Sodium hyaluronate is the high molecular weight fractions of purified natural sodium hyaluronic acid. It is used clinically as an intra-articular, intradermal, and ophthalmic viscoelastic agent and applied topically to protect against abrasion, friction, and desiccation. Hyaluronic acid is a naturally occurring polysaccharide that is widely distributed in body tissues and intracellular fluids and is secreted by specific cells of the synovial membrane. In healthy synovial joints, hyaluronic acid maintains viscosity of the synovial fluid and supports the lubricating and shock-absorbing properties of the articular cartilage. In the eye, hyaluronic acid is naturally found in the extracellular matrix of vitreous and aqueous humor and protects corneal endothelial cells and other ocular structures. Hyaluronic acid products are classified as medical devices, rather than drug products. A medical device is a product that is intended to affect the structure or function of the body, but which does not achieve its primary intended purposes through the chemical action of a drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Other Injectable Administration
-Do not inject sodium hyaluronate, hyaluronic acid into blood vessels or outside of specified treatment area.
-Use care in selecting products for administration to avoid mix-ups in choosing appropriate products for ophthalmology, orthopedic, or cosmetic use.
Intra-articular Injection Administration
-Use in locations other than the knee and for conditions other than osteoarthritis have not been established.
-Safety and efficacy of use with concomitant intra-articular injectables have not been established.
-Use strict aseptic technique.
-If product requires refrigeration, remove product from refrigerator at least 20 to 30 minutes prior to use.
-The contents of the syringe must be used immediately after the syringe has been removed from the packaging.
-Do not use concomitant disinfectants that contain quaternary ammonium salts for skin preparation as hyaluronan can precipitate in their presence.
-Lidocaine or similar local anesthetic can be used prior to the injection of sodium hyaluronate, hyaluronic acid.
-Remove any effusion before injecting each dose of sodium hyaluronate, hyaluronic acid. Do not use the same syringe for removing synovial fluid and injecting sodium hyaluronate.
-Use a 17- to 23-gauge needle (see specific product information for needle recommendation).
-Inject the entire contents of the syringe into single knee only. The syringe is intended for single use only.
-If treatment will be bilateral, use a separate syringe for each knee.
-Avoid any strenuous activities or prolonged weight-bearing activities for approximately 48 hours after the injection.
Intraocular Injection Administration
-Use strict aseptic technique.
-The syringe is intended for single use only.
-Refrigerated sodium hyaluronate, hyaluronic acid should be removed from refrigeration and allowed to reach room temperature prior to use (approximately 20 to 40 minutes).
-The ProVisc delivery system is not designed to be attached to reusable (metal-hubbed) instruments or to disposable instruments other than the one provided with the product. Follow the product instructions for use of the device.
-Do not overfill the anterior chamber.
-For cataract surgery / intraocular lens (IOL) implantation: Slowly insert a cannula or needle and carefully inject the required amount of sodium hyaluronate, hyaluronic acid into the anterior chamber of the eye before or after cataract extraction. Additional product may be used to coat surgical instruments and the intraocular lens prior to implantation. Additional product may be injected as required to facilitate surgical procedures. Some manufacturers recommend that sodium hyaluronate, hyaluronic acid be injected prior to cataract extraction and insertion of the IOL for optimal use.
-For corneal transplant surgery: Remove the corneal button and fill the anterior chamber with sodium hyaluronate, hyaluronic acid until it is level with the surface of the cornea. Then place the donor graft on top of the sodium hyaluronate, hyaluronic acid and suture it in place. Additional product may be used as required to aid the surgical procedure.
-For glaucoma filtration surgery: Inject the sodium hyaluronate, hyaluronic acid through a corneal paracentesis to restore and maintain anterior chamber volume during the performance of the trabeculectomy. Additional product may be used as required to aid the surgical procedure.
-For intraocular injection in conjunction with scleral buckling procedure for retinal reattachment: After release of subretinal fluid and development of buckling by tying the mattress sutures, inject air into the vitreous cavity and then exchange with sodium hyaluronate, hyaluronic acid injected through a needle (22- to 30-gauge) passed via the pars plana epithelium. The volume of the product (2 to 4 mL) with vary with the volume of the subretinal fluid released and the space occupied by the buckle. By directing the injection, sodium hyaluronate, hyaluronic acid may be used to separate membranes away from the retina for safe excision and release of traction. It may also help maneuver tissues into the desired position.
-Remove the sodium hyaluronate, hyaluronic acid by irrigation and/or aspiration at the close of surgery to minimize postoperative increases in intraocular pressure (except in glaucoma surgery).
Intradermal Injection Administration
NOTE: Soft tissue fillers should only be injected by individuals with appropriate training or experience. There are reports of unintentional injection into blood vessels resulting in blocked blood vessels and restricted blood supply to tissues. Embolization may occur leading to serious consequences including vision impairment, blindness, stroke (cerebral hemorrhage and ischemia), skin necrosis, and damage of the underlying facial structures.
-The syringe is intended for single use only.
-Follow product instructions for assembly of the specific device.
-Prior to treatment, wash the face with soap and water and dry with a clean towel. Further cleanse the area with alcohol or another suitable antiseptic solution.
-Anesthetic treatment may be appropriate to use prior to the procedure (topical anesthetic, local anesthetic, nerve block). Although some products contain lidocaine, supplementary anesthesia may be used for additional pain management during and after the injection.
-Sterile gloves should be worn for the procedure.
-Administer using a thin gauge needle (see manufacturer information for specific recommendation for each product) into the deep dermis to superficial layer of the subcutis.
-For products that contain lidocaine, initiate treatment by injecting only a small amount of material. Prior to proceeding with the rest of the injection, wait a full 3 seconds to allow the lidocaine time to take effect.
-Apply even pressure on the plunger rod while slowly pulling the needle backwards. The injection should be stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up to superficially in the skin.
-Injection techniques may vary according to the physician's preferences and patient characteristics and may include serial puncture, linear threading, serial threading, or cross-hatching (see manufacturer information for specific details).
-Subdermal application should be avoided as this may not provide optimal correction. If the product is injected too deep, the duration of effect may be shorter. If the product is injected to superficially, this may result in visible lumps or discoloration.
-Only correct to 100% of the desired volume effect. Do not overcorrect. Typical volume used varies by product (see manufacturer information for specific details).
-If immediate blanching occurs, stop the injection and massage the area until it returns to normal color.
-Gently massage the area when the injection is complete so that it conforms to the contour of the surrounding tissue.
-If overcorrection has occurred, massage the area between your fingers or against an underlying superficial bone.
-If further treatment is needed, repeat the procedure until a satisfactory result is obtained.
-Localized swelling may impair the ability to judge for re-treatment; therefore, additional sessions should be resumed after 1 to 2 weeks.
-An ice pack may be applied to the area after the injection.
-Within the first 24 hours after the procedure, patients should avoid strenuous exercise, extensive sun or extreme temperatures, and alcoholic beverages to avoid local reactions. Make-up may be applied a few hours after treatment if no complications are present.
Topical Administration
Cream/Ointment/Lotion Formulations
Xclair cream
-Apply to affected area and massage gently into the skin.
-If skin is broken, cover the affected area with a sterile dressing after application of the cream.
Bionect cream, foam, or gel
-Clean and disinfect wounds or ulcers prior to treatment. For long-standing ulcers, surgical or enzymatic cleaning / debridement may be necessary.
-Apply a thin layer to affected area without extensive rubbing onto the wound surface.
-Cover the lesion area with a sterile gauze pad and, if necessary, with an elastic or compressive bandage.
Hylase Wound Gel
-Cleanse the wound or ulcer with normal saline prior to administration. Other cleansing agents are not recommended. Debridement or surgical cleaning may be performed at the discretion of the healthcare professional.
-Remove excess moisture with dry gauze.
-Apply liberally into the cavity of the ulcer or wound and to surrounding area.
-Cover with a non-stick gauze dressing (e.g., Tefla pad) and wrap with a self-adhesive bandage or suitable tape adhesive.
HyGel 2.5% Gel
-Prior to treatment, clean affected area with saline solution; remove excess moisture.
-Generously apply gel to surface area and margins around the wound.
-Cover the treated area with sterile dressing after application of the gel.
Increased intraocular pressure or ocular hypertension (2.1% to 2.3%) may occur after the use of intra-ocular administration of sodium hyaluronate, hyaluronic acid. If post-operative intraocular pressure increases above expected values, corrective therapy should occur.
Injection site reaction (0.3% to 5.7%) may occur with intra-articular or intradermal use of sodium hyaluronate, hyaluronic acid. Injection site bleeding (0.7% to 1.3%), ecchymosis (14%), effusion (0.5% to 5.7%), erythema (0% to 1%), edema (0.4% to 13%), infection (0.5%), itching (0.3%), mass (0.5%), meniscus injury (0.5%), pain (0.3% to 23.7%), joint pain (0.5% to 2.5%), procedural pain (0.5%), phlebitis, purpura, skin abrasion (0.5%), swelling (0.5% to 4.1%), tenderness (0.5%), warmth (1%), and other, non-specified injection site reaction (0.2% to 0.8%) have been reported in patients receiving the intra-articular injection. Subcutaneous nodule and Baker's cyst each occurred in 0.5% of patients. In patients receiving the intradermal injection, injection site reactions have been reported in up to 99% of patients. These reactions included redness/erythema (47.7% to 93%), pain (5% to 90%), tenderness (50% to 94%), swelling/edema (24% to 90.8%), lumps/bumps (50% to 83%), bruising (19% to 86.5%), itching (15.9% to 47.2%), discoloration (mainly hyperpigmentation) (4% to 78%), firmness (86% to 94%), and peeling (20.5%). The duration of these reactions may last longer than 14 days. Generally, there are fewer reports of injection site pain and tenderness in patients who received the intradermal injections containing lidocaine as compared to those receiving products without lidocaine. Inflammation, bleeding, granuloma, scarring, numbness/tingling, and necrosis at the injection site have been noted in postmarketing reports. Telangiectasis and capillary disorders (i.e., broken capillaries) have been reported as well. A delayed inflammatory reaction, including swelling, redness, tenderness, induration, and acneiform papules at the injection site has been reported with the onset occurring several weeks after the initial injection with an average duration of 2 weeks.
Post-operative inflammatory reactions have been reported with the use of intra-ocular sodium hyaluronate, hyaluronic acid including hypopyon, iritis (34.2% to 44.8%), corneal edema, corneal decompensation, conjunctival hemorrhage (0.6% to 1.1%), corneal opacification (0.6%), and ocular pain (0.6%). The relationship to sodium hyaluronate, hyaluronic acid has not been established. Vision abnormalities have been reported with the use of the intradermal products and have been associated with swelling and overcorrection. Reports consist of blurred vision, double vision, or watery eyes.
Transient pain and swelling of the injected joint may occur after intra-articular injection with sodium hyaluronate, hyaluronic acid. Musculoskeletal adverse reactions reported with the use of intra-articular sodium hyaluronate, hyaluronic acid include arthralgia (1.3% to 25.2%), myalgia (0.2%), arthropathy/arthrosis/arthritis (0.4% to 11%), exostosis (0.5%), neck pain (0.5%), back pain (0.63% to 11.5%), leg pain (less than 4%), leg discomfort (less than 4%), joint disorder (0.4% to 1.25%), joint effusion (0.2% to 5.7%), joint/knee swelling (0.4% to 4.1%), joint warmth (0.2% to 1.6%), joint discoloration (0.6%), joint crepitation (0.2% to 2.5%), joint lock (0.2% to 0.3%), decreased joint range of motion (0.5%), hemarthrosis (0.2%), tendonitis (1.88%), knee pain (53%), musculoskeletal pain (2.6% to 3%), muscle spasm (0.2%), muscle strain (0.5% to 1%), musculoskeletal discomfort (0.6% to 1.8%), muscular weakness (0.6%), extremity pain (0.2% to 4.7%), total knee replacement (3%), bursitis (0.8% to 1.1%), joint stiffness (0.4% to 8.1%), localized osteoarthritis (0.4% to 1.7%), aggravated osteoarthritis (0.4%), synovitis (0.2% to 0.5%), knee arthroplasty (0.5%), knee muscle spasms (0.4%), gait disturbance (0.8%), sensation of heaviness (0.3%), and peripheral edema (0.5% to 1%). Cases of acute inflammation characterized by joint pain, swelling, effusion, and sometimes joint warmth and/or stiffness have been reported; analysis of synovial fluid reveals aseptic fluid with no crystals. This inflammation often responds to nonsteroidal antiinflammatory drugs, intra-articular steroids, and/or arthocentesis within a few days. Gouty arthritis, knee cooling, muscle cramps, peripheral edema, and psoitis have been reported during postmarketing experience.
Gastrointestinal adverse events have been reported with the use of sodium hyaluronate, hyaluronic acid. Nausea (0.63% to 4%), peptic ulcer (3%), abdominal pain (4% or less), diarrhea (4% or less), toothache (3.6%), and dyspepsia (4% or less) were reported in patients receiving the intra-articular injection. Vomiting and dysgeusia (metallic taste) were noted in postmarketing reports. Hemorrhoid problems have been reported. Nausea has also been reported with the use of the intradermal injection.
General adverse events have been reported with the use of sodium hyaluronate, hyaluronic acid. Cough (1% to 1.5%), headache (0.4% to 18%), unspecified pain (0.8% to 18.4%), fatigue (1.25% to 1.88%), asthenia (3%), oropharyngeal pain (1.6%), increased blood pressure (1.88% to 3.75%), tachyarrhythmia (arrhythmia exacerbation), phlebitis with varicosities, fever (0.4% to 2.6%), inflicted injury, fall, contusion (0.5%), low back sprain, feeling sick (1.88%), chills, heaviness (0.7%), leukocytosis (0.4%), increased blood glucose (0.2%), and increased alanine aminotransferase (0.4%) have been reported with the use of some of the intra-articular injections. There have been rare reports of thrombocytopenia with a 3-injection intraarticular regimen. Hypoesthesia, headache, malaise, and vascular events have been reported with the use of the intradermal injection.
Allergic reactions have been reported with the use of sodium hyaluronate, hyaluronic acid. Adverse reactions reported with the use of the intra-articular injection include ecchymosis, hay fever, reaction on the face and neck, cutaneous reaction on the forearms/knees, undefined allergic or hypersensitivity reaction (0.4% to 2%), pruritus (0.3% to 7%), angioedema (swelling of face, eyelids, mouth) (3%), swelling of extremities, rash (3%), hives, and redness of the face. Anaphylactoid reactions accompanied by a transient drop in blood pressure, giant urticaria and edema in both legs, skin eruption, burning and itching sensations, and unspecified inflammatory symptoms have been noted in postmarketing reports. Allergic and dermatologic reactions have also been associated with the use of the intradermal products and include swelling, pruritus, itchy eyes, shortness of breath (dyspnea), telangiectasis, blister, skin rash, urticaria, blanching, angioedema, and dermatitis. A sensitization phenomena has been reported with the use of sodium hyaluronate, hyaluronic acid topical cream, foam, and gel. Discontinue the topical product if this occurs.
Infection has been reported in patients using sodium hyaluronate, hyaluronic acid. Upper respiratory tract infection (1% to 6%), naso-pharyngitis (1.5% to 9.9%), influenza-like symptoms (4% or less), influenza (1.6%), sinusitis (4% or less), tonsillitis with nausea, urinary tract infection (1% to 2.1%), cystitis (0.5%), bronchitis (4% or less), rhinitis (4% or less), unspecified infection (1.25%), unspecified viral infection (0.5%), herpes simplex (3%), herpes zoster (1% to 3%), and bacterial arthritis (0.4%) have been reported in patients using the intraarticular injection. Infection (1%), including abscess at the injection site, has also been reported with the use of the intradermal products. Symptoms associated with herpetic eruptions have been reported and commonly occurred within 2 days to 1 month after intradermal injection. Flu-like symptoms have also been noted in postmarketing reports with the intradermal injection. Ocular infection has been reported in 0.6% of patients with the use of the intraocular injection.
Dizziness (0.8%), anxiety (0.2%), contusion (0.4%), depression (0.2%), nervousness (0.2%), paresthesias (1.25%), sciatica (0.5% to 1%), and sensory disturbance (0.3%) have been reported with intra-articular injections of sodium hyaluronate, hyaluronic acid. Paresthesias have also been noted with the use of the intradermal injection.
Use sodium hyaluronate products intended for intra-articular administration with caution in patients with pre-existing chondrocalcinosis. The injection may lead to an acute exacerbation of the condition.
Use of the intradermal sodium hyaluronate, hyaluronic acid products in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
Laser treatment, chemical peeling, epilation, UV irradiation, or other procedures administered after the use of intradermal sodium hyaluronate, hyaluronic acid may increase the risk of eliciting an inflammatory reaction at the implant site. Additionally, if intradermal sodium hyaluronate, hyaluronic acid is used before the skin has healed completely after laser treatment, chemical peeling or other procedures, increased inflammatory reactions are possible. Minimize exposure to excessive sun, UV lamps, and extreme cold weather until initial swelling and redness is gone.
There have been isolated reports of diffuse particulates or haziness appearing after the intra-ocular injection of sodium hyaluronate, hyaluronic acid. While this is seldom associated with any effects on ocular tissues, physicians should be aware and the particulate matter should be removed by irrigation and/or aspiration. In vitro laboratory studies suggest that this may be related to interactions with certain concomitantly administered ophthalmic medication.
The use of sodium hyaluronate, hyaluronic acid is contraindicated in patients with known hyaluronan (sodium hyaluronate) hypersensitivity. The Xclair brand of hyaluronic acid topical cream contains a nut oil that may cause allergic reactions in patients with known hypersensitivity to nuts or nut oils. Some products are obtained from microbial fermentation or are derived from bacterial cells, which may produce allergic responses in some individuals. Hymovis, OrthoVisc, Monovisc, and products for intradermal injection are contraindicated in patients with hypersensitivity to gram positive bacterial proteins. Some products may be produced/extracted from avian tissues; therefore, use caution when administering to patients with allergies to avian proteins, feathers, and egg products (egg hypersensitivity). In Gel-One, strands of hyaluronan are bound to each other via dimers of cinnamic acid; use caution when administering this product to patients who are allergic to cinnamon. Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, Juvederm Voluma XC, Juvederm Vollure XC, Prevelle Silk, Perlane-L and Restylane-L contain 0.3% lidocaine and are contraindicated in patients with a history of lidocaine allergy. The products used for intradermal injection are contraindicated for use by patients with a history of anaphylaxis or multiple severe allergies.
Do not administer intradermal sodium hyaluronate, hyaluronic acid products into anatomical spaces other than the dermis or superficial layer of the subcutis. Do not inject the sodium hyaluronate, hyaluronic acid products into blood vessels (intraarterial administration or intravenous administration) as introduction of these products into the vasculature may occlude blood vessels and could cause infarction or embolization. This may ultimately result in vision impairment, blindness, stroke, or damage and/or necrosis of the skin and underlying facial structures. Unintentional injection into blood vessels may occur at any area of the face but has been reported more frequently with injections in the glabella region, in and around the nose, forehead, and the periorbital region. Immediately stop the injection if a patient exhibits any signs or symptoms associated with injection into a blood vessel, such as changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Instruct patients to seek medical attention after the procedure if they experience signs and symptoms associated with injection into a blood vessel.
Increased intraocular pressure has been reported with the use of the intraocular injection of sodium hyaluronate, hyaluronic acid. Caution is warranted in patients predisposed to increases in intraocular pressure, such as patients with glaucoma or diabetes mellitus patients with aphakia.
The use of intra-articular sodium hyaluronate, hyaluronic acid is contraindicated in patients with an infection or skin disease in the area of the knee. The intradermal products should not be used at sites that have an active inflammatory process (skin eruptions such a cysts, pimples, rashes, or hives) or if an infection is present. Additionally in patients with a history of previous herpetic eruptions, use of the intradermal products may be associated with the reactivation of the herpes infection.
The safety and efficacy of intra-articular and intradermal sodium hyaluronate, hyaluronic acid products have not been established in neonates, infants, children, and adolescents. Although the manufacturers do not provide specific information or precautions regarding the use of intra-ocular sodium hyaluronate, hyaluronic acid in pediatric patients, its use has been noted in small case series in patients as young as 4 years. Although the manufacturer does not provide a specific precaution regarding the use of topical sodium hyaluronate, hyaluronic acid in pediatric patients, there are no data available describing use in this population.
The safety and efficacy of sodium hyaluronate, hyaluronic acid used in pregnancy have not been established. Animal studies using intra-articular sodium hyaluronate, hyaluronic acid revealed no evidence of impaired fertility or harm to the fetus. Administer to a pregnant woman only if potential benefits outweigh the potential risks.
According to the manufacturer, the safety and effectiveness of sodium hyaluronate, hyaluronic acid have not been established in lactating women. It is unknown if sodium hyaluronate, hyaluronic acid is excreted in breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The Monovisc, Restylane, Restylane-L, Perlane, and Restylane Lyft (formerly Perlane-L) formulations of sodium hyaluronate, hyaluronic acid are specifically contraindicated in patients with known systemic bleeding disorders (e.g., coagulopathy, hemophilia, or aplastic anemia). Use caution during intra-articular or intradermal injection in patients with coagulopathies, thrombocytopenia, pancytopenia, or in those taking anticoagulant therapy, as increased bleeding or bruising may occur at injection sites.
For the management and symptom relief of skin irritation and dermatitis:
-for the relief of symptoms, such as burning, itching, and pain, associated with radiation dermatitis:
Topical dosage (Xclair cream):
Adults: Apply to the affected skin area(s) 3 times daily or as needed. Cover with a sterile dressing.
-for the management of skin irritation:
Topical dosage (Bionect cream, foam, and gel):
Adults: Apply a thin layer to affected area 2 to 3 times daily. Cover the lesion with a sterile gauze pad or with an elastic or compressive bandage.
For the relief of pain from burns:
-for the treatment of first- or second-degree burns:
Topical dosage (Bionect foam):
Adults: Apply a thin layer to affected area 2 to 3 times daily. Cover the lesion with a sterile gauze pad or with an elastic or compressive bandage.
-for the treatment of second- or third-degree burns:
Topical dosage (Xclair cream):
Adults: Apply to the affected skin area(s) 3 times daily or as needed. Cover with a sterile dressing.
Topical dosage (Bionect cream or gel):
Adults: Apply a thin layer to affected area 2 to 3 times daily. Cover the lesion with a sterile gauze pad or with an elastic or compressive bandage.
For wound management of dermal ulcers (pressure sores / decubitus ulcer, venous stasis ulcers, arterial ulcers, leg ulcers, diabetic foot ulcer), for management of wounds that are prone to bleeding including wounds that have been mechanically or surgically debrided, donor sites, and post-operative incisions, and to aid in the healing of minor skin abrasion and cuts:
Topical dosage (Bionect cream, foam, and gel):
Adults: Apply a thin layer to affected area 2 to 3 times daily. Cover the lesion with a sterile gauze pad or with an elastic or compressive bandage.
Topical dosage (Hylase Wound Gel):
Adults: Cleanse ulcer or wound with normal saline solution (other cleansing agents are not recommended). Debridement or surgical cleaning of the ulcer or wound may be performed at the discretion of the healthcare professional. Remove excess moisture using dry gauze. Apply gel liberally into cavity of the ulcer or wound and to surrounding area and cover with a non-stick gauze dressing (e.g., Tefla pad). Wrap a self-adhesive bandage over the non-stick dressing. Repeat daily.
Topical dosage (HyGel 2.5% gel):
Adults: Cleanse ulcer or wound with normal saline solution (other cleansing agents are not recommended). Remove excess moisture using dry gauze. Apply gel liberally to the surface and surrounding area of the wound. Cover treated area with a self-adhesive bandage or suitable tap. Repeat daily.
For use as a surgical aid during ophthalmic surgery or ocular surgery:
-for use as an ophthalmic surgical aid in the anterior segment during cataract extraction and intraocular lens (IOL) implantation:
Intraocular dosage (Amvisc, Amvisc One, Provisc, Healon, Healon GV, Biolon):
Adults: Slowly administer a sufficient amount via intraocular injection into the anterior chamber of the eye before or after cataract extraction. Some manufacturers suggest that use is optimized when the injection is performed prior to cataract extraction and IOL insertion.
Children* and Adolescents*: Although the manufacturers do not provide specific information regarding the use of sodium hyaluronate, hyaluronic acid in pediatric patients, its use has been noted in small case series in patients as young as 3 years. Slowly administer a sufficient amount via intraocular injection into the anterior chamber of the eye.
-for use as an ophthalmic surgical aid during corneal transplant surgery:
Intraocular dosage (Amvisc, Amvisc One, Healon, Healon GV):
Adults: Administer a sufficient amount via intraocular injection into the anterior chamber of the eye after the corneal button is removed.
-for use as an ophthalmic surgical aid during glaucoma filtration surgery:
Intraocular dosage (Amvisc, Amvisc One, Healon, Healon GV):
Adults: Administer a sufficient amount slowly via intraocular injection into the corneal paracentesis to reconstitute the anterior chamber during the trabeculectomy.
-for use as an ophthalmic surgical aid in conjunction with scleral buckling procedures for retinal reattachement:
Intraocular dosage (Amvisc, Amvisc One, Healon, Healon GV):
Adults: Administer a sufficient amount slowly via intraocular injection into the vitreous cavity after the release of subretinal fluid and development of buckling by tying the mattress sutures.
For the treatment of pain in osteoarthritis of the knee when response to conservative nonpharmacologic therapy and simple analgesics (e.g., acetaminophen) has been inadequate:
Intra-articular dosage (Durolane):
Adults 22 years and older: 3 mL (60 mg sodium hyaluronate) intra-articularly once. Only a single injection is necessary to complete a treatment course. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Euflexxa, SynoJoynt):
Adults: 2 mL (20 mg sodium hyaluronate) intra-articularly once weekly for a total of 3 injections. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Gel-One):
Adults 22 years or more: 3 mL (30 mg sodium hyaluronate) intra-articularly once. Only a single injection is necessary to complete a treatment course. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Gel-Syn):
Adults: 2 mL (16.8 mg sodium hyaluronate) intra-articularly once weekly for a total of 3 injections.
Intra-articular dosage (GenVisc):
Adults 22 years or more: 2.5 mL (25 mg sodium hyaluronate) intra-articularly once weekly for a total of 5 injections. Some patients may experience benefit with 3 injections given at weekly intervals.
Intra-articular dosage (Hyalgan):
Adults: 2 mL (20 mg sodium hyaluronate) intra-articularly once weekly for a total of 5 injections. Some patients may experience benefit with 3 injections given at weekly intervals. The effectiveness of a single treatment cycle of less than 3 injections has not been established. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Hymovis):
Adults 22 years and older: 3 mL (24 mg sodium hyaluronate) intra-articularly once weekly for a total of 2 injections. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Monovisc):
Adults 22 years or more: 4 mL (88 mg sodium hyaluronate) intra-articularly once. Only a single injection is necessary to complete a treatment course. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (OrthoVisc):
Adults: 2 mL (30 mg sodium hyaluronate) intra-articularly once weekly for a total of 3 to 4 injections. The effectiveness of a single treatment cycle of less than 3 injections has not been established. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Supartz):
Adults: 2.5 mL (25 mg sodium hyaluronate) intra-articularly once weekly for a total of 5 injections. Some patients may experience benefit with 3 injections given at weekly intervals. The effectiveness of a single treatment cycle of less than 3 injections has not been established. The effectiveness of more than 1 treatment course has not been established.
Intra-articular dosage (Trivisc, Visco-3):
Adults 22 years and older: 2.5 mL (25 mg sodium hyaluronate) intra-articularly once weekly for a total of 3 injections. The effectiveness of more than 1 treatment course has not been established.
For the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds:
NOTE: The safety and efficacy of the intradermal products for treatment of anatomic regions other than facial wrinkles and folds (i.e. the lips) has not been established.
Intradermal dosage (Restylane, Perlane, Restylane-L, Perlane-L):
Adults: Inject appropriate volume into the mid to deep dermis until the wrinkle is inapparent; do not overfill. Based on clinical studies, the treatment volume should be limited to 6 mL per patient per treatment.
Intradermal dosage (Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus):
Adults: Inject appropriate volume into the mid to deep dermis until the wrinkle is inapparent; do not overfill. After the initial treatment, additional treatments (from 1 to 2 weeks later) may be required to achieve the desired level of correction. The typical total volume of gel needed to achieve optimal correction during the initial treatment is 1.6 mL per treatment site. For repeat treatments, the typical volume to achieve optimal correction is 0.7 mL per treatment site. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year.
Intradermal dosage (Juvederm Ultra XC, Juvederm Ultra Plus XC):
NOTE: These products contain trace amounts of lidocaine.
Adults: Inject appropriate volume into the mid to deep dermis until the wrinkle is inapparent; do not overfill. After the initial treatment, additional treatments (from 1 to 4 weeks later) may be required to achieve the desired level of correction. The typical total volume of gel needed to achieve optimal correction during the initial treatment is 1.6 mL per treatment site. For repeat treatments, the typical volume to achieve optimal correction is 0.7 mL per treatment site. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year.
Intradermal dosage (Juvederm Vollure XC):
NOTE: This product contains trace amounts of lidocaine.
Adults 22 years and older: Inject appropriate volume into the mid to deep dermis until the wrinkle is inapparent; do not overfill. The typical total volume of gel needed to achieve optimal correction is 1.7 mL per treatment site. To maintain optimal correction, approximately one-third of the volume per treatment site is needed at repeat treatments. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year.
-for lip augmentation and correction of perioral rhytids (wrinkles):
Intradermal dosage (Juvederm Ultra XC):
NOTE: This product contains trace amounts of lidocaine.
Adults 22 years and older: Inject appropriate volume into the lips and perioral area; do not overfill. After the initial treatment, additional treatments (from 1 to 4 weeks later) may be required to achieve the desired level of correction. The typical total volume of gel needed to achieve optimal correction during the initial treatment is 2.2 mL per treatment site. For repeat treatments, the typical volume to achieve optimal correction is 1.5 mL per treatment site. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year.
Intradermal dosage (Juvederm Volbella XC):
NOTE: This product contains trace amounts of lidocaine.
Adults 22 years and older: Inject appropriate volume into the lips and perioral area; do not overfill. The typical total volume of gel needed to achieve optimal correction during the initial treatment is 2.6 mL. For repeat treatments, the typical volume to achieve optimal correction is 1.6 mL. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year. Injection of more than 6 mL have not been studied for lip augmentation and correction of perioral rhytids.
-for cheek augmentation to correct age-related volume deficit in the mid-face:
Intradermal dosage (Juvederm Voluma XC):
NOTE: This product contains trace amounts of lidocaine.
Adults 35 to 65 years: Inject small boluses of 0.1 to 0.2 mL over a large area to reduce the risk of persistent lumpiness. The area of lost facial volume should be lifted by the end of the injection. When injection is completed, massage the treatment site to mold the product to the contour of the surrounding tissue and assure even distribution. Based on preclinical studies, patients should be limited to 20 mL per 60 kg (130 pounds) body weight per year.
For the treatment of atopic dermatitis and contact dermatitis:
Topical dosage (Hygel 2.5% gel):
Adults: Cleanse wound with normal saline solution (other cleansing agents are not recommended). Remove excess moisture using dry gauze. Apply gel liberally to the surface and surrounding area of the wound. Cover treated area with a self-adhesive bandage or suitable tap. Repeat daily.
Maximum Dosage Limits:
-Adults
35 years and older: Maximum dosage is not available for topical or intraocular dosage forms. For intra-articular injection, maximum dosage is 1 injection (2 mL/dose/knee Euflexxa, Hylagan, Gel-Syn, OrthoVisc, SynoJoynt; 2.5 mL/dose/knee GenVisc, Supartz, Trivisc, Visco-3; 3 mL/dose/knee Durolane, Gel-One, Hymovis; 4 mL/dose/knee Monovisc). For intradermal injection, maximum dosage is based on the specific product. For Restylane, Perlane, Restylane-L, and Perlane-L, a maximum of 6 mL should be used per treatment. For Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus, Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, Juvederm Vollure XC, and Juvederm Voluma XC, a maximum of 20 mL per 60 kg (130 lb) body weight per year should be used.
22 to 34 years: Maximum dosage is not available for topical or intraocular dosage forms. For intra-articular injection, maximum dosage is 1 injection (2 mL/dose/knee Euflexxa, Hylagan, Gel-Syn, OrthoVisc, SynoJoynt; 2.5 mL/dose/knee GenVisc, Supartz, Trivisc, Visco-3; 3 mL/dose/knee Durolane, Gel-One, Hymovis; 4 mL/dose/knee Monovisc). For intradermal injection, maximum dosage is based on the specific product. For Restylane, Perlane, Restylane-L, and Perlane-L, a maximum of 6 mL should be used per treatment. For Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus, Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, and Juvederm Vollure XC, a maximum of 20 mL per 60 kg (130 lb) body weight per year should be used. Safety and efficacy have not been established for Juvederm Voluma XC.
18 to 21 years: Maximum dosage is not available for topical or intraocular dosage forms. For intra-articular injection, maximum dosage is 1 injection (2 mL/dose/knee Euflexxa, Hylagan, Gel-Syn, OrthoVisc; 2.5 mL/dose/knee Supartz). Safety and efficacy of Durolane, GenVisc, Hymovis, Monovisc, SynoJoynt, Trivisc, and Visco-3 have not been established. For intradermal injection, maximum dosage is based on the specific product. For Restylane, Perlane, Restylane-L, and Perlane-L, a maximum of 6 mL should be used per treatment. For Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus, Juvederm Ultra XC, and Juvederm Ultra Plus XC, a maximum of 20 mL per 60 kg (130 lb) body weight per year should be used. Safety and efficacy have not been established for Juvederm Volbella XC, Juvederm Vollure XC, and Juvederm Voluma XC.
-Geriatric
66 years and older: Maximum dosage is not available for topical or intraocular dosage forms. For intra-articular injection, maximum dosage is 1 injection (2 mL/dose/knee Euflexxa, Hylagan, Gel-Syn, OrthoVisc, SynoJoynt; 2.5 mL/dose/knee GenVisc, Supartz, Trivisc, Visco-3; 3 mL/dose/knee Durolane, Gel-One, Hymovis; 4 mL/dose/knee Monovisc). For intradermal injection, maximum dosage is based on the specific product. For Restylane, Perlane, Restylane-L, and Perlane-L, a maximum of 6 mL should be used per treatment. For Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus, Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, and Juvederm Vollure XC, a maximum of 20 mL per 60 kg (130 lb) body weight per year should be used. Safety and efficacy have not been established for Juvederm Voluma XC.
65 years: Maximum dosage is not available for topical or intraocular dosage forms. For intra-articular injection, maximum dosage is 1 injection (2 mL/dose/knee Euflexxa, Hylagan, Gel-Syn, OrthoVisc, SynoJoynt; 2.5 mL/dose/knee GenVisc, Supartz, Trivisc, Visco-3; 3 mL/dose/knee Durolane, Gel-One, Hymovis; 4 mL/dose/knee Monovisc). For intradermal injection, maximum dosage is based on the specific product. For Restylane, Perlane, Restylane-L, and Perlane-L, a maximum of 6 mL should be used per treatment. For Prevelle Silk, Juvederm Ultra, Juvederm Ultra Plus, Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, Juvederm Vollure XC, and Juvederm Voluma XC, a maximum of 20 mL per 60 kg (130 lb) body weight per year should be used.
-Adolescents
Safety and efficacy of the intradermal and intra-articular products have not been established. The manufacturers do not provide specific information regarding the use of topical and intraocular products in pediatric patients.
-Children
Safety and efficacy of the intradermal and intra-articular products have not been established. The manufacturers do not provide specific information regarding the use of topical and intraocular products in pediatric patients.
-Infants
Safety and efficacy of the intradermal and intra-articular products have not been established. The manufacturers do not provide specific information regarding the use of topical and intraocular products in pediatric patients.
-Neonates
Safety and efficacy of the intradermal and intra-articular products have not been established. The manufacturers do not provide specific information regarding the use of topical and intraocular products in pediatric patients.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Sodium Hyaluronate, Hyaluronic Acid products.
Sodium hyaluronate helps to improve the elasticity and viscosity of the synovial fluid. Intra-articular administration of sodium hyaluronate, hyaluronic acid may reduce inflammatory mediators in the synovial fluid and may affect the release of arachidonic acid. The antiinflammatory effects may produce an analgesia by modulating pain perception via the inhibition of nociceptors or through the binding of substance P. Sodium hyaluronate, hyaluronic acid may have an antiinflammatory effect due to its effects on leukocyte function which may include inhibiting phagocytosis, adherence, and mitogen-induced stimulation. Intra-articular administration may also stimulate de novo hyaluronic acid production within the joint. Animal models have also demonstrated that hyaluronic acid may possess a disease-modifying chondroprotective effect.
Topically, sodium hyaluronate, hyaluronic acid is a biological polysaccharide (glycosaminoglycan) and is a major component of the extracellular matrix of connective tissues. Use is intended to protect against abrasion, friction, and desiccation.
Intradermally, cross-linked sodium hyaluronate, hyaluronic acid provides volume and shape for correction of dermal wrinkles.
Intraocularly, sodium hyaluronate, hyaluronic acid is used to re-establish intraocular volume, assist in separating membranes adherent to the retina, manipulate retinal detachments and mechanically flatten a detached retina.
Sodium hyaluronate, hyaluronic acid is administered via intra-articular injection, topically, intraocular injection, and intradermal injection. Specific pharmacokinetic parameters are not available regarding human use. No metabolism is expected to occur, consistent with the definition of an FDA-approved medical device. Duration of effects is dependant on treatment type and patient specific factors.