Hyaluronate and derivatives (available as Juvederm and other brands) are widely distributed in the extracellular matrix. They are used as an intraarticular injection for osteoarthritis, intradermally for wrinkles, and for cheek augmentation.

Hyaluronate derivatives Uses:

• Intra-articular injection:

  • It is indicated for pain management in knee osteoarthritis, that is non-responsive to nonpharmacologic treatment or simple analgesics or non steroidal anti-inflammatory drugs (NSAIDS).

• Intradermal:

  • Juvederm (all formulations except Volbella XC and Voluma XC), Perlane, Restylane, Restylane Defyne, Restylane Lyft, Restylane-L, Restylane Refyne:
    • These brands are used for the correction of moderate to severe facial wrinkles or folds
  • All formulation of juvederm
    • Juvederm Volbella XC and Restylane Silk: Correction of perioral rhytids in adults older than 21 years of age.

• Subcutaneous:

  • Restylane Lyft: It is used to correct the volume deficit of the dorsal hand in adults older than 21 years.

• Subcutaneous/ supraperiosteal:

  • Juvederm Voluma XC, Restylane Lyft:
    • Correction of age-related volume deficit (deep injection subcutaneous and/or supra-periosteal injection) for cheek augmentation in the mid-face in adults older than 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 older than 21 years (Restylane, Restylane-L, 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)

• Off Label Use of Hyaluronate in Adults:

  • Refractory interstitial cystitis

Hyaluronate Dose in Adults

Hyaluronate Dose in the Cheek augmentation: Subcutaneous/Supraperiosteal:

• Adults >21 years:

  • Juvederm Voluma XC:
    • Inject as required for the cosmetic results
    • The treatment regimen typically 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;
    • A maximum of 20 mL/60 kg/year.
  • Restylane Lyft:
    • Maximum: 6 mL per treatment

Hyaluronate Dose in the treatment of Dermatoses:

• Topical: Therapevo gel: Apply to the affected area twice or three times a day.

Hyaluronate Dose in the treatment of 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 the cosmetic result; typical regimen requires 1.6 to 1.7 mL/treatment site; typical volume for repeat treatment is 0.56 to 0.7 mL/treatment site;
  • The maximum dose is 20 mL/60 kg/year
• Perlane, Restylane Lyft:
  • Inject as required into deep dermis/superficial subcutis for the cosmetic result;
  • The median total dose: 3 mL (Perlane);
  • The maximum volume of treatment is 6 mL per treatment
• Restylane, Restylane-L:
  • Inject as required for the cosmetic result; median total dose: 3 mL; maximum: 6 mL per treatment
• Restylane Defyne:
  • Inject as required for the cosmetic result; typical treatment is generally about 1.4 mL/treatment site; typical repeat treatment is about 0.7 mL/treatment site
• Restylane Refyne:
  • Inject as required for the cosmetic result; typical treatment is generally about 1.5 mL/treatment site; typical repeat treatment is about 1 mL/treatment site

Hyaluronate Dose in the Hand augmentation: Subcutaneous:

• Adults >21 years:

  • Restylane Lyft:
    • Inject small boluses in the subcutaneous plane in the dorsum of the hand;
    • The maximum dose is 3 mL per hand per treatment session

Hyaluronate Dose in the treatment of Interstitial cystitis, refractory (off-label):

• Intravesical (off-label route): 40 mg in 50 mL saline intravesically (retain in the bladder for at least 30 minutes) once a week for 4 weeks, then monthly for up to one year in patients showing an initial response.

Hyaluronate Dose in the 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;
    • The maximum dose is 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;
    • The maximum dose is 20 mL/60 kg/year
  • Restylane, Restylane-L, Restylane Silk:
    • Maximum: 1.5 mL per lip (upper or lower) per treatment session

Hyaluronate Dose in the treatment of Osteoarthritis of the knee: Intra-articular:

• Durolane:
  • Inject 60 mg (3 mL) once
• Euflexxa:
  • Inject 20 mg (2 mL) once a week for 3 weeks (total of 3 injections)
• Gel-One:
  • Inject 30 mg (3 mL) once
• Gelsyn-3:
  • Inject 16.8 mg (2 mL) once a week for 3 weeks (total of 3 injections)
• GenVisc 805, Supartz, Supartz FX:
  • Inject 25 mg (2.5 mL) once a week for five weeks (total of 5 injections);
  • Some patients may benefit from a total of 3 injections
• Hyalgan:
  • Inject 20 mg (2 mL) once a week for 5 weeks (total of 5 injections);
  • Some patients may benefit from 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 a week for 3 to 4 weeks (total of 3 to 4 injections)
• Synvisc:
  • Inject 16 mg (2 mL) once a week for 3 weeks (total of 3 injections)
• Synvisc-One:
  • Inject 48 mg (6 mL) once
• TriVisc:
  • Inject 25 mg (2.5 mL) once a week for 3 weeks (total of 3 injections)
• Visco-3:
  • Inject 25 mg (2.5 mL) once a week for 3 weeks (total of 3 injections)

Hyaluronate Dose in the treatment of Perioral rhytids: Intradermal:

• Adults >21 years:

  • Restylane Silk:
    • Maximum: 1 mL per correction per treatment session
  • Juvederm Volbella XC:
    • Refer to lip augmentation dosing

Hyaluronate Dose in the treatment of Skin ulcers and wounds: Topical:

• Bionect cream, gel:
  • Apply a thin layer to a clean and disinfected wound or ulcer twice or three times a day.
• Therapevo gel:
  • Apply liberally to clean and dried wounds or ulcers and the surrounding area once a day.

Hyaluronate Dose in the treatment of Surgical aid:

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

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• Studies on animal reproduction have not shown any adverse effects. Safety in human pregnancy has not yet been established.

Use during breastfeeding:

• It is not known if it is present in breast milk.
• Manufacturers recommend that it be used with caution in lactating mothers.

Dose in Kidney Disease:

The manufacturer has not provided any dose adjustment in labeling.

Dose in Liver disease:

The manufacturer has not provided any dose adjustment in labeling.

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

Common Side Effects of Hyaluronate (Juvederm):

• Central Nervous System:

  • Headache

• Dermatologic:

  • Skin Discoloration At Injection Site

• Hematologic & Oncologic:

  • Bruise

• Local:

  • Swelling At Injection Site
  • Tenderness At Injection Site
  • Bruising At Injection Site
  • Erythema At Injection Site
  • Induration At Injection Site
  • Pain At Injection Site
  • Residual Mass At Injection Site
  • Itching At Injection Site
  • Muscle Rigidity At Injection Site
  • Hematoma At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Joint Swelling
  • Joint Effusion

• Miscellaneous:

  • Swelling

Less Common Side Effects Of Hyaluronate (Juvederm):

• Cardiovascular:

  • Presyncope
  • Hypertension
  • Increased Blood Pressure
  • Edema

• Central Nervous System:

  • Dizziness
  • Hyperesthesia
  • Hypoesthesia
  • Malaise
  • Tingling In The Lips
  • Falling
  • Fatigue
  • Paresthesia
  • Sciatica

• Dermatologic:

  • Ecchymoses
  • Hyperpigmentation
  • Exfoliation Of Skin
  • Cheilosis
  • Fine Wrinkling
  • Local Acneiform Eruptions
  • Local Dryness
  • Papule Of Skin
  • Rash At Injection Site
  • Skin Tightness

• Gastrointestinal:

  • Oral Herpes Simplex Infection
  • Toothache
  • Abdominal Pain
  • Diarrhea
  • Dyspepsia
  • Nausea

• Genitourinary:

  • Urinary Tract Infection

• Infection:

  • Infection
  • Influenza
  • Herpes Zoster Infection

• Local:

  • Bleeding At Injection Site
  • Injection Site Reaction
  • Injection Site Nodule
  • Injection Site Numbness
  • Local Skin Exfoliation
  • Injection Site Infection

• Neuromuscular & Skeletal:

  • Back Pain
  • Limb Pain
  • Puffiness Of Cheeks
  • Arthropathy
  • Connective Tissue Disease
  • Lower Extremity Pain
  • Musculoskeletal Disease
  • Musculoskeletal Pain
  • Osteoarthritis
  • Tendonitis
  • Localized Osteoarthritis
  • Muscle Strain
  • Joint Stiffness

• Ophthalmic:

  • Increased Intraocular Pressure
  • Punctate Keratitis
  • Superficial Keratitis
  • Cystoid Macular Edema
  • Opacity Of Ocular Lens Capsule
  • Conjunctivitis
  • Corneal Edema
  • Corneal Erosion
  • Corneal Injury
  • Injury To Eye Region
  • Uveitis

• Respiratory:

  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Flulike Symptoms
  • Bronchitis
  • Rhinitis
  • Sinusitis
  • Cough
  • Oropharyngeal Pain
  • Respiratory Tract Infection

• Miscellaneous:

  • Laceration
  • Soft Tissue Injury
  • Wound
  • Accidental Injury
  • Fever

Frequency of side effects not defined:

• Central nervous system:

  • Tingling sensation

• Ophthalmic:

  • Ophthalmic inflammation (postoperative; iritis, hypopyon)

Contraindications to Hyaluronate (Juvederm):

Allergies to hyaluronate and any component of the formulation

Submucosal and Intradermal:

• You may also be contraindicated if you have anaphylaxis, multiple severe allergies, or a history (Juvederm [all formulas], Perlane and Restylane Lyft; Restylane Refyne; Restylane Silk; Restylane-L).
• Bleeding disorders: Perlane, Restylane and Restylane Lyft; Restylane Silk and Restylane-L.
• History of hypersensitivity to gram positive bacterial proteins (Juvederm [all forms], Restylane, Restylane Defyne. Restylane Lyft. Restylane Refyne. Restylane Silk. Restylane-L).
• Implantation or injection of Perlane, Restylane Silk, Restylane L into locations other than those recommended by labeling (Perlane and Restylane),

Intra-articular

• Other contraindications include infections of the knee joints or skin diseases at injection sites (Durolane and Euflexxa. Gel-One, Gelsyn-3. GenVisc.850. Hyalgan. Hymovis. Monovisc. OrthoVisc. Supartz. Supartz FX. Synvisc. Synvisc-One. TriVisc. Visco-3).
• Hypersensitivity to gram positive bacterial proteins (Hymovis Monovisc, Orthovisc)
• Systemic bleeding disorders (Monovisc)

Intraocular:

• The manufacturer's labeling does not contain any contraindications (Amvisc Plus, Biolon and Healon [all formulations], Provisc].

Subcutaneous/Supraperiosteal:

• Other contraindications include anaphylaxis history, multiple severe allergies (Juvederm Voluma XC and Restylane Lyft).
• Patients who have had a history of allergies to gram positive bacterial proteins or lidocaine (Juvederm Voluma XC and Restylane Lyft).

Monitoring parameters:

• Monitor intraocular pressure (ophthalmic formulations);
• Observe for signs and symptoms of local inflammation or infection (intradermal formulations)

How to administer Hyaluronate?

Intra-articular:

• Inject directly into the knee joint; Avoid injecting extra-articularly or into the synovial capsule or tissues.
• Avoid using disinfectants containing quaternary ammonium salts for skin cleansing prior to injection.
• Remove synovial fluid or effusion, if present, prior to injection.
• Separate syringes should be used for each knee.
• Refer to the manufacturer's labeling for additional instructions on injection technique.

Intradermal/ Submucosal/ Subcutaneous/ Supraperiosteal:

• Avoid injecting into a blood vessel.
• Following injection, slowly massage the area so that it conforms to the contour of the surrounding tissue.
• May apply ice pack to the injection site for a short period immediately after administration if treatment area swollen.
• Refer to manufacturer's labeling for additional instructions on injection technique.
• The patients should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John's wort, or high doses of vitamin E supplements before treatment as 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.
• Juvederm Ultra XC is also intended for submucosal injection (lip augmentation).
• Perlane is intended for injection into the deep dermis to the 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 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.

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.

Mechanism of action of Hyaluronate (Juvederm):

• Sodium hyaluronate, a biological polysaccharide, is widely distributed. 
• It is found in the extracellular matrix, which includes the vitreous, aqueous humor, skin, and umbilical chord.
• It forms a viscoelastic solution when water is at a physiological pH and ionic strength.
• This makes it suitable for vitreous and aqueous humor in eye surgery. 
• It is also a tissue and joint lubricant, which plays an important role in modulating interactions between adjacent tissues.
• It can be injected intradermally to reduce the depth of facial lines. 
• Transcutaneous injections can also be used to augment the lips and correct perioral hypertids.
• It can also be subcutaneously or supra-periosteal injected to augment cheek volume.
• When applied topically to wounds or ulcers, it may protect the skin against abrasions and friction injuries.

Distribution:

• Intravitreous injections: The process of fusion takes place slowly

Excretion:

• Ophthalmic: Via Canal of Schlemm

International Brand Names of Hyaluronate:

• Amvisc
• Amvisc Plus
• Bionect
• Durolane
• Euflexxa
• Gel-One
• Gelsyn-3
• GenVisc 850
• Healon
• Healon EndoCoat
• Healon GV
• Healon5
• Hyalgan
• HyGel [DSC]
• Hymovis
• Juvederm Ultra
• Juvederm Ultra Plus
• Juvederm Ultra Plus XC
• Juvederm Ultra XC
• Juvederm Voluma XC
• Monovisc
• Orthovisc
• Perlane
• Perlane-L
• Provisc
• Restylane Lyft
• Restylane Silk
• Restylane
• Restylane-L
• Supartz FX
• Supartz
• Synvisc
• Synvisc-One
• Therapevo
• Cystistat
• Durolane
• OrthoVisc
• Suplasyn
• Adant Dispo
• Amvisc
• Aragan
• Aragan Plus
• Artz
• Atri
• Biolon
• Curiosin
• Duovisc
• Durolane
• Eyecon
• Gengigel
• Go-On
• Halubone
• Healon
• Healon GV
• Healonid
• Helo
• Hialid
• Hyal
• Hyal Forte
• Hyalein
• Hyalgan
• Hyalgun
• Hyaludrop
• Hylo-Comod
• Hyronate
• Hyruan
• IAL
• Iolvisc
• Kynex
• Lacure
• Laservis
• Lghyal
• Osflex
• Oxyal
• Provisc
• Suplasyn
• Synvisc
• Synvisc One
• Synvisc-One
• Tearbalance
• Toptear
• Viscoseal
• Visiol
• Vivial

Hyaluronate derivatives Brand Names in Pakistan: