DEOXYCHOLIC ACID: 2,277 Adverse Event Reports & Safety Profile

KYBELLA (deoxycholic acid) injection, 10 mg/mL is a clear colorless, sterile solution for subcutaneous use. It contains a cytolytic agent, deoxycholic acid, as the active ingredient. The chemical name of deoxycholic acid is 3α,12α-dihydroxy-5β-cholan-24-oic acid, and its molecular formula is C 24 H 40 O 4 , and its molecular weight is 392.57 g/mol. The chemical structure of deoxycholic acid is: Each 2 mL vial of KYBELLA injection contains 20 mg synthetic deoxycholic acid as the active ingredient and the following inactive ingredients: benzyl alcohol (18 mg), dibasic sodium phosphate (2.84 mg), sodium chloride (8.76 mg), sodium hydroxide (2.86 mg) in water for injection, USP. Hydrochloric acid and additional sodium hydroxide are added as necessary to adjust the formulation to pH 8.3. Each vial is for single patient use. The chemical structure of deoxycholic acid.

AND USAGE KYBELLA ® (deoxycholic acid) injection is indicated for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults. Limitations of use The safe and effective use of KYBELLA for the treatment of subcutaneous fat outside the submental region has not been established and is not recommended. KYBELLA is a cytolytic drug indicated for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults. ( 1 ) Limit ation s of use The safe and effective use of KYBELLA for the treatment of subcutaneous fat outside the submental region has not been established and is not recommended. ( 1 )

AND ADMINISTRATION 0.2 mL injections spaced 1 cm apart until all sites in the planned treatment area have been injected. ( 2.1 ) Up to 50 injections or 10 mL may be injected in a single treatment. ( 2.1 ) Up to 6 single treatments may be administered at intervals no less than 1-month apart. ( 2.1 )

See General

Considerations for Administration and Injection Technique before injection. ( 2.2 , 2.3 )

Figure

1. Avoid the Marginal Mandibular Nerve Area Figure 2.

Sagittal

View of Platysma Area Figure 3.

Injection

Pattern

2.1 Dos age KYBELLA injection is injected into subcutaneous fat tissue in the submental area using an area-adjusted dose of 2 mg/cm 2 . A single treatment consists of up to a maximum of 50 injections, 0.2 mL each (up to a total of 10 mL), spaced 1 cm apart. Up to 6 single treatments may be administered at intervals no less than 1 month apart.

See General

Considerations for Administration ( 2.2 ) and Injection Technique ( 2.3 ) before injection.

2.2 General Considerations for Administration KYBELLA should be administered by a healthcare professional. Screen patients for other potential causes of submental convexity/fullness (e.g., thyromegaly and cervical lymphadenopathy). Give careful consideration to the use of KYBELLA in patients with excessive skin laxity, prominent platysmal bands or other conditions for which reduction of submental fat may result in an aesthetically undesirable outcome. Use caution in patients who have had prior surgical or aesthetic treatment of the submental area. Changes in anatomy/landmarks or the presence of scar tissue may impact the ability to safely administer KYBELLA or to obtain the desired aesthetic result. KYBELLA is clear, colorless and free of particulate matter. Visually inspect KYBELLA vials for particulate matter and/or discoloration, and discard the vial if the solution is discolored and/or contains particulate matter. After use, discard any remaining solution in the vial. 2. 3 Injection Technique The safe and effective use of KYBELLA depends on the use of the correct number and locations for injections, proper needle placement, and administration techniques. Healthcare professionals administering KYBELLA must understand the relevant submental anatomy and associated neuromuscular structures in the area involved and any alterations to the anatomy due to prior surgical or aesthetic procedures [ see W a r n in g s a n d Preca u ti o ns ( 5 ) ]. Avoid injections near the area of the marginal mandibular nerve Needle placement with respect to the mandible is very important as it reduces the potential for injury to the marginal mandibular nerve, a motor branch of the facial nerve. Injury to the nerve presents as an asymmetrical smile due to paresis of lip depressor muscles [ see Warnings and Precautions ( 5.1 ) ] . To avoid injury to the marginal mandibular nerve: Do not inject above the inferior border of the mandible. Do not inject within a region defined by a 1-1.5 cm line below the inferior border (from the angle of the mandible to the mentum). Inject KYBELLA only within the target submental fat treatment area (see Figures 1 and 3 ).

Figure

1. Avoid the Marginal Mandibular Nerve Area Avoid injection into the platysma Prior to each treatment session, palpate the submental area to ensure sufficient submental fat and to identify subcutaneous fat between the dermis and platysma (pre-platysmal fat) within the target treatment area ( Figure 2 ). The number of injections and the number of treatments should be tailored to the individual patient’s submental fat distribution and treatment goals.

Figure

2 .

Sagittal

View of Platy s ma Area Injecting into the treatment area Use of ice/cold packs, topical and/or injectable local anesthesia (e.g., lidocaine) may enhance patient comfort. Outline the planned treatment area with a surgical pen and apply a 1 cm injection grid to mark the injection sites ( Figures 2 and 3 ).

Figure

3 .

Treatment

Area and Injection Pattern Do not inject KYBELLA outside the defined parameters [see Warnings and Precautions ( 5.1 , 5.4 , 5.6 )] . Using a large bore needle, draw 1 mL of KYBELLA into a sterile 1 mL syringe and expel any air bubbles in the syringe barrel. Have the patient tense the platysma. Pinch the submental fat and, using a 30 gauge (or smaller) 0.5 inch needle, inject 0.2 mL of KYBELLA into the pre-platysmal fat (see Figure 2 ) next to each of the marked injection sites by advancing the needle perpendicular to the skin. Injections that are too superficial (into the dermis) may result in skin ulceration and necrosis. Do not withdraw the needle from the subcutaneous fat during injection as this could increase the risk of intradermal exposure and potential skin ulceration and necrosis. Avoid injecting into the post-platysmal fat by injecting KYBELLA into fat tissue at the depth of approximately mid-way into the subcutaneous fat layer ( Figure 2 ). If at any time resistance is met as the needle is inserted, indicating the possibility of contact with fascial or nonfat tissue, the needle must be withdrawn to an appropriate depth before the injection is administered. Avoid injecting into other tissues such as the muscle, salivary glands, lymph nodes; and artery or vein. Upon needle withdrawal, pressure may be applied to each injection site as necessary to minimize bleeding; an adhesive dressing may be applied.

KYBELLA injection is contraindicated in the presence of infection at the injection sites. KYBELLA is contraindicated: In the presence of infection at the injection sites . ( 4 )

REACTIONS The most common adverse reactions (>20% of subjects) include injection site edema/swelling, hematoma, pain, numbness, erythema and induration. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6 . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two double-blind, placebo-controlled clinical trials 513 subjects were treated with KYBELLA injection and 506 subjects were treated with placebo. The population was 19-65 years old, 85% were women, 87% Caucasian, 8% African American. At baseline the population had a mean BMI of 29 kg/m 2 , moderate to severe submental convexity (graded as 2 or 3 on a 0 to 4 scale) and without excessive skin laxity. Subjects received up to 6 treatments at least 1 month apart and were followed for up to 6 months after the last received treatment. The most commonly reported adverse reactions are listed below ( Table 1 ).

Table

1.

Adverse

Reactions in the Pooled Trials 1 and 2 a Adverse reactions KYBELLA (N=513) n (%) Placebo (N=506) n (%) Injection site reactions 492 (96%) 411 (81%) edema/swelling 448 (87%) 218 (43%) hematoma/bruising 368 (72%) 353 (70%) pain 356 (70%) 160 (32%) numbness 341 (66%) 29 (6%) erythema 136 (27%) 91 (18%) induration 120 (23%) 13 (3%) paresthesia 70 (14%) 20 (4%) nodule 68 (13%) 14 (3%) pruritus 64 (12%) 30 (6%) skin tightness 24 (5%) 6 (1%) site warmth 22 (4%) 8 (2%) nerve injury b 20 (4 %) 1 (<1%)

Headache

41 (8%) 20 (4%) Oropharyngeal pain 15 (3%) 7 (1%)

Hypertension

13 (3%) 7 (1%)

Nausea

12 (2%) 3 (1%)

Dysphagia

10 (2%) 1 (<1%) a Adverse reactions that occurred in ≥ 2% KYBELLA treated subjects and at greater incidence than placebo b Marginal mandibular nerve paresis Other adverse reactions associated with the use of KYBELLA include: injection site hemorrhage, injection site discoloration, pre-syncope/syncope, lymphadenopathy, injection site urticaria, and neck pain. Adverse reactions that lasted more than 30 days and occurred in more than 10% of subjects were injection site numbness (42%), injection site edema/swelling (20%), injection site pain (16%), and injection site induration (13%).

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of KYBELLA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to KYBELLA exposure. Administration site conditions : injection site ulceration, necrosis, infection, alopecia, scarring, and mass.

Immune System

Disorders: Hypersensitivity reactions including rash, urticaria, and itching.

Nervous System

Disorders: Oral hypoaesthesia and oral paraesthesia.

Procedural

Complications: Vascular injury due to inadvertent intravascular injection.

AND PR E CAUTIONS Marginal mandibular nerve (MMN) injury: Follow injection technique to avoid this injury. ( 2.3 , 5.1 ) Dysphagia may occur with KYBELLA use. Use in patients with pre-existing dysphagia may exacerbate the condition. ( 5.2 ) Submental hematoma/bruising occurs frequently after KYBELLA administration. Use with caution in patients who are being treated with antiplatelet or anticoagulant therapy or have coagulation abnormalities. ( 5.3 ) Avoid injecting in proximity to vulnerable anatomic structures due to the increased risk of tissue damage and vascular injury. ( 2.3 , 5.4 ) Injection site alopecia: Withhold subsequent treatments until resolution. ( 5.5 ) Injection site ulceration, necrosis, and infection: Do not administer to the affected area until complete resolution. ( 5.6 ) 5 . 1 Marginal mandibular nerve injury Cases of marginal mandibular nerve injury, manifested as an asymmetric smile or facial muscle weakness (paresis), were reported during clinical trials. To avoid the potential for nerve injury, KYBELLA injection should not be injected into or in close proximity to the marginal mandibular branch of the facial nerve. All marginal mandibular nerve injuries reported from the trials resolved spontaneously (range 1-298 days, median 44 days). 5 . 2 Dysphagia Difficulty swallowing (dysphagia) occurred in clinical trials in the setting of administration site reactions, e.g., pain, swelling, and induration of the submental area. Cases of dysphagia spontaneously resolved (range 1-81 days, median 3 days). Subjects with current or prior history of dysphagia were excluded from clinical trials. Avoid use of KYBELLA in these patients as current or prior history of dysphagia may exacerbate the condition.

5.3 Injection site hematoma /bruising In clinical trials, 72% of subjects treated with KYBELLA experienced injection site hematoma/bruising <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ) ]</span> . KYBELLA should be used with caution in patients with bleeding abnormalities or who are currently being treated with antiplatelet or anticoagulant therapy as excessive bleeding or bruising in the treatment area may occur.

5.4 Risk of injecting in proximity to vulnerable anatomic structure s To avoid potential tissue damage, KYBELLA should not be injected into or in close proximity (1-1.5 cm) to salivary glands, lymph nodes and muscles. Care should be taken to avoid inadvertent injection directly into an artery or a vein as it can result in vascular injury.

5.5 Injection site alopecia Cases of injection site alopecia have been reported with the administration of KYBELLA. The onset and duration of this adverse reaction may vary among individuals and may persist. Consider withholding subsequent treatments until resolution of the adverse reaction.

5.6 Injection site ulceration , necrosis , and infection Injections that are too superficial (into the dermis) may result in skin ulceration and necrosis <span class="opacity-50 text-xs">[see Injection Technique ( 2.3 )]</span> . Cases of injection site ulceration, necrosis, and infection have been reported with the administration of KYBELLA. Some cases of injection site infection have included cellulitis and abscess requiring intravenous antibiotic treatment and incision and drainage. Do not administer KYBELLA into the affected area until complete resolution of the adverse reaction.