Proposed hyaluronic acid (HA) mechanism of action*

The precise mechanism of action of HA is unknown; however, proposed mechanisms of HA activity include:


OA synovial fluid with higher HA concentration—improves viscosity10


shock-absorbing, lubricating ability of depleted synovial fluid11


boundary layer around nociceptors, reducing pain12,13

Exogenous HA can catalyze physiological response

The synthesis of hyaluronan within synovial joints may be influenced by the concentration and molecular weight of hyaluronan in the extracellular environment.

HYALGAN® is a viscous solution with a molecular weight (500,000-730,000 daltons) fraction of purified natural sodium hyaluronate in buffered physiological sodium chloride, having a pH of 6.8-7.5. The sodium hyaluronate is extracted from rooster combs. Hyaluronate (also known as hyaluronan or HA) is a natural complex sugar of the glycosaminoglycan family and is a long-chain polymer containing repeating disaccharide units of Na-glucuronate-N-acetylglucosamine.14

Clinical significance in vivo has not been demonstrated.
Within the molecular-weight range of US-approved HAs used in the treatment of OA knee pain, it is unknown what role these physiological processes may play in clinical benefit.

Important Safety Information

HYALGAN is contraindicated in patients with known hypersensitivity to hyaluronate preparations. Intra-articular injections are contraindicated in cases of present infections or skin diseases in the area of the injection site to reduce the potential for developing septic arthritis.

Transient increases in inflammation in the injected knee following HYALGAN injection have been reported in some patients with inflammatory arthritis such as rheumatoid arthritis or gouty arthritis. Physicians should evaluate whether HYALGAN treatment should be initiated when objective signs of inflammation are present.

The effectiveness of a single treatment cycle of less than 3 injections has not been established.

Patients should be advised to avoid any strenuous or prolonged weight-bearing activities within 48 hours following intra-articular injection.

Use caution when injecting HYALGAN into patients who are allergic to avian proteins, feathers and egg products.

Joint effusion, if present, should be removed prior to injection.

The safety and effectiveness of HYALGAN has not been established in children or in pregnant or lactating women. It is unknown whether HYALGAN is excreted in human milk.

In the US clinical trial of 495 patients, the only adverse event showing statistical significance vs placebo was injection-site pain. Other adverse events included gastrointestinal complaints, headache, local ecchymosis and rash, local joint pain and swelling, and local pruritus. However, the incidence of these events was similar in the HYALGAN-treated and placebo groups. In other clinical studies, the frequency and severity of adverse events occurring during repeat treatment cycles did not increase over that reported for a single treatment cycle.


HYALGAN is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and to simple analgesics, eg, acetaminophen.

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