Synvisc

SIDE EFFECTS

Potential Adverse Effects Of The Device On Health

Reported Device-Related Adverse Events

The most commonly reported adverse events associated with SYNVISC (hylan g-f 20) are the following:

• Pain in the injected knee
• Swelling in the injected knee
• Joint effusion

Potential Adverse Events

The following adverse events are among those that may occur in association with intra-articular injections, including SYNVISC (hylan g-f 20) :

• Arthralgia
• Joint stiffness
• Joint effusion
• Joint swelling
• Joint warmth
• Injection site pain
• Arthritis
• Arthropathy
• Gait disturbance

A summary of adverse events identified in the clinical studies is provided in the Adverse Event section below.

Post-marketing Experience

SYNVISC® (hylan g-f 20) (3-injection regimen) post-marketing experience has identified the following systemic events to occur rarely with administration: rash, hives, itching, fever, nausea, headache, dizziness, chills, muscle cramps, paresthesia, peripheral edema, malaise, respiratory difficulties, flushing and facial swelling. There have been rare reports of thrombocytopenia coincident with SYNVISC (hylan g-f 20) (3-injection regimen) injection.

Adverse Events

Adverse Events Involving the Injected Joint

Clinical Trials: A total of 511 patients (559 knees) received 1771 injections in seven clinical trials of SYNVISC (hylan g-f 20) . There were 39 reports in 37 patients (2.2% of injections, 7.2% of patients) of knee pain and/or swelling after these injections. Ten patients (10 knees) were treated with arthrocentesis and removal of joint effusion. Two additional patients (two knees) received treatment with intra-articular steroids. Two patients (two knees) received NSAIDs. One of these patients also received arthrocentesis. One patient was treated with arthroscopy. The remaining patients with adverse events localized to the knee received no treatment or only analgesics.

A total of 157 patients have received 553 injections in the three clinical trials of repeated courses of SYNVISC (hylan g-f 20) treatment. The reports in these trials describe a total of 48 reports of adverse events localized to the injected knee in 35 patients that occurred after injections that patients had received during their second course of treatment. These adverse events accounted for 6.3% of injections in 22.3% of patients as compared to 2.2% of injections in 7.2% of patients in a single course of SYNVISC (hylan g-f 20) injections. In addition, reports of two retrospective studies during the post-marketing period have described adverse events localized to the injected knee that have occurred after 4.4% and 8.5% of injections that patients had received during one or more repeated courses of SYNVISC (hylan g-f 20) treatment.

Postmarket Experience: The most common adverse events reported have been pain, swelling and/or effusion in the injected knee. In some cases the effusion was considerable and caused pronounced pain. In some instances, patients have presented with knees that were tender, warm and red. It is important to rule out infection or crystalline arthropathies in such cases. Synovial fluid aspirates of varying volumes have revealed a range of cell counts, from very few to over 50,000 cells/mm³. Reported treatments included symptomatic therapy (e.g., rest, ice, heat, elevation, simple analgesics and NSAIDs) and/or arthrocentesis. Intra-articular corticosteroids have been used when infection was excluded. Rarely, arthroscopy has been performed. The occurrence of post-injection effusion may be associated with patient history of effusion, advanced stage of disease and/or the number of injections or treatment courses a patient receives. Reactions generally abate within a few days. Clinical benefit from the treatment may still occur after such reactions. The clinical trials described above included 38 patients who received a second course of SYNVISC (hylan g-f 20) injections (132 injections). There were twelve reports in nine patients (9.1% of injections, 23.7% of patients) of knee pain and/or swelling after these injections. Reports of two additional clinical trials in which patients received repeated courses of SYNVISC (hylan g-f 20) treatment have appeared during the post-marketing period. One of these trials included 48 patients who received 210 injections during a second course of SYNVISC (hylan g-f 20) treatment; the other contained 71 patients who received 211 injections during a second course of SYNVISC (hylan g-f 20) treatment.

Intra-articular infections did not occur in any of the clinical trials and have been reported only rarely during clinical use of SYNVISC (hylan g-f 20) .

Other Adverse Events

Clinical Trials: In three concurrently controlled clinical trials with a total of 112 patients who received SYNVISC (hylan g-f 20) and 110 patients who received either saline or arthrocentesis, there were no statistically significant differences in the numbers or types of adverse events between the group of patients that received SYNVISC (hylan g-f 20) and the group that received control treatments.

Systemic adverse events each occurred in 10 (2.0%) of the SYNVISC (hylan g-f 20) treated patients. There was one case each of rash (thorax and back) and itching of the skin following SYNVISC (hylan g-f 20) injections in these studies. These symptoms did not recur when these patients received additional SYNVISC (hylan g-f 20) injections. The remaining generalized adverse events reported were calf cramps, hemorrhoid problems, ankle edema, muscle pain, tonsillitis with nausea, tachyarrythmia, phlebitis with varicosities and low back sprain.

Postmarket Experience: Other adverse events reported include: rash, hives, itching, fever, nausea, headache, dizziness, chills, muscle cramps, paresthesia, peripheral edema, malaise, respiratory difficulties, flushing and facial swelling. There have been rare reports of thrombocytopenia coincident with SYNVISC (hylan g-f 20) injection. These medical events occurred under circumstances where causal relationship to SYNVISC (hylan g-f 20) is uncertain. (Adverse events reported only in worldwide postmarketing experience, not seen in clinical trials, are considered more rare and are italicized.)

Read the entire FDA prescribing information for Synvisc (Hylan G-F 20)