Euflexxa Injections for Knee Osteoarthritis

Euflexxa is an injectable medication used to treat knee pain in people with osteoarthritis ("wear-and-tear arthritis"). Euflexxa contains a synthetic version of hyaluronan, the key ingredient of synovial fluid found naturally in the joint space. This fluid thins and become less able to lubricate and protect the knee joint as the inflammatory stress of osteoarthritis takes its toll. By injecting Euflexxa into the area, the viscosity and shock-absorbing properties of the synovial fluid can be restored, reducing joint pain and stiffness.

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The synthetic hyaluronan also appears to interfere with inflammatory substances (such as cytokines and prostaglandins) that cause swelling and pain. There is even evidence that it may increase the body's natural production of hyaluronan (also known as hyaluronic acid or sodium hyaluronate), thereby preserving the remaining joint cartilage.

Euflexxa is commonly prescribed for people who have not found relief with more conservative forms of treatment, including exercise, physical therapy, or over-the-counter analgesics like Advil (ibuprofen) or Tylenol (acetaminophen). It is the first form of hyaluronan not derived from avian (bird) protein and is instead extracted from biologically modified bacteria.


Euflexxa is administered in a series of three weekly intra-articular injections. Each dose is supplied in a pre-filled glass syringe. Prior to the injection, your healthcare provider may need to drain excess fluid from around the knee. This not only helps reduce the localized swelling, but it also prevents the dilution of hyaluronan when injected. The two-step process of drainage and joint lubrication is known as arthrocentesis plus viscosupplementation.

After drainage, the Euflexxa injection is delivered into the joint space in the mid-kneecap region. While the initial needle prick may cause discomfort, most people will tell you that the injection itself doesn't cause any stinging or burning. It is only afterward that the body may react to the hyaluronan, triggering short-term inflammation and pain.

Your healthcare provider will likely advise you to avoid sports, strenuous exercise, running, or heavy lifting for the first 48 hours following the injection. Even standing for a long period of time should be avoided.

Following the completion of the three-shot series, it generally takes around five weeks to feel the full benefits of the treatment. Benefits typically last for at least three months.


Despite the potential benefits of treatment, viscosupplementation success rates can vary dramatically.

According to a report from the Arthritis Foundation, around 30 percent of users may experience complete pain relief for up to two years, while 20 percent will experience no relief at all. To date, scientists have been unable to explain this disparity.

What most healthcare providers will agree to is that viscosupplementation is not a quick fix. It is really only considered when conservative options have failed or as a means to delay more invasive procedures, such as knee surgery or knee replacement.

It is also often used in place of traditional corticosteroid knee injections. While corticosteroids can provide fast pain relief, usually within a few days, the benefits tend to last for only a month or so. Furthermore, repeated corticosteroid shots can actually accelerate cartilage damage.

Given the high variability of hyaluronan success rates, some healthcare providers will give their patients two shots—one with hyaluronan and the other with a corticosteroid—to provide fasting-acting, long-lasting relief.

Common Side Effects

The most common side effect of Euflexxa use is musculoskeletal pain. The symptoms tend to mild and short-lasting and rarely result in treatment termination. According to the pre-market clinical research, the following side effects were experienced in more than 1 percent of users:

  • Joint pain, swelling, and/or stiffness
  • Back pain
  • Increased blood pressure
  • Runny or stuffy nose
  • Tendon inflammation
  • Nausea
  • Leg pain
  • Numbness
  • Fatigue
  • Injection site infection

The risk of allergy is considered low to negligible.

If you experience persistent or worsening pain, fever, swelling, redness, and body aches, call your healthcare provider immediately. These are signs of an infection that may require treatment.

Contraindications and Considerations

You need to avoid Euflexxa if you have a known hypersensitivity to hyaluronan, sodium hyaluronate, or hyaluronic acid. The shot should also be delayed if you have a knee infection or a skin infection in or around the injection site.

Unlike avian-derived hyaluronan, which can cause reactions in people with an egg or poultry allergy, Euflexxa is purified from specially bioengineered from bacteria and is not believed to be as immunogenic. (By contrast, avian-derived formulations such as Hyalgan, Orthovisc, Supartz, and Synvisc are made from chicken or rooster combs and should not be used if you have an egg or poultry allergy.)

While Euflexxa is not contraindicated in pregnancy, there is limited research into the effect of the drug on a developing fetus. It is also not known if Euflexxa is excreted in breast milk. Speak to your healthcare provider if you are pregnant or trying to get pregnant so that you can make an informed choice as to whether Euflexxa is right for you.

Cost and Insurance

While Euflexxa is may be less costly than other brands of viscosupplementation, it is still expensive, retailing at around $5,000 for the three-shot series. Therefore, it may be out of reach for even insured individuals who have a high copay or coinsurance costs.

Euflexxa is included in many drug formularies and will generally be approved if your healthcare provider can demonstrate that all other forms of conservative treatment have failed you.

There are no copay or patient assistance programs offered by the drug manufacturer.

A Word From Verywell

It is important to remember that Euflexxa is not a cure-all. While effective, it only provides short-term relief of knee stiffness and pain. It does not regrow lost cartilage or reverse the symptoms of osteoarthritis. While it has been suggested that Euflexxa may significantly slow the course of the disease if started early, there is yet no evidence to support these claims.

If you are unable to access Euflexxa, speak with your healthcare provider about alternative treatments such as intra-articular cortisone injections if your symptoms are especially severe.

If you are overweight, make an effort to lose weight with an appropriate diet and exercise plan whatever the stage of disease or treatment. Doing so may reduce the weight-bearing stress on your knee and help you better control your symptoms without the need for intra-articular medications.

7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Goldberg VM, Goldberg L. Intra-articular hyaluronans: the treatment of knee pain in osteoarthritisJ Pain Res. 2010;3:51–56. doi:10.2147/jpr.s4733

  3. American Academy of Orthopaedic Surgeons. Viscosupplementation Treatment for Knee Arthritis.

  4. Bannuru RR, Natov NS, Obadan IE, Price LL, Schmid CH, Mcalindon TE. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61(12):1704-11. doi:10.1002/art.24925

  5. U.S. Food and Drug Administration. Product Information Euflexxa.

  6. de Rezende MU, de Campos GC. VISCOSUPPLEMENTATIONRev Bras Ortop. 2015;47(2):160–164. doi:10.1016/S2255-4971(15)30080-X

  7. Arthritis Foundation. Benefits of Weight Loss.

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.