Proper Technique for Administration of ATX-101

(Deoxycholic Acid Injection): Insights From an Injection

Practicum and Roundtable Discussion
Derek H. Jones, MD,* Jeffrey M. Kenkel, MD,† Steven Fagien, MD,‡ Dee Anna Glaser, MD,x
Gary D. Monheit, MD,k Karen Stauffer, PhD, CMPP,¶ and Jonathan M. Sykes, MD**
Downloaded from https://journals.lww.com/dermatologicsurgery by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3tjcLwhL8g9a8Clf3LIPrl55NlYlt3w4C8Xk9CeL6kvtwgdm075cAWw== on 12/16/2018

Abstract
ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Bio-
pharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) is the first aesthetic
injectable approved for reduction of submental fat. In February 2014, an injection practicum was conducted in the
anatomy laboratory at the University of Texas Southwestern Medical Center to explore the proper injection technique
for ATX-101 and the importance of its appropriate, safe anatomical placement within the submental area. Sub-
sequent to the injection practicum, a structured roundtable discussion was conducted in which potential implications
of the various injection protocols evaluated during the practicum were reviewed. Furthermore, the faculty had the
opportunity to provide additional perspectives based on their clinical experience with facial injectables and ATX-101
specifically. In this article, the findings from the injection practicum and roundtable discussion are reported.

D.H. Jones is a consultant and investigator for Kythera Biopharmaceuticals, Inc.; was loaned equipment,
materials, or medications for this study; received equipment, materials, or medications for this study; received
funding to support research for this article; received honoraria, payment, or other compensation for work on this
study; and received outside financial support for travel or lectures to present the information covered in this
study from Kythera Biopharmaceuticals, Inc. J.M. Kenkel has been on an advisory board for Allergan and Kythera
Biopharmaceuticals, Inc. S. Fagien is on an advisory board for Allergan and is an investigator for Kythera Bio-
pharmaceuticals, Inc. D.A. Glaser is an advisor to Kythera Biopharmaceuticals, Inc.; was loaned equipment,
materials, or medications for this study, and received funding to support research for this article from Kythera
Biopharmaceuticals, Inc. G.D. Monheit was loaned equipment, materials, or medications for this study; received
equipment, materials, or medications for this study; and received funding to support research for this article from
Kythera Biopharmaceuticals, Inc. J.M. Sykes received equipment, materials, or medications for this study, and
received honoraria, payment, or other compensation for work on this study from Kythera Biopharmaceuticals,
Inc. The injection practicum was sponsored by Kythera Biopharmaceuticals, Inc. (an affiliate of Allergan plc,
Dublin, Ireland). This review was sponsored by Allergan plc, Dublin, Ireland. All authors met the ICMJE
authorship criteria. Neither honoraria nor payments were made for authorship. Allergan was not involved in the
development of the manuscript with the authors or the vendor. Allergan had the opportunity to review the final
version of the manuscript and provide comments; however, the authors maintained complete control over the
content of the paper. Writing and editorial assistance was provided to the authors by K. Stauffer, PhD, CMPP, of
Evidence Scientific Solutions, Philadelphia, Pennsylvania, and funded by Allergan plc, Dublin, Ireland.

affiliate of Allergan plc, Dublin, Ireland]) is the first

A TX-101 (deoxycholic acid injection; Kybella in
the United States and Belkyra in Canada; Kythera
Biopharmaceuticals, Inc., Westlake Village, CA [an
aesthetic injectable approved for reduction of
submental fat.1 Unlike other aesthetic injectable

*Department of Dermatology, University of California Los Angeles and Private Practice (Skin Care and Laser Physicians
of Beverly Hills), Los Angeles, California; †Department of Plastic Surgery, University of Texas Southwestern Medical
Center, Dallas, Texas; ‡Private Practice, Boca Raton, Florida; xDepartment of Dermatology, Saint Louis University School
of Medicine, St. Louis, Missouri; kPrivate Practice (Total Skin & Beauty Dermatology Center, P.C.), Birmingham,
Alabama and Departments of Dermatology and Ophthalmology, University of Alabama at Birmingham, Birmingham,
Alabama; ¶Evidence Scientific Solutions, Philadelphia, Pennsylvania; **Department of Otolaryngology/Facial Plastic
Surgery, University of California Davis Medical Center, Sacramento, California

A supplemental digital content video is available for this article and can be accessed using the following link: https://app.
box.com/s/tir1ckmkd3s6rqpkujmiqqc2pph8icqn.

© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2016;42:S275–S281 DOI: 10.1097/DSS.0000000000000875

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 PROPER TECHNIQUE FOR ATX-101
treatments currently available, such as
neuromodulators, which are injected into muscle, and
fillers, which are injected into other soft tissue in
addition to subcutaneous tissue, ATX-101 is injected
into subcutaneous fat. Moreover, ATX-101 is
administered within the submentum, an area of the
face not commonly addressed by neuromodulators
and fillers. Therefore, physician education on relevant
anatomy of the lower face and anterior neck (as
reviewed in article 3 of the supplement titled
“Anatomy of the cervicomental region: insights from
an anatomy laboratory and roundtable discussion”)
and training on the proper technique for
administration of ATX-101 are important for
supporting desired aesthetic outcomes while reducing
the risk of potential adverse events.
In February 2014, an injection practicum was con-
ducted in the anatomy laboratory at the University of
Texas Southwestern Medical Center (Dallas, TX). The
objective of this activity was to explore the proper
injection technique for ATX-101 and the importance
of its appropriate, safe anatomical placement within
the submental area.
Methodology for the Injection Practicum
The 6 faculty were divided into 3 teams with each team
comprising a plastic surgeon and a dermatologist (with
one physician having clinical experience injecting ATX-
101). Each team was assigned a fresh-frozen cadaver
(including the head and full neck) to carefully evaluate,
mark the relevant external anatomic landmarks, and
inject with simulated ATX-101. Marking of anatomic
landmarks was dictated by the previous cadaver dis-
sections detailed in article 3 of the supplement. Key
anatomic landmarks included the inferior mandibular
border, the anterior border of the sternocleidomastoid
muscle, the antegonial notch (a bony landmark at the
anterior masseter that approximates the location of the
marginal mandibular nerve as it courses superficially
over the mid-mandible), and the thyroid cartilage.
Additionally, the submental fat compartment, corre-
sponding to the ATX-101 treatment area, was delin-
eated by marking the submental crease anteriorly, the
hyoid bone posteriorly, and the lateral boundaries as
judged on palpation (note that the lateral boundaries
S276 DERMATOLOGIC SURGERY
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have been described in the literature as approximated by
the caudal continuations of the labiomandibular folds).2
Once the markings were complete, an injection grid with
spacing between injection sites of 1 cm was applied to the
treatment area to control injection spacing. Methylene
blue dye was used as a surrogate for ATX-101 in this
exercise to allow visualization of the injected material
within the cadaver tissue. Following a structured plan
(Figure 1), simulated ATX-101 (methylene blue dye) was
injected into the submentum using a 30-G 0.5-inch needle
attached to a 1-mL syringe. In the first section of the
treatment area (Figure 1A), scoping injections were per-
formed to select the appropriate methylene blue dye for-
mulation for this exercise. A solution of 0.02% methylene
blue dye and 2% glycerol was shown to approximate the
diffusion characteristics (i.e., radius of effect) of ATX-101
in adipose tissue (Data on file; Kythera Bio-
pharmaceuticals, Inc. [an affiliate of Allergan plc]) and
thus was subsequently used in the injection practicum. In
Figure 1. Schematic of the injection plan followed during
the injection practicum. In section (A), scoping injections for
selection of the appropriate methylene blue dye formulation
were performed. In section (B), refinement injections with
the selected methylene blue dye formation were performed.
In this section, the depth, pressure, and volume of injections
were varied. Injection depth (sites shown in blue) included:
(1) standard, (2) superficial, and (3) deep injections. Injection
pressure (sites shown in green) included: (1) standard, (2)
low, and (3) high-pressure injections. Injection volume (sites
shown in brown) included: (1) 0.1-mL, (2) 0.2-mL, and (3)
0.4-mL injections. In section (C), additional injections to
explore other variables and techniques were performed.

the second section of the treatment area (Figure 1B),
refinement injections were performed to visualize the
anatomic implications of varying the depth (standard
[midpoint into the preplatysmal submental fat], superfi-
cial, and deep), pressure (standard [moderate], low, and
high), and volume of injections (0.2 [standard], 0.1, and
0.4 mL). In the third section of the treatment area (Figure
1C), the faculty performed additional injections to
explore other variables and techniques.
After the injections, the cadavers were dissected to
show the anatomic placement and diffusion charac-
teristics of the simulated ATX-101 (Figure 2). Sub-
sequent to the dissections, a structured roundtable
discussion was conducted to review the potential
implications of the various injection protocols evalu-
ated during the practicum. Furthermore, the faculty
had the opportunity to provide additional perspectives
based on their clinical experience with facial inject-
ables and ATX-101 specifically.
Results of the Injection Practicum
Injection to standard depth midway into the sub-
cutaneous tissue (oriented perpendicularly to the skin)
resulted in consistent deposition of simulated ATX-
101 within the preplatysmal submental fat. In con-
trast, overly cautious and/or superficial injections led
to deposition of simulated ATX-101 close to the der-
mis. Similarly, pinching the skin instead of the
underlying fat tissue when injecting resulted in diffu-
sion of simulated ATX-101 under the dermis. Deep
injections often resulted in deposition of simulated
ATX-101 into the platysma muscle itself or within the
postplatysmal submental fat.
Figure 2. Overview of the injection practicum. (A) Simulated ATX-101 (methylene blue dye) was injected at alternating 1-cm
marks on the 1-cm injection grid. (B) Removal of the dermis illustrated the 1.0- to 1.5-cm radius of effect of simulated ATX-
101 (methylene blue dye) within the subcutaneous fat tissue.
© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
JONES ET AL
Overall, there was no advantage to either reducing
or increasing injection pressure during administra-
tion of simulated ATX-101. Upon dissection, the
diffusion pattern was found to be less predictable
with increased injection pressure, which may
reflect inadvertent placement of product because
of streaming effects within the subcutaneous fat
tissue.
The area of diffusion varied with the volume of sim-
ulated ATX-101 injected (e.g., approximately 10-mm
radius of diffusion with 0.1 mL, 15-mm radius with
0.2 mL, and 30-mm radius with 0.4 mL). Upon dis-
section, it was observed that the 1.0-cm spacing of
0.2-mL standard depth injections resulted in an even
distribution of simulated ATX-101 within the pre-
platysmal submental fat. This observation is consis-
tent with the known radius of cytolytic effect of
ATX-101 when injected into subcutaneous fat (i.e.,
1.0–1.5 cm for a 0.2-mL injection volume; Data on file;
Kythera Biopharmaceuticals, Inc. [an affiliate of
Allergan plc]). Overall, this exercise helped illustrate
and validate the ATX-101 injection protocol used in
the Phase 3 clinical trials (i.e., 0.2-mL injections spaced
at 1.0-cm intervals within the submental area)3–6 and
reinforced the importance of injecting ATX-101 per
recommended instructions.1
Recommendations From the Panel for Proper
Administration of ATX-101
During the roundtable discussion, the importance of
appropriate selection of patients for submental con-
touring with ATX-101 was emphasized by the faculty.
To identify appropriate candidates for treatment,
42:11S:NOVEMBER SUPPLEMENT 2016 S277
 PROPER TECHNIQUE FOR ATX-101

a thorough physical examination is recommended to

identify the presence of conditions that could either
result in undesirable aesthetic outcomes (e.g., prom-
inent platysmal bands or marked soft tissue descent and
laxity within the submental area) or complicate/con-
traindicate treatment (e.g., history of surgical/aesthetic
procedures within the submental area, history of dys-
phagia or facial nerve paresis, or inflammation/indu-
ration/infection within the treatment area). To
consistently and objectively evaluate submental full-
ness, patients should be examined from multiple
vantage points, including having the patient posi-
tioned in the Frankfort plane (parallel to the ground)
(Figure 3). Physicians should confirm that submental
fullness is due to excess subcutaneous fat rather than
another cause (e.g., thyromegaly, cervical lymph-
adenopathy). Therefore, physicians should palpate
the submental area while patients animate their pla-
tysma muscle to isolate the preplatysmal fat. In
addition, patients should be asked to smile (to iden-
tify any asymmetry) and swallow (to identify any
dysfunction), which could impact ATX-101 admin-
istration and/or the outcome after treatment. Careful Figure 3. During the physical examination, patients should
assessment of submental skin laxity is also important be viewed by the physician from multiple vantage points,
including the Frankfort plane. The Frankfort plane includes
during the examination as reduction of submental fat a line approximating the base of the cranium, passing
in patients with excessive laxity may result in an from the infraorbital rim (infraorbitale) to the midline of
the occiput, and intersecting the superior margin of the
undesirable aesthetic outcome. external auditory meatus (porion). During evaluation, the
Frankfort horizontal should parallel the ground, assuring
It is recommended that the initial office visit serve as a neutral and reproducible head position.

a consultation providing the opportunity for the

physician to set treatment expectations with the
patient. Key topics to highlight with patients are that
subcutaneous injections are required to deliver ATX-
101 to the target tissue; ATX-101 treatment results
in acute, intermittent exposure to deoxycholic acid;
ATX-101 is a locally acting drug, and therefore
multiple injections are needed; the number of injec-
tions administered at each treatment session is
dependent on the amount and distribution of sub-
mental fat for an individual patient; multiple treat-
ment sessions (up to 61) may be needed to achieve
a satisfactory reduction in submental fat; and treat-
ments must be spaced at least 1 month apart.1
Overall, physicians should emphasize that ATX-101
treatment results in a gradual reduction in submental
fat. In addition, common local adverse reactions
after ATX-101 treatment (e.g., bruising, numbness,
pain, and swelling); the expected recovery time; and
the importance of avoiding other treatments/inter-
ventions within the submental area while undergo-
ing ATX-101 treatment should be discussed with the
patient.
Once a patient has been deemed a candidate for ATX-
101 treatment, the lower face and anterior neck are
cleansed with a topical antiseptic. Using a marking
pen, the anterior, posterior, and lateral boundaries of
the submental fat compartment are marked (Figure 4),
representing the planned treatment area. In addition,
a “no treatment zone” is marked around the probable
location of the marginal mandibular nerve (Figure 4).
Posterior to the facial artery, the marginal mandib-
ular nerve is deep to the platysma and courses from 1
to 4 cm below the inferior mandibular border.7 The

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 JONES ET AL

Figure 4. Illustration of pretreatment markings of the planned treatment area (corresponding to the submental fat com-
partment [bordered by the submental crease anteriorly, the hyoid bone posteriorly, and the lateral boundaries]) and the “no
treatment zone” (corresponding to the potential location of the marginal mandibular nerve).

radius of effect of ATX-101 should be considered the supplement titled “Management of patient expe-
when injecting near the marginal mandibular nerve rience with ATX-101 (deoxycholic acid injection)
as ATX-101 diffuses within the fat tissue once injec- treatment for reduction of submental fat” presents the
ted. Injecting too close to the marginal mandibular results from an ATX-101 clinical trial that evaluated
nerve could result in direct effects of ATX-101 on the various patient comfort modalities.
nerve manifesting clinically as paresis. Preliminary
experiences with ATX-101 suggest that marginal
mandibular nerve paresis can be avoided in most
situations by placing injections distant from this
nerve. Therefore, ATX-101 should not be injected
above a line drawn 1.0 to 1.5 cm below the inferior
border of the mandible.1 Although patients with
larger necks and/or those with widely distributed
submental fat may benefit from injection of ATX-101
more laterally or inferiorly, there is increased risk of
injury to neurovascular and glandular structures
adjacent to the submentum. Therefore, more lateral
injections should be avoided. Once the markings are
complete, the 1-cm injection grid is applied (Figure 5).
ATX-101 injections should be placed adjacent to grid
markings, but not directly through them to avoid
potentially tattooing the skin.

Patients may experience pain and discomfort with

ATX-101 treatment; this should be explained before
treatment. To enhance patient comfort, oral analgesics
can be given 60 minutes before treatment, topical
anesthetics can be applied 45 minutes before treat-
ment, injectable anesthetic can be administered
15 minutes before treatment, and/or ice/cold packs can Figure 5. Illustration of the 1-cm injection grid applied
be applied for 5 minutes before treatment. Article 5 of before treatment with ATX-101.

42:11S:NOVEMBER SUPPLEMENT 2016 S279

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 PROPER TECHNIQUE FOR ATX-101
In preparation for injection of ATX-101, the
number of 1-mL syringes needed should be
determined by counting the grid markings within
the treatment area and dividing by 5. To prepare
the syringes, 1 mL of ATX-101 should be drawn
into a syringe using a large bore needle (i.e., 21-G).
After expelling any air bubbles, the large-bore
needle should be replaced with a 30-G 0.5-inch
needle.
When administering ATX-101, the subcutaneous
fat should be pinched between 2 fingers and injec-
tions should be perpendicular to the skin surface
until the needle is midway into the preplatysmal
submental fat (Figure 6). As illustrated during the
injection practicum, both superficial injection of
ATX-101 and pinching the skin (vs the pre-
platysmal submental fat) when injecting could
expose the dermis to ATX-101 and potentially
result in skin ulceration. To reduce the risk of skin
ulceration and to ensure reproducible deposition of
ATX-101 within the target tissue (preplatysmal
submental fat), injections should be based on the
amount and thickness of submental fat for an indi-
vidual patient (vs arbitrarily based on absolute
needle length). In addition, standard injection
pressure should be used to ensure predictable
placement of ATX-101 within the target tissue.
ATX-101 is administered through 0.2-mL injec-
tions (maximum of 10 mL per treatment session). It
is recommended that injections begin at the inferior
Figure 6. When administering ATX-101, physicians should
pinch the fat between 2 fingers, pull it away from the
underlying tissue, and inject perpendicular to the skin until
the needle is midway into the underlying preplatysmal fat.
S280 DERMATOLOGIC SURGERY
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portion of the preplatysmal fat pad and continue
horizontally in rows upward.
After ATX-101 treatment, the physician may assess
the smile for any asymmetry and evaluate swallowing
to ensure that any swelling/edema within the sub-
mental area is not causing swallowing dysfunction. It
should be noted, however, that dysfunction related to
ATX-101 injection is both uncommon and likely
delayed in onset (hours to days), and that patients who
have had injectable local anesthetic before treatment
may simply be experiencing the temporary effects
from the anesthetic. The anesthetic effect should
resolve within hours. If swallowing dysfunction wor-
sens after injection, it is possible that the dysfunction is
related to the injection. Ice/cold packs can be applied
immediately after completion of treatment. The phy-
sician should reiterate to the patient that they may
experience bruising, pain, numbness, swelling, red-
ness, tingling, formation of areas of hardness, or
itching around the treatment area. Patients should be
directed to use ice/cold packs, compression, and/or
oral analgesics as needed to reduce these potential
adverse effects. However, patients should call their
physician if they notice any asymmetry in their smile,
have difficulty swallowing, or experience any other
unexpected reaction after treatment. The injection grid
and markings should be gently removed using a cotton
swab thoroughly dampened with alcohol. Patients
must wait at least 1 month before receiving another
ATX-101 treatment. An overview of the ATX-101
injection procedure is illustrated in Supplemental
Digital Content 1, Video 1, https://app.box.com/s/
tir1ckmkd3s6rqpkujmiqqc2pph8icqn.
Overall, the injection practicum offered the opportu-
nity to challenge the injection protocol for ATX-101.
The use of methylene blue dye as a surrogate for ATX-
101 allowed visualization of the anatomic implica-
tions of injections administered too deep or too
superficially within the submental area, or superior,
inferior, or lateral to the recommended treatment area.
Consequently, this exercise reinforced that the
appropriate, safe treatment area for ATX-101 is well
defined by the submental crease anteriorly, the hyoid
bone posteriorly, and the lateral borders of the sub-
mental fat pad.

Limitations to the Injection Practicum
To allow for visualization of the injected material,
methylene blue dye was used as a surrogate for ATX-
101 in the injection practicum. Although the diffusion
characteristics of the methylene blue dye formulation
used in this exercise are similar to ATX-101, the dif-
fusion characteristics are not identical. In addition, the
injection practicum was conducted in cadaveric
specimens (vs live patients) to allow for subsequent
dissection and visualization of the injected material.
However, interaction between simulated ATX-101
(methylene blue dye) and cadaveric tissue may not be
identical to interaction between ATX-101 and living
tissue. Furthermore, only 3 cadavers were used for this
exercise. Although this limited sample size does not
represent the diversity of patient types who may seek
ATX-101 treatment, it did serve to validate the current
ATX-101 injection protocol used in clinical practice. It
is also worth noting that some of the assessments
during the injection practicum were subjective in
nature (e.g., injection pressure) and based on the
clinical experience of the faculty.
Conclusions
ATX-101 is the only pharmacological treatment
approved for reduction of submental fat. The injection
practicum provided greater understanding of the
optimum injection technique as it relates to anatomic
placement and product diffusion characteristics and
© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
JONES ET AL
corroborated the recommended ATX-101 injection
paradigm. Further experience will likely shed
more light on advanced injection techniques and
protocols to deliver optimum treatment outcomes
with ATX-101.
References
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[prescribing information]. Available from: http://www.mykybella.com/
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Accessed August 24, 2016.
2. Hatef DA, Koshy JC, Sandoval SE, Echo AP, et al. The submental fat
compartment of the neck. Semin Plast Surg 2009;23:288–91.
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reported outcomes and safety profile of ATX-101 (deoxycholic acid), an
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a phase III, randomized, placebo-controlled study. J Eur Acad Dermatol
Venereol 2014;28:1707–15.
4. Humphrey S, Sykes J, Kantor J, Bertucci V, et al. ATX-101 for reduction
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5. Jones DH, Carruthers J, Joseph JH, Callender VD, et al. REFINE-1,
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Address correspondence and reprint requests to: Derek H.
Jones, MD, 9201 West Sunset Boulevard, Suite 602, Los
Angeles, CA 90069, or e-mail: derekjonesmd@gmail.com
42:11S:NOVEMBER SUPPLEMENT 2016 S281