SYNVISC ONE
HYLANG - F 2 0

COMPOSITION
Hylan GF 20 is available as
• Synvisc-One , 6 ml prefilled syringe
Hylan GF 20 is a sterile, pyrogen-free, viscoelastic liquid containing hylan. Hylans are derivatives of hyaluronate (the sodium salt of hyaluronic acid) and consist of repeating disaccharide units of N-acetylglucosamine and sodium glucuronate. Hylan A has an average molecular weight of approximately 6,000,000 daltons, and hylan B is a hydrogel. Hylan GF 20 contains hylan A and B (8.0 mg ± 2.0 mg per ml) in sodium chloride buffered saline (pH 7.2 ± 0.3).

FEATURES
Hylan GF 20 is biologically similar to hyaluronate. Hyaluronate is a component of synovial fluid and determines its viscoelasticity. The mechanical (viscoelastic) properties of Hylan GF 20 are, however, superior to those of synovial fluid and to those of hyaluronate-based solutions of similar concentrations. Hylan GF 20 has an elasticity (storage modulus G'') at 2.5 Hz of 111 ± 13 Pascal (Pa) and a viscosity (loss modulus G'') of 25 ± 2 Pa. The elasticity and viscosity of synovial fluid of the knee in subjects aged 18 to 27 years, measured with a superimposable technique, at 2.5 Hz are G' = 117 ± 13 Pa and G'' = 45 ± 8 Pa, respectively. Hylans are physiologically metabolized through the same process as hyaluronates, and the breakdown products are non-toxic.

INDICATIONS AND USE
Hylan GF 20
• temporarily restores the viscoelasticity of synovial fluid.
• provides clinical benefits to patients in all stages of joint osteoarthritis.
• it is more effective in patients who actively and regularly use the affected joint.
• it achieves its therapeutic effect through viscosupplementation, a process through which the physiological state and rheological characteristics of the synovial fluid of the arthritic joint are restored.
Viscosupplementation with Hylan GF 20 is indicated for the relief of pain and functional limitations, allowing greater joint movement. In vitro studies have shown that Hylan GF 20 protects cartilage cells from damage caused by physical and chemical agents.
Synvisc-One is indicated only for intra-articular use by a physician in the treatment of pain associated with osteoarthritis of the knee.

CONTRAINDICATIONS
• Hylan GF 20 should not be injected into the joint in the presence of venous or lymphatic stasis in the affected limb.
• Hylan GF 20 should not be used in the presence of severe infections or inflammations or skin diseases or infections in the injection area.

WARNINGS
• Do not inject intravascularly.
• Do not inject extra-articularly or into synovial tissue or capsule. Injection site complications have generally been caused by extra-articular spread of Synvisc .
• Do not use disinfectants containing quaternary ammonium salts for skin preparation concurrently, as hyaluronate may precipitate in their presence.

PRECAUTIONS
• Hylan GF 20 should not be used if significant intra-articular effusion has occurred prior to injection.
• As with all invasive joint procedures, it is recommended that the patient avoid any excessive motor activity after the intra-articular injection and resume full activity within a few days.
• Hylan GF 20 has not been tested in pregnant women or children/adolescents under 18 years of age.
• Hylan GF 20 contains small amounts of avian protein and should not be used in patients with hypersensitivity to this protein.

SIDE EFFECTS
• Adverse reactions that may affect the injected joint: Following intra-articular injections of Hylan GF 20, transient pain and/or swelling and/or effusion in the injected joint may occur. Following intra-articular injection of Synvisc-One , cases of acute inflammation characterized by joint pain, swelling, effusion and sometimes a feeling of warmth and/or stiffness in the joint have been reported. Synovial fluid analysis reveals crystal-free aseptic fluid. This reaction often responds within a few days to treatment with non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular steroids and/or arthrocentesis. The clinical benefit of treatment may still be evident after such reactions.
• Intra-articular infections were not reported during clinical trials with Synvisc-One and have been rarely encountered during clinical use of Synvisc .
• Hypersensitivity reactions, including anaphylactic reaction, anaphylactoid reaction, anaphylactic shock and angioedema, have also been reported.
• In the controlled clinical trial with Synvisc-One , the frequency and type of adverse reactions were similar between the group of patients treated with Synvisc-One and the group of patients who received placebo treatment.

DOSAGE AND ADMINISTRATION
• Do not use Hylan GF 20 if the packaging is open or damaged.
• The contents of the syringe should be used immediately after opening the package.
• Remove synovial fluid or effusion before each injection of Hylan GF 20.
• Inject at room temperature.
• To remove the syringe from the blister (or container), hold it firmly against your body, without touching the plunger rod.
• Administer using strictly aseptic procedures, paying particular attention to removing the nozzle.
• Unscrew the gray spout before removing it to minimize product spillage.
• Use needles of appropriate size:
• Synvisc-One – 18 to 20 gauge
• To ensure a perfect seal and avoid leakage during administration, make sure the needle is firmly attached to the syringe.
• Do not squeeze or apply excessive pressure when attaching the needle or removing the needle guard, as this may break the syringe tip.
• Inject only into the synovial space, performing the operation under instrumental guidance if necessary, for example fluoroscopy, especially in the case of hip and shoulder treatment.
• The contents of the syringe are for single use only. The recommended dosing instructions indicate injecting the entire volume (6 mL for Synvisc-One ) of the syringe. Discard any unused Synvisc-One .
• Do not reuse the syringe and/or needle. Reuse of syringes, needles and/or product from a used syringe may result in loss of sterility, contamination of the product and/or incomplete treatment.
• Under fluoroscopic supervision, ionic or nonionic contrast media may be used. Do not use more than 1 ml of contrast media per 2 ml of Hylan GF 20.
• Do not resterilize Hylan GF 20.

DOSAGE
The dosage regimen of Hylan GF 20 depends on the joint being treated.
Knee osteoarthritis:
Synvisc-One
The recommended treatment regimen for Synvisc-One is a single 6 ml injection into the knee, which can be repeated after six months if the patient's symptoms warrant it.


DURATION OF EFFECT
Treatment with Hylan GF 20 only affects the injected joint and does not produce a general systemic effect.
Synvisc-One
Data from a prospective clinical trial conducted in patients with knee osteoarthritis showed pain reduction for up to 52 weeks after a single injection of Synvisc-One , as well as improvements in joint stiffness and function.

Clinical data from a double-blind, randomized, controlled trial in patients with osteoarthritis of the knee demonstrated a statistically significant reduction in pain compared to placebo. A total of 253 patients were treated (124 received Synvisc-One and 129 received placebo). Over 26 weeks, patients treated with Synvisc-One experienced a mean percent change from baseline in pain of 36%, while patients in the placebo group experienced a mean percent change from baseline in pain of 29%.

Additional prospective clinical data from two open-label, multicenter studies in patients with knee osteoarthritis showed statistically significant improvements in pain relief from baseline for up to 52 weeks after a single administration of Synvisc-One .

In the first study, 394 patients treated with Synvisc-One experienced a statistically significant change from baseline in the WOMAC A1 pain walking subscale score (-28 ± 19.89 mm on a 100 mm VAS) at week 26. In addition, statistically significant changes from baseline were observed in WOMAC A1 and WOMAC A, B and C scores for all six observation periods between weeks 1 and 52, demonstrating improvements in pain on walking and pain at rest (WOMAC A1 -32.7 ± 19.95 mm; WOMAC A -29.18 ± 19.158 mm), stiffness (WOMAC B -25.77 ± 22.047 mm) and joint function (WOMAC C -25.72 ± 19.449 mm) over the 52 weeks.

CONTENT PER ml (hylan GF 20)
Each ml contains: hylan 8.0 mg, sodium chloride 8.5 mg, disodium hydrogen phosphate 0.16 mg, disodium phosphate hydrate 0.04 mg, water for injections as required.

PACKAGING
The contents of each syringe are sterile and pyrogen-free. Store at a temperature between +2°C and +30°C. Do not freeze.
Synvisc-One is supplied in a 10 ml glass syringe, prefilled with 6 ml of Hylan GF 20.

Code 002420