Description
S YNVISC
HYLAN G - F 2 0
HYLAN G - F 2 0
COMPOSITION
Hylan GF 20 is available as
• Synvisc , 2 ml pre-filled syringe
Hylan GF 20 is a sterile, non-pyrogenic, viscoelastic liquid containing hylan. Hylans are derivatives of hyaluronate (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).
CHARACTERISTICS
Hylan GF 20 is biologically similar to hyaluronate. Hyaluronate is one of the components of synovial fluid and determines its viscoelastic characteristics. The mechanical (viscoelastic) properties of Hylan GF 20 are, however, superior to those of synovial fluid and those of hyaluronate-based solutions of similar concentration. 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 the synovial fluid of the knee in subjects aged between 18 and 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 metabolised through the same process as hyaluronates and the decomposition products are non-toxic.
INDICATIONS AND USE
Hylan GF 20
• temporarily restores the viscoelasticity of the synovial fluid.
• provides clinical benefits to patients at all stages of joint osteoarthritis.
• it is more effective in patients who actively and regularly use the affected joint.
• 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 reintegrated.
Viscosupplementation with Hylan GF 20 is indicated to relieve pain and functional limitations, allowing a more extensive movement of the joint. In vitro studies have shown that Hylan GF 20 protects cartilage cells from damage due to the action of physical and chemical agents.
Synvisc is indicated only 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 GF 20 should not be injected into the joint in the presence of venous or lymphatic stasis in the affected limb.
• Hylan GF 20 must not be used in the presence of infections or severe inflammation 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. In general, complications in the injection area have been caused by extra-articular spread of Synvisc .
• Do not use disinfectants containing quaternary ammonium salts concomitantly for skin preparation, as in their presence the hyaluronate may precipitate.
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 avoids any excessive motor activity following the intra-articular injection, and resumes full activity within a few days.
• Hylan GF 20 has not been tested in pregnant women or in 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: Transient pain and/or swelling and/or effusion in the injected joint may occur following intra-articular injections of Hylan GF 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 intra-articular injection of Synvisc . Analysis of the synovial fluid reveals aseptic fluid without crystals. 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.
• No intra-articular infections were recorded during the clinical trials with Synvisc , 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.
• Systemic effects related to the administration of Synvisc that have rarely emerged from post-marketing experience have been the following: rash, urticaria, pruritus, fever, nausea, headache, dizziness, chills, muscle cramps, paraesthesia, peripheral oedema, malaise, respiratory difficulty, hot flushes and facial oedema.
• Controlled clinical studies with Synvisc have shown no statistically significant differences in the number or types of systemic adverse reactions between the group of patients treated with Synvisc and the group of patients who received control treatments.
DOSAGE AND ADMINISTRATION
• Do not use Hylan GF 20 if the package is open or damaged.
• The contents of the syringe must be used immediately after opening the package.
• Remove synovial fluid or effusion prior to each injection of Hylan GF 20.
• Inject at room temperature.
• To remove the syringe from the blister (or container), hold it tightly by the body without touching the plunger rod.
• Administer using strictly aseptic procedures, taking particular care when removing the nozzle.
• Unscrew the grey nozzle before removing it, to minimize product spillage.
• Use appropriately sized needles:
• Synvisc - 18 gauge to 22 gauge
• Use the needle of the appropriate length for the joint to be treated.
• 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 case of treatment of the hip and shoulder.
• The contents of the syringe are for single use only. Recommended dosing guidelines indicate to inject the entire volume (2 ml for Synvisc ) of the syringe. Discard any unused Synvisc .
• Do not reuse the syringe and/or needle. Reusing syringes, needles and/or the product from a used syringe may lead to loss of sterility, contamination of the product and/or incomplete treatment.
• Under fluoroscopic guidance, either 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 to be treated.
Knee osteoarthritis:
Synvisc
The recommended treatment regimen for Synvisc is three injections of 2 ml into the knee, one week apart. To achieve the optimal effect, it is essential to administer all three injections. The maximum recommended dosage is of 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 from pain is not achieved. Clinical data have shown that patients benefit from this second injection. if practiced one to three months after the first.
DURATION OF EFFECT
Treatment with Hylan GF 20 affects only the injected joint and does not produce a general systemic effect.
Synvisc
A maximum duration of effect for patients who respond well to treatment has generally been found to be up to 26 weeks, although shorter or longer periods have been observed. Data from prospective clinical trials in patients with knee osteoarthritis have demonstrated treatment benefits of up to 52 weeks, following a single treatment course of three injections of Synvisc .
Clinical data from a double-blind, randomized, controlled study in patients with knee OA demonstrated a statistically significant clinical and pain reduction compared to the placebo group. A total of 253 patients were treated (124 received Synvisc-One and 129 received placebo). Over 26 weeks, patients treated with Synvisc-One showed a mean percent change from baseline in pain of 36%, while patients in the placebo group showed a mean percent change from baseline in pain 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 up to 52 weeks following 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 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, sodium dihydrogen phosphate hydrate 0.04 mg, water for injections as required.
PACKAGING
The contents of each syringe are sterile and non-pyrogenic. Store at a temperature between +2°C and +30°C. Do not freeze.
Synvisc is supplied in a 2.25 ml glass syringe pre-filled with 2 ml of Hylan GF 20.
Cod. 010144
Hylan GF 20 is available as
• Synvisc , 2 ml pre-filled syringe
Hylan GF 20 is a sterile, non-pyrogenic, viscoelastic liquid containing hylan. Hylans are derivatives of hyaluronate (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).
CHARACTERISTICS
Hylan GF 20 is biologically similar to hyaluronate. Hyaluronate is one of the components of synovial fluid and determines its viscoelastic characteristics. The mechanical (viscoelastic) properties of Hylan GF 20 are, however, superior to those of synovial fluid and those of hyaluronate-based solutions of similar concentration. 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 the synovial fluid of the knee in subjects aged between 18 and 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 metabolised through the same process as hyaluronates and the decomposition products are non-toxic.
INDICATIONS AND USE
Hylan GF 20
• temporarily restores the viscoelasticity of the synovial fluid.
• provides clinical benefits to patients at all stages of joint osteoarthritis.
• it is more effective in patients who actively and regularly use the affected joint.
• 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 reintegrated.
Viscosupplementation with Hylan GF 20 is indicated to relieve pain and functional limitations, allowing a more extensive movement of the joint. In vitro studies have shown that Hylan GF 20 protects cartilage cells from damage due to the action of physical and chemical agents.
Synvisc is indicated only 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 GF 20 should not be injected into the joint in the presence of venous or lymphatic stasis in the affected limb.
• Hylan GF 20 must not be used in the presence of infections or severe inflammation 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. In general, complications in the injection area have been caused by extra-articular spread of Synvisc .
• Do not use disinfectants containing quaternary ammonium salts concomitantly for skin preparation, as in their presence the hyaluronate may precipitate.
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 avoids any excessive motor activity following the intra-articular injection, and resumes full activity within a few days.
• Hylan GF 20 has not been tested in pregnant women or in 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: Transient pain and/or swelling and/or effusion in the injected joint may occur following intra-articular injections of Hylan GF 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 intra-articular injection of Synvisc . Analysis of the synovial fluid reveals aseptic fluid without crystals. 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.
• No intra-articular infections were recorded during the clinical trials with Synvisc , 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.
• Systemic effects related to the administration of Synvisc that have rarely emerged from post-marketing experience have been the following: rash, urticaria, pruritus, fever, nausea, headache, dizziness, chills, muscle cramps, paraesthesia, peripheral oedema, malaise, respiratory difficulty, hot flushes and facial oedema.
• Controlled clinical studies with Synvisc have shown no statistically significant differences in the number or types of systemic adverse reactions between the group of patients treated with Synvisc and the group of patients who received control treatments.
DOSAGE AND ADMINISTRATION
• Do not use Hylan GF 20 if the package is open or damaged.
• The contents of the syringe must be used immediately after opening the package.
• Remove synovial fluid or effusion prior to each injection of Hylan GF 20.
• Inject at room temperature.
• To remove the syringe from the blister (or container), hold it tightly by the body without touching the plunger rod.
• Administer using strictly aseptic procedures, taking particular care when removing the nozzle.
• Unscrew the grey nozzle before removing it, to minimize product spillage.
• Use appropriately sized needles:
• Synvisc - 18 gauge to 22 gauge
• Use the needle of the appropriate length for the joint to be treated.
• 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 case of treatment of the hip and shoulder.
• The contents of the syringe are for single use only. Recommended dosing guidelines indicate to inject the entire volume (2 ml for Synvisc ) of the syringe. Discard any unused Synvisc .
• Do not reuse the syringe and/or needle. Reusing syringes, needles and/or the product from a used syringe may lead to loss of sterility, contamination of the product and/or incomplete treatment.
• Under fluoroscopic guidance, either 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 to be treated.
Knee osteoarthritis:
Synvisc
The recommended treatment regimen for Synvisc is three injections of 2 ml into the knee, one week apart. To achieve the optimal effect, it is essential to administer all three injections. The maximum recommended dosage is of 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 from pain is not achieved. Clinical data have shown that patients benefit from this second injection. if practiced one to three months after the first.
DURATION OF EFFECT
Treatment with Hylan GF 20 affects only the injected joint and does not produce a general systemic effect.
Synvisc
A maximum duration of effect for patients who respond well to treatment has generally been found to be up to 26 weeks, although shorter or longer periods have been observed. Data from prospective clinical trials in patients with knee osteoarthritis have demonstrated treatment benefits of up to 52 weeks, following a single treatment course of three injections of Synvisc .
Clinical data from a double-blind, randomized, controlled study in patients with knee OA demonstrated a statistically significant clinical and pain reduction compared to the placebo group. A total of 253 patients were treated (124 received Synvisc-One and 129 received placebo). Over 26 weeks, patients treated with Synvisc-One showed a mean percent change from baseline in pain of 36%, while patients in the placebo group showed a mean percent change from baseline in pain 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 up to 52 weeks following 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 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, sodium dihydrogen phosphate hydrate 0.04 mg, water for injections as required.
PACKAGING
The contents of each syringe are sterile and non-pyrogenic. Store at a temperature between +2°C and +30°C. Do not freeze.
Synvisc is supplied in a 2.25 ml glass syringe pre-filled with 2 ml of Hylan GF 20.
Cod. 010144
