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Treatment Comparison

Synvisc-One vs Euflexxa

Compare Synvisc-One and Euflexxa hyaluronic acid injections for knee osteoarthritis. Understand differences in molecular weight, injection schedules, sources, costs, and which might work better for you.

Side-by-Side Comparison

Number of Injections

Synvisc-One 1 (single injection)
Euflexxa 3 (weekly series)

Molecular Weight

Synvisc-One High (6 million Daltons)
Euflexxa Low-medium (2.4-3.6 million Daltons)

Source

Synvisc-One Avian (chicken comb)
Euflexxa Bacterial fermentation (non-avian)

Volume per Injection

Synvisc-One 6 mL (one time)
Euflexxa 2 mL (each of 3 injections)

Egg Allergy Concern

Synvisc-One Yes - contraindicated
Euflexxa No - safe for egg allergies

Duration of Effect

Synvisc-One Up to 6 months
Euflexxa Up to 6 months

Medicare Coverage

Synvisc-One Yes
Euflexxa Yes

It Depends on Your Situation

Both are effective HA injections for knee OA. Synvisc-One offers convenience with a single injection, while Euflexxa's three-injection series may provide more sustained delivery. Choice often depends on scheduling preferences, insurance coverage, and any avian allergies.

Best for: Synvisc-One for convenience; Euflexxa for patients with egg allergies or who prefer non-avian sources.

Understanding HA Injection Options

If your doctor has recommended hyaluronic acid (HA) injections for knee osteoarthritis, you may have heard of different brand names. Synvisc-One and Euflexxa are two of the most commonly prescribed options—but they have important differences.

Both work by restoring lubrication and cushioning to your knee joint, but they differ in molecular structure, source material, and how they’re administered.


Side-by-Side Comparison

FactorSynvisc-OneEuflexxa
Injections needed13 (weekly)
Molecular weightHigh (6 million Da)Low-medium (2.4-3.6 million Da)
SourceAvian (chicken comb)Bacterial fermentation
Volume6 mL single injection2 mL × 3 injections
Egg allergy safeNoYes
Cross-linkingYes (hylan polymer)No (native HA)
Duration of reliefUp to 6 monthsUp to 6 months
Medicare coveredYesYes
ManufacturerSanofiFerring

Synvisc-One: Single-Injection Convenience

What It Is

Synvisc-One is a high molecular weight, cross-linked hyaluronic acid (called hylan G-F 20) derived from chicken combs. The cross-linking process creates a gel-like substance that provides significant cushioning.

Advantages

One-and-done convenience - Single injection means one appointment, one copay
Full dose in one visit - No need to return for weekly injections
High molecular weight - May provide more cushioning effect
Extensive track record - Widely studied and used for decades

Considerations

Egg/chicken allergy - Contraindicated for patients with avian allergies
Larger injection volume - 6 mL at once may cause more initial swelling
Pseudoseptic reactions - Rare but more commonly reported with high MW products

Best For

  • Patients wanting minimal appointments
  • Those with no avian allergies
  • Anyone with scheduling constraints (travel, work)
  • Patients who’ve responded well to Synvisc (original three-injection) formulation

Euflexxa: Non-Avian Alternative

What It Is

Euflexxa contains native (non-cross-linked) hyaluronic acid produced through bacterial fermentation. This means it’s not derived from any animal source, making it suitable for patients with egg or poultry allergies.

Advantages

Safe for egg allergies - Non-avian source eliminates allergy concerns
Smaller injection volume - 2 mL per injection may mean less initial discomfort
Gradual delivery - Three injections spread treatment over time
Well-tolerated - Low rate of local reactions

Considerations

Multiple appointments - Requires three weekly visits
Multiple copays - May mean higher out-of-pocket costs
Treatment interruption risk - Missing a weekly appointment may affect results

Best For

  • Patients with egg or poultry allergies
  • Those who prefer smaller injection volumes
  • Patients who’ve had reactions to avian-derived HA
  • Anyone who can easily attend three weekly appointments

The Science: Molecular Weight Matters?

The Debate

There’s ongoing discussion about whether high molecular weight (HMW) or low-medium molecular weight (LMW) HA works better:

High MW Theory (Synvisc):

  • More viscous = better cushioning
  • Longer residence time in joint
  • Better shock absorption

Low-Medium MW Theory (Euflexxa):

  • Better tissue penetration
  • More similar to natural HA
  • Less inflammatory response

What Research Shows

Clinical studies comparing different HA products have found:

  • Similar efficacy across most molecular weights
  • Duration of effect comparable (both ~6 months)
  • No clear winner in head-to-head trials
  • Individual variation - some patients respond better to one than the other

Bottom line: Both work. The “best” choice often comes down to practical factors like allergies, scheduling, and insurance coverage.


Allergy Considerations

Important: Avian Allergies

If you have allergies to:

  • Eggs
  • Chicken
  • Feathers
  • Other poultry products

You should avoid Synvisc-One (and original Synvisc) and choose a non-avian alternative like Euflexxa.

Always inform your doctor about any allergies before receiving HA injections.


Insurance and Cost Comparison

Medicare Coverage

Both Synvisc-One and Euflexxa are covered by Medicare Part B when medically necessary criteria are met:

  • Documented knee osteoarthritis
  • Failed conservative treatment (3+ months)
  • Meets Local Coverage Determination (LCD) requirements

Cost Factors

FactorSynvisc-OneEuflexxa
Office visits13
Copays (typical)1 × $50-1503 × $20-50
Injection feesOnceThree times
Total out-of-pocketSimilarSimilar

Note: Actual costs vary by insurance plan, deductible status, and provider billing.


Other HA Products to Know

Synvisc-One and Euflexxa aren’t your only options. Other FDA-approved HA products include:

Single-Injection Products

ProductSourceMolecular Weight
Synvisc-OneAvianHigh
MonoviscAvianHigh
DurolaneBacterialMedium
Gel-OneAvianHigh

Multi-Injection Products

ProductInjectionsSource
Euflexxa3 weeklyBacterial
Supartz FX3-5 weeklyAvian
Hyalgan3-5 weeklyAvian
Orthovisc3-4 weeklyAvian

Making Your Decision

Questions to Ask Your Doctor

  1. Do I have any allergies that would rule out certain products?
  2. What product do you have the most experience with?
  3. How many appointments can I realistically attend?
  4. What does my insurance cover?
  5. Have you seen different results with different products?

Decision Framework

Choose Synvisc-One if:

  • You want one appointment
  • You have no avian allergies
  • Scheduling multiple visits is difficult
  • Your provider recommends it based on experience

Choose Euflexxa if:

  • You have egg/chicken allergies
  • You prefer smaller injection volumes
  • You can easily attend three appointments
  • You’ve had reactions to avian-derived products

The Bottom Line

Both Products Work

Synvisc-One and Euflexxa are both effective treatments for knee osteoarthritis:

  • Clinical efficacy is similar
  • Duration of relief is comparable (~6 months)
  • Both are covered by Medicare
  • Both have good safety profiles

The choice often comes down to:

  • Allergy status (avian vs. non-avian)
  • Scheduling preference (1 vs. 3 visits)
  • Insurance coverage specifics
  • Your doctor’s experience and recommendation

Don’t overthink it—the best HA product is one that fits your situation and that you’ll actually use.

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References

  1. Synvisc-One (hylan G-F 20) Prescribing Information. Sanofi.

  2. Euflexxa (sodium hyaluronate) Prescribing Information. Ferring Pharmaceuticals.

  3. Comprehensive review of viscosupplementation in osteoarthritis. Orthopedic Reviews. Full Text

  4. Comparison of high and low molecular weight hyaluronic acid. PMC. PMC8567800

  5. CMS LCD L39529 - Intraarticular Knee Injections. Medicare Coverage Database

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