Deoxycholic acid is a cytolytic drug indicated for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults. Safety and efficacy have not been established for use outside of the submental area or in adolescent patients. Deoxycholic acid (Kybella) was approved by the FDA in April 2015.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect the deoxycholic acid vials for particulate matter and discoloration. Deoxycholic acid is clear, colorless, and free of particulate matter. Discard the vial if the solution is discolored or contains particulate matter.
-Injections should be administered by a trained health care professional.
Subcutaneous Administration
Subcutaneous Injection into the Submental Area:
-Health care professionals must understand submental anatomy and neuromuscular structures in the submental area and be aware of any alterations to anatomy due to prior surgical or aesthetic procedures. Using the correct number and location of injections, proper needle placement, and administration techniques are vital for the safe and effective use of deoxycholic acid.
-Topical or local injectable anesthesia and ice or cold packs may provide patient comfort.
-Outline the treatment area with a surgical pen and apply a 1-centimeter injection grid mark to the injection sites (see prescribing information for figures).
-Use aseptic technique.
-Using a large-bore needle, draw 1 mL deoxycholic acid from the vial into a sterile 1 mL syringe and expel any air bubbles.
-Instruct the patient to tense the platysma muscle.
-Pinch the submental fat and using a 30-gauge (or smaller) 0.5-inch needle, inject 0.2 mL into the pre-platysma fat next to each of the marked injection sites by advancing the needle perpendicular to the skin.
-Do not inject deoxycholic acid outside of the defined parameters.
-Skin ulceration may occur from injections that are too superficial into the dermis. Do not remove the needle from the subcutaneous fat during injection; this could increase the risk of intradermal exposure and potential skin ulceration.
-Inject into fat tissue at the depth of approximately mid-way into the subcutaneous fat mater; avoid injecting into the post-platysmal fat.
-During administration, if any resistance is felt as the needle is inserted, indicating the possibility of contact with fascial or nonfat tissue, withdraw the needle to an appropriate depth before injecting the drug.
-Avoid injecting into other tissues such as muscle, salivary glands, and lymph nodes. Avoid injecting into an artery or vein.
-Apply pressure to each injection site upon needle withdrawal and apply ad adhesive dressing, if needed.
-Discard any remaining solution in the vial after use.
AVOID INJECTIONS NEAR THE AREA OF THE MARGINAL MANDIBULAR NERVE (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 to 1.5 cm line below the inferior border (from the angle of the mandible to the mentum).
-Inject deoxycholic acid only within the target submental fat treatment areas (see prescribing information for figures).
AVOID INJECTION INTO THE PLATYSMA MUSCLE.
-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 area (see prescribing information for figures).
-Tailor the number of injections and treatments to the patient's submental fat distribution and treatment goals.
The most common adverse reactions reported during placebo-controlled clinical trials of deoxycholic acid were injection site reactions (96% vs. 81%). Specific injection site reaction types included edema (87% vs. 43%), hematoma (72% vs. 70%), pain (70% vs. 32%), numbness (66% vs. 6%), erythema (27% vs. 18%), induration (23% vs. 3%), paresthesias (14% vs. 4%), nodule (13% vs. 3%), pruritus (12% vs. 6%), skin tightness (5% vs. 1%), and warmth at the site (4% vs. 2%). Other adverse reactions reported at the injections site (incidence not reported) included local hemorrhage (bleeding) or ecchymosis, skin discoloration, and urticaria. Injection site reactions lasting more than 30 days included numbness (42%), edema (20%), pain (16%), and induration (13%). Lymphadenopathy also was reported in clinical trials. Injection site reactions (i.e., ulceration, necrosis, infection, alopecia, scarring) and hypersensitivity reactions (i.e., rash, pruritus, urticaria) have also been reported during postmarketing use of the drug. For cases of injection site alopecia, the onset and duration may vary among individuals and may persist; whereas a skin ulcer or skin necrosis occurs when the dose is injected too superficially (i.e., into the dermis). Injection site infections (i.e., cellulitis, abscesses) may require treatment with intravenous antibiotics and incision and drainage. If these reactions develop, avoid subsequent treatments into the affected area until complete resolution of the adverse reaction.
Marginal mandibular nerve injury, characterized by an asymmetric smile or facial muscle paresis, was reported in 4% of patients during deoxycholic acid clinical trials. The mandibular nerve is the largest of the three branches or divisions of the trigeminal nerve, the fifth cranial nerve, thus injury creates the appearance similar to cranial nerve palsies. All reported injuries resolved spontaneously (median 44 days, range 1 to 298 days). To avoid injury, deoxycholic acid should not be administered into or in close proximity to the marginal mandibular branch of this facial nerve. During postmarketing use of the drug, cases of oral hypoesthesia and oral paresthesia have been reported. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
During clinical trials of deoxycholic acid, nausea was reported in 2% (vs. 1% placebo) of patients and oropharyngeal pain was reported in 3% of patients (vs. 1% placebo).
Dysphagia was reported during deoxycholic acid clinical trials (2% vs. less than 1% placebo). Cases of dysphagia resolved spontaneously (median 3 days, range 1 to 81 days).
Headache was reported in 8% of patients in deoxycholic acid clinical trials (vs. 4% placebo). Pre-syncope and syncope also were reported (incidence not reported).
Hypertension was reported in 3% of patients during deoxycholic acid injection clinical trials (vs. 1% placebo). During postmarketing use of the drug, cases of vascular injury have resulted from the inadvertent injection of deoxycholic acid directly into an artery or vein.
Deoxycholic acid is contraindicated if signs of infection are present at the injection sites. Administration of the drug has been associated with injection site infections, including cellulitis and abscesses requiring treatment with intravenous antibiotics and incisions and drainage.
Screen patients for other potential causes of submental convexity or fullness (e.g., thyromegaly or goiter, cervical lymphadenopathy, other potential neck area conditions). In addition, carefully consider the use of deoxycholic acid in patients with excessive skin laxity, prominent platysmal bands, or other conditions for which reduction of submental fat could result in an aesthetically undesirable outcome. Use deoxycholic acid with caution in patients with a current or prior history of dysphagia. During clinical trials, dysphagia was reported, and use in patients with a current or prior history of dysphagia may exacerbate the condition.
Use deoxycholic acid with caution in patients with clotting abnormalities (e.g., coagulopathy) or who are undergoing treatment with antiplatelet or anticoagulant therapy. Excessive bleeding or bruising in the treatment area may occur.
Use deoxycholic acid with caution in patients who have had prior surgery or aesthetic treatment of the submental area. The presence of scar tissue and changes in anatomy or landmarks may impact the ability to safety administered deoxycholic acid or to obtain the desired result.
Agents for cosmetic procedures are not medically necessary during pregnancy. There are no adequate or well-controlled studies of deoxycholic acid during human pregnancy. Animal reproduction studies have shown no fetal harm with the subcutaneous administration of deoxycholic acid to rats during organogenesis at doses up to 5 times the maximum human dose. In animal studies involving rabbits, a missing intermediate lung lobe was noted in rabbits at all doses tested including the lowest dose, which is 2-fold the maximum recommended human dose.
It is unknown if deoxycholic acid is present in human breast milk or if it has any effect on a breast-fed infant or on maternal milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to an internally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Deoxycholic acid injection is not intended for use in children or adolescents. Safety and efficacy have not been established in pediatric patients less than 18 years of age. There is no known indication for use of this drug product in infants.
Take care to avoid intraarterial administration or intravenous administration of deoxycholic acid as this can result in vascular injury. To avoid potential tissue damage, do not inject the drug into or in close proximity (1 to 1.5 cm) to vulnerable anatomic structures including salivary glands, lymph nodes, and muscles (i.e., intramuscular administration). Similarily, deoxycholic acid should not be injected into or in close proximity to the marginal mandibular branch of the facial nerve. Mandibular nerve injury has been reported with deoxycholic acid use.
For the improvement in the appearance of moderate to severe convexity or fullness associated with submental fat:
Subcutaneous dosage:
Adults: 0.2 mL subcutaneously per injection site. A single treatment session consists of up to a maximum of 50 injections (10 mL total dose), with each injection spaced 1 centimeter apart. Up to 6 single treatments may be administered at intervals of no less than 1 month apart. Injections are made into the subcutaneous fat of the submental region, between the dermis and the platysma. Do not inject into the platysma. The safety and efficacy of deoxycholic acid for the treatment of subcutaneous fat other than that found in the submental region has not been established and is not recommended.
Maximum Dosage Limits:
-Adults
Per treatment session: 10 mL total dose subcutaneously into the submental region, administered as up to fifty 0.2 mL injections spaced 1 centimeter apart. Maximum treatment sessions: 6 sessions, each 1 month apart.
-Geriatric
Per treatment session: 10 mL total dose subcutaneously into the submental region, administered as up to fifty 0.2 mL injections spaced 1 centimeter apart. Maximum treatment sessions: 6 sessions, each 1 month apart.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Not indicated.
-Neonates
Not indicated.
Patients with Hepatic Impairment Dosing
Based on the pharmacokinetics of deoxycholic acid, it appears that no dosage adjustments are needed. Formal studies in hepatic impairment are not available.
Patients with Renal Impairment Dosing
No dosage adjustments are recommended.
*non-FDA-approved indication
Abciximab: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Anagrelide: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Anticoagulants: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Antithrombin III: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Apixaban: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Argatroban: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Aspirin, ASA; Dipyridamole: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Betrixaban: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Bivalirudin: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Cilostazol: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Clopidogrel: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Dabigatran: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Dalteparin: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Dipyridamole: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Edoxaban: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Enoxaparin: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Eptifibatide: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Fondaparinux: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Heparin: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Pentosan: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Platelet Inhibitors: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Prasugrel: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Rivaroxaban: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Ticagrelor: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Tirofiban: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Vorapaxar: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Warfarin: (Moderate) Use deoxycholic acid with caution in patients receiving anticoagulants. Excessive bruising or bleeding may occur in and around the treatment area.
Deoxycholic acid is an endogenous compound that is a natural component of bile and is sequestered in the enterohepatic circulation loop. Endogenous deoxycholic acid is highly variable within and between individuals. When administered subcutaneously, deoxycholic acid produces adipolysis, destroying the cell membranes and completely ablating fat.
Deoxycholic acid is administered subcutaneously. Deoxycholic acid is 98% bound to plasma proteins. Deoxycholic acid is not metabolized under normal conditions. A natural product of cholesterol metabolism, endogenous deoxycholic acid is excreted intact in feces. When administered subcutaneously, deoxycholic acid joins the endogenous bile acid pool in the enterohepatic circulation and is excreted along with endogenous deoxycholic acid.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters:
Deoxycholic acid does not inhibit or induce cytochrome P450 enzymes at clinically relevant concentrations when injected into the submental area. No drug transporters are affected with local submental injection.
-Route-Specific Pharmacokinetics
Subcutaneous Route
After subcutaneous injection, deoxycholic acid is rapidly absorbed. Maximum plasma concentrations were observed after a median maximum time of 18 minutes following dosing with the maximum recommended single treatment (100 mg). Compared to a 24-hour baseline endogenous period, the maximum plasma concentration was 3.2-fold higher and the maximum AUC was 1.6-fold higher. No accumulation of deoxycholic acid is expected with the proposed treatment frequency.
-Special Populations
Hepatic Impairment
Deoxycholic acid has not been studied in patients with hepatic impairment; however, pharmacokinetics of deoxycholic acid are unlikely to be influenced by hepatic impairment. Deoxycholic acid is administered intermittently, and the dose administered represents approximately 3% of the total bile acid pool.
Gender Differences
The pharmacokinetic parameters of deoxycholic acid are not influenced by gender.