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Original Article

Proper Technique for Administration of ATX-101 (Deoxycholic Acid Injection): Insights From an Injection Practicum and Roundtable Discussion

Jones, Derek H. MD*; Kenkel, Jeffrey M. MD; Fagien, Steven MD; Glaser, Dee Anna MD§; Monheit, Gary D. MD; Stauffer, Karen PhD, CMPP; Sykes, Jonathan M. MD**

Author Information
doi: 10.1097/DSS.0000000000000875


ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) is the first aesthetic injectable approved for reduction of submental fat.1 Unlike other aesthetic injectable 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 conducted 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 dissections 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, corresponding to the ATX-101 treatment area, was delineated by marking the submental crease anteriorly, the hyoid bone posteriorly, and the lateral boundaries as judged on palpation (note that the lateral boundaries 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 performed to select the appropriate methylene blue dye formulation 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 Biopharmaceuticals, Inc. [an affiliate of Allergan plc]) and thus was subsequently used in the injection practicum. In 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], superficial, 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.

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.

After the injections, the cadavers were dissected to show the anatomic placement and diffusion characteristics of the simulated ATX-101 (Figure 2). Subsequent to the dissections, a structured roundtable discussion was conducted to review the potential implications of the various injection protocols evaluated during the practicum. Furthermore, the faculty had the opportunity to provide additional perspectives based on their clinical experience with facial injectables and ATX-101 specifically.

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.

Results of the Injection Practicum

Injection to standard depth midway into the subcutaneous tissue (oriented perpendicularly to the skin) resulted in consistent deposition of simulated ATX-101 within the preplatysmal submental fat. In contrast, overly cautious and/or superficial injections led to deposition of simulated ATX-101 close to the dermis. Similarly, pinching the skin instead of the underlying fat tissue when injecting resulted in diffusion 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.

Overall, there was no advantage to either reducing or increasing injection pressure during administration 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 simulated 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 dissection, 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 preplatysmal submental fat. This observation is consistent 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 contouring with ATX-101 was emphasized by the faculty. To identify appropriate candidates for treatment, a thorough physical examination is recommended to identify the presence of conditions that could either result in undesirable aesthetic outcomes (e.g., prominent platysmal bands or marked soft tissue descent and laxity within the submental area) or complicate/contraindicate treatment (e.g., history of surgical/aesthetic procedures within the submental area, history of dysphagia or facial nerve paresis, or inflammation/induration/infection within the treatment area). To consistently and objectively evaluate submental fullness, patients should be examined from multiple vantage points, including having the patient positioned 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 lymphadenopathy). Therefore, physicians should palpate the submental area while patients animate their platysma muscle to isolate the preplatysmal fat. In addition, patients should be asked to smile (to identify any asymmetry) and swallow (to identify any dysfunction), which could impact ATX-101 administration and/or the outcome after treatment. Careful assessment of submental skin laxity is also important during the examination as reduction of submental fat in patients with excessive laxity may result in an undesirable aesthetic outcome.

Figure 3.:
During the physical examination, patients should be viewed by the physician from multiple vantage points, including the Frankfort plane. The Frankfort plane includes a line approximating the base of the cranium, passing from the infraorbital rim (infraorbitale) to the midline of the occiput, and intersecting the superior margin of the external auditory meatus (porion). During evaluation, the Frankfort horizontal should parallel the ground, assuring a neutral and reproducible head position.

It is recommended that the initial office visit serve as 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 injections administered at each treatment session is dependent on the amount and distribution of submental fat for an individual patient; multiple treatment sessions (up to 61) may be needed to achieve a satisfactory reduction in submental fat; and treatments 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/interventions within the submental area while undergoing 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 mandibular nerve is deep to the platysma and courses from 1 to 4 cm below the inferior mandibular border.7 The radius of effect of ATX-101 should be considered when injecting near the marginal mandibular nerve as ATX-101 diffuses within the fat tissue once injected. Injecting too close to the marginal mandibular nerve could result in direct effects of ATX-101 on the 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.

Figure 4.:
Illustration of pretreatment markings of the planned treatment area (corresponding to the submental fat compartment [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).
Figure 5.:
Illustration of the 1-cm injection grid applied before treatment with ATX-101.

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 treatment, injectable anesthetic can be administered 15 minutes before treatment, and/or ice/cold packs can be applied for 5 minutes before treatment. Article 5 of the supplement titled “Management of patient experience with ATX-101 (deoxycholic acid injection) treatment for reduction of submental fat” presents the results from an ATX-101 clinical trial that evaluated various patient comfort modalities.

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 injections 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 preplatysmal 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 individual 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 injections (maximum of 10 mL per treatment session). It is recommended that injections begin at the inferior portion of the preplatysmal fat pad and continue horizontally in rows upward.

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.

After ATX-101 treatment, the physician may assess the smile for any asymmetry and evaluate swallowing to ensure that any swelling/edema within the submental 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 worsens 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 physician should reiterate to the patient that they may experience bruising, pain, numbness, swelling, redness, 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,

Overall, the injection practicum offered the opportunity 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 implications 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 submental 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 diffusion 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.


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 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.


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© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.