BEUDAMED
    FDA Adverse Event Other Summary report: N

    SYNVISC (HYLAN G-F 20) INJECTION

    MDR report key: 2564029 · Received May 3, 2012

    Report

    Report Number
    2246315-2012-00117
    Event Type
    Other
    Date Received
    May 3, 2012
    Date of Event
    January 1, 2011
    Report Date
    April 11, 2012
    Manufacturer
    GENZYME BIOSURGER (RIDGEFIELD)
    Product Code
    MOZ
    PMA / PMN Number
    P940015
    Adverse Event
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    NY, US
    Reporter Occupation
    OTHER

    Narratives

    Additional Manufacturer Narrative · 1

    MANUFACTURER'S COMMENT: THE BENEFIT-RISK RELATIONSHIP OF THE PRODUCT IS NOT AFFECTED BY THIS REPORT. REPORT SOURCE LITERATURE DESCRIPTION: JOURNAL: OSTEOARTHRITIS AND CARTILAGE. AUTHOR: DR AGOMIR CL, SCOTT JL, PERINO G, ADLER R, FEALY S, GOLDRING MB. TITLE: ACUTE INFLAMMATION WITH INDUCTION OF ANAPHYLATOXIN C5A AND TERMINAL COMPLEMENT COMPLEX C5B-9 ASSOCIATED WITH MULTIPLE INTRA-ARTICULAR INJECTIONS OF HYLAN G-F 20: A CASE REPORT. YEAR: 2012, PAGES: 1-5. EVALUATION SUMMARY: THE PRODUCT LOT NUMBER WAS NOT PROVIDED; THEREFORE A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR SPECIFICATION CONFORMANCE PRIOR TO RELEASE. ANY OUT OF SPECIFICATION RESULT IS IDENTIFIED AND MITIGATED. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS.

    Description of Event or Problem · 1

    PSEUDO-SEPTIC ACUTE INFLAMMATORY REACTION [INFLAMMATION]. LEFT KNEE SYNOVITIS [SYNOVITIS]. LEFT KNEE JOINT SWELLING [JOINT SWELLING]. LEFT KNEE JOINT PAIN [ARTHRALGIA]. LEFT KNEE JOINT PAIN EFFUSION [JOINT EFFUSION]. CASE DESCRIPTION: LITERATURE-SPONT REPORT WAS RECEIVED ON (B)(4) 2012 FROM AN AUTHOR REGARDING A (B)(6) FEMALE PT, INITIALS UNK, WITH BILATERAL OSTEOARTHRITIS. THIS REPORT IS FROM A LITERATURE ARTICLE ENTITLED "ACUTE INFLAMMATION WITH INDUCTION OF ANAPHYLATOXIN C5A AND TERMINAL COMPLEMENT COMPLEX C5B-9 ASSOCIATED WITH MULTIPLE INTRA-ARTICULAR INJECTIONS OF HYLAN G-F 20: A CASE REPORT". THE PT'S MEDICAL HISTORY WAS SIGNIFICANT FOR LEFT KNEE MENISCECTOMY. THE RADIOGRAPH DIAGNOSED A SEVERE GRADE 4 OSTEOARTHRITIS IN THE LEFT KNEE WITHOUT EVIDENCE OF CHONDROCALCINOSIS IN EITHER KNEE. ON AN UNSPECIFIED DATE IN 2011, THE PT INITIATED TREATMENT WITH SYNVISC (HYLAN G-F 20) INJECTION, 2 ML, WEEKLY, IN BOTH KNEES. ON AN UNSPECIFIED DATE IN 2011, THE PT RECEIVED THIRD INJECTION OF SYNVISC. APPROX 12 H AFTER THE THIRD INJECTION IN BOTH KNEES THE PT PRESENTED WITH LOCAL MASSIVE SWELLING ACCOMPANIED BY SEVERE PAIN LIMITED TO THE LEFT KNEE JOINT. DECOMPRESSION BY ULTRASOUND-GUIDED ASPIRATION OF THE LEFT KNEE JOINT WAS PERFORMED IN THE NEXT 12 H YIELDING 65 ML OF YELLOWISH SYNOVIAL FLUID FILLED WITH INFLAMMATORY CELLS (WBC 33,950/MM3, RBC 1500/MM3, NEUTROPHILS 60%, EOSINOPHILS 18%, MONOCYTES 19% AND LYMPHOCYTES 3%). THE SWELLING AND PAIN RETURNED RAPIDLY TO THE PREVIOUS STATE AND AN EMERGENCY ARTHROSCOPIC IRRIGATION AND DEBRIDEMENT WERE PERFORMED THE FOLLOWING DAY. SYNOVIAL FLUID AND TISSUE WERE COLLECTED FOR FURTHER PROCESSING. THE BLOOD REPORTS INDICATED ACUTE PHASE REACTANTS WITH SLIGHTLY ELEVATED ESR AT 33 MM/H (WESTERGREN METHOD, NORMAL VALUES =0 TO 27 MM/H) AND HIGH C-REACTIVE PROTEIN (CRP) AT 6.4 MG/DL (NORMAL VALUES RANGE FROM 0 TO 1 MG/DL). MICROSCOPIC EXAMINATION OF FRESHLY PREPARED SYNOVIAL FLUID FOR CRYSTAL DEPOSITS, GRAM'S STAIN, AND CULTURES OF THE SYNOVIAL FLUID WERE ALL NEGATIVE. THE TREATMENT INCLUDED ORAL CIPROFLOXACIN FOR SEVEN DAYS AND -STEROIDAL ANTI-INFLAMMATORY DRUGS, ANALGESICS AND REST. THE PREDOMINANT PRESENCE OF MACROPHAGES (34%) AND T LYMPHOCYTES (29%) WITH ONLY 2% B LYMPHOCYTES AND 1.5% MAST CELLS IN THE INFLAMMATORY INFILTRATE WAS REPORTED. ENZYME-LINKED IMMUNOSORBENT ASSAYS (ELISAS) FOR MARKERS OF COMPLEMENT ACTIVATION AND CYTOKINES WERE PERFORMED. THE CONCENTRATIONS OF INTERLEUKIN-1 BETA (IL-1B): 210 PG/ML; C5A: 9 NG/ML AND C5B-9: 5500 NG/ML WERE DETERMINED USING COMMERCIALLY AVAILABLE ELISAS. THREE MARKER GENES WITH MAJOR ROLES IN LOCAL JOINT INFLAMMATION, IL-1B, IL-6 AND A NEUTROPHIL MARKER MYELOPEROXIDASE (MPO), WERE ALSO ANALYZED BY QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION (RT-PCR) IN SYNOVIAL TISSUES OF THE PT. IT WAS REPORTED THAT THE PT EXPERIENCED ACUTE FLARE REACTION IN THE LEFT KNEE, POSSIBLY AN IMMUNE MECHANISM WITH FEATURES OF A REACTIVE-LIKE ARTHRITIS WITH COMPLEMENT ACTIVATION AND PRODUCTION OF INFLAMMATORY CYTOKINES AND DIAGNOSED WITH PSEUDO-SEPTIC ACUTE INFLAMMATORY REACTION AND LEFT KNEE SYNOVITIS. THE EVENTS OF LEFT KNEE SYNOVITIS, PSEUDO-SEPTIC ACUTE INFLAMMATORY REACTION, LEFT KNEE JOINT SWELLING, LEFT KNEE JOINT PAIN AND LEFT KNEE JOINT EFFUSION WAS RECOVERED. CONCOMITANT MEDICATIONS WERE NOT PROVIDED. THE INTENSITY FOR ALL THE EVENTS WAS NOT PROVIDED. THE ACTION TAKEN WITH SYNVISC TREATMENT WAS NOT PROVIDED. REPORTING AUTHOR ASSESSED THE RELATIONSHIP BETWEEN SYNVISC AND ALL THE EVENTS AS POSSIBLE. THE QA (QUALITY ASSURANCE) INVESTIGATION SUMMARY WAS RECEIVED ON (B)(4) 2012. THE PRODUCT LOT NUMBER WAS NOT PROVIDED; THEREFORE A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR SPECIFICATION CONFORMANCE PRIOR TO RELEASE. ANY OUT OF SPECIFICATION RESULT IS IDENTIFIED AND MITIGATED. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    1 SYNVISC (HYLAN G-F 20) INJECTION INTRA-ARTICULAR HYALURONIC ACID MOZ GENZYME BIOSURGER (RIDGEFIELD) UNK UNKNOWN

    Patients

    Seq Age Sex Outcome Treatment
    1 55 YR Required Intervention