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.⁸

*Clinical significance in vivo has not been demonstrated.

Proposed dual mechanism of action

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

Stage 1: Mechanical/Physical

Replaces OA synovial fluid with higher HA concentration—improves viscosity²
Restores shock-absorbing, lubricating ability of depleted synovial fluid³
Maintains boundary layer around nociceptors, reducing pain induction^4,5

Stage 2: Physiological

Induces biosynthesis of HA and extracellular matrix components⁶
Reduces proteoglycan loss in cartilage^2,3 and apoptosis of chondrocytes⁷
Reduces inflammatory cell activities to reduce HA degradation²
Reduces induction of pain mediators^2,4,5

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. Stimulation of endogenous HA synthesis in vitro was observed after adding exogenous HA with an average molecular weight >500,000.⁶

Clinical significance in vivo has not been demonstrated.

Optimal HA stimulation
Picture of Optimal HA stimulation

Adapted from Smith MM, Ghosh P.
Rheumatol Int. 1987;7:113-122.

^†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 for HYALGAN®

HYALGAN® is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpha-rmacologic therapy, and to simple analgesics, eg, acetaminophen
HYALGAN® is contraindicated in patients with known hypersensitivity to hyaluronate preparations. Intra-articular injections are contraindicated in cases of past and present infections or skin diseases in the area of the injection site
The effectiveness of a single treatment cycle of less than 3 injections has not been established
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

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