteglasset skal kas­tes hvis vakuumet ikke trekker fortynningsmidlet inn. Rekonstituert oppløsning skal være klar, far­geløs til litt gulaktig og fri for partikler.

Ved uhell under håndtering av preparatet, enten i vaku­umtørret eller rekonstituert tilstand, må relevante tiltak iverksettes umiddelbart. Se pakningsved­legg.

Administrering: Anbefalt injeksjonsvolum pr. injeksjonssted er 0,1 ml (se fortynningstabell over). For nærmere beskrivelse av administrering (med figurer), se SPC. Glabellalinjer som er syn­lige når man rynker pannen maksimalt: Rekonstituert preparat (50 enheter/1,25 ml) injiseres med steril 30 G kanyle. 0,1 ml (4 enheter) administreres på hvert av de 5 injeksjonsstedene: 2 injeksjoner i hver øyenbrynsrynke (korrugatormuskel) og 1 injeksjon i prokerusmuskelen, totaldose på 20 en­heter. Før injeksjon skal tommel eller pekefinger plasseres fast under kanten av øyehulen for å unn­gå ekstravasasjon nedenfor kanten. Kanylen skal rettes oppover og mot midtlinjen under injeksjo­nen. For å redusere risikoen for øyelokksptose skal maksimaldose på 4 enheter for hvert injeksjons­sted og antallet injeksjonssteder ikke overskrides. I tillegg må injeksjoner nær løftemuskelen unn­gås, spesielt hos pasienter med større pannedepressoriske komplekser (depressor supercilii). Injek­sjoner i øyebrynsrynkeren skal settes sentralt i muskelen, med en avstand på minst 1 cm over øye­brynsbuen.

Kråketær som er synlige ved maksimal smiling: Rekonstituert preparat (50 enheter/1,25 ml) injiseres med en steril 30 G kanyle. 0,1 ml (4 enheter) administreres på hvert av de 3 injeksjons­stedene på hver side (6 injeksjonssteder totalt) av den laterale orbicularis oculi-ringmuskelen, to­taldose på 24 enheter i et totalt volum på 0,6 ml (12 enheter på hver side). For å redusere risikoen for øyelokksptose, skal maksimaldose på 4 enheter for hvert injeksjonssted og antallet injeksjons­steder ikke overskrides. I tillegg må injeksjonene settes temporalt til orbitalranden, med en sikker avstand fra muskelen som kontrollerer øyelokkheving. Injeksjoner for kråketær skal gis med kany­letuppens skråkant opp og rettet bort fra øyet. Den første injeksjonen skal gjøres rundt 1,5-2 cm temporalt til den laterale kantalen, og såvidt temporalt til den orbitale randen. Se nærmere beskri­velse i SPC. Når vifteformede rynker ved øyekroken, som er synlige ved maksimal smiling, be­handles samtidig med vertikale rynker mellom øyenbrynene, som er synlige når man rynker pannen maksimalt, er behandlingsdosen 24 enheter for kråketær og 20 enheter for glabellalinjer, totaldose på 44 enheter i et totalt volum på 1,1 ml. Forbedring av alvorlighetsgraden på kråketær skjedde van­ligvis innen 1 uke etter behandling. Behandlingen har vist seg å være virksom i median 4 måneder etter injisering. Pannerynker som er synlige ved maksimal heving av øyebrynene: Rekonstituert preparat (50 enheter/1,25 ml) injiseres med steril 30 G kanyle. 0,1 ml (4 enheter) administreres på hvert av de 5 injeksjonsstedene i frontalismuskelen, totaldose på 20 enheter i et totalt volum på 0,5 ml. Totaldosen for behandling av pannerynker (20 enheter) samtidig med glabellalinjer (20 enhe­ter) er 40 enheter/1 ml. For å identifisere plasseringen av de aktuelle injeksjonsstedene i fronta­lismuskelen, bør det generelle forholdet mellom størrelsen på pasientens panne og fordelingen av muskelaktivitet i frontalis tas i betraktning. Følgende horisontale behandlingsrader skal plasseres ved lett palpasjon av en avslappet panne og med maksimalt hevede øyebryn: 1) Øvre rand for fron­talisaktivitet: Ca. 1 cm over den øverste pannefolden, 2) Nedre behandlingsrad:

Midtveis mellom den øvre randen for frontalisaktivitet og øyebrynene, minst 2 cm over øyebrynene, 3) Øvre behand­lingsrad: Midtveis mellom den øvre randen for frontalisaktivitet og den nedre behandlingsraden. De 5 injeksjonene skal plasseres i krysningspunktene mellom de horisontale behandlingsradene og følgende vertikale orienteringspunkter: 1) På den nederste behandlingsraden på ansiktets midtlinje og 0,5-1,5 cm medialt til den palperte temporallinjen; gjenta for den andre siden, 2) På den øvre be­handlingsraden, midtveis mellom laterale og mediale områder på den nedre behandlingsraden; gjenta for den andre siden (se SPC). Forbedring av alvorlighetsgraden av pannerynker, som er syn­lige ved maksimal heving av øyebrynene, skjedde innen 1 uke etter behandling. Det ble påvist ef­fekt i omtrent 4 måneder etter injeksjon. For samtidig behandling av glabellalinjer og kråketær er den totale dosen 64 enheter, bestående av 20 enheter for pannerynker, 20 enheter for glabellalinjer og 24 enheter for kråketær.

Kontraindikasjoner: Kjent overfølsomhet for innholdsstoffene. Myasthenia gravis eller Eaton Lambert-syndrom. Infeksjon på foreslåtte injeksjonssteder.

Forsiktighetsregler: Spesiell forsiktighet bør utvises ved håndtering av preparatet.

Dette legemid­let inneholder <1 mmol natrium (23 mg) pr. dose, dvs. så godt som natriumfritt. Før administrering må den aktuelle anatomien og ev. endringer i den som følge av tidligere kirurgiske inngrep være kjent, og injeksjon i sårbare anatomiske strukturer må unngås. Anbefalte doseringer og doserings­hyppighet bør ikke overstiges.

Det kan i svært sjeldne tilfeller oppstå anafylaktiske reaksjoner etter injeksjon av botulinumtoksin. Adrenalin eller andre tiltak mot anafylaktiske reaksjoner bør derfor være tilgjengelige. Pasienter med udiagnostiserte nevromuskulære lidelser kan ha økt risiko for kli­ nisk signifikante systemiske effekter, inkl. alvorlig dysfagi og respirasjonshemming, ved vanlige doser av botulinumtoksin type A. I noen av disse tilfellene har dysfagi vedvart i flere måneder og krevd bruk av magesonde (se Kontraindikasjoner). Bivirkninger med mulig årsakssammenheng til spredning av toksin fjernt fra injeksjonsstedet er meget sjeldent rapportert med botulinumtoksin (se Bivirkninger). Pasienter som behandles med terapeutiske doser kan oppleve betydelig muskelsvak­het. Svelge- og pustevansker er alvorlige og kan medføre dødsfall. Injeksjon av preparatet anbefa­les ikke til pasienter som har hatt dysfagi eller aspirasjon. Pasienten eller omsorgspersoner bør rå­des til å oppsøke lege umiddelbart hvis det oppstår plager med svelg, tale eller åndedrettsforstyr­relser. For hyppig eller overdreven dosering kan øke faren for dannelse av antistoffer. Dannelse av antistoffer kan medføre behandlingssvikt med botulinumtoksin type A selv ved andre injeksjoner. Forsiktighet bør utvises ved betennelse på et foreslått injeksjonssted eller hvis målmuskelen viser uttalt svakhet eller atrofi. Forsiktighet bør også utvises i behandlingen av pasienter med amyotro­fisk lateral sklerose eller med perifere nevromuskulære lidelser. Lokale smerter, inflammasjon, pa­ restesi, hypoestesi, ømhet, hevelse/ødem, erytem, lokal infeksjon, blødninger og/eller blåmerker har vært forbundet med injeksjonen. Nålerelaterte smerter og/eller angst har medført vasovagale re­sponser, inkl. forbigående symptomatisk hypotensjon og synkope. Bilførere og maskinførere må være oppmerksomme på den mulige risikoen for asteni, muskelsvakhet, svimmelhet og synsfor­styrrelser som kan gjøre det farlig å kjøre bil eller betjene maskiner.

Interaksjoner: For utfyllende informasjon om relevante interaksjoner, bruk interaksjonsanalyse.

Teoretisk kan virkningen av botulinumtoksin forsterkes av aminoglykosidantibiotika, spektinomy­cin eller andre legemidler som påvirker nevromuskulær overføring (f.eks. nevromuskulærblokke­ rende midler). Effekten av å administrere ulike serotyper av botulinumnevrotoksin samtidig eller med flere måneders mellomrom er ukjent. Uttalt nevromuskulær svakhet kan forverres ved admi­nistrering av et nytt botulinumtoksin før virkningen av et tidligere administrert botulinumtoksin har opphørt.

Graviditet, amming og fertilitet: Graviditet: Det foreligger ikke tilstrekkelig data på bruk hos gravide. Dyrestudier har vist reproduksjonstoksiske effekter. Risikoen for mennesker er ukjent. Preparatet anbefales ikke under graviditet eller hos kvinner i fertil alder som ikke bruker preven­sjonsmidler. Amming: Opplysninger mangler. Bruk under amming anbefales ikke. Fertilitet: Det foreligger ikke tilstrekkelige data vedrørende påvirkning av fertilitet ved bruk av botulinumtoksin type A hos fertile kvinner. Studier med hann- og hunnrotter har vist redusert fertilitet.

Bivirkninger: Bivirkninger oppstår vanligvis i løpet av de første dagene etter injeksjon, og er for­bigående. De fleste rapporterte bivirkningene er milde til moderate. Lokal muskelsvakhet represen­ terer den forventede farmakologiske bivirkningen av botulinumtoksin. Svakhet i nærliggende mus­ kler og/eller muskler langt fra injeksjonsstedet er imidlertid rapportert. Blefaroptose, som kan være forbundet med teknikk, har sammenheng med preparatets farmakologiske virkning. Smerte/bren­ning/ stikking, ødem og/eller bloduttredelser kan være forbundet med injeksjonen. Feber og influ­ ensasymptomer er rapportert. Glabellalinjer: Vanlige (≥1/100 til <1/10): Gastrointestinale: Kval­me. Hud: Erytem, stram hud. Muskel-skjelettsystemet: Lokalisert muskelsvekkelse. Nevrologiske: Hodepine, parestesi. Øye: Øyelokksptose. Øvrige: Smerter i ansiktet, ødem på injeksjonsstedet, ekkymose, smerte på injeksjonsstedet, irritasjon på injeksjonsstedet. Mindre vanlige (≥1/1000 til <1/100): Gastrointestinale: Munntørrhet. Hud: Ødem (ansikt, øyelokk, området rundt øyet), foto­sensitivitetsreaksjon, kløe, tørr hud. Infeksiøse: Infeksjon. Muskel-skjelettsystemet: Muskelryk­ ninger.

Nevrologiske: Svimmelhet. Psykiske: Angst. Øye: Blefaritt, øyesmerte, synsforstyrrelse (inkl. tåkesyn). Øvrige: Influensasymptomer, asteni, feber. Kråketær med eller uten glabellalin­jer: Vanlige (≥1/100 til <1/10): Øvrige: Hematom på injeksjonsstedet1.

Mindre vanlige (≥1/1000 til <1/100): Øye: Øyelokksødem. Øvrige: Blødning på

120 injeksjonstedet1, smerter på injeksjonste­ det1, parestesi på injeksjonsstedet1.

Pannerynker og glabellalinjer med eller uten kråketær: Van­lige (≥1/100 til <1/10): Hud: Stram hud. Nevrologiske: Hodepine. Øye: Øyelokksptose. Øvrige: Blåmerker på injeksjonsstedet1, hematom på injeksjonsstedet1. Mindre vanlige (≥1/1000 til <1/100): Hud: Øyebrynsptose. Øvrige: Smerte på injeksjonsstedet1. (1Bivirkningen er relatert til pro­sedyren.) Det ble ikke observert noen endringer i den samlede sikkerhetsprofilen etter gjentatt do­ sering. Rapportert etter markedsføring: Ukjent frekvens: Gastrointestinale: Magesmerter, diaré, tørr munn, dysfagi, kvalme, oppkast. Hud: Alopesi, øyebrynsptose, psoriasislignende eksem, eryt­hema multiforme, hyperhidrose, madarose, kløe, utslett. Immunsystemet: Anafylaksi, angioødem, serumsykdom, urticaria. Luftveier: Aspirasjonspneumoni, dyspné, bronkospasme, respirasjonsde­presjon, respirasjonssvikt.

Muskel-skjelettsystemet: Muskelatrofi, myalgi, lokale muskelryknin­ ger/ufrivillige muskelsammentrekninger. Nevrologiske: Brakial pleksopati, dysfoni, dysartri, an­ siktsparese, hypoestesi, muskelsvakhet, myasthenia gravis, perifer nevropati, parestesi, radikulopa­ti, synkope og ansiktsparalyse. Stoffskifte/ernæring: Anoreksi. Øre: Hypakusi, tinnitus, vertigo. Øye: Vinkelblokkglaukom (for behandling av blefarospasme), øyelokksptose, lagoftalmus, strabis­me, tåkesyn, synsforstyrrelser, tørre øyne. Øvrige: Denervasjonsatrofi, generell sykdomsfølelse, feber.

Overdosering/Forgiftning: Overdosering med botulinumtoksin type A er et relativt begrep og av­henger av dose, injeksjonssted og underliggende vevsegenskaper. Det er ikke rapportert om syste­misk toksisitet som følge av utilsiktet injeksjon. For høye doser kan medføre generell og uttalt nev­ romuskulær paralyse lokalt eller langt unna injeksjonsstedet. Det oppstår ingen synlige tegn på overdosering umiddelbart etter injeksjon. Dersom preparatet utilsiktet injiseres eller svelges, må pasienten holdes under medisinsk overvåking i flere dager for å oppdage ev. tegn eller symptomer på systemisk svekkelse eller muskellammelser. Pasienter som viser symptomer på botulinumtoksin type A-forgiftning (generell svekkelse, ptose, diplopi, problemer med tale- og svelgefunksjon eller parese av åndedrettsmuskler), bør vurderes innlagt på sykehus. Se Giftinformasjonens anbefalinger M03A X01 på www.felleskatalogen.no.

Egenskaper: Virkningsmekanisme: Botulinumtoksin type A (Clostridium botulinum nevrotoksin) blokkerer perifer frisetting av acetylkolin ved presynaptiske kolinerge nerveterminaler ved å spalte SNAP-25, et protein som er nødvendig for en vellykket binding og frisetting av acetylkolin fra ve­sikler i nerveendene. Dette fører til denervering og paralyse av muskelen. Etter injeksjon oppstår det innledningsvis en rask høyaffinitetsbinding av toksin til spesifikke celleoverflatereseptorer. Deretter overføres toksinet gjennom plasmamembranen ved reseptormediert endocytose. Toksinet frisettes til slutt i cytosol. Sistnevnte prosess etterfølges av progressiv hemming av acetylkolinfri­ gjøring. Kliniske tegn vises i løpet av 2-3 dager, med maks. effekt innen 5-6 uker etter injeksjon. Restitusjon etter i.m. injeksjon skjer normalt innen 12 uker, etter hvert som nerveterminaler vokser ut og kobles til endeplatene. Det er i studier vist at opptil 80% av pasientene fikk betydelig reduk­sjon av glabellalinjene ved rynking av pannen. Det er også vist signifikant reduksjon av glabella­ linjene når musklene er avslappet. Pga. preparatets beskaffenhet er det ikke utført konvensjonelle studier av absorpsjon, fordeling, metabolisme og utskillelse. Det antas at systemisk distribusjon i li­ten grad finner sted ved terapeutiske doser.

Oppbevaring og holdbarhet: Oppløsningen anbefales brukt umiddelbart etter rekonstituering. Kjemisk og fysisk bruksstabilitet er imidlertid påvist i 24 timer ved 2-8°C. Oppbevares i kjøleskap (2-8°C).

Andre opplysninger: Det foreligger ikke undersøkelser vedrørende uforlikeligheter, og Vistabel bør derfor ikke blandes med andre preparater. Destruksjon: Hetteglass, sprøyter og annet utstyr skal ikke tømmes og må kastes i egnede beholdere og destrueres som medisinsk biorisikoavfall i overensstemmelse med lokale krav. Ubrukt oppløsning i hetteglasset og/eller sprøyten inaktiveres med 2 ml fortynnet 0,5% eller 1% natriumhypokloritt, og det bør destrueres i overensstemmelse med lokale krav.

Pakninger og priser: 1 stk. (hettegl.) 022250.

Katso tarkemmat tiedot valmisteyhteenvedosta. Vasta-aiheet: Yliherkkyys A-tyypin botuliinitoksiinille tai jollekin valmisteen apuaineelle. Myasthenia gravis tai Eaton-Lambertin oireyhtymä. Infektio suunnitelluissa injektion antopaikoissa.

Varoitukset ja käyttöön liittyvät varotoimet: Injektioita vaurioitumiselle alttiille alueille tulee välttää. Hyvin harvinaisen anafylaktisen reaktion varalta tulee olla saatavilla anafylaksian hoitoon tarvittavia välineitä. VISTABEL-injektion antaminen potilaille, joilla on ollut nielemisvaikeuksia ja aspiraatiota, ei ole suositeltavaa.

Potilaita tulee neuvoa hakeutumaan välittömästi lääkärin hoitoon nielemis-, puhetai hengityshäiriöiden ilmetessä. Hoitoannoksia saavilla potilailla voi ilmetä liiallista lihasheikkoutta, myös injektiokohdasta kaukana olevissa lihaksissa. Valmistetta on käytettävä varoen, jos suunnitellussa injektiokohdassa on todettu tulehdus tai kun kohdelihas on hyvin heikko tai surkastunut ja jos potilas sairastaa amyotrofista lateraaliskleroosia tai hänellä on perifeerisiä neuromuskulaarisia sairauksia. On varmistuttava huolella siitä, että VISTABEL-valmistetta ei injektoida verisuoneen. Hoidon jälkeinen silmäluomen ptoosin riski on olemassa. Liian tiheä tai liiallinen annostus voi aiheuttaa vasta-aineiden muodostumisen riskin.

Neutraloivien vasta-aineiden muodostuminen voi tehdä A-tyypin botuliinitoksiinihoidon tehottomaksi myös muiden käyttöaiheiden osalta.

Yhteisvaikutukset: Botuliinitoksiinin vaikutus voi teoriassa voimistua hermolihastransmissiota estävien lääkeaineiden (aminoglykosidiantibiootit, spektinomysiini, hermo-lihasliitosta salpaavat lihasrelaksantit) vaikutuksesta.

Botuliinineurotoksiinin eri serotyyppien samanaikaisen annon tai useiden kuukausien aikana tapahtuvan annon vaikutuksia toisiinsa ei tunneta. Liian voimakas neuromuskulaarinen heikkous voi olla seurauksena, jos toista botuliinitoksiinia annetaan ennen kuin edellisen botuliinitoksiinin vaikutus on kadonnut. Mahdollista yhteisvaikutusta muiden lääkeaineiden kanssa ei ole erityisesti tutkittu. Hedelmällisyys, raskaus ja imetys: Käyttöä ei suositella raskauden aikana tai hedelmällisessä iässä oleville naisille, jotka eivät käytä ehkäisyä, eikä imetyksen aikana. Vaikutus ajokykyyn ja koneiden käyttökykyyn: VISTABEL voi aiheuttaa heikkoutta, lihasheikkoutta, heitehuimausta ja näköhäiriötä, jotka voivat vaikuttaa autolla ajoon ja koneiden käyttöön. Haittavaikutukset: Yleensä haittavaikutukset ilmenevät injektion antoa seuraavina päivinä ja ovat ohimeneviä. Useimmat raportoidut haitat ovat olleet lieviä tai kohtalaisia. Glabellaariuurteet: Yleiset: päänsärky, parestesiat, silmäluomen ptoosi, pahoinvointi, eryteema, ihon kireys, paikallinen lihasheikkous, kasvokipu, injektiokohdan turvotus, mustelmat, injektiokohdan kipu tai ärsytys.

Naururypyt ilman glabellaariuurteita tai niiden kanssa: Yleiset: Injektiokohdan hematooma. Otsarypyt ja glabellaariuurteet ilman naururyppyjä tai niiden kanssa: Yleiset: Päänsärky, silmäluomen ptoosi, ihon kireys, injektiokohdan mustelma, injektiokohdan hematooma. Melko harvinaiset ja myyntiluvan saamisen jälkeen ilmoitetut haittavaikutukset, ks. valmisteyhteenveto. Yhteensopimattomuudet: Yhteensopivuustutkimusten puuttuessa tätä lääkeainetta ei pidä sekoittaa muiden lääkeaineiden kanssa. Kestoaika: Liuottamisen jälkeen valmiste suositellaan käytettäväksi välittömästi. Säilytys: Säilytä jääkaapissa (2 °C – 8 °C). Käyttö- ja käsittelyohjeet: Ks. valmisteyhteenveto ”Toimintasuositukset vaaratilanteissa botuliinitoksiinia käsiteltäessä” Pakkaukset ja hinnat (TMH ilman alv 8/2018): 1 x 50 U (91,14€).

Korvattavuus: Ei SV-korvattava reseptilääke. Tutustu valmisteyhteenvetoon ennen lääkkeen määräämistä. Tämä teksti perustuu valmisteyhteenvetoon13.8.2018. Lisätiedot: Pharmaca Fennica ja ALLERGAN NORDEN AB, puh 0800-115 003.

Sist endret: 02.10.2018

VISTABEL®, 4 Allergan-enheter/0,1 ml, pulver till injektionsvätska, lösning, Botulinumtoxin typ A, EF, Rx., ATC: M03AX01. Indikationer: För tillfällig förbättring av måttliga till uttalade: -vertikala rynkor mellan ögonbrynen som uppkommer vid maximal rynkning av pannan (glabellaveck) och/eller; -rynkor i ögats utkanter som uppkommer vid maximalt leende (kråksparkar/skrattrynkor) och/eller: -pannrynkor som uppkommer vid maximalt höjda ögonbryn, då ansiktsrynkornas omfattning har en betydande psykologisk påverkan på vuxna patienter. Kontraindicerad: Vid känd överkänslighet mot botulinumtoxin typ A eller mot något hjälpämne, myasthenia gravis eller Eaton-Lamberts syndrom och infektion vid det planerade injektionsstället. Varningar och försiktighet: Rekommenderad dos och administreringsfrekvens bör inte överskridas. Enheter av botulinumtoxin är inte utbytbara mellan olika produkter. I sällsynta fall kan en anafylaktisk reaktion förekomma efter injektion av botulinumtoxin.

Rekommenderas inte under graviditet eller under amningsperioden. Vistabel ska endast ges av läkare med lämplig kompetens och erfarenhet. Biverkningar som möjligen har ett samband med spridning av toxin från administreringsstället har rapporterats i mycket sällsynta fall med botulinumtoxin. För ytterligare information om produkten se www.fass.se.

Datum för senast godkänd produktresumé 2018-08-24.

Basert på SPC godkjent av SLV: 07.09.2018 FI VISTABEL 4 Allergan-yksikköä/0,1 ml, injektiokuiva-aine, liuosta varten (Tyypin A botuliinitoksiini) Käyttöaiheet: VISTABEL on tarkoitettu käytettäväksi tilapäisesti silottamaan kohtalaisia tai syviä pystysuoria ryppyjä, joita syntyy kulmakarvojen väliin otsaa voimakkaasti rypistettäessä ja/tai leveimmän hymyn aiheuttamia silmäkulman sivun juonteita ja/tai otsaryppyjä, joita syntyy kulmakarvoja voimakkaasti kohotettaessa, tapauksissa joissa kasvoissa esiintyvien ryppyjen ja juonteiden vakavuudella on huomattava psykologinen vaikutus aikuispotilaaseen. Annostus ja antotapa: VISTABEL-hoitoa saavat antaa vain lääkärit, joilla on tähän hoitoon tarvittavien välineiden käyttöön vaadittava pätevyys ja perehtyneisyys.

Botuliinitoksiiniyksiköt ovat valmistekohtaisia ja annosten vastaavuus ei ole sama eri valmisteilla. Käyttövalmiiksi saatettu liuos tulee käyttää vain yhdellä antokerralla vain yhdelle potilaalle. Suositeltava injektiomäärä yhteen injektiokohtaan on 0,1 ml. Suositeltavaa annostusta ja antotiheyttä ei pidä ylittää.

Hoitokertojen välillä on pidettävä vähintään kolmen kuukauden väli. Käyttöä ei suositella alle 18-vuotiailla. Tietoa on niukasti yli 65-vuotiaiden potilaiden osalta.

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