Intra-articular hyaluronans: A review of product-specific safety profiles

• Published in: Seminars in arthritis and rheumatism 2003-04, Vol.32 (5), p.296-309
• Main Authors: Hamburger, Max I., Lakhanpal, Sharad, Mooar, Pekka A., Oster, David
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Arthralgia - drug therapy; Arthralgia - etiology; Biological and medical sciences; Clinical Trials as Topic; Consumer Product Safety; Drug toxicity and drugs side effects treatment; Humans; Hyaluronans; Hyaluronic Acid - administration & dosage; Hyaluronic Acid - adverse effects; immunogenicity; Injections, Intra-Articular; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); osteoarthritis of the knee; Osteoarthritis, Knee - complications; Osteoarthritis, Knee - drug therapy; Pharmacology. Drug treatments; Practice Guidelines as Topic; safety
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1053/sarh.2002.50008

Background and Objectives: Intra-articular (IA) hyaluronans (HAs) are indicated for pain relief of osteoarthritis (OA) of the knee. Hyalgan (sodium hyaluronate), Supartz (sodium hyaluronate), and Synvisc (hylan G-F 20) are Food and Drug Administration-approved HA products. They are derived from rooster combs; Hyalgan and Supartz are naturally derived (unmodified); Synvisc is chemically modified to increase its molecular weight. This article reviews and updates the safety data for IA HAs used for the treatment of knee OA. Methods: References were taken from Medline through July 2002; respective product information services and information from the searchable United States Food and Drug Administration Manufacturer and User Facility Device Experience Database also were used. Results: All products demonstrated favorable safety profiles in clinical trials and practice compared to other standard therapies for management of OA knee pain. The most common adverse event associated with HAs is mild injection site pain and swelling. Each product has had rare reports of pseudogout and anaphylactoid reactions. Product-specific adverse events, severe acute inflammatory reactions (pseudoseptic knee), in patients receiving Synvisc have been reported. One such patient developed antibodies to chicken proteins and hylan, suggesting an immunologic basis for the severe acute inflammatory reaction. Data from an animal study support a possible immunogenic difference between Synvisc and Hyalgan. Conclusions and Relevance: Overall, HA therapy is a safe treatment for OA knee pain, although there may be interproduct variability in safety profiles. Semin Arthritis Rheum 32:296-309. Copyright 2003, Elsevier Inc. All rights reserved.