INFORMATION FOR HEALTH PROFESSIONALS
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Each syringe contains:
16 mg hylan polymer (hylan A fluid and hylan B gel ) in 2 mL buffered physiological sodium chloride solution.
Synvisc is a sterile, nonpyrogenic elastoviscous fluid containing hylan polymers, for injection. Hylans are crosslinked derivatives of hyaluronan (sodium hyaluronate), a natural complex linear polysaccharide of the glycosaminoglycan family. The polysaccharide chain of hylans contains repeating disaccharide units of N-acetylglucosamine-Na-glucuronate. . The active ingredients of Synvisc are hylan A, with an average molecular weight of 6,000,000; and hylan B gel particles, in a buffered physiological sodium chloride solution, pH 7.2 ± 0.3. Due to this specific composition, Synvisc is an elastoviscous fluid with elasticity (storage modulus G') at 2.5 Hz of 111 ± 13 Pascals (Pa) and a viscosity (loss modulus G'') of 25 ± 2 Pa. Thus Synvisc has rheological properties similar to those of the healthy synovial fluid of a young individual. This means that the dynamic elastic and viscous modulus (G', G") are greater than human synovial fluid at low deformation frequencies (0.0001 to 2 Hz) and similar at high frequencies (2 to 10Hz).
Synvisc is indicated for use as a temporary replacement and supplement for synovial fluid to treat pain associated with osteoarthritis in the knee joint and to increase the mobility of this joint by reducing or eliminating pain. There is no data on the long term use of Synvisc.
Synvisc is administered by intra-articular injection once a week (one week apart) for a total of three injections
The recommended dose is 2mL per intra-articular injection in the knee.
There is no data on repeated courses of administration with Synvisc, after the first treatment period.
Intra-articular treatment with Synvisc can be applied to more than one knee joint at the same time.
The use of intra-articular steroids, if needed, is not contraindicated.
Do not inject Synvisc in severely inflamed joints. Do not inject Synvisc in an infected joint or in patients with a history of infections to the joint, or in patients having skin diseases or infections in the area of the injection site.
Do not inject synvisc if there is large intra-articular effusion. Synvisc is contraindicated in patients with known hypersensivity to Hylan G-F 20 or to any of the other excipients.
Do not inject Synvisc extra-articularly or in the synovial or capsular tissue, or into intra-articular ligaments. Adverse events, generally in the area of the injection, have occurred following extra-articular injection of Synvisc.
Do not administer X-ray contrast media into the joint prior or simultaneously with Synvisc injection.
If local anaesthetic fluid is used to decrease pain associated with arthrocentesis, take care that none of the fluid is injected into the joint space.
Do not inject Synvisc intravascularly. Intravascular injection of Synvisc may cause serious systemic adverse events
Do not concomitantly use disinfectants containing quaternary ammonium salts for skin preparation because hyaluronan can precipitate in their presence
Administer using strict aseptic arthrocentesis procedures, taking particular care when removing the tip cap.
Remove synovial fluid or effusion if present, before injecting Synvisc.
Use separate syringe to remove effusion.
Use the same needle (without removing it from the joint) for removal of effusion and for injection of Synvisc.
Synvisc should be used with caution when there is evidence of lymphatic or venous stasis around or peripheral to the joint.
Synvisc contains small amounts of avian protein and should not be used in patients with related hypersensitivites.
Synvisc does not interact with analgesics or anti-inflammatory drugs (NSAIDs, steroids); therefore, these drugs can be applied during Synvisc therapy.
There are no reports of abnormal laboratory test results attributed to Synvisc administration, either alone or in conjunction with any other treatments.
Synvisc has not been tested in pregnant or lactating women. Animal studies show that Synvisc does not adversely affect male or female reproduction performance or the viability, external morphology and growth or function of the offspring.
Synvisc does not provide a general systemic effect and will not cause drowsiness or impair the ability to drive or use machinery
Within 48 hours after Synvisc injection, in approximately three percent of the cases, the patient may experience pain swelling and/or effusion in the injected joint that is greater than previously experienced during the course of the disease. This is transient and in the majority of cases, does not interfere with the long-term beneficial effect of Synvisc treatment.
If this occurs after the first or second injection, depending of the severity of the reaction, the next injection(s) should not be given or should be postponed until the symptoms subside.
Pain and swelling can be treated with rest, cold packs, peroral analgesics or nonsteroidal anti-inflammatory drugs.
If large volume of effusion is present it should be removed by arthrocentesis; infection, if suspected, should be ruled out.
When reported, systemic adverse events have been varied; however, causal relationship to Synvisc was not ruled out.
The post-marketing experience has identified the following systemic events to occur rarely with Synvisc administration: rash, hives, itching, fever, nausea, headache, dizziness, chills, muscle cramps, paresthesia, peripheral oedema, malaise, respiratory difficulties, flushing and facial swelling. In the controlled clinical trials, there were no statistically significant differences in the number or types of systemic adverse events between the group of patients that received Synvisc and the group that received control treatments.
Intra-articular infections did not occur in any of the clinical trials and have been reported only rarely during clinical use of Synvisc.
Intra-articular infections did not occur in any of the clinical trials and have been reported only rarely during clinical use of Synvisc.
Experience with the same class does not show any systemic affects attributable to these products when they have been administered locally.
No information available.
Safety/toxicity studies have been conducted in which the dose of hylan was artificially elevated to levels which were much higher than clinical levels. There was no evidence of any adverse or toxic reaction to these high doses of hylan.
Synvisc, a hyaluronan derivative, has rheological (elastoviscous) properties which are similar to the normal adult human synovial fluid. Hyaluronan in the synovial fluid and joint tissues is responsible for the elastoviscosity of the intercellular matrix of these tissues and of the synovial fluid. Intra-articular Synvisc functions by supplementing the mechanical properties of osteoarthritic synovial fluid (viscosupplementation) which has a reduced viscosity and elasticity relative to normal synovial fluid.
By restoring the fluid's rheological properties to a normal range, Synvisc coats and protects tissue surfaces, fills the intercellular space of the soft connective tissues of the joint, thereby protecting cells and the fibrous intercellular matrix structure. Synvisc also reduces both the steady state and motion-induced firing of nociceptors (pain receptors), and thereby reduces joint pain and restores joint mobility
In vitro and animal experiments demonstrated that Synvisc protects the cartilage surface and cells from certain physical and chemical (oxidative, enzymatic) damage and inflammatory processes.
Once hyaluronan has passed into the blood it is rapidly taken up and degraded, primarily by liver endothelial calls via a receptor-mediated endocytic pathway. Low molecular weight hyaluronan fraction can be eliminated via the kidney, but this pathway is believed to contribute only 1% to the removal of hyaluronan from the blood.
In addition, cells of the reticuloendothelial system other than liver endothelial cells also contribute to both the local and systemic turnover of hyaluronan, though the fraction of total hyaluronan turnover which can be accounted for by this route is difficult to estimate.
There is no evidence that the metabolism of hyaluronan (or hylan) is significantly affected by any renal or hepatic conditions in either humans or experimental animals.
The pharmacokinetic profile of Synvisc was studied in rabbits and rats. The elimination pathway was evaluated as two distinct steps: (1) slow removal from the intra-articular injection site: (2). rapid systemic clearance after passage into the circulatory system. This type of evaluation is necessitated by the pharmacokinetic characteristics of Synvisc, as it clears the blood much more rapidly than it clears the joint.
The hylan B gel component of Synvisc clears the rabbit joint with a half-life of 8.8 ( ± 0.9) days. The hylan A fluid component of Synvisc clears the rabbit joint with a half -life of 1.5 (± 0.2) days. For both the gel and fluid components of Synvisc, clearance from the injection compartment (synovial fluid space) is more rapid than from the exit compartment (joint tissue through which Synvisc moves into the lymphatic circulation). This slower clearance from the soft tissues of the joint demonstrates that Synvisc has a prolonged residence time at its site of action.
After direct intravenous injection, both hylan A (hylan fluid) and hylan B (hylan gel in degraded form) clear the circulation with a half-life of less than 30 minutes. Blood elimination of both hylan A and hylan B were independent of the dosage administered over the range tested, indicating that the capacity for hylan elimination from the blood is not saturated by direct administration of dosages up to 10,000-fold higher than the endogenous hyaluronan levels in blood. After intra-articular administration, no significant levels of Synvisc or its metabolites were detected outside the joint including the major organs.
Sodium chloride, Disodium hydrogen phosphate, Sodium dihydrogen phosphate monohydrate, Water for injection
There are no known incompatibilities to treatment with Synvisc.
24 months at temperature between 2° to 30°C. Expiry date is noted on the syringe.
Synvisc should not be frozen.
1 box contains 3 syringes of 2ml each.
Do not use Synvisc if package is opened or damaged
Synvisc can be stored in the original package at room temperature below 30°C
(86°F). Protect from freezing.
The Synvisc syringe is intended for single use. Discard partially used Synvisc syringes. Do not re-sterilise Synvisc
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New Zealand
20 November 2007