Synvisc Sir Intra-Art 2Ml 3Pz

COMPOSITION
Hylan G-F 20 is available as
• Synvisc, pre-filled syringe 2 ml
Hylan G-F 20 is a sterile, apyrogenic viscoelastic fluid containing hylan. The hyalans are derivatives of hyaluronate (sodium salt of hyaluronic acid) and consist of repetitive disaccharide units of N-acetylglucosamine and sodium glucuronate. Hylan A has an average molecular weight of about 6,000,000 daltons, and hylan B is a hydrogel. Hylan G-F 20 contains hylan A and B (8.0 mg ± 2.0 mg per ml) in a buffered saline solution of sodium chloride (pH 7.2 ± 0.3).

FEATURES
Hylan G-F 20 is biologically similar to hyaluronate. Hyaluronate is one of the components of synovial fluid and determines its viscoelastic characteristics. The mechanical properties (viscoelastic) of Hylan G-F 20 are, however, superior to those of synovial fluid and those of hyaluronate-based solutions of similar concentration. Hylan G-F 20 has a '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 knee synovial fluid in subjects aged between 18 and 27 years, measured with a comparable technique, at 2.5 Hz are respectively G' = 117 ± 13 Pa and G'' = 45 ± 8 Pa. The hyalans are metabolized physiologically through the same process as hyaluronates, and the decomposition products are non-toxic.

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

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

WARNINGS
• Do not inject via the endovascular route.
• Do not inject via the extra-articular route or into tissues or the synovial capsule. In general, complications at the injection site have been caused by extra-articular diffusion of Synvisc.
• Do not use in conjunction with disinfectants containing quaternary ammonium salts for skin preparation, as hyaluronate may precipitate in their presence.

PRECAUTIONS
• Hylan G-F 20 should not be used if a significant intra-articular effusion has occurred before injection.
• As with all invasive procedures related to joints, 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 G-F 20 has not been tested in pregnant women or in children/adolescents under 18 years of age.
• Hylan G-F 20 contains small amounts of avian protein and should not be used in patients with hypersensitivity to such protein.

ADVERSE EFFECTS
• Adverse effects that may affect the joint in which the injection was performed: transient pain and/or swelling and/or effusion in the injected joint may occur following intra-articular injections of Hylan G-F 20. Cases of acute inflammation characterized by joint pain, swelling, effusion, and sometimes a sensation of warmth and/or stiffness of the joint have been reported following the intra-articular injection of Synvisc. Analysis of the synovial fluid reveals aseptic fluid without crystals. Often this reaction responds in a few days to treatment with non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular steroids, and/or arthrocentesis. The clinical benefit derived from treatment may still be evident after such reactions.
• During clinical trials on Synvisc, no intra-articular infections were recorded, and they were rarely encountered during clinical use of Synvisc.
• Hypersensitivity reactions have also been reported, including anaphylactic reaction, anaphylactoid reaction, anaphylactic shock, and angioedema.
• Systemic effects related to the administration of Synvisc rarely emerged from post-marketing experience and included the following: rash, urticaria, itching, fever, nausea, headache, dizziness, chills, muscle cramps, paresthesia, peripheral edema, malaise, respiratory difficulties, hot flashes, and facial edema.
• Controlled clinical studies with Synvisc did not reveal statistically significant differences in the number or types of systemic adverse effects between the group of patients treated with Synvisc and the group of patients who received control treatments.

DOSAGE AND ADMINISTRATION
• Do not use Hylan G-F 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 G-F 20.
• Inject at room temperature.
• To extract the syringe from the blister (or container), hold it tightly by the body without touching the plunger stem.
• Administer using strictly aseptic procedures, paying particular attention to the removal of the cap.
• Unscrew the gray cap before extracting it to minimize product leakage.
• Use appropriately sized needles:
• Synvisc – from 18 gauge to 22 gauge
• Use a needle of suitable length for the joint to be treated.
• To ensure a perfect seal and avoid leakage during administration, ensure that the needle is securely inserted on the syringe.
• Do not tighten or apply excessive pressure during the application of the needle or the removal of the needle protection, as the tip of the syringe may break.
• Inject only into the synovial space, performing the procedure if necessary under instrumental guidance, for example, fluoroscopy, especially when treating the hip and shoulder.
• The contents of the syringe are for single use only. The recommended dosing guidelines indicate injecting the entire volume (2 ml for Synvisc) of the syringe. Discard any unused Synvisc.
• Do not reuse the syringe and/or needle. The reuse of syringes, needles, and/or the contents of a used syringe can lead to loss of sterility, product contamination, and/or incomplete treatment.
• Under fluoroscopic guidance, an ionic or non-ionic contrast agent may be used. Do not use more than 1 ml of contrast agent for 2 ml of Hylan G-F 20.
• Do not re-sterilize Hylan G-F 20.

DOSAGE
The dosage scheme of Hylan G-F 20 depends on the joint being treated.
Knee osteoarthritis:
Synvisc
The recommended treatment regimen for Synvisc is three injections of 2 ml into the knee, one week apart. To achieve optimal effect, it is essential to perform all three injections. The maximum recommended dosage is six injections over six months, with a break of at least four weeks between treatment regimens.

Osteoarthritis of the hip, ankle, and shoulder:
Synvisc
The recommended initial treatment regimen is a single injection of 2 ml. However, a second injection of 2 ml is recommended if adequate symptomatic relief of pain is not achieved. Clinical data have shown that patients benefit from this second injection when administered one to three months after the first.

DURATION OF EFFECT
Treatment with Hylan G-F 20 only affects the joint at the injection site and does not produce a general systemic effect.
Synvisc
Generally, a maximum duration of effect has been found for patients who respond well to treatment up to 26 weeks, although shorter or longer periods have been observed. Data extrapolated from prospective clinical studies conducted on patients with knee osteoarthritis have shown treatment benefits lasting up to 52 weeks after a single treatment cycle of three injections of Synvisc.

Clinical data from a double-blind, randomized, controlled study in patients with knee OA evidenced a clinically significant reduction in pain compared to the placebo group. A total of 253 patients were treated (124 received Synvisc-One and 129 received placebo). Over the 26 weeks, patients treated with Synvisc-One showed an average percentage change in pain from baseline of 36%, while patients in the placebo group showed an average percentage change in pain from baseline of 29%.

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

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

CONTENT PER ml (hylan G-F 20)
Each ml contains: hylan 8.0 mg, sodium chloride 8.5 mg, sodium hydrogen phosphate 0.16 mg, sodium dihydrogen phosphate hydrate 0.04 mg, water for injectable preparations as needed.

PACKAGING
The contents of each syringe are sterile and apyrogenic. Store at a temperature between +2° C and +30°C. Do not freeze.
Synvisc is supplied in three 2.25 ml glass syringes, each pre-filled with 2 ml of Hylan G-F 20.

Cod.002344