For the sustained relief of pain in osteoarthritis of the knee.
Posology and method of administration
Adults (including the elderly)
- The contents of one pre-filled syringe (20 mg/2mL) to be injected into the affected joint once a week to a total of five injections, using a standard technique. No adjustment of dose is required in elderly patients.
- This can be repeated at not less than 6 monthly intervals.
- At present there is not enough evidence to recommend a dosage regimen for use in children.
- Intra-articular injection of Hyalgan should be made using precise, anatomical localisation into the joint cavity of the knee to be treated. The injection site in the knee is determined by that location which is easier to reach. Usually a lateral approach can be followed, but in some cases a medial approach is preferable. Strict aseptic precautions should be observed during the administration in order to avoid the possibility of developing infections in the injection site. The solution in the pre-filled syringe is ready for use and requires only a sterile disposable needle. To ensure sterility the injection site must be carefully cleansed with antiseptic. Care should be taken to expel any trapped air bubbles from the syringe containing Hyalgan prior to administration.
- Joint effusion, if present, should be aspirated by arthrocentesis prior to injection of Hyalgan.
- The arthrocentesis should be made using a 20 gauge needle and the joint should be aspirated to almost dryness, but not to degree that would compromise the accuracy of the subsequent Hyalgan injection. An appropriate examination of the joint fluid present should be carried out to exclude bacterial infection, prior to injection.
- The intra-articular injection of Hyalgan can be given using the same needle as used for the arthrocentesis by simply detaching the aspirating syringe and attaching the syringe containing Hyalgan. To make sure the needle is correctly positioned, some synovial fluid should be aspirated prior to the slow injection of Hyalgan. If the patient experiences pain during injection, the procedure may need to be stopped.
- For the first 48 hours after the injection, the patient should be advised to rest the treated knee, with as little exercise as possible, avoiding any strenuous or prolonged activity.
- Subsequently, they may gradually return to their normal level of activity.
- Discard any unused Hyalgan.
- Hyalectin, the active ingredient in Hyalgan, is of avian origin. Do not administer to patients with known hypersensitivity to any ingredient of the product or to avian proteins.
- Intra-articular injections are contraindicated in cases of infection of the knee joint or infection and diseases of the skin in the area of the injection site to reduce the potential for developing septic arthritis.
Special warnings and precautions for use
- Remove joint effusion, if present, before injecting Hyalgan.
- Patients should be carefully examined prior to administration to determine signs of acute inflammation and the physician should evaluate whether Hyalgan treatment should be initiated when objective signs of inflammation are present.
- As with any invasive joint procedure, it is recommended that care be taken not to overburden the joint immediately following the intra-articular injection.
Interaction with other medicinal products and other forms of interaction
- Since there is limited experience available, Hyalagan should not be administered simultaneously or mixed with other intra-articular injections.
- Do not use concomitantly with disinfectants containing quaternary ammonium salts because hyaluronic acid can precipitate in their presence.
Fertility, pregnancy and lactation
- No embroytoxicity or teratogenicity has been observed in animal studies. However, there is no experience of the use of Hyalgan in pregnant women and therefore the expected benefit to the mother should be weighed against any potential risk to the foetus.
- If Hyalgan is prescribed to a woman of child-bearing potential, she should be advised to contact her physician regarding discontinuance of the product if she intends to become, or suspects that she is, pregnant.
- Although it is not expected that Hyalgan would be present in human milk, because many drugs are excreted by this route, caution should be exercised when Hyalgan is administered to a nursing mother and the expected benefit to the mother should be weighed against any potential risk to the neonate.
Effects on ability to drive and use machines
- Hyalgan is not expected to have any effect on the patient’s ability to drive or operate machinery.
- Local reactions such as pain, swelling/effusion, and warmth or redness at the injection site have been reported. Usually such symptoms are transient and disappear spontaneously within a few days by resting the affected joint and applying ice locally. Only sporadically have these events been more severe and longer lasting.
- When evident signs of chronic inflammation are present, the administration of Hyalgan has aggravated the said condition in some cases.
- Very rare cases of intra-articular infection have been reported. Strict aseptic technique must be followed in administering Hyalgan.
- Systemic allergic reactions have been rarely recorded. Isolated cases of an anaphylactic like reaction have been reported in post-marketing experience and they had favourable outcomes.
- Allergic-type signs and symptoms such as rash, pruritus and urticaria are also very rare.
- Some cases of fever have been also reported. In some cases fever was associated with local reactions.
- Hyalgan was investigated in a pivotal clinical investigation conducted in the United States in which there were three arms (164 subjects treated with Hyalgan; 168 with placebo; and 163 with naproxen). The following adverse events occurred with a frequency greater than 5% in the Hyalgan group (versus placebo): headache 18% (17%), rash 7% (9%), ecchymosis 7% (6%) and pruritus 7% (4%). As these events occurred with equal frequency in the placebo group, there is no proven causality in respect of Hyalgan. Hyalgan - treated subjects had 48/164 (29%) incidents of gastrointestinal complaints that were not statistically different from the placebo-treated group.Gastrointestinal adverse events were significantly more common in the naproxen group than the HA or the placebo groups and 14 naproxen treated patients (8.3%) discontinued prematurely due to these events.
- The adverse reactions reported in the table as MedDRA terms derived from patients who received Hyalgan in controlled, and open-label clinical trials, and from post-marketing experience gained from a real-life use of the product. Frequency of occurrence of undesiderable effects is presented in accordance with MedDRA convention: Very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to <1/100); rare ( 1/10,000 to < 1/1,000); very rare (<1/10,000), not known (cannot be estimated form the available data).
Rare ( 1/10,000 to < 1/1,000)
- Injection site reactions, such as: Injection site joint pain Injection site joint effusion Injection site joint swelling Injection site joint inflammation Injection site irritation
- Injection site joint movement impairment Injection site hypersensitivity
Very rare (< 1/10,000)
- Other local reactions, such as: Injection site nodule
- Injection site haemorrhage Injection site paraesthesia Injection site pustule
- Injection site vesicles
- Feeling hot Pyrexia
Very rare (< 1/10,000)
- Arthritis reactive Synovitis
- Joint stiffness
Very rare (< 1/10,000)
- Hypersensitivity Urticaria Anaphylactoid reaction Anaphylactic shock Serum sickness Angioedema
Very rare (< 1/10,000)
- Rash Pruritus Eczema Erythema Dermatitis
- Overdosage is unlikely given the route of administration and the single use pack of the drug. No case of overdosage has been reported to date.
- Hyalgan is a sterile, non-pyrogenic, viscous, aqueous buffered solution of a defined high molecular weight fraction of highly purified hyaluronic acid sodium salt (Hyalectin). Hyaluronic acid is an important component of the body’s extracellular matrix and is present in a particularly high concentration in cartilage and synovial fluid. Endogenous hyaluronic acid provides viscosity and elasticity to synovial fluid, which is fundamental for its lubricating and shock absorbing properties, and it is essential for the correct structure of proteoglycans in articular cartilage.
- In osteoarthritis there is an insufficient amount of, and a change in the quality of, hyaluronic acid in synovial fluid and cartilage. The intra-articular administration of hyaluronic acid into arthritic joints with degenerating cartilage surfaces and pathologically altered synovial fluid improved joint functions. The observed beneficial effects of exogenous hyaluronic acid may be related to its interactions with various components of the synovial cavity (synoviocytes and chondrocytes).
- In controlled clinical studies, treatment cycles with Hyalgan have been shown to ameliorate the symptoms of osteoarthritis for up to 6 months following the end of treatment.
- Sodium Hyaluronate (Hyalectin) administered intra-articularly is eliminated from the synovial fluid within 2 to 3 days. Pharmacokinetic studies have shown that it is quickly distributed to the synovial membrane. The highest concentrations of labelled hyaluronic acid have been detected in the synovial fluid and the articular capsule, followed by, in decreasing order, the synovial membrane, the ligaments and the adjacent muscle.
- Hyaluronic acid in synovial fluid has been shown to be not significantly metabolised. Animal studies have shown that some degradation occurs in the tissue surrounding the joints, but the major site for metabolism is the liver and excretion is mainly through the kidneys.