Orthovisc vs Synvisc: Key Differences in Composition, Indications, and Outcomes

Viscosupplementation with hyaluronic acid (HA) injections has become a widely accepted treatment for knee osteoarthritis (OA), especially in patients who do not respond adequately to conservative therapy. Among the available options, ORTHOVISC® and Synvisc (including Synvisc-One) are two of the most commonly prescribed HA products. While they share the same clinical indication, their composition, administration protocols, safety profiles, and efficacy differ in certain ways. This article provides a detailed comparison designed to help medical professionals and informed patients make educated treatment decisions.

Overview of Orthovisc and Synvisc

For patients and physicians who may be wondering – what is ORTHOVISC? It is important to know that ORTHOVISC® is a sterile, non-animal-derived, high molecular weight sodium hyaluronate solution. It is biofermented using bacterial cultures and suspended in a 1% sodium chloride solution, providing 30 mg of HA per 2 mL dose. The product’s solution shows a thick, highly purified gel-like substance. Since hyaluronic acid is naturally found in the body, this type of injection therapy is generally considered safe. As a result, ORTHOVISC® lubricates and cushions the joint as it restores the lost hyaluronic acid. 

Synvisc and Synvisc-One are composed of Hylan G-F 20, a crosslinked hyaluronic acid derivative made from rooster combs (which is an avian source). The formulation includes Hylan A (soluble) and Hylan B (gel form) in a 6 mL solution. Synvisc is administered as three 2 mL weekly injections, while Synvisc-One is a single 6 mL injection designed to simplify dosing and improve patient compliance. Once they are administered directly into the joint, Synvisc injections act as lubricants and shock absorbers that provide patients with improved and pain-free joint movement. 

Differences in Composition

The key distinction between the two products lies in their molecular structure and source:

• ORTHOVISC® contains linear, biofermented sodium hyaluronate with a high molecular weight of 1.0 to 2.9 million Daltons.
• Synvisc is made up of crosslinked hylan polymers (Hylan A & B), and the molecular weight is around 6 million Daltons.

Because Synvisc is avian-derived, it may bring a higher risk of allergic reaction, especially in patients with known sensitivity to avian proteins. The crosslinked structure of Hylan G-F 20 makes Synvisc more viscous, which could influence joint mechanics and post-injection response.

On the other hand, ORTHOVISC’s biofermented, non-animal origin minimises the risk of adverse reactions, and makes it a safer option for patients concerned about animal-based components or allergies.

Indications and Approved Uses

Both products are FDA-approved for the treatment of pain due to knee OA in patients who have failed to respond to conservative non-pharmacologic and pharmacologic therapy (e.g., NSAIDs, physical therapy).

While off-label use of Synvisc in hip and shoulder OA has been documented in literature, the formal approval remains restricted to the knee. ORTHOVISC®, similarly, is approved for knee osteoarthritis only.

Administration Protocols

ORTHOVISC® is administered as three separate intra-articular injections of 2 mL each, spaced one week apart, totalling 6 mL over the course of treatment. Synvisc also follows a three-dose regimen with 2 mL injections given weekly. Synvisc-One, a variation of Synvisc, is designed for single-dose administration and delivers the entire 6 mL treatment volume in one injection.

The choice between multi-injection regimens and a single-dose protocol can influence patient adherence and convenience. While Synvisc-One offers the advantage of fewer office visits and potentially higher patient compliance, the weekly schedule of ORTHOVISC® may allow for closer clinical monitoring and flexibility in treatment planning.

Clinical Outcomes and Efficacy

Both Orthovisc and Synvisc have shown efficacy in reducing pain and improving joint function for up to six months. According to comparative studies, there are no statistically significant differences in long-term outcomes between the two in terms of pain scores, functional improvements, or overall patient satisfaction.

A review in Orthopaedic Reviews noted that both agents produced clinically meaningful results when used according to FDA-labelled regimens. 

Safety and Tolerability

Even though ORTHOVISC® and Synvisc are generally well-tolerated by patients, there are potential reactions that physicians and patients should be aware of. 

Common side effects for both products include:

• Joint stiffness or swelling
• Injection site pain
• Mild-local inflammation

Rare but significant adverse events include:

• Pseudosepsis 
• Infections
• Hypersensitivity reactions (more likely with Synvisc due to avian origin)

A 2018 pharmacovigilance report identified a slightly higher incidence of post-injection flare reactions with Synvisc and Synvisc-One, likely attributed to their avian protein content. ORTHOVISC®, on the other hand, had fewer reported hypersensitivity events.

If you are a patient who feels like it is time for re-injection, it is also important to discuss it with your physician how often can you get ORTHOVISC injections or Synvisc treatments. This protocol should also be tailored depending on each patient’s health condition.

Cost and Access Considerations

Costs for viscosupplementation vary widely depending on regional pricing, insurance reimbursement, and distribution agreements.

• Synvisc-One, while more expensive per dose, requires only one injection, potentially reducing overall administrative costs and patient time off work.
• ORTHOVISC® and Synvisc (three-dose regimens) may be lower in per-dose cost but involve multiple visits.

Clinic inventory logistics may also influence product choice. ORTHOVISC’s standard 2 mL format is easier to store and manage in practices already accustomed to multi-dose viscosupplementation schedules.

Reimbursement eligibility and payer preferences can also affect access. Some insurers may favor Synvisc-One for its one-time administration, while others may only reimburse for multi-injection products.

Which Product to Choose and When?

Choosing whether to suggest and buy ORTHOVISC or Synvisc requires an individualised approach, and the final decision must be an agreement between the patient and a trained physician. Factors to consider include:

• Allergy risk: Patients with known allergies should not choose to have Synvisc injected
• Convenience: Synvisc-One is ideal for patients seeking fewer injections
• Provider experience: Clinician familiarity can influence product preference and outcomes, and it can also witness to the efficacy of a particular product
• Cost and access: Reimbursement and supply availability should be assessed before the final decision.

Conclusion

ORTHOVISC and Synvisc are both effective HA-based viscosupplements for managing knee OA symptoms in patients unresponsive to conservative therapy. While clinical outcomes are broadly similar, key distinctions in composition, allergy risk, dosing convenience, and cost can guide product selection. In the end, the choice should be based on clinical presentation, patient preference, safety considerations, and access to reimbursement. A tailored approach ensures optimal joint care and patient satisfaction.

References: 

Peck J, Slovek A, Miro P, et al. A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee. Orthopedic Reviews. 2021;13(2).

Orthovisc, Synvisc (hyaluronic-acid-and-derivatives) dosing, indications, interactions, adverse effects, and more.

reference.medscape.com.

Brandt KD, Block JA, Michalski JR, Moreland LW, Caldwell J, Lavin PT. Efficacy and Safety of Intraarticular Sodium Hyaluronate in Knee Osteoarthritis. 2001;385:130-143.