Hylan G-F 20 products are classified by the FDA as medical devices, rather than drug products. A medical device is a product intended to affect the structure or function of the body, but which does not achieve its primary purposes through the chemical action of a drug -- nor is it dependent on being metabolized. These products relieve pain via viscosity and lubrication.
Hylan G-F 20 (Synvisc and Synvisc-One) is used as an intra-articular treatment for the pain of osteoarthritis. Hylan G-F 20 is an elastoviscous fluid containing cross-linked polymers of hyaluronan (hyaluronic acid) known as hylans. Hylan G-F 20 is produced from chicken combs and is used clinically as a viscoelastic agent. Synvisc is administered as 3 injections, but a single injection option (same material and total treatment volume as Synvisc) is provided by Synvisc-One. Synvisc was approved by the FDA in August 1997 and Synvisc-One was approved in February 2009.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Other Injectable Administration
Intra-articular Injection Administration (Synvisc or Synvisc-One)
-Use strict aseptic technique.
-The syringe is intended for single use only.
-The contents of the syringe must be used immediately after the syringe has been removed from the packaging.
-Do not use concomitant disinfectants that contain quaternary ammonium salts for skin preparation as hyaluronan can precipitate in their presence.
-Remove any synovial fluid or effusion before injecting each dose of hylan G-F 20.
-Do not use the same syringe for removing synovial fluid and injecting hylan G-F 20; however, use the same 18- to 22-gauge needle.
-Twist the tip cap before pulling it off to minimize leakage.
-To ensure a tight seal and prevent leaking during administration, secure the needle tightly while firmly holding the luer hub.
-Do not over tighten or apply excessive leverage when attaching the needle or removing the needle guard to avoid breaking the syringe tip.
-Inject the entire contents of the syringe into one knee only.
-If treatment will be bilateral, use a separate syringe for each knee.
-Do not give other intra-articular injections at the same time.
A local injection site reaction may be associated with the intra-articular injection of hylan G-F 20 and may include mild/moderate pain (0.8-23.7%), swelling (4.1%), and effusion (1.6-5.7%). These events are generally transient and usually resolve on their own with conservative treatment. Other local adverse events include arthralgia (1.6-25.2%), arthritis (0.8-1.3%), arthropathy (0.8%), joint stiffness (8.1%), joint warmth (1.6%), gait disturbances (0.8%), and injection site hematoma (1.3%). Additionally, in some post-marketing reports, joint effusion may be large and cause pronounced pain. Analyze the fluid in these cases to rule out an infectious process or crystalline arthropathies.
Adverse reactions occurring at sites outside of the affected knee have been reported, regardless of device-relatedness. Muscle pain (musculoskeletal pain), back pain (> 5%), low back sprain, and muscle cramps of the calf have been reported with hylan G-F 20 administration.
Intra-articular infection did not occur during clinical trials with hylan G-F 20; however, rare reports have been noted with clinical use. Strict aseptic technique must be observed during use. Adverse infectious reactions occurring at sites outside of the affected knee have been reported, regardless of device-relatedness. Influenza was also reported in > 5% of patients during clinical trials.
Rash (unspecified) (0.9%), itching/pruritus (0.9%), and hives have been noted in post-marketing reports with hylan G-F 20. Facial swelling and angioedema have been noted in post-marketing reports.
General adverse events noted during post-marketing reports with hylan G-F 20 include fever, chills, malaise, and flushing.
Adverse reactions occurring at sites outside of the affected knee have been reported, regardless of device-relatedness. Nausea and hemorrhoids were noted in post-marketing reports and clinical trials with hylan G-F 20.
Adverse reactions occurring at sites outside of the affected knee have been reported, regardless of device-relatedness. Headache (> 5%), dizziness, and paresthesias were noted in post-marketing reports with hylan G-F 20.
Adverse reactions occurring at sites outside of the affected knee have been reported, regardless of device-relatedness. Nasopharyngitis/pharyngitis (> 5%) were reported with the use of hylan G-F 20; respiratory difficulties (dyspnea) and tonsillitis were reported rarely.
Ankle/peripheral edema and tachyarrhythmias, and phlebitis with varicosities have been generalized adverse events infrequently reported with the use of hylan G-F 20.
There have been rare reports postmarketing of thrombocytopenia coincident with the use of hylan G-F 20; a causal relationship is not certain.
The use of hylan G-F 20 is contraindicated in patients with known hyaluronan (sodium hyaluronate) hypersensitivity. Use caution when administering hylan G-F 20 to patients who are allergic to avian proteins, feathers, or egg products (egg hypersensitivity) as the hylan polymers are produced from chicken combs.
Hylan G-F 20 is contraindicated in patients with knee joint infections (septic arthritis) or a local skin disease or infection in the area of the injection site. Use caution when there is evidence of lymphatic or venous stasis in the leg to be injected. Safety and efficacy in joints with severe inflammation have not been established.
Do not inject hylan G-F 20 extra-articularly or into the synovial tissues or capsule. Do not administer intravascularly (intraarterial administration/intravenous administration). Local and systemic adverse events may occur after extra-articular injection.
The safety and efficacy of hylan G-F 20 have not been established in neonates, infants, children, adolescents, and adults <= 21 years.
The safety and effectiveness of hylan G-F 20 use in pregnancy have not been established.
It is unknown if hylan G-F 20 is excreted in human breast milk. The safety and effectiveness of hylan G-F 20 have not been established in breast-feeding women.
For the treatment of pain in osteoarthritis of the knee when response to conservative nonpharmacologic therapy and simple analgesics (e.g., acetaminophen) has been inadequate:
NOTE: Use in locations other than the knee and for conditions other than osteoarthritis have not been established. The safety and effectiveness with concomitant intra-articular injectables have not been established.
Intra-articular dosage (Synvisc, 8 mg/mL):
Adults > 21 years: Inject 2 mL (16 mg hylan polymers) intra-articularly once per week for a total of 3 injections. If treatment is bilateral, use a separate 2 mL vial/syringe for each knee. The effectiveness of a single treatment cycle of less than 3 injections has not been established. Avoid any strenuous activities or prolonged weight-bearing activities for approximately 48 hours after the injection. Each treatment cycle delivers up to 6 months of pain relief.
Adults <= 21 years, Adolescents, Children, Infants, and Neonates: Safety and efficacy have not been established.
Intra-articular dosage (Synvisc-One, 48 mg/6 mL):
Adults > 21 years: Inject 6 mL (48 mg hylan polymers) intra-articularly as a single injection. If treatment is bilateral, use a separate 6 mL vial/syringe for each knee. Avoid any strenuous activities or prolonged weight-bearing activities for approximately 48 hours after the injection. Each injection delivers up to 6 months of pain relief.
Adults <= 21 years, Adolescents, Children, Infants, and Neonates: Safety and efficacy have not been established.
Maximum Dosage Limits:
-Adults
> 21 years: 1 injection (2 mL of Synvisc OR 6 mL of Synvisc-One) per knee per dose.
<= 21 years: Safety and efficacy have not been established.
-Geriatric
1 injection (2 mL of Synvisc OR 6 mL of Synvisc-One) per knee per dose.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
Benzalkonium Chloride: (Major) Do not use concomitant disinfectants that contain quaternary ammonium salts (e.g., benzalkonium chloride) for skin preparation prior to hylan G-F 20 intra-articular injection, as hyaluronan can precipitate in the presence of these disinfectants.
Benzalkonium Chloride; Benzocaine: (Major) Do not use concomitant disinfectants that contain quaternary ammonium salts (e.g., benzalkonium chloride) for skin preparation prior to hylan G-F 20 intra-articular injection, as hyaluronan can precipitate in the presence of these disinfectants.
Betamethasone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Dexamethasone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Hydrocortisone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Intra-articular Corticosteroids: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Methylprednisolone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Prednisolone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Triamcinolone: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
Hylan G-F 20 is a mixture of hylan A and hylan B polymers. Hylans are derivatives of hyaluronan (sodium hyaluronate/ hyaluronic acid), which is the main constituent of synovial fluid, which accounts for its viscoelastic properties. In the treatment of osteoarthritis, hylan G-F 20 can help to improve the elasticity and viscosity of the synovial fluid. Additionally, hyaluronic acid may have an antiinflammatory effect due to its effects on leukocyte function which may include inhibiting phagocytosis, adherence, and mitogen-induced stimulation. Intra-articular administration may reduce inflammatory mediators in the synovial fluid and may affect the release of arachidonic acid. The antiinflammatory effects may produce an analgesia by modulating pain perception via the inhibition of nociceptors or through the binding of substance P. Intra-articular administration may also stimulate de novo hyaluronic acid production within the joint. Animal models have also demonstrated that hyaluronic acid may possess a disease-modifying chondroprotective effect.
Hylan G-F 20 is administered via intra-articular injection. Specific pharmacokinetic parameters are not available regarding human use. No metabolism is expected to occur, consistent with the definition of an FDA-approved medical device. Each treatment cycle is expected to provide activity for up to 6 months.