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Hyaluronate and Derivatives

Medically reviewed by Drugs.com. Last updated on Jun 29, 2020.

Pronunciation

(hye al yoor ON ate & dah RIV ah tives)

Index Terms

  • Durolane
  • Hyaluronan
  • Hyaluronate Sodium
  • Hyaluronic Acid
  • Hylan G-F 20
  • Hylan Polymers
  • Restylane Kysse
  • Sodium Hyaluronate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, topical [sodium hyaluronate]:

Bionect: 0.2% (25 g, 100 g)

Foam, topical [sodium hyaluronate]:

Bionect: 0.2% (113.4 g)

Gel, topical [sodium hyaluronate]:

Bionect: 0.2% (30 g, 60 g, 100 g)

HyGel: 2.5% (10 g [DSC])

Therapevo: 2.5% (10 g [DSC], 75 g [DSC])

Injection, gel, intra-articular [hyaluronic acid]:

Durolane: 20 mg/mL (3 mL) [derived from or manufactured from bacterial source]

Injection, gel, intra-articular [cross-linked hyaluronate]:

Gel-One: 10 mg/mL (3 mL) [derived from or manufactured using an avian source]

Injection, gel, intradermal [hyaluronic acid]:

Juvederm Ultra: 24 mg/mL (0.4 mL, 0.8 mL) [derived from or manufactured from bacterial source]

Juvederm Ultra Plus: 24 mg/mL (0.4 mL, 0.8 mL) [derived from or manufactured from bacterial source]

Juvederm Ultra Plus XC: Hyaluronic acid 24 mg/mL and lidocaine 0.3% (0.4 mL, 0.8 mL) [derived from or manufactured from bacterial source]

Juvederm Ultra XC: Hyaluronic acid 24 mg/mL and lidocaine 0.3% (0.4 mL, 0.8 mL) [derived from or manufactured from bacterial source]

Perlane: 20 mg/mL (1 mL [DSC]) [derived from or manufactured from bacterial source]

Perlane-L: Hyaluronic acid 20 mg/mL and lidocaine 0.3% (1 mL [DSC], 2 mL [DSC]) [derived from or manufactured from bacterial source]

Restylane: 20 mg/mL (1 mL [DSC]) [derived from or manufactured from bacterial source]

Restylane-L: Hyaluronic acid 20 mg/mL and lidocaine 0.3% (0.5 mL [DSC], 1 mL [DSC], 2 mL [DSC]) [derived from or manufactured from bacterial source]

Restylane Lyft: Hyaluronic acid 20 mg/mL and lidocaine 0.3% [derived from or manufactured from bacterial source]

Restylane Silk: Hyaluronic acid 20 mg/mL and lidocaine 0.3% [derived from or manufactured from bacterial source]

Injection, gel, subcutaneous/supraperiosteal [cross-linked hyaluronic acid]:

Juvederm Voluma XC: Hyaluronic acid 20 mg/mL and lidocaine 0.3% [derived from or manufactured from bacterial source]

Injection, solution, intra-articular [hyaluronan]:

Monovisc: 88 mg/4 mL (4 mL) [derived from or manufactured from bacterial source]

Hymovis: 24 mg/3 mL (3 mL) [derived from or manufactured from bacterial source]

Orthovisc: 30 mg/2 mL (2 mL) [derived from or manufactured from bacterial source]

Injection, solution, intra-articular [hylan polymers A and B]:

Synvisc-One: 8 mg/mL (6 mL) [derived from or manufactured using an avian source]

Synvisc: 8 mg/mL (2 mL) [derived from or manufactured using an avian source]

Injection, solution, intra-articular [sodium hyaluronate]:

Euflexxa: 10 mg/mL (2 mL)

Gelsyn-3: 8.4 mg/mL (2 mL) [derived from or manufactured from bacterial source]

GenVisc 850: 25 mg/2.5 mL (2.5 mL) [derived from or manufactured from bacterial source]

Hyalgan: 10 mg/mL (2 mL) [derived from or manufactured using an avian source]

Supartz: 10 mg/mL (2.5 mL [DSC]) [derived from or manufactured using an avian source]

Supartz FX: 25 mg/2.5 mL (2.5 mL) [derived from or manufactured using an avian source]

Triluron: 20 mg/2 mL (2 mL) [derived from or manufactured using an avian source]

Visco-3: 10 mg/mL (2.5 mL) [derived from or manufactured using an avian source]

Injection, solution, intraocular [sodium hyaluronate]:

Amvisc: 12 mg/mL (0.5 mL, 0.8 mL)

Amvisc Plus: 16 mg/mL (0.5 mL, 0.8 mL)

Healon: 10 mg/mL (0.4 mL, 0.55 mL, 0.85 mL)

Healon5: 23 mg/mL (0.6 mL)

Healon EndoCoat: 30 mg/mL (0.85 mL)

Healon GV: 14 mg/mL (0.55 mL, 0.85 mL)

Provisc: 10 mg/mL (0.4 mL, 0.55 mL, 0.85 mL) [contains natural rubber/natural latex in packaging]

Lotion, topical [sodium hyaluronate]:

Hylinate: 0.1% (340 mL) [DSC]

Brand Names: U.S.

  • Amvisc
  • Amvisc Plus
  • Bionect
  • Durolane
  • Euflexxa
  • Gel-One
  • Gelsyn-3
  • GenVisc 850
  • Healon
  • Healon EndoCoat
  • Healon GV
  • Healon5
  • Hyalgan
  • HyGel [DSC]
  • Hylinate [DSC]
  • Hymovis
  • Juvederm Ultra
  • Juvederm Ultra Plus
  • Juvederm Ultra Plus XC
  • Juvederm Ultra XC
  • Juvederm Voluma XC
  • Monovisc
  • Orthovisc
  • Perlane [DSC]
  • Perlane-L [DSC]
  • Provisc
  • Restylane Lyft
  • Restylane Silk
  • Restylane [DSC]
  • Restylane-L [DSC]
  • Supartz FX
  • Supartz [DSC]
  • Synvisc
  • Synvisc-One
  • Therapevo [DSC]
  • Triluron

Pharmacologic Category

  • Antirheumatic Miscellaneous
  • Cosmetic Agent, Implant
  • Ophthalmic Agent, Viscoelastic
  • Skin and Mucous Membrane Agent, Miscellaneous

Pharmacology

Sodium hyaluronate is a biological polysaccharide which is distributed widely in the extracellular matrix of connective tissue in man (vitreous and aqueous humor of the eye, synovial fluid, skin, and umbilical cord). Sodium hyaluronate and its derivatives form a viscoelastic solution in water (at physiological pH and ionic strength) which makes it suitable for aqueous and vitreous humor in ophthalmic surgery, and functions as a tissue and/or joint lubricant which plays an important role in modulating the interactions between adjacent tissues. Intradermal injection may decrease the depth of facial wrinkles. Transcutaneous injection for lip augmentation may correct perioral rhytids. Subcutaneous and/or supraperiosteal injection for cheek or chin augmentation may correct age-related volume deficit. In the topical management of wounds and ulcers, sodium hyaluronate protects the skin against friction and abrasion.

Distribution

Intravitreous injection: Diffusion occurs slowly

Excretion

Ophthalmic: Via Canal of Schlemm

Use: Labeled Indications

Intra-articular injection: Treatment of pain in osteoarthritis of the knee in patients who have failed nonpharmacologic treatment or simple analgesics (Durolane, Euflexxa, Gel-One, Gelsyn-3, GenVisc 850, Hyalgan, Hymovis, Monovisc, OrthoVisc, Supartz, Supartz FX, Synvisc, Synvisc-One, Triluron, TriVisc, Visco-3) or nonsteroidal anti-inflammatory drugs (Gel-One).

Intradermal:

Juvederm (all formulations except Volbella XC and Voluma XC), Perlane, Restylane, Restylane Defyne, Restylane Lyft, Restylane-L, Restylane Refyne: Correction of moderate to severe facial wrinkles or folds.

Juvederm Volbella XC, Restylane Kysse, and Restylane Silk: Correction of perioral rhytids in adults >21 years.

Subcutaneous: Restylane Lyft: Correction of volume deficit of the dorsal hand in adults >21 years.

Subcutaneous/supraperiosteal: Juvederm Voluma XC, Restylane Lyft: Correction of age-related volume deficit for cheek augmentation in the mid-face in adults >21 years; Juvederm Voluma XC: Chin region augmentation in adults >21 years.

Ophthalmic: Surgical aid in cataract extraction (Amvisc, Amvisc Plus, Biolon, Provisc); intraocular lens implantation (Amvisc, Amvisc Plus, Biolon, Provisc); corneal transplant (Amvisc, Amvisc Plus); glaucoma filtration (Amvisc, Amvisc Plus); and retinal attachment surgery (Amvisc, Amvisc Plus); anterior segment surgery (Biolon, Healon [all formulations]).

Submucosal: Lip augmentation in adults >21 years (Restylane, Restylane-L, Restylane Kysse, Restylane Silk, Juvederm Ultra XC, Juvederm Volbella XC).

Topical cream, gel: Management of skin ulcers and wounds (Bionect, Therapevo); management and relief of symptoms associated with dermatoses (eg, atopic dermatitis, allergic contact dermatitis, radiodermatitis), including burning, itching, and pain (Therapevo).

Topical lotion: Treatment of symptoms associated with xerosis.

Off Label Uses

Refractory interstitial cystitis

Contraindications

Hypersensitivity to hyaluronate or any component of the formulation

Intradermal/Submucosal: Additional contraindications include history of anaphylaxis or presence of multiple severe allergies (Juvederm [all formulations], Perlane, Restylane, Restylane Defyne, Restylane Kysse, Restylane Lyft, Restylane Refyne, Restylane Silk, Restylane-L); bleeding disorders (Perlane, Restylane, Restylane Lyft, Restylane Silk, Restylane-L); history of hypersensitivity to gram-positive bacterial proteins (Juvederm [all formulations], Perlane, Restylane, Restylane Defyne, Restylane Kysse, Restylane Lyft, Restylane Refyne, Restylane Silk, Restylane-L), or local anesthetics of the amide type, such as lidocaine (Juvederm Ultra XC, Juvederm Ultra Plus XC, Juvederm Volbella XC, Juvederm Vollure XC, Restylane Defyne, Restylane Kysse, Restylane Lyft, Restylane Refyne, Restylane Silk); implantation/injection into sites other than the anatomical spaces recommended per labeling (Perlane, Restylane, Restylane Silk, Restylane-L)

Intra-articular: Additional contraindications include knee joint infections or infections or skin diseases at the site of injection (Durolane, Euflexxa, Gel-One, Gelsyn-3, GenVisc 850, Hyalgan, Hymovis, Monovisc, OrthoVisc, Supartz, Supartz FX, Synvisc, Synvisc-One, Triluron, TriVisc, Visco-3); hypersensitivity to gram-positive bacterial proteins (Hymovis, Monovisc, Orthovisc); systemic bleeding disorders (Monovisc)

Intraocular: There are no contraindications in the manufacturer's labeling (Amvisc, Amvisc Plus, Biolon, Healon [all formulations], Provisc).

Subcutaneous/Supraperiosteal: Additional contraindications include history of anaphylaxis or history or presence of multiple severe allergies (Juvederm Voluma XC, Restylane Lyft); patients with a history of allergies to gram-positive bacterial proteins or lidocaine (Juvederm Voluma XC, Restylane Lyft).

Dosing: Adult

Cheek augmentation: Subcutaneous/Supraperiosteal: Adults >21 years:

Juvederm Voluma XC: Inject as required for cosmetic result; typical treatment regimen requires small boluses of 0.1 to 0.2 mL over a large area to volumize and contour the cheek; an additional treatment may be needed to achieve the desired level of correction; maximum: 20 mL/60 kg/year.

Restylane Lyft: Maximum: 6 mL per treatment.

Chin augmentation: Subcutaneous/Supraperiosteal: Adults >21 years: Juvederm Voluma XC: Inject as required for cosmetic result; typical treatment regimen requires small boluses of 0.1 to 0.2 mL over a large area to volumize and contour the chin; an additional treatment may be needed to achieve the desired level of correction; maximum: 20 mL/60 kg/year.

Dermatoses: Topical: Therapevo gel: Apply liberally to affected area 2 to 3 times daily.

Facial wrinkles/folds: Intradermal:

Note: Formulations differ in terms of recommended injection depth: Juvederm (all formulations except Voluma XC), Restylane, Restylane Defyne, Restylane-L, and Restylane Refyne are intended for mid to deep intradermal injection; Perlane and Restylane Lyft are intended for injection into the deep dermis to superficial subcutis.

Juvederm (all formulations except Voluma XC): Inject as required for cosmetic result; typical treatment regimen requires 1.6 to 1.7 mL/treatment site; typical volume for repeat treatment is 0.56 to 0.7 mL/treatment site; maximum: 20 mL/60 kg/year.

Perlane, Restylane Lyft: Inject as required into deep dermis/superficial subcutis for cosmetic result; median total dose: 3 mL (Perlane); maximum: 6 mL per treatment.

Restylane, Restylane-L: Inject as required for cosmetic result; median total dose: 3 mL; maximum: 6 mL per treatment.

Restylane Defyne: Inject as required for cosmetic result; typical treatment is generally ~1.4 mL/treatment site; typical repeat treatment is ~0.7 mL/treatment site.

Restylane Refyne: Inject as required for cosmetic result; typical treatment is generally ~1.5 mL/treatment site; typical repeat treatment is ~1 mL/treatment site.

Hand augmentation: Subcutaneous: Adults >21 years: Restylane Lyft: Inject small boluses in the subcutaneous plane in the dorsum of the hand; maximum: 3 mL per hand per treatment session.

Interstitial cystitis, refractory (off-label use): Intravesical (off-label route): 40 mg in 50 mL saline intravesically (retain in bladder for at least 30 minutes) once weekly for 4 weeks, then monthly for up to 1 year in patients showing an initial response (Morales 1996).

Lip augmentation: Submucosal: Adults >21 years:

Juvederm Ultra XC: Approximately 2.2 mL to the lips and perioral area; correct to 100% of desired volume effect (do not overcorrect); repeat treatment is generally 1.5 mL; maximum: 20 mL/60 kg/year.

Juvederm Volbella XC: Approximately 2.6 mL to the lips and perioral area; correct to 100% of desired volume effect (do not overcorrect); repeat treatment is generally 1.6 mL; maximum: 20 mL/60 kg/year.

Restylane, Restylane-L, Restylane Silk: Maximum: 1.5 mL per lip (upper or lower) per treatment session.

Restylane Kysse: ≤1.5 mL per lip (upper or lower) per treatment session; optional treatment of perioral rhytids and philtral column may be performed; correct to 100% of desired volume effect (do not overcorrect). Maximum: 6 mL per treatment session (3 mL for lips, 3 mL for perioral area).

Osteoarthritis of the knee: Intra-articular:

Durolane: Inject 60 mg (3 mL) once.

Euflexxa: Inject 20 mg (2 mL) once weekly for 3 weeks (total of 3 injections).

Gel-One: Inject 30 mg (3 mL) once.

Gelsyn-3: Inject 16.8 mg (2 mL) once weekly for 3 weeks (total of 3 injections).

GenVisc 805, Supartz, Supartz FX: Inject 25 mg (2.5 mL) once weekly for 5 weeks (total of 5 injections); some patients may benefit from a total of 3 injections.

Hyalgan: Inject 20 mg (2 mL) once weekly for 5 weeks (total of 5 injections); some patients may benefit with a total of 3 injections.

Hymovis: Inject 24 mg (3 mL) once weekly for 2 weeks (total of 2 injections).

Monovisc: Inject 88 mg (4 mL) once.

Orthovisc: Inject 30 mg (2 mL) once weekly for 3 to 4 weeks (total of 3 to 4 injections).

Synvisc: Inject 16 mg (2 mL) once weekly for 3 weeks (total of 3 injections).

Synvisc-One: Inject 48 mg (6 mL) once.

Triluron: Inject 20 mg (2 mL) once weekly for 3 weeks (total of 3 injections).

TriVisc: Inject 25 mg (2.5 mL) once weekly for 3 weeks (total of 3 injections).

Visco-3: Inject 25 mg (2.5 mL) once weekly for 3 weeks (total of 3 injections).

Perioral rhytids: Intradermal: Adults >21 years:

Restylane Kysse: Refer to lip augmentation dosing.

Restylane Silk: Maximum: 1 mL per correction per treatment session.

Juvederm Volbella XC: Refer to lip augmentation dosing.

Skin ulcers and wounds: Topical:

Bionect cream, gel: Apply a thin layer to clean and disinfected wound or ulcer 2 to 3 times daily.

Therapevo gel: Apply liberally to clean and dried wound or ulcer and the surrounding area once daily.

Surgical aid: Ophthalmic (Amvisc, Amvisc Plus, Biolon, Healon [all formulations], Provisc): Intraocular: Depends upon procedure (slowly introduce a sufficient quantity into eye).

Xerosis: Topical: Hylinate lotion: Apply liberally to affected area 2 to 3 times daily or as directed.

Dosing: Geriatric

Refer to adult dosing.

Administration

Intra-articular: Inject directly into the knee joint; do not inject extra-articularly or into the synovial capsule or tissues. Do not use disinfectants containing quaternary ammonium salts for skin cleansing prior to injection. Remove synovial fluid or effusion, if present, prior to injection. If used for bilateral treatment, use a separate syringe for each knee. Refer to manufacturer's labeling for additional instructions on injection technique.

Intradermal/Submucosal/Subcutaneous/Supraperiosteal: Do not inject into a blood vessel. Topical or injectable anesthesia may be used during and after injection to manage pain. Following injection, slowly massage area so that it conforms to the contour of the surrounding tissue. May apply ice pack to injection site for a short period immediately after administration if treatment area swollen. Refer to manufacturer's labeling for additional instructions on injection technique. Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John's wort, or high doses of vitamin E supplements; these agents may increase bruising and bleeding at the injection site.

Juvederm (all formulations except Voluma XC) is intended for mid-to-deep intradermal injection.

Juvederm Voluma XC is intended for subcutaneous and/or supraperiosteal injection; if administering as cannula injection, safety has only been established with the TSK STERiGLIDE 25-gauge, 1.5-inch cannula.

Juvederm Ultra XC is also intended for submucosal injection (lip augmentation).

Perlane is intended for injection into the deep dermis to superficial subcutis.

Restylane and Restylane-L are intended for mid-to-deep intradermal injection (facial wrinkles) or submucosal injection (lip augmentation).

Restylane Defyne and Restylane Refyne are intended for mid-to-deep intradermal injection (facial wrinkles).

Restylane Kysse is intended for mid-dermis (perioral rhytids and philtral column) or submucosal injection (lip augmentation).

Restylane Lyft is intended for deep dermis to superficial subcutis (facial wrinkles), subcutaneous and/or supraperiosteal (cheek augmentation), or into the subcutaneous plane of the dorsal hand (rapid flow/injection should be avoided). When the injection is completed for treatment of dorsal hand, apply a lubricating agent (eg, ultrasound gel, petrolatum ointment) and ball hand into a fist; a deep hand massage should be performed to smooth out filler and push product into empty areas.

Restylane Silk is intended for mid to deep dermis (periorbital rhytids) or submucosal injection (lip augmentation).

Ophthalmic: Allow to reach room temperature prior to use. Drug may become cloudy or form a slight precipitate after administration; clinical significance unknown, but cloudy or precipitated material should be removed by irrigation or aspiration. Refer to the manufacturer's labeling for additional procedure-specific instructions.

Topical:

Bionect products: Clean and disinfect wound prior to use (do not use quaternary ammonium salts due to potential for hyaluronic acid precipitation), and debride if necessary; apply a thin layer to wound or ulcer without extensive rubbing. After application, cover the area with a sterile gauze pad and if necessary, an elastic or compressive bandage.

Hylinate: Rub in thoroughly after application. Avoid contact with eyes, lips, and mucous membranes.

Therapevo: For the management of wounds or ulcers, clean wound or ulcer with normal saline prior to use and debride if necessary. Remove excess moisture with dry gauze. Apply liberally into ulcer cavity or to wound and the surrounding area. After application, cover the area with a non-stick gauze dressing. For the management of dermatoses, apply directly and liberally to affected area.

Storage

Amvisc, Amvisc Plus: Store at 2°C to 8°C (36°F to 46°F); do not freeze.

Biolon: Store at 2°C to 8°C (36°F to 46°F) or at room temperature (≤25°C [77°F]) for up to 1 month; do not freeze. Protect from light. Remove from refrigerator 20 to 30 minutes before use.

Bionect products: Store at room temperature. Cream and gel may be stored up to 24 months.

Durolane: Store at 0°C to 30°C (32°F to 86°F). Transient spikes up to 40°C (104°F) for ≤24 hours are permitted. Do not freeze; refrigeration is not necessary. Store in original package and use immediately once opened.

Euflexxa: Store refrigerated or at room temperature, 2°C to 25°C (36°F to 77°F); do not freeze. Protect from light. If refrigerated, remove from refrigeration ≥20 to 30 minutes before use.

Gel-One, Hymovis, Supartz FX, Triluron, Visco-3: Store below 25°C (77°F); do not freeze. Store Hymovis, Triluron, and Visco-3 in their original packages.

Gelsyn-3, Hyalgan, Monovisc, Orthovisc: Store below 25°C (77°F); do not freeze. Protect from light. Store Gelsyn-3 in original package and use immediately once opened.

GenVisc 850, Supartz, Synvisc, Synvisc-One: Store below 30°C (86°C); do not freeze. Store in original package to protect from light.

Healon, Healon GV, Healon5: Store at 2°C to 8°C (36°F to 46°F).

Healon EndoCoat: Store at 2°C to 25°C (36°F to 77°F); do not freeze. Protect from light.

Hylinate: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Brief exposure up to 40°C (104°F) tolerated. Avoid freezing.

Juvederm (all formulations), Perlane, Restylane, Restylane Defyne, Restylane Kysse, Restylane Lyft, Restylane Refyne, Restylane Silk, Restylane-L: Store up to 25°C (77°F); do not freeze. Protect from light. Do not use if gel separates or becomes cloudy.

Provisc: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Prior to use, allow refrigerated product to reach room temperature (~20 to 40 minutes). Protect from light.

Therapevo: Store at room temperature, 15°C to 30°C (59°F to 86°F) in a dry place; do not freeze or expose to temperatures above 35°C (95°F).

TriVisc: Store below 30°C (86°F); do not freeze. Protect from light. Store in original package and use immediately once opened.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Type of local reactions may vary by formulation and site of application/injection. Some reports include concomitant lidocaine.

>10%:

Central nervous system: Headache (≤18%)

Dermatologic: Skin discoloration at injection site (4% to 78%), ecchymoses (≤14%), skin rash (≤14%)

Hematologic & oncologic: Bruise (≤28%; more common in older patients)

Local: Swelling at injection site (3% to 98%), tenderness at injection site (17% to 95%), bruising at injection site (3% to 93%), erythema at injection site (≤93%), induration at injection site (6% to 92%), pain at injection site (≤92%), residual mass at injection site (3% to 90%), itching at injection site (7% to 47%), muscle rigidity at injection site (25%), hematoma at injection site (8% to 18%)

Neuromuscular & skeletal: Arthralgia (1% to 25%), joint swelling (knee; ≤14%), joint effusion (≤11%)

Miscellaneous: Swelling (18% to 28%)

1% to 10%:

Cardiovascular: Presyncope (≤5%), hypertension (4%), increased blood pressure (4%), edema (1%)

Central nervous system: Dizziness (≤5%), hyperesthesia (injection site; ≤5%), hypoesthesia (≤5%), malaise (≤5%), tingling in the lips (≤5%), falling (≤4%), fatigue (1%), paresthesia (1%), sciatica (1%)

Dermatologic: Hyperpigmentation (≤9%; postinflammatory; in patients of African-American heritage and Fitzpatrick Skin Types IV, V, and VI), exfoliation of skin (2% to 8%), cheilosis (≤5%), fine wrinkling (≤5%), local acneiform eruptions (≤5%), local dryness of skin (≤5%), papule of skin (injection site; ≤5%), rash at injection site (≤5%), skin tightness (≤5%), xanthoderma (≤5%)

Gastrointestinal: Oral herpes simplex infection (≤5%), toothache (4%), abdominal pain (≤4%), diarrhea (≤4%), dyspepsia (≤4%), nausea (≤4%)

Genitourinary: Urinary tract infection (4%)

Infection: Infection (1% to 4%), influenza (2%), herpes zoster infection (1%)

Local: Bleeding at injection site (5% to 7%), injection site reaction (1% to 6%), injection site nodule (≤5%), injection site numbness (≤5%), local skin exfoliation (≤5%), injection site infection (1%)

Neuromuscular & skeletal: Back pain (≤10%), limb pain (≤8%), puffiness of cheeks (≤5%), arthropathy (≤4%; including joint crepitation), connective tissue disease (≤4%), lower extremity pain (≤4%), musculoskeletal disease (≤4%; including pain and discomfort), musculoskeletal pain (2%), osteoarthritis (2%), tendonitis (2%), localized osteoarthritis (≤2%), muscle strain (1%), joint stiffness (≤1%)

Ophthalmic: Increased intraocular pressure (requiring treatment: 7%), punctate keratitis (≤4%; conjunctival), superficial keratitis (≤4%), cystoid macular edema (3%), opacity of ocular lens capsule (3%), conjunctivitis (1%), corneal edema (1%), corneal erosion (1%), corneal injury (1%; including Seidel Phenomenon and corneo-scleral leak), injury to eye region (1%; ocular sphincter), uveitis (1%)

Respiratory: Nasopharyngitis (2% to 10%), upper respiratory tract infection (1% to 6%), flu-like symptoms (1% to ≤4%), bronchitis (≤4%), rhinitis (≤4%), sinusitis (≤4%), cough (2%), oropharyngeal pain (2%), respiratory tract infection (2%)

Miscellaneous: Laceration (injection site; ≤5%), soft tissue injury (lips; ≤5%), wound (≤5%), accidental injury (≤4%), fever (3%)

Frequency not defined:

Central nervous system: Tingling sensation

Ophthalmic: Ophthalmic inflammation (postoperative; iritis, hypopyon)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormal sensory symptoms, abscess, acne vulgaris, anaphylactic shock, anaphylaxis, angioedema, anterior chamber fibrin deposition, anxiety, application site reaction (implant migration), atrophy at injection site, bacterial infection, blindness, blurred vision, burning sensation, bursitis, capillary fragility, central nervous system disease, cerebrovascular accident, cerebrovascular occlusion, cutaneous nodule, cystitis, depression, dermatitis, dislocation (joint), dyspnea, edema, erythema of skin, eyelid edema, eye pain, facial swelling, feeling of heaviness, fistula, gouty arthritis, granuloma, hemarthrosis, hematoma, herpetic lesion, hypersensitivity reaction, hypotension, increased serum alanine aminotransferase, increased serum glucose, inflammation, injection site infection (abscess/necrosis), injection site ischemia, injection site scarring, keloids, leukocytosis, metallic taste, mouth edema, muscle spasm (knee), myalgia, myasthenia, neck pain, nervousness, neuralgia, nonimmune anaphylaxis, peripheral edema, popliteal cyst, pruritic rash, pruritus, red face, rhinorrhea, sensation of cold (knee), skin blister, skin or other tissue necrosis, sore throat, subconjunctival hemorrhage (including hyphema and hematic Tyndall), subcutaneous nodule, swelling of extremities, swelling of eye, syncope, synechiae of iris, synovitis (knee), telangiectasia, thrombocytopenia (rare), tissue necrosis, urticaria, vasodepressor syncope, vertebral disk disease (protrusion), viral infection, visual disturbance, vitreous disorder (anterior chamber), vomiting, wound secretion, xeroderma

Warnings/Precautions

Dosage form specific issues:

• Injection (gel): Intradermal, submucosal, subcutaneous, supraperiosteal:

- All formulations: May be administered by intradermal (Juvederm [all formulations except Voluma XC], Perlane, Restylane, Restylane Defyne, Restylane Kysse, Restylane Lyft, Restylane Refyne, Restylane Silk), submucosal (Restylane, Restylane Kysse, Restylane Silk), or subcutaneous and/or supraperiosteal (Juvederm Voluma XC, Restylane Lyft) injection. Treatment may result in bruising/bleeding; use caution in patients with bleeding disorders and patients receiving or recently exposed (≤3 weeks) to thrombolytics, anticoagulants, platelet inhibitors, or NSAIDs. Do not inject into site of active inflammation (skin eruptions such as cysts, pimples, rashes, or hives) or infection. Injection into a blood vessel may cause localized superficial necrosis or may cause occlusion and lead to embolism, ischemia, or infarction. Symptoms of vascular occlusion or embolization (eg, pain disproportionate to the procedure or remote from the injection site, immediate blanching extending beyond the injected area, dusky or reticular-appearing tissue) require intervention. Use of Juvederm in patients susceptible to keloid formation, hypertrophic scarring, or pigmentation disorders has not been studied; use cautiously. Hyperpigmentation at the injection site has been reported with some formulations and may last for ≤6 weeks after treatment; keloid formation may also occur. Use caution in patients receiving immunosuppressive treatment. Use in patients with prior herpetic eruption may result in reactivation. Delayed inflammatory papules may result from injections, necessitating evaluation and treatment as soft tissue infection. If laser treatment, chemical peeling, or any other procedure based on an active dermal response is considered after treatment, there is a risk of acute inflammatory reaction at the injection site if performed following intradermal treatment and before the skin has healed completely. The safety of treatment with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical, or chemical peeling procedures has not been evaluated. Patient must avoid exposure to UV rays (sun and UV lamp) or severe cold until swelling and redness is resolved.

- For facial administration, do not use in vascular-rich areas, such as glabella and nose; rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Treatment site reactions usually improve in ≤7 days (chin augmentation, nasolabial folds), <18 days (lips), or <4 weeks (cheek augmentation). Strenuous exercise and ethanol consumption should be avoided for 24 hours following use. Supplemental "touch up" treatments may be required. Use of larger than recommended volumes per injection result in an increase in adverse events; if larger amounts are needed, follow-up treatment sessions are recommended.

- For dorsal hand administration, avoid injection into veins or tendons of the hand; may weaken tendons or cause tendons to rupture or cause embolization or thrombosis of veins. Use with caution in patients with disabilities, diseases, or injuries of the hand, including autoimmune diseases affecting the hand, hand implants, Dupuytren's contracture, history of hand tumor, vascular malformations, Raynaud disease and patients at risk for tendon rupture; use has not been studied. Injection of the dorsum of the hand may cause pain and swelling. Treatment site reactions (eg, redness, swelling, tenderness, pain) usually improve in ≤7 days. Increased risk for delayed onset adverse reactions may occur with strenuous use of hands or trauma to hands after injection into the hand. Reduced thumb flexion range lasting >3 months has been reported.

• Injection (gel, solution): Intra-articular: Not for use in infected joints; do not use disinfectants containing quaternary ammonium salts for skin preparation (may cause precipitation of hyaluronate). Remove synovial fluid or effusion, if present, prior to injection; do not use in cases of severe intra-articular effusion. Do not inject intravascularly, extra-articularly, or into synovium. Use with caution if venous or lymphatic stasis is present in the leg. Transient increases in reddening or inflammation, pain, or sensation of heat may occur after injection into the knee in patients with inflammatory arthritis. Avoid strenuous or prolonged weight bearing activities for 48 hours after injection. Some products are produced from avian sources; use with caution in patients with hypersensitivity to avian proteins, feathers, or egg products. Use Gel-One with caution in patients allergic to cinnamon. Use Durolane with caution in patients with preexisting chondrocalcinosis; may cause acute attack.

• Latex: Some products may contain natural latex rubber.

• Ophthalmic: Do not overfill the anterior chamber. Postoperative increases in intraocular pressure have occurred following use of sodium hyaluronate; remove from the anterior chamber at the end of surgery and monitor intraocular pressure closely. Mixing of quaternary ammonium salts (eg, benzalkonium chloride) with sodium hyaluronate results in the formation of a precipitate; do not irrigate the eye with any solution containing benzalkonium chloride during surgery.

• Topical: Bionect products (cream, gel): Do not use disinfectants containing quaternary ammonium salts for skin preparation (may cause precipitation of hyaluronate).

Other warnings/precautions:

• Appropriate patient selection: Juvederm Voluma XC: Safety for use in patients <35 years or >65 years of age (cheek augmentation) and <22 years or >80 years of age (chin augmentation) or with very thin skin in the mid-face region has not been established.

• Appropriate use: Chin augmentation: Treatment in the chin region may be obscured by skin laxity of the chin, neck, or jaw; has not been studied in patients with significant chin, neck, or jaw skin laxity. Effect on chin facial hair growth has not been studied.

• Appropriate use: Juvederm Voluma XC: Safety of cannula injection for cheek augmentation in patients with Fitzpatrick Skin Types V and VI has not been established.

• Appropriate use: Restylane Defyne, Restylane Refyne: Do not inject in a site that has been treated with a permanent implant.

• Appropriate use: Restylane Lyft: Safety and effectiveness for treatment beyond one year has not been established.

• Experienced physician: Should be administered by an experienced health care provider who has appropriate training, experience, knowledge of anatomy at injection site, and knowledge of aseptic technique.

Monitoring Parameters

Intraocular pressure (ophthalmic formulations); signs and symptoms of excess local inflammation or infection (intradermal formulations)

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

What is this drug used for?

For use in the eye:

• It is used for eye surgeries.

Injection (when given in the knee):

• It is used to treat arthritis of the knee.

All skin products:

• It is used to promote healing of skin ulcers and wounds.

All products:

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Bruising

• Knee rigidity or pain

• Sensation of warmth in knee

• Back pain

• Muscle pain

• Application site swelling or irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Vision changes

• Eye pain

• Severe eye irritation

• Injection site skin discoloration

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.