What is sodium hyaluronate used for in knee injections. How does sodium hyaluronate work to treat osteoarthritis pain. What are the potential side effects of sodium hyaluronate injections. Who should avoid sodium hyaluronate treatment for knee pain.

What is Sodium Hyaluronate and How Does it Work?

Sodium hyaluronate is a substance similar to the natural fluid that surrounds joints in the body. When injected into the knee, it acts as a lubricant and shock absorber. This makes sodium hyaluronate injections an effective treatment option for knee pain caused by osteoarthritis, especially when other arthritis medications have not provided adequate relief.

The mechanism of action involves:

• Lubricating the joint to reduce friction
• Absorbing shock and impact on the knee
• Potentially reducing inflammation in the joint
• Improving the overall function and mobility of the knee

Is sodium hyaluronate considered a drug or a medical device? While it is injected like a medication, sodium hyaluronate actually falls under the category of a medical device. This is because its primary mode of action is mechanical – it physically lubricates and cushions the joint rather than having a pharmacological effect.

Approved Uses and Administration of Sodium Hyaluronate Injections

The FDA has approved sodium hyaluronate injections for treating knee osteoarthritis pain in patients who have not responded adequately to conservative non-drug treatments and simple pain relievers like acetaminophen. Common brand names include Durolane, Euflexxa, Gel-One, Hyalgan, Supartz, and several others.

How are sodium hyaluronate injections administered?

1. The injection is given directly into the knee joint by a healthcare provider
2. Treatment typically involves one injection per week for 3-5 weeks
3. The exact dosage and injection schedule may vary by brand
4. Patients are often advised to rest the knee and apply ice after the injection

Are repeated courses of treatment possible? Yes, many patients receive multiple courses of sodium hyaluronate injections over time as needed to manage their knee osteoarthritis symptoms. The treatment can often be repeated after 6 months if the initial course provided good relief.

Potential Side Effects and Risks of Sodium Hyaluronate Treatment

While generally considered safe, sodium hyaluronate injections can cause some side effects. The most common include:

• Pain, warmth, redness, or swelling at the injection site
• Temporary increase in knee pain or stiffness
• Difficulty walking for a short period after injection
• Nausea or stomach discomfort
• Headache or dizziness
• Muscle or joint pain in other areas

Can sodium hyaluronate cause serious side effects? In rare cases, more serious reactions may occur. Patients should seek immediate medical attention if they experience signs of an allergic reaction such as hives, difficulty breathing, or swelling of the face, lips, tongue, or throat.

Who Should Not Receive Sodium Hyaluronate Injections?

Certain patients may not be good candidates for sodium hyaluronate treatment. Contraindications include:

• Active infection in the knee or surrounding skin
• Known allergy to sodium hyaluronate or its components
• Age under 21 years (safety and efficacy not established)

Are there precautions for patients with certain medical conditions? Patients should inform their doctor if they have a history of blood clots, circulation problems in the legs, or allergies to birds, feathers, or egg products. The safety of sodium hyaluronate during pregnancy or breastfeeding has not been conclusively established.

Special Considerations for Patients with Allergies

Why might bird or egg allergies be relevant for sodium hyaluronate treatment? Some formulations of sodium hyaluronate are derived from rooster combs or contain avian proteins. Patients with known allergies to birds or egg products should discuss this with their healthcare provider before receiving treatment.

Effectiveness of Sodium Hyaluronate for Knee Osteoarthritis Pain

Clinical studies have shown that sodium hyaluronate injections can provide significant pain relief and improved knee function for many patients with osteoarthritis. However, individual results may vary.

How long does pain relief typically last after a course of treatment?

• Many patients experience pain relief for 6 months or longer
• Some may have benefits lasting up to a year
• The duration of effect can vary based on the severity of osteoarthritis and other factors

Does sodium hyaluronate work for all patients with knee osteoarthritis? While many patients benefit from this treatment, it may not be effective for everyone. Factors that can influence response include the stage of osteoarthritis, overall health, and adherence to post-injection care instructions.

Comparing Sodium Hyaluronate to Other Osteoarthritis Treatments

Sodium hyaluronate is one of several treatment options for knee osteoarthritis. How does it compare to other common approaches?

• Oral pain relievers: Sodium hyaluronate may provide longer-lasting relief with fewer systemic side effects
• Corticosteroid injections: While steroids may provide faster initial relief, sodium hyaluronate often has a longer duration of effect
• Physical therapy: Sodium hyaluronate can complement exercise-based treatments by improving joint lubrication and reducing pain
• Surgery: For some patients, sodium hyaluronate injections may delay or reduce the need for knee replacement surgery

Is sodium hyaluronate more effective than other injectable treatments for knee osteoarthritis? The relative effectiveness can vary by individual. Some studies suggest sodium hyaluronate may provide longer-lasting benefits compared to corticosteroid injections, but more research is needed for definitive comparisons.

Post-Injection Care and Activity Recommendations

Proper care after receiving sodium hyaluronate injections can help maximize benefits and minimize potential side effects. Healthcare providers typically recommend:

• Avoiding strenuous activity for at least 48 hours after injection
• Refraining from high-impact sports or prolonged weight-bearing activities
• Applying ice to the knee to reduce swelling
• Gradually resuming normal activities as tolerated

When can patients return to their usual exercise routines? Most patients can resume low-impact activities within a few days of injection. However, it’s important to follow individual guidance from your healthcare provider, as recommendations may vary based on your specific condition and treatment plan.

Long-Term Management of Knee Osteoarthritis

While sodium hyaluronate injections can provide significant relief, they are typically part of a comprehensive approach to managing knee osteoarthritis. Other important components may include:

• Weight management to reduce stress on the knees
• Regular low-impact exercise to maintain strength and flexibility
• Use of assistive devices when needed
• Dietary changes to support joint health
• Ongoing communication with healthcare providers to adjust treatment as needed

Cost and Insurance Coverage for Sodium Hyaluronate Treatment

The cost of sodium hyaluronate injections can vary widely depending on factors such as the specific product used, geographic location, and healthcare provider. Many insurance plans cover this treatment for approved indications, but coverage policies and patient out-of-pocket costs can differ.

What should patients consider regarding the cost of treatment?

• Check with your insurance provider about coverage and any pre-authorization requirements
• Discuss potential out-of-pocket costs with your healthcare provider’s office
• Ask about any available patient assistance programs or payment plans
• Consider the long-term cost-effectiveness compared to other treatment options

Are there generic versions of sodium hyaluronate available? While there are multiple brands of sodium hyaluronate injections on the market, true generic versions are limited due to the complex nature of these products. However, some newer formulations may offer more cost-effective options.

Future Directions in Osteoarthritis Treatment and Joint Fluid Therapy

Research into improved treatments for knee osteoarthritis is ongoing. Some promising areas of investigation related to sodium hyaluronate and similar therapies include:

• Development of longer-lasting formulations requiring fewer injections
• Combination therapies pairing hyaluronic acid with other active ingredients
• Use of hyaluronic acid in regenerative medicine approaches
• Exploration of sodium hyaluronate for treating osteoarthritis in other joints

How might future advancements improve outcomes for patients with knee osteoarthritis? Potential benefits could include more personalized treatment approaches, longer-lasting pain relief, improved joint function, and possibly even slowing the progression of osteoarthritis in some cases.

Emerging Technologies in Joint Fluid Therapy

Several innovative approaches are being explored to enhance the effectiveness of joint fluid therapies like sodium hyaluronate:

• Nano-engineered hyaluronic acid formulations for improved joint penetration
• Smart hydrogels that respond to mechanical stress
• Targeted drug delivery systems using hyaluronic acid as a carrier
• Combination with growth factors or stem cells for tissue regeneration

These emerging technologies hold the potential to revolutionize the treatment of osteoarthritis and other joint disorders, potentially offering more effective and longer-lasting relief for patients.

Patient Education and Informed Decision-Making

When considering sodium hyaluronate injections for knee osteoarthritis, patients should be well-informed about the treatment process, expected outcomes, and potential risks. Key points to discuss with healthcare providers include:

• Realistic expectations for pain relief and functional improvement
• The importance of following post-injection care instructions
• Potential side effects and when to seek medical attention
• How sodium hyaluronate fits into an overall osteoarthritis management plan
• Alternative treatment options and their relative benefits and risks

How can patients actively participate in their treatment decisions? By staying informed, asking questions, and openly discussing their goals and concerns with their healthcare team, patients can play an active role in choosing the most appropriate treatment approach for their individual needs.

The Role of Lifestyle Modifications

While sodium hyaluronate injections can provide significant relief, they are most effective when combined with appropriate lifestyle changes. Patients should be encouraged to:

• Maintain a healthy weight to reduce stress on the knees
• Engage in regular low-impact exercise to strengthen muscles around the joint
• Use proper body mechanics during daily activities
• Consider dietary changes that may support joint health
• Manage stress, which can influence pain perception

By adopting these lifestyle modifications in conjunction with medical treatments like sodium hyaluronate, patients can often achieve better long-term outcomes in managing their knee osteoarthritis.

Sodium hyaluronate injection Uses, Side Effects & Warnings

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Generic name: sodium hyaluronate (injection) [ SO-dee-um-HYE-al-yoo-RON-ate ]
Brand names: Durolane, Euflexxa, Gel-One, Gelsyn-3, Hyalgan,
… show all 11 brands
Supartz, Supartz FX, Visco-3, Trivisc, GenVisc 850, Triluron

Dosage form: intra-articular solution (10 mg/mL; 16.8 mg/2 mL; 20 mg/mL)
Drug class: Viscosupplementation agents

Medically reviewed by Drugs.com on Mar 17, 2023. Written by Cerner Multum.

What is sodium hyaluronate?

Sodium hyaluronate is similar to the fluid that surrounds the joints in your body. This fluid acts as a lubricant and shock absorber for the joints.

Sodium hyaluronate is used to treat knee pain caused by osteoarthritis.

Sodium hyaluronate is usually given when other arthritis medications have not been effective.

Sodium hyaluronate may also be used for purposes not listed in this medication guide.

Warnings

You should not receive a sodium hyaluronate injection if you have an infection in your knee or in the skin around your knee.

Before taking this medicine

You should not receive sodium hyaluronate if you are allergic to it, or if you have an infection in your knee or in the skin around your knee.

Sodium hyaluronate is not approved for use by anyone younger than 21 years old.

Tell your doctor if you have ever had:

• blood clots or circulation problems in your legs; or

• an allergy to birds, feathers, or egg products.

It is not known whether sodium hyaluronate will harm an unborn baby. Tell your doctor if you are pregnant.

It may not be safe to breast-feed a baby while you are using this medicine. Ask your doctor about any risks.

How is sodium hyaluronate given?

Sodium hyaluronate is injected directly into your knee joint. A healthcare provider will give you this injection.

Sodium hyaluronate is usually given once every week for 3 to 5 weeks. Follow your doctor’s dosing instructions very carefully.

To prevent pain and swelling, your doctor may recommend resting your knee or applying ice for a short time after your injection.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Tell your doctor if your symptoms do not improve, or if they get worse.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your sodium hyaluronate injection.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving sodium hyaluronate?

For at least 48 hours after your injection, avoid jogging, strenuous activity, or high-impact sports such as soccer or tennis. Also avoid weight-bearing activity or standing for longer than 1 hour at a time. Ask your doctor how long to wait before you resume these activities.

Sodium hyaluronate side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Sodium hyaluronate may cause serious side effects. Call your doctor at once if you have:

Common side effects of sodium hyaluronate may include:

• warmth, pain, redness, stiffness, bruising, or puffiness where the medicine was injected;

• nausea, stomach pain;

• trouble walking;

• swelling in your hands or feet;

• back pain, joint pain, muscle pain;

• numbness or tingly feeling;

• headache, dizziness; or

• runny or stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sodium hyaluronate dosing information

Usual Adult Dose for Osteoarthritis:

Hyalgan: 2 mL by intra-articular injection into the knee once weekly for 5 weeks
Supartz: 2.5 mL by intra-articular injection into the knee once weekly for 5 weeks

Use: For the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g., acetaminophen)

What other drugs will affect sodium hyaluronate?

Other drugs may affect sodium hyaluronate, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

More about sodium hyaluronate

• Check interactions
• Compare alternatives
• Reviews (614)
• Side effects
• Dosage information
• During pregnancy
• Drug class: viscosupplementation agents

Patient resources

• Advanced Reading
• Hyaluronate and Derivatives Injection (Knee)

Other brands

Euflexxa, Durolane, Hyalgan, Supartz, . .. +2 more

Related treatment guides

• Osteoarthritis

Further information

• Your doctor can provide more information about sodium hyaluronate.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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Copyright 1996-2023 Cerner Multum, Inc. Version: 4.02.

Sodium Hyaluronate Intra-Articular: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

This medication is used to treat knee pain in patients with joint inflammation (osteoarthritis). It is usually used in patients who have not responded to other treatments such as acetaminophen, exercise, or physical therapy. Hyaluronate (also known as hyaluronan) is similar to a substance that occurs naturally in the joints. It may work by acting as a lubricant and shock absorber in the joint, helping the knee to move smoothly, thereby lessening pain.

How to use Sodium Hyaluronate 10 Mg/Ml Intra-Articular Syringe Visco-Elastics

Read the Patient Information Leaflet provided by your health care professional before you start using hyaluronate and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Your doctor will give this medication by injection into the affected joint, usually once a week. Skin disinfectants that contain ammonium salts (such as benzalkonium chloride) should not be used to prepare the injection site. Your doctor may need to remove extra fluid from the joint before injecting the medicine. Dosage is based on your medical condition and response to treatment.

Hyaluronate should not be injected into a vein or artery because increased side effects may occur.

After receiving an injection of hyaluronate, you should avoid any activities that put stress on your knee (such as jogging, tennis, heavy lifting, standing on your feet for more than an hour) for 48 hours.

Also, after the injection, you may experience increased pain and swelling in the knee at first. If the pain or swelling continues or worsens, talk to your doctor promptly.

It is important to have this medication injected on schedule. It may take up to 3 injections before the full benefits of this medication occur.

Tell your doctor if your condition lasts or gets worse.

Side Effects

See also How to Use section.

Pain, swelling, redness/warmth/bruising at the injection site, or headache may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: back pain, severe headache, fast/pounding heartbeat, fever, tingling skin.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before using hyaluronate, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. For some brands, also tell your doctor or pharmacist if you are allergic to bird proteins, feathers, or egg products. This product may contain inactive ingredients (such as latex found in the rubber syringe cap of some brands), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: knee joint infections, skin infections/problems in the area around the injection site, circulation problems in the legs.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Does Sodium Hyaluronate 10 Mg/Ml Intra-Articular Syringe Visco-Elastics interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.

Not applicable. This medication is given in a clinic and will not be stored at home.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Benefits of using sodium hyaluronate in articular pathology of small joints in polymorbid patients | Eliseeva L.N., Zhdamarova O.I., Blednova A.Yu., Kartashova S.V., Bocharnikova M.I.

Introduction

According to the data of the Federal State Statistics Service in the Russian Federation for 2017, people over the working age make up about 25% of the total population, while the contingent younger than the working age is only 18. 3% of the total population [1]. The increase in the proportion of older people in the population is inevitably accompanied by certain difficulties associated with the organization of the health care system. One of the leading problems is the aggregation of age-associated diseases, among which degenerative-dystrophic lesions of the musculoskeletal system, primarily osteoarthritis (OA), occupy one of the leading places. It should be noted that the actual incidence of OA is 5 times higher than official statistics [2].

OA in elderly patients is associated with severe pain, limited mobility, reduced social status, late seeking medical help, as well as limited options for the use of drugs due to the presence of comorbid diseases, which leads to dissatisfaction with the results of therapy. Specialists pay special attention to the presence of comorbid chronic conditions (diabetes mellitus, cardiovascular diseases, obesity), which are often found in people with OA, since these conditions have a significant impact on the persistence and progression of not only OA of the hip and knee joints, but even OA of the small joints of the hands. It has been noted that the presence or development of diabetes mellitus and/or cardiovascular diseases reduces the likelihood of symptomatic and functional improvement in terms of assessing clinical and radiological data against the background of standard OA therapy [3]. Therefore, when deciding on the tactics of managing patients with OA (using both pharmacological and non-pharmacological methods of treatment), the relationship between OA and common comorbidities should be taken into account, i.e., a multidisciplinary approach is needed for a final conclusion [4, 5].

Despite the fact that the literature discusses the diagnosis and treatment of OA of many joints, including the shoulder, elbow and spinal joints, OA of the knee, hip and small joints of the hands is the most significant in terms of disability and deterioration in the quality of life [6]. According to epidemiological studies, the association of the development of OA with age, low level of education, and frequent simultaneous damage to several articular groups has been confirmed.

Given the pronounced prevalence of OA in the population [7], it should be noted that the main burden in the diagnosis and primary routing of these patients falls on general practitioners (district therapists). This requires the development of evidence-based unified strategies for diagnosing, differentiating and applying proven methods of therapy available for mass use, with the need for their regular updating, taking into account modern advances in solving OA problems. In this aspect, regularly updated recommendations of medical associations of rheumatologists and orthopedists from different countries are significant, containing reviews of modern international databases and taking into account the functioning of various healthcare systems, which minimizes resource costs and optimizes the choice of the most adequate approach to therapy for specific groups of patients. Such recommendations provide general practitioners with diagnostic criteria, provide clear guidance for action in situations that require additional expert advice from narrow specialists. Recommendations improve patient outcomes and reduce the number of unnecessary procedures [3, 8, 9].

To date, the pathogenesis of OA has been well studied and a large number of studies have been conducted to evaluate the effectiveness of various types of its treatment, however, it is still not possible to eliminate the already developed damage to the components of the joint, so the goal of therapy is to reduce the level of pain, slow down the rate of joint damage and maintain functional activity. joints [10, 11].

At the present stage, OA is considered as a heterogeneous group of diseases of various etiologies, which determines the phenotype of the disease, but with similar biological, morphological and clinical manifestations and outcome, which are based on damage to all components of the joint, primarily cartilage, as well as subchondral bone, synovial membranes, ligaments, capsules and periarticular tissues and muscles [8, 12, 13].

The recommendations of leading experts from different countries on the management of patients with OA of the hip, knee and small joints of the hands include non-drug approaches, drug therapy, indications for surgical correction of the joints, and have minor differences. All documents regulating the management of patients with OA are based primarily on drugs intended to relieve pain and correct lost joint functions. Pay attention to the obligatory participation of the patient in the choice of the optimal variant and duration of treatment jointly with the doctor. Significant is the correction of overweight, the use of self-control programs, the choice of adequate physical activity, the use of canes, arch supports, orthoses. From drug therapy, the use of analgesic and anti-inflammatory therapy is discussed with the appointment of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic slow-acting drugs as the leading agents, including their combination with hyaluronic acid preparations, including during surgical interventions [14, 15].

In addition to clinical recommendations, many communities of doctors use step-by-step algorithms that allow, in a limited time, to make optimal decisions regarding the diagnosis and treatment of patients of various profiles, which is of particular importance in the work of primary care physicians [9, 11, 16].

Osteoarthritis of the small joints of the hand: pathophysiological aspects, clinical manifestations and approaches to therapy

It should be noted that researchers paid little attention to OA of the small joints of the hands. An analysis of literature data indicates that the therapy for OA of the hands is practically not developed, and largely repeats the recommendations for the treatment of knee and hip joints. This dictates the need for further studies of hand OA and evaluation of the effect of various treatment regimens [17, 18]. Existing recommendations from various societies consider OA of the knee, hip and joints of the hands as different diseases, although there is not much difference in drug treatment in the recommendations. Meanwhile, in modern society, the load on the joints of the hands, especially the joints of the first finger, is significantly increasing. The functionality of the opposition of the first finger determines the uniqueness of the human hand, but the complex biomechanics of the joint, the variety of movements and significant loads often lead to degenerative processes in the joints of the first finger. They were found in 16–25% of women and 6% of men older than 45 years [19] and exceed the population frequency of OA of other joints (in some populations, lesions of the hands are noted in 22.4% of cases against 17.4% and 16.5% of cases of damage to the knee and hip joints, respectively) [20].

The first carpometacarpal (trapezio-metacarpal) joint is a joint that resembles a saddle, as a result of which it is called the saddle. The peculiar anatomy of the joint allows you to perform movements in three planes with a significant amplitude, including various types of grip and holding objects between the first and three phalangeal fingers. OA of the first carpometacarpal joint most often develops as a result of degenerative changes of idiopathic or inflammatory origin, however, the causes of its occurrence can be post-traumatic changes after fractures, increased trauma in people with connective tissue dysplasia, sports loads and the use of all types of modern information devices [19].

W.P. Cooney et al. (1977) found that the kinematic chain of the first beam increases the load on the saddle joint by 4–5 times compared to the actual impact force [20]. This also determines the involvement of tendons and ligamentous apparatus in degenerative lesions. In the medical literature, a special term is used to refer to osteoarthritis of the first carpometacarpal joint – rhizomelic arthrosis ( a. rhizomelica , from Greek rhiza – “root, beginning, base”, melos – “part of the body, limb”). The state of the saddle joint is assessed on the basis of clinical manifestations and radiological picture, according to which 4 stages of the disease are distinguished [21]. A high functional load on the joint inevitably leads to the progression of the disease, although there are observations in which rhizarthrosis may not be clinically manifested until the late stages of degenerative changes [22].

The first recommendations for the diagnosis and treatment of OA of the joints of the hands were proposed by EULAR in 2006; later versions of the recommendations take into account the wishes of orthopedic surgeons and even patients [6]. Particular attention is paid to the erosive variant of hand OA, which is associated with a more aggressive course of the disease and severe pain syndrome with impaired joint function. All recommendations primarily focus on the use of NSAIDs in patients with severe pain and signs of inflammation. However, in elderly and senile patients against the background of polymorbidity, the use of this type of therapy presents great difficulties in relation to both the group of NSAIDs (the use of which in certain situations is not possible at all) and the choice of the route of administration of the drug [23, 24].

A promising direction in the treatment of OA is the use of synovial fluid prostheses. The idea of ​​using hyaluronic acid preparations is associated with an attempt to correct violations in the quality of synovial fluid, which has a trophic effect on all joint structures, including articular cartilage, and also provides a sliding effect. In a healthy joint, hyaluronic acid is a component of synovial fluid and cartilage matrix and has a molecular weight of 5 to 20,000 kDa (on average about 3000 kDa). During the formation of degenerative changes in patients with OA, there is a violation of the quality of the synovial fluid with a decrease in the molecular weight of endogenous hyaluronic acid [25], which can be considered as one of the mechanisms for the progression of intraarticular degradation. Evidence of this may be studies that have shown a positive effect of exogenously administered hyaluronic acid in the form of an increase in the proliferation of chondrocytes and a decrease in their apoptosis, a decrease in the activity of interleukin-1β through the surface CD44 receptors and blockade of matrix metalloproteinases. In experimental studies with a positive effect of hyaluronic acid on articular cartilage with stimulation of the production of glycosaminoglycans and on the synovial membrane, hyaluronic acid preparations with an average molecular weight (800–1000 kDa) were used [26, 27]. There is evidence of the effect of endogenous hyaluronic acid on the production of prostaglandin E2, which may explain the effect of reducing neoangiogenesis, stimulating the synthesis of glycosaminoglycans, and slowing down the degradation of subchondral bone tissue [25, 28, 29].

Hyaluronic acid preparations differ in the method of preparation, molecular weight (low – 500,000–730,000 Da; medium – 800,000–2,000,000 Da; high – more than 7,000,000 Da), molecular structure (linear, cross-linked or other), method cross-linking, concentration (0.8-30 mg / ml), the volume that is used for a single injection (0.5-6.0 ml). There are two methods for obtaining hyaluronic acid: physicochemical (extraction of hyaluronate from animal tissues) and microbial (based on bacteria-producers). For many years, cockscombs have been the traditional source of hyaluronic acid for intra-articular injection due to the availability of raw materials, but the method of microbial synthesis based on bacterial strains-producers (the method of bacterial fermentation) has become more cost-effective.

Clinical studies have shown the effectiveness of hyaluronic acid preparations to reduce the severity of pain in gonarthrosis and coxarthrosis, which, compared with intra-articular use of glucocorticosteroids, had a later, but long-term effect with a lower need for the use of NSAIDs (over 6 months in total). According to a number of studies, including a Russian multicenter 12-month study, in patients with primary OA of the knee and hip joints, a single or multiple administration of hyaluronic acid significantly reduced pain, morning stiffness, and improved functional status over a long period of follow-up. There was a significant improvement from baseline in all pain and activity scores (VAS, WOMAC) [30-32].

Of particular interest is the use of a 1% hyaluronic acid preparation (Fermatron ^® ), ^{whose molecular weight (1.1–2.2 million Da) corresponds to that in normal synovial fluid. Sodium hyaluronate as part of the drug is a biopolymer consisting of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine (long-chain polysaccharide). This biopolymer, synthesized by the bacterium Streptococcus equi , is identical to sodium hyaluronate found in the human body. Fermatron ® is available in 2 ml prefilled syringes (Hyaltech Ltd. , UK) [33]. Fermatron ® is widely used in clinical practice to correct pain symptoms and improve functional activity in OA of the knee, hip, shoulder, and temporomandibular joints [34]. It has been shown that intraarticular administration of sodium hyaluronate is an effective and safe method in the complex treatment of comorbid patients with OA, can reduce the severity of pain, reduce the need for NSAIDs, and increase the time before arthroplasty [35]. Sodium hyaluronate in combination with traditional treatment of osteoarthritis can be used in all age groups, the best effect of the therapy is observed with repeated repetition of courses at intervals of 8 to 12 months. All studies noted the safety, good tolerability and high efficacy of sodium hyaluronate in OA of large joints; indicates an increase in the joint symptomatic action of hyaluronic acid and chondroitin sulfate. The use of a combination of these drugs led to a slowdown in the rate of progression of OA of the knee joints, which allows them to be classified as structure-modifying drugs. Among synovial fluid prostheses, 1% drug Fermatron 9 remains the drug of choice.0047 ®} [36–39]. This drug restores the viscoelastic and protective properties of the joint fluid, reduces inflammatory reactions, eliminates pain, increases joint mobility, restores cartilage homeostasis, stimulates the synthesis of hyaluronic acid, is indicated at any stage of osteoarthritis and after arthroscopic interventions, a clinically significant result is noted after the 4th injections. The drug is administered intra-articularly, if repeated injections are necessary, the interval between them is 7 days, there is a long-term effect and the absence of adverse reactions. The only contraindication to the use of this drug is the presence of infection in the injection area. Sodium hyaluronate was also used to correct rigid deformity of the big toe joints, which may be significant in patients with a combination of OA and chronic forms of gouty arthritis [40].

Possibilities of using synovial fluid prostheses in OA of the joints of the hand

Of particular interest is the positive Russian and international experience in the use of a hyaluronic acid prosthesis in OA of the hand joints. Many authors confirm that the hyaluronic acid preparation, with a sufficiently high efficiency, causes significantly fewer side and undesirable effects than the local use of glucocorticosteroids and NSAIDs, with undoubted advantages over the systemic use of these groups of drugs, especially in patients with comorbid conditions [41, 42] . In clinical observations, it has been demonstrated that even one course of three 1% intra-articular injections of sodium hyaluronate is effective in relieving pain and improving function in patients with rhizarthrosis. Comparison with injectable forms of corticosteroids established a faster analgesic and anti-inflammatory effect of steroid therapy, but the duration of the effect of intraarticular injection of sodium hyaluronate reached 6–12 months, which undoubtedly has a pharmacological advantage in elderly patients [43, 44]. The addition of 1% hyaluronic acid to steroid injections for the treatment of de Quervain’s disease has been shown to improve outcome and reduce relapse rates [45, 46].

De Quervain’s disease (tenosynovitis, stenosing ligamentitis, stenosing tendovaginitis) is a disease of the hand that manifests itself as a sharp pain in the wrist during exercise. The disease occurs when the channel in the wrist joint is narrowed, in which the tendons are located, which extend and abduct the thumb, which increases the friction of the tendons, causes local inflammation and severe pain. Repeated intraarticular or paraarticular administration of glucocorticosteroids is accompanied by the development of adverse reactions, the use of hyaluronic acid derivatives (alone or in combination with corticosteroids) is safer [47]. There is evidence of an additional positive effect of hyaluronic acid preparations in patients with osteonecrosis [31].

Along with the listed additional positive effects of hyaluronic acid preparations on the course of OA and its clinical manifestations, the economic and biological prospects of using intra-articular injection of exogenous hyaluronic acid should be noted. It has been established that the use of these drugs is not accompanied by additional economic burdens on the healthcare system, improves the quality of life, reduces pain symptoms and increases the functional activity of the joints in OA of various localizations [48, 49].

Conclusion

Thus, according to Russian and international guidelines for the management of patients with OA, a comprehensive approach to the treatment of OA of any localization is required, including the correction of systemic disorders in the patient and the choice of rational approaches to the treatment of articular pathology, taking into account a set of indicators. The use of 1% hyaluronic acid preparations can be carried out both in monotherapy mode and as complementary treatments for degenerative lesions of both large and small joints, which, with a sufficiently high efficiency, makes it possible to reduce the overall drug load, reduce the need for potentially dangerous (especially for patients) older age group) drugs.

Gratitude

The authors and the editors would like to thank SISTEMA PLUS JSC for providing the full texts of foreign articles required for the preparation of this publication.

Acknowledgment

The authors and Editorial Board are grateful to SYSTEMA PLUS, Jsc. for providing full-text foreign articles required to write the review.

Information about authors:

Eliseeva Lyudmila Nikolaevna — Doctor of Medical Sciences, Professor, Head of the Department of Faculty Therapy, ORCID iD 0000-0002-5275-3261;

Zhdamarova Olga Ilyinichna – Candidate of Medical Sciences, Assistant of the Department of Faculty Therapy, ORCID iD 0000-0002-5071-703Х;

Blednova Anna Yuryevna – Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department of Faculty Therapy, ORCID iD 0000-0002-1840-8130;

Kartashova Svetlana Vladimirovna – post-graduate student of the Department of Faculty Therapy, ORCID iD 0000-0002-8383-5032;

Bocharnikova Marina Ivanovna – Candidate of Medical Sciences, Associate Professor of the Department of Propaedeutics of Internal Diseases, ORCID 0000-0001-8999-6331.

Kuban State Medical University of the Ministry of Health of Russia. Russia, 350063, Krasnodar, st. Sedina, 4.

Contact information: Eliseeva Lyudmila Nikolaevna, e-mail: [email protected].

Financial transparency: the authors have no financial interest in the submitted materials or methods. There is no conflict of interest. The article was received on March 11, 2020.

About the authors:

Lyudmila N. Eliseeva – MD, PhD, Professor, Head of the Department of Faculty Therapy, ORCID 0000-0002-5275-3261;

Olga I. Zhdamarova – MD, PhD, assistant of the Department of Faculty Therapy, ORCID 0000-0002-5071-703Х;

Anna Yu. Blednova – MD, PhD, Associate Professor, associate professor of the Department of Faculty Therapy, ORCID 0000-0002-1840-8130;

Svetlana V. Kartashova – MD, postgraduate student of the Department of Faculty Therapy, ORCID 0000-0002-8383-5032;

Marina I. Bocharnikova – MD, PhD, Associate Professor of the Department of Propaedeutics of Internal Diseases, ORCID 0000-0001-8999-6331.

Kuban State Medical University. 4, Sedin str., Krasnodar, 350063, Russian Federation.

Contact information: Lyudmila N. Eliseeva, e-mail: [email protected] Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interest. Received 03/11/2020.

Flexotron Solo viscoelastic sterile implant for intra-articular injection sodium hyaluronate 2.2% 22 mg/ml syringe 2 ml No. 1

Medical device name

Sterile viscoelastic implant for intra-articular injection FLEXOTRON 901 61 ® SOLO (FLEXOTRON ^® Solo), sodium hyaluronate 2.2%, 22 mg/ml, 2 ml.

Composition

1 ml contains:

• Sodium hyaluronate 2.2% / 22 mg.
• Sodium chloride 8. 500 mg.
• Sodium hydrogen phosphate dihydrate
• Na2HPO4*2h3O
• 0.563 mg
• Sodium dihydrogen phosphate dihydrate Nah3PO4 * 2h3O 0.045 mg.
• Water for injection up to a volume of 1 ml.

Scope of delivery and packaging

• implant (liquid mixture of components, see table above) in a pre-filled syringe in a blister pack;
• 3 implant stickers;
• instructions for use.

Description, technical and functional characteristics

FLEXOTRON ^® Solo – synovial fluid prosthesis, sterile, transparent viscoelastic gel containing sodium hyaluronate, obtained by bacterial fermentation, in phosphate buffer. The implant does not contain a medicinal product for medical use, materials of animal and (or) human origin.

Technical specifications:

Sterility Sterile; sterilized by autoclaving according to EN ISO 17665-1 with a sterility assurance level (SAL) of 10-6.
Appearance of pure homogeneous solution (gel).
Odor odorless
Colourless, transparent.
Implant viscosity at zero shear rate: from 50,000 (300,000) mPa*s
Implant pH 6.8 – 7.4
Molecular weight 1.7-2 million Da
Implant recoverable volume ≥ 2 ml
Osmolality 270 – 400 mOsmol/kg
Bacterial endotoxins 0.5 IU/ml.

Mechanical impurities in the implant:

• 10 µm
• 25 µm subvisible particles
• ≤ 25,000 pcs/ml
• ≤ 5,000 pcs/ml

Recommended needle sizes (not part of this medical device) 21G, single use, sterile.

Indication

Viscoelastic prosthetics of synovial fluid in patients with degenerative-dystrophic and post-traumatic joint lesions, as well as in persons with increased stress on damaged joints.

Indications for use

• Osteoarthritis / osteoarthritis (OA) and other degenerative-dystrophic and post-traumatic lesions of the knee, hip and other synovial joints.
• Restoration of the properties of synovial fluid in orthopedic joint surgery, as well as in persons with increased stress on damaged joints. The administration of the product should be carried out under aseptic conditions of treatment and manipulation rooms by medical professionals who are proficient in the technique of intra-articular injections. The volume of one implant is close to the safe volume of medium and large adult joints. There are no restrictions on the anthropometric and anatomical features of the target patient.

Properties and principle of action glucosamine linked in turn by β-1,4- and β-1,3-glycosidic bonds. Due to this polymeric three-dimensional structure, large negatively charged aggregates are formed that retain water. These aggregates are responsible for the moisture content, firmness and elasticity of the cartilaginous tissue (its resistance to compression). Intra-articular enrichment of synovial fluid with injections of sodium hyaluronate improves or restores the viscoelastic properties of natural synovial fluid.

Sodium hyaluronate is responsible for the viscoelastic properties of the synovial fluid, thus viscoelastic prosthetics can compensate for the lack of hyaluronic acid in the synovial fluid or reduce its viscosity, soften external loads on the joint, provide lubrication, restore elasticity and viscosity, cushioning, moisturizing and enveloping the articular surfaces, covering the lubricating
protective layer of cartilage and synovial receptors. This helps to increase the range of motion and provides mechanical protection of the tissues of the joint cavity, which in turn can improve the course of osteoarthritis / osteoarthritis and other degenerative-dystrophic and post-traumatic joint pathologies. Based on clinical information about the features of biodegradation and the duration of the therapeutic effects of intra-articular injection of hyaluronic acid, it is assumed that the biodegradation of each version of the FLEXOTRON 9 viscoelastic implant0160 ^® SOLO occurs between 12 and 24 weeks. The clinical effect of treatment persists for at least 6 months.

Contraindications

The product should not be used in the treatment of patients:

• who are hypersensitive to any of the components of the product;
• septic arthritis sufferers;
• suffering from skin infections or dermatological diseases in the injection area;
• taking anticoagulants such as, for example, Phenoprocoumon or Warfarin.

Precautions

Because septic arthritis is a serious side effect, all standard precautions for surgery should be followed. The product is intended for intra-articular administration. Intravascular or interstitial administration of the product should be avoided. Due to the lack of clinical data on the use of hyaluronic acid in the treatment of children, pregnant or lactating women, the use of the product in these patient groups should be avoided. The product should be used before the expiry date indicated on the package. In the first days after the injection, oral analgesics or
anti-inflammatory drugs. The use of the product in conjunction with quaternary ammonium compounds is prohibited. Re-sterilization and use of the product is prohibited due to the risk of infection, cross-infection and/or product defect. For single use only. Do not use a syringe from an open and / or damaged sterile package. Do not use a syringe with an open or damaged sterile syringe cap. In case of violation of sterility or suspicion of a violation of the sterility of the implant, the device must be disposed of.

Prescription and dosing

Injections are carried out by medical specialists under aseptic conditions. Prior to implant insertion, the contents of the syringe should be visually inspected for transparency and homogeneity. Turbidity, crystallization, the appearance of color and / or foreign inclusions may indicate a violation of the rules for transporting and storing the product. If the above signs appear, the introduction of the implant is prohibited. Application of the product involves removing the cap from the Luer lock of a pre-filled syringe and screwing a suitable sterile pointed needle onto the attachment. For injection, you must use a 21G disposable sterile needle (not included). It is necessary to disinfect the skin with an antiseptic. The drug is injected exactly into the joint cavity according to standard methods, taking into account the anatomical features of the patient. The introduction into the joint cavity should be stopped if pain increases during the injection. Unused product is not subject to storage. It is possible to treat several joints at the same time. In the event of intra-articular edema, before the introduction of hyaluronic acid, it is necessary to remove the fluid by aspiration. Repeated treatment cycles are allowed. The 2 ml pre-filled syringe is intended for the treatment of knee, hip, shoulder and ankle joints. The following frequency of administration can be recommended for a treatment cycle: FLEXOTRON ^® SOLO: 1 injection, repeated after a few months (according to
individual condition).

Side effects

The use of intra-articular forms of hyaluronic acid in degenerative-dystrophic and post-traumatic joint lesions is a well-studied method with an established safety profile that has been used for several decades. In extremely rare cases, local temporary inflammatory symptoms may occur (pain, fever, redness and swelling, an increase in the content of exudate in the joint cavity). After an intra-articular injection, reversible local reactions may occur, such as short-term limitation of mobility (stiffness), discomfort or heaviness in the joint, hematomas. The manifestation of these symptoms can be reduced by applying ice to the injection site for 5-10 minutes.
There are reports of isolated cases of allergic reactions (eg, itching, rash, urticaria) and anaphylactic reactions, septic arthritis, interstitial bleeding or hemorrhage in the joint cavity, tendinitis, phlebitis, paresthesia, dizziness, headaches, muscle cramps, feeling hot, general malaise, peripheral edema with intra-articular injection of hyaluronic acid solutions. If you experience local or general symptoms, you should consult your doctor.

Biodegradation

Hyaluronic acid is degraded by a family of enzymes called hyaluronidases, most of which are lysosomal, to form monomeric non-toxic degradation products (primary degradation products are low molecular weight oligosaccharides and hyaluronates). There are at least seven types of hyaluronidase-like enzymes in the human body. The rate of biodegradation depends on the state and characteristics of the metabolism of a particular patient. Degradation of high molecular weight extracellular hyaluronate occurs in a series of separate steps that generate hyaluronic chains of decreasing size. There are no data on the negative impact of degradation products on the implant or on any of their systemic effects in the human body. Some degradation products can be used in endogenous resynthesis processes.

Implant removal

In case of severe manifestations, it may be recommended to remove the implant from the joint cavity, including using lavage, in accordance with current clinical guidelines. If the reaction to the implant was not associated with individual intolerance to the components of the product, it is possible to re-insert the implant 3 weeks after the inflammation subsides.

Interaction

FLEXOTRON Implants ^® SOLO has successfully passed pre-clinical tests and confirmed compatibility with biological tissues, cells and body fluids with which they come into contact in the implantable state. Disinfectants containing quaternary ammonium salts should not be used, as hyaluronic acid precipitates in the presence of these substances. Information on incompatibility with other drugs, substances and intra-articular injectable products is not currently available, however, the medical specialist should carefully read the information in the instructions for these drugs / substances / products and use with caution.

Special instructions

During the first 2 days after the procedure, it is recommended not to overload the joint, especially prolonged stress should be avoided. When receiving aspirated fluid before conducting viscosupplementary therapy, appropriate studies should be carried out to exclude the bacterial etiology of arthritis.
The product does not affect a person’s ability to drive vehicles, engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Electromagnetic fields and ionizing radiation

Viscoelastic implants are compatible for use in magnetic resonance imaging with a magnetic field induction of at least 3 Tesla. Radiation, electromagnetic and magnetic fields do not have a direct effect on the FLEXOTRON ^® SOLO implants and their properties, and do not cause any known corresponding subsequent effects in the human body. Viscoelastic implants are not amenable to visualization by radiological, ultrasound and other scanning procedures due to the closeness of their physical properties to the natural components of human tissues.

Transport and storage conditions

• 2 °C to 25 °C in original packaging,
• at 30-60% relative humidity;
• protect from light;
• do not freeze;
• avoid shock and sudden shaking.

Keep out of reach of children.

This medical device is transported by all means of transport in covered vehicles in accordance with the requirements, rules and regulations for the carriage of goods in force for each type of transport.

Expiration date

FLEXOTRON ^® SOLO expiration date limited to 3.5 years. The expiration date is indicated on the packaging and is valid under the conditions of transportation and storage. Do not use after the expiration date.

Environmental protection and recycling.

The content of the syringe is not toxic or flammable. Unused syringes can be disposed of as household waste. Glass should be disposed of with care.