Synvisc

Synvisc
Tradename	Synvisc, Synvisc-One, others
Drugs.com	monograph, synvisc
MedlinePlus	a607007
Pregnancy AU	B1
Routes of administration	Intra-articular injection
CAS number	9050-30-0
ATC prefix	M09
ATC suffix	AX01
DrugBank	DB09115
ChemSpiderID	none
UNII	6KZ6H5I8E7
KEGG	D08718

Synvisc. It is a viscosupplement used in the treatment of osteoarthritis, specifically for pain in the knee that has not responded adequately to conservative non-pharmacologic therapy and simple analgesics like acetaminophen. The product is a sterile, elastic, and viscous fluid consisting of hylan polymers derived from sodium hyaluronate, which is a natural component of healthy synovial fluid and articular cartilage. Manufactured by Sanofi under its Genzyme biosurgery division, Synvisc is administered via intra-articular injection directly into the affected joint space to restore the cushioning and lubricating properties of synovial fluid.

Medical uses

Synvisc is indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics. Its use is supported by clinical guidelines from organizations like the American College of Rheumatology under specific conditions, though recommendations can vary. It is not intended for the treatment of other forms of arthritis, such as rheumatoid arthritis or gout, and is contraindicated in patients with infections in or around the target knee or known hypersensitivity to hyaluronan preparations. The therapy is often considered after options like physical therapy and nonsteroidal anti-inflammatory drugs have been exhausted but before more invasive procedures like arthroplasty.

Mechanism of action

The primary component, hylan polymer, is a cross-linked derivative of sodium hyaluronate, a glycosaminoglycan naturally found in synovial fluid and the extracellular matrix of cartilage. In osteoarthritis, the concentration and molecular weight of native hyaluronan are diminished, reducing the fluid's viscoelasticity and protective functions. Upon injection, Synvisc supplements this deficient environment, restoring the viscosity and elasticity of the synovial fluid, which improves joint lubrication and shock absorption. This mechanical action may also influence nociception by cushioning nerve endings and potentially exerting anti-inflammatory effects through interactions with cell surface receptors like CD44.

Adverse effects

The most common adverse events are local, transient reactions at the injection site, such as pain, swelling, warmth, and effusion, often described as a "post-injection flare." These events are typically mild to moderate and resolve within a few days. Serious adverse events are rare but can include severe pseudoseptic arthritis reactions, which mimic septic arthritis with significant pain and swelling but without infection. Cases of anaphylaxis or severe allergic reactions have been reported, particularly in patients with avian or egg-related allergies due to the manufacturing process. Other potential risks include bleeding in patients on anticoagulant therapy or damage from improper injection technique.

Clinical evidence

Clinical trials, such as those reviewed by the Food and Drug Administration for approval, have demonstrated that Synvisc can provide statistically significant pain relief and functional improvement compared to baseline or saline placebo, with effects potentially lasting several months. Meta-analyses published in journals like the Journal of Bone and Joint Surgery have shown mixed results regarding its superiority over placebo or other interventions, contributing to ongoing debate. Major studies, including some funded by Genzyme, support its efficacy, while other research, such as evaluations by the Cochrane Collaboration, highlight variability in patient response and the influence of a strong placebo effect common in osteoarthritis trials.

Composition and formulation

Synvisc is composed of hylan A and hylan B polymers, which are chemically cross-linked derivatives of sodium hyaluronate. The hyaluronan is sourced from rooster combs through a purification process. Hylan A is a water-insoluble gel, while Hylan B is a soluble polymer; their combination creates a viscoelastic fluid with enhanced residence time in the joint compared to non-cross-linked hyaluronan. The formulation is preserved in a sodium chloride phosphate buffer and is supplied as a sterile, non-pyrogenic solution in pre-filled glass syringes. Different product versions, such as the original three-injection regimen and the single-injection Synvisc-One, vary in total hylan content and concentration.

Administration and dosage

Synvisc is administered strictly as an intra-articular injection into the synovial cavity of the knee under aseptic conditions, often guided by anatomical landmarks or ultrasound. The classic regimen involves three separate injections given one week apart, with each injection containing 2 mL (16 mg) of hylan polymers. The Synvisc-One formulation is designed as a single 6 mL (48 mg) injection. Prior to administration, joint effusion should be aspirated, and the product must not be injected into blood vessels or periarticular tissues. Patients are typically advised to avoid strenuous activities, such as prolonged weight-bearing or high-impact sports like jogging or tennis, for 48 hours post-injection.

Category:Drugs