MAUDE Adverse Event Report: GENZYME BIOSURGERY (RIDGEFIELD) SYNVISC ONE; MOZ

GENZYME BIOSURGERY (RIDGEFIELD) SYNVISC ONE; MOZ

Lot Number 7RSL021

Device Problems Microbial Contamination of Device (2303); Loss of Data (2903); Device Contamination With Biological Material (2908); Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Contusion (1787); Hypersensitivity/Allergic reaction (1907); Muscle Spasm(s) (1966); Pain (1994); Loss of Range of Motion (2032); Urinary Tract Infection (2120); Visual Impairment (2138); Arthralgia (2355); Joint Swelling (2356); Depression (2361); Joint Disorder (2373); Neck Pain (2433); Shaking/Tremors (2515); No Code Available (3191)

Event Date 01/01/2017

Event Type Injury

Event Description

This unsolicited case from united states was received on 02-jan-2018 from patient.This case concerns a patient (demographics not provided) who received treatment with synvisc one injection and after unknown latency can't bend knee/ get in and out of car and use the bathroom, unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain and had excruciating pain.No past drug, concomitant medication and concurrent condition was provided.Patient had a hearing impairment.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number, expiration date; indication: not provided) in left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was found by the dog-sitter and an ambulance was called around 19:30.On an unknown date in 2017, after unknown latency, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Also reported that the patient had i.Vs in place.On an unknown date, after unknown latency, patient had back pain that was killing her ever since and currently patient was in rehab.Action taken: unknown corrective treatment: iv antibiotics for excruciating pain and knee was swollen as a basketball all the way down to foot; not reported for other events outcome: not recovered for can't bend knee/ get in and out of car and use the bathroom and unknown for other events a pharmaceutical technical complaint (ptc) was initiated and results were pending for the same.Seriousness criteria: hospitalization for can't bend knee/ get in and out of car, use the bathroom and unable to move or walk or even talk, excruciating pain, knee was swollen as a basketball all the way down to foot; required intervention for excruciating pain and knee was swollen as a basketball all the way down to foot additional information was received on 10-jan-2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Treatment start and stop date, dose and frequency of synvisc one was added.Corrective treatment for excruciating pain was added.Clinical course was updated and text was amended accordingly.Pharmacovigilance comment: sanofi company comment for follow up dated 10-jan-2018: this case concerns a patient who received synvisc one injection and was hospitalised for having excruciating pain, left knee swelling, unable to walk and could not bend the knee.Based upon the available information, the causal role of the product cannot be denied with the occurrence of events.Further information regarding patient's current clinical presentation, technique of injection, medical history, concomitant medications and other risk factors would help in the complete medical assessment of the case.

Event Description

Device malfunction [device malfunction].Pain was attributed to a hypersensitivity reaction to the synvisc [hypersensitivity reaction] ([knee pain], [swelling of l knee], [leg edema], [pain upon movement]) can't bend knee [joint range of motion decreased] unable to move or walk or even talk / unsteady gait [unable to walk] effusion, left knee [effusion (l) knee] uti [uti] ([dysuria], [hesitancy]) weight bearing difficulty [weight bearing difficulty] leg cramps [leg cramps] difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation [musculoskeletal disorder] back pain [back pain] limping [limping] bruising [bruising] neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting [neck pain] ([radiating pain], [shoulder pain], [tingling], [headache], [numbness], [neck stiffness], [dizzy], [weakness]) tremors [tremor] blurred vision [blurred vision] depression [depression] total nucleated cell count high / mononuclear cells high [lab test abnormal].Case narrative: based on additional information received on 30-mar-2018, this case became medically confirmed.This unsolicited case from united states was received on 02-jan-2018 from patient.This case concerns a (b)(6) female patient who received treatment with synvisc one injection and after unknown latency had weight bearing difficulty, leg cramps, musculoskeletal disorder, limping, bruising, had neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, can't bend knee, unable to move or walk or even talk, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc, effusion, left knee, uti.Also, device malfunction was identified for the reported lot number.Patient had a hearing impairment.The patient was a former smoker.Relevant medical history included osteoarthritis, osteoporosis, basal cell carcinoma, squamous cell carcinoma, gerd, mechanical valve replacement, intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder (4 glasses of wine), hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain, motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), osteoarthritis of left knee.Since an unknown date, the patient had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The patient denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections which she completed in (b)(6) 2014.It was reported that patient was given depo-medrol and lidocaine at the pes anserinus, left knee.The patient tolerated the procedure well and post injection instructions were reviewed.The patient was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics).Relevant concurrent conditions included wrist contusion, weakness of both hipensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism.Relevant concomitant medications included zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, cholecalciferol (vitamin d3), escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate (suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien), warfarin, biotin, acetazolamide.Patient's mother had diabetes type ii, patient's father had heart disease and ulcers.Patient's chronic polyarticular osteoarthritis with left knee involvement was complicated in (b)(6) 2017 by a fall on same knee, for which she received a series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the patient started to develop a great deal of pain.The same day, patient's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h).The injection was given at 7:30 and at 2:30 patient was crying (latency: unknown).Patient could not be touched.Present to ed for significant pain and swelling left knee.Patient was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Patient had effusion, left knee.The same day patient's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the patient in an ambulance to the emergency room.During that time, one of the patient's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Patient was transferred to drh for admission for pain control and pt.Then the patient was in the hospital for a full week and then in rehab for a full week.Then patient had to stay at a friend's house.Patient had to take the auto train which was total agony the back was in and still was bothering the patient.It was the worst trip patient had in her life.Patient was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain (all over knee, on the inside; gradual insidious onset; sharp, stabbing, popping, chronic) and concern for 'increase erthrytema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that patient presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.The knee pain was associated with gait instability, joint swelling, some limping.Pain occurred at night with activity and intermittently.It occurred with weight bearing.Due to pain, patient was on a bad day on an average day.The problem limited patient to difficulty getting up from a chair, difficulty sitting, standing, walking, difficulty with recreational sports, using toilet (in and out of car).There was initially concern for possible hemarthrosis given that patient was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and patient's pain was thus attributed to a hypersensitivity reaction to the synvisc.On (b)(6) 2017, patient's x-ray knee left and right showed left greater than right djd, moderate arthritis, joint space narrowing and chondrocalcinosis, subchondral sclerosis/ subchondral cyst formation.She was started on empiric steroids of prednisone 40 mg qday x5 days ((b)(6)).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, patient had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On (b)(6) 2017, the patient had left knee arthrocentesis.On (b)(6) 2017, x-ray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On (b)(6) 2017, the patient was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, gerd, lower anterior resection of rectum, urinary tract infection, major depressive disorder recurrent, insomnia.Patient endorsed groin pain on several occasions during hospitalization.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the patient's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On an unknown date in 2017, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknown latency, the patient experienced uti.Patient endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Patient was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date (b)(6) 2017.Urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On (b)(6) 2017, the patient was discharged.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Patient had back pain that was killing her ever since and currently patient was in rehab.Post injection, the leg and knee swelled up and it looked like patient had an elephants leg.When patient was getting in and out of the car going to the bathroom it was still very painful.On an unknown date, the patient had left knee pain located on the inside of the knee and all over the knee (diffuse).The knee pain had been present for 4 years.The left knee pain occurred intermittently with activity, at night, and occurred with weight bearing.The knee pain was best described as aching, stabbing, associated with popping, throbbing, sharp, acute, and chronic and was associated with joint swelling, limping, bruising, and gait instability.The knee pain was 7 out of 10 on an average day, 10 out of 10 on a bad day, and 7 out of 10 currently.She had been treated with tylenol.Since an unknown date, the patient had difficulty sitting, difficulty with recreational sports participation, difficulty walking, difficulty getting up from a chair, difficulty standing, and using toilet, getting in and out of the car.X-rays of the left knee were ordered and obtained, demonstrating normal alignment.Visual inspection of the joint reveals bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue examination showed normal soft tissue.She did have bone-on-bone arthritis.On an unknown date in 2017, patient had mild effusion (effusion left knee) offered to aspirate and inject her knee and send this fluid off for evaluation but at this point she wanted to talk to her attorney about and decide if she wanted to aspirate inject this knee.On (b)(6) 2018, the patient's left knee was evaluated.The patient came in with continued complaints of pain in her left knee and her attorney came in and this brought with her that a tablet which is 1 of never heard of.This point though the also said that her cultures never grew anything.The patient was told that it was probably not infection of the pseudo-septic reaction to the synvisc now regular with arthritis.The knee was aspirated, obtained about 15 cc of serosanguineous fluid injected some depo-medrol marcaine was since office novasure but also defensive test as well as culture and cell count but did not think this was infectious in etiology and think this was all degenerative disease.The same day, lab test showed high total nucleated cell count (mononuclear cells high) with the value of 649/mcl (reference range: less than 150; mononuclear cells: 86.9%) (reference range: less than 75.0).The same day, culture test was done which showed no growth in aerobic and anerobic culture.On an unknown date, the patient had hand pain.The pain had been present for 5 months.The right hand pain was described as associated with clicking and associated with finger numbness and finger tingling.The right hand pain was 3 out of 10 currently.The right wrist and hand special tests: positive 'liners sign, positive durkan's compression test and positive pheten's test.Patient had carpal tunnel for 8 months or more.She had nerve testing in connecticut showing carpal tunnel.She had failed splinting.On an unknown date, patient had neck pain, involving the cervical spine.The cervical spine pain worsens with neck movement and worsens with lifting.The cervical spine pain is described as radiating, acute, and radiating into both hands and associated with shoulder pain, tingling, headaches, and numbness.The cervical spine pain is 10 out of 10 currently.On an unknown date, patient had musculoskeletal disorder, joint swelling, unsteady gait, headache, tremors, leg cramps, blurred vision.Pt.Was counselled about natural history of degenerative joint disease of the knee which typically has exacerbations and remissions.On an unknown date, pt had pain in her neck (down the left arm but this was resolved also distended feel well she does feels dizzy and weak some recommend she see an internist or even go to emergency room given the names of some disability meantime her neck is very stiff when asked to get in a collar which she has at home start on medial dosepak and work with therapist use warm soaks and x-ray showed marked degenerative disease of multiple levels.Action taken: unknown.Corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc; ceftriaxone, cefuroxime for utire commending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; ; not reported for back pain outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc, unable to move or walk or even talk, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain, depression; unknown for rest a pharmaceutical technical complaint (ptc) was initiated with global ptc number: 51745 an investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hospitalization for device malfunction, uti, effusion, left knee, unable to move or walk or even talk, pain was attributed to a hypersensitivity reaction to the synvisc, can't bend knee.Additional information was received on 10-jan-2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Additional information was received on 15-jan-2018 from patient.Gender of the patient was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Additional information was received on 16-feb-2018.Ptc investigation results were added additional information was received on 30-mar-2018 from healthcare professional (case became medically conformed).Patient's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like patient had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Follow up information was received on 12-apr-2018.No new information was received.Additional information was received on 09-may-2018 from the healthcare professional.The additional events of weight bearing difficulty, leg cramps, difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation, limping, bruising, neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, total nucleated cell count high / mononuclear cells high were added with details.The medical history was added.Clinical course updated.Additional information was received on 31-may-2018.Medical history (osteoporosis) was added.X-ray results (knee) dated (b)(6) 2017 were updated.Clinical course was updated.Text was amended accordingly.

Event Description

This unsolicited case from united states was received on 02-jan-2018 from patient.This case concerns a female patient (age not provided) who received treatment with synvisc one injection and after unknown latency can't bend knee, unable to move or walk or even talk, when getting in and out of the car going to the bathroom it was [still] very painful, knee was swollen as a basketball all the way down to foot/knee swelled, back pain and had excruciating pain, leg swelled up/ looked like patient had an elephants leg.No past drug, concomitant medication and concurrent condition was provided.Patient had a hearing impairment.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number, expiration date; indication: not provided) in left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was given a contaminated shot that put her in absolute agony.The injection was given at 7:30 and at 2:30 patient was crying (latency: unknown).Patient could not be touched.They put the patient in an ambulance to the emergency room.During that time, one of the patient's hearing aids was lost which cost a good amount of money to replace it.Then the patient was in the hospital for a full week and then in rehab for a full week.Then patient had to stay at a friend's house.Patient had to take the auto train which was total agony the back was in and still was bothering the patient.It was the worst trip patient had in her life.Patient was found by the dog-sitter and an ambulance was called around 19:30.On an unknown date in 2017, after unknown latency, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Also reported, that the patient had ivs in place.On an unknown date, after unknown latency, patient had back pain that was killing her ever since and currently patient was in rehab.Post injection, the leg and knee swelled up and it looked like patient had an elephants leg (latency: unknown).When patient was getting in and out of the car going to the bathroom it was still very painful.Patient was very upset and agitated.Action taken: unknown corrective treatment: iv antibiotics for excruciating pain and knee was swollen as a basketball all the way down to foot/knee swelled; not reported for other events outcome: not recovered for can't bend knee, when getting in and out of the car going to the bathroom it's [still] very painful and back pain; unknown for other events a pharmaceutical technical complaint (ptc) was initiated and results were pending for the same.Seriousness criteria: hospitalization for can't bend knee and unable to move or walk or even talk, excruciating pain, knee was swollen as a basketball all the way down to foot, leg swelled up/ looked like i had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful; required intervention for excruciating pain and knee was swollen as a basketball all the way down to foot additional information was received on 10-jan-2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Treatment start and stop date, dose and frequency of synvisc one was added.Corrective treatment for excruciating pain was added.Clinical course was updated and text was amended accordingly.Additional information was received on 15-jan-2018 from patient.Gender of the patient was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Event verbatim of knee was swollen as a basketball all the way down to foot/knee swelled up was updated.Event outcome of back pain was updated.Clinical course was updated and text was amended accordingly.Pharmacovigilance comment: sanofi company comment for follow up dated 15-jan-2018: this case concerns a patient who received synvisc one injection and was hospitalised for having excruciating pain, left knee swelling, unable to walk and could not bend the knee.Based upon the available information, the causal role of the product cannot be denied with the occurrence of events.Further information regarding patient's current clinical presentation, technique of injection, medical history, concomitant medications and other risk factors would help in the complete medical assessment of the case.

Event Description

This unsolicited case from united states was received on 02-jan-2018 from patient.This case concerns a female patient (age not provided) who received treatment with synvisc one injection and after unknown latency can't bend knee, unable to move or walk or even talk, when getting in and out of the car going to the bathroom it was [still] very painful, knee was swollen as a basketball all the way down to foot/knee swelled, back pain and had excruciating pain, leg swelled up/ looked like patient had an elephants leg.No past drug, concomitant medication and concurrent condition was provided.Patient had a hearing impairment.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number, expiration date; indication: not provided) in left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was given a contaminated shot that put her in absolute agony.The injection was given at 7:30 and at 2:30 patient was crying (latency: unknown).Patient could not be touched.They put the patient in an ambulance to the emergency room.During that time, one of the patient's hearing aids was lost which cost a good amount of money to replace it.Then the patient was in the hospital for a full week and then in rehab for a full week.Then patient had to stay at a friend's house.Patient had to take the auto train which was total agony the back was in and still was bothering the patient.It was the worst trip patient had in her life.Patient was found by the dog-sitter and an ambulance was called around 19:30.On an unknown date in 2017, after unknown latency, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Also reported, that the patient had ivs in place.On an unknown date, after unknown latency, patient had back pain that was killing her ever since and currently patient was in rehab.Post injection, the leg and knee swelled up and it looked like patient had an elephants leg (latency: unknown).When patient was getting in and out of the car going to the bathroom it was still very painful.Patient was very upset and agitated.Action taken: unknown corrective treatment: iv antibiotics for excruciating pain and knee was swollen as a basketball all the way down to foot/knee swelled; not reported for other events outcome: not recovered for can't bend knee, when getting in and out of the car going to the bathroom it's [still] very painful and back pain; unknown for other events a pharmaceutical technical complaint (ptc) was initiated with global ptc number: (b)(4) the product lot number was not provided; therefore, a batch record review is not possible.Based on the lack of information provided, no capa is required.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 through the ncr process.Sanofi global pharmacovigilance and epidemiology continuously monitors adverse event reports with or without lot numbers, and assesses possible associations with their corresponding product lot, as part of routine safety surveillance effort to detect safety signals.This review has not indicated any safety issue.Sanofi will continue to monitor adverse events to determine if a capa is required.Seriousness criteria: hospitalization for can't bend knee and unable to move or walk or even talk, excruciating pain, knee was swollen as a basketball all the way down to foot, leg swelled up/ looked like i had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful; required intervention for excruciating pain and knee was swollen as a basketball all the way down to foot additional information was received on 10-jan-2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Treatment start and stop date, dose and frequency of synvisc one was added.Corrective treatment for excruciating pain was added.Clinical course was updated and text was amended accordingly.Additional information was received on 15-jan-2018 from patient.Gender of the patient was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Event verbatim of knee was swollen as a basketball all the way down to foot/knee swelled up was updated.Event outcome of back pain was updated.Clinical course was updated and text was amended accordingly.Additioal information was received on 16-feb-2018.Ptc investigation results were added pharmacovigilance comment: sanofi company comment for follow up dated 16-feb-2018: this case concerns a patient who received synvisc one injection and was hospitalised for having excruciating pain, left knee swelling, unable to walk and could not bend the knee.Based upon the available information, the causal role of the product cannot be denied with the occurrence of events.Further information regarding patient's current clinical presentation, technique of injection, medical history, concomitant medications and other risk factors would help in the complete medical assessment of the case.

Event Description

Device malfunction [device malfunction].Pain was attributed to a hypersensitivity reaction to the synvisc [hypersensitivity reaction] ([knee pain], [swelling of l knee], [leg edema], [pain upon movement]) can't bend knee [joint range of motion decreased].Unable to move or walk or even talk / unsteady gait [unable to walk].Effusion, left knee [effusion (l) knee].Uti [uti] ([dysuria], [hesitancy]).Weight bearing difficulty [weight bearing difficulty].Leg cramps [leg cramps].Difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation [musculoskeletal disorder].Back pain [back pain].Limping [limping].Bruising [bruising].Neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting [neck pain] ([radiating pain], [shoulder pain], [tingling], [headache], [numbness], [neck stiffness], [dizzy], [weakness]) tremors [tremor].Blurred vision [blurred vision].Depression [depression].Total nucleated cell count high / mononuclear cells high [lab test abnormal].Case narrative: based on additional information received on 30-mar-2018, this case became medically confirmed.This unsolicited case from united states was received on (b)(6) 2018 from patient.This case concerns a 84 year old female patient who received treatment with synvisc one injection and after unknown latency had weight bearing difficulty, leg cramps, musculoskeletal disorder, limping, bruising, had neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, can't bend knee, unable to move or walk or even talk, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc, effusion, left knee, uti.Also, device malfunction was identified for the reported lot number.Patient had a hearing impairment.The patient was a former smoker.Relevant medical history included osteoarthritis, osteoporosis, basal cell carcinoma, squamous cell carcinoma, gerd, mechanical valve replacement, intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder (4 glasses of wine), hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain, motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), osteoarthritis of left knee.Since an unknown date, the patient had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The patient denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections which she completed in aug-2014.It was reported that patient was given depo-medrol and lidocaine at the pes anserinus, left knee.The patient tolerated the procedure well and post injection instructions were reviewed.The patient was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics).Relevant concurrent conditions included wrist contusion, weakness of both hipensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism.Relevant concomitant medications included zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, colecalciferol (vitamin d3), escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate (suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien), warfarin, biotin, acetazolamide.Patient's mother had diabetes type ii, patient's father had heart disease and ulcers.Patient's chronic polyarticular osteoarthritis with left knee involvement was complicated in jun-2017 by a fall on same knee, for which she received a series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the patient started to develop a great deal of pain.The same day, patient's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h).The injection was given at 7:30 and at 2:30 patient was crying (latency: unknown).Patient could not be touched.Present to ed for significant pain and swelling left knee.Patient was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Patient had effusion, left knee.The same day patient's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the patient in an ambulance to the emergency room.During that time, one of the patient's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Patient was transferred to drh for admission for pain control and pt.Then the patient was in the hospital for a full week and then in rehab for a full week.Then patient had to stay at a friend's house.Patient had to take the auto train which was total agony the back was in and still was bothering the patient.It was the worst trip patient had in her life.Patient was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain (all over knee, on the inside; gradual insidious onset; sharp, stabbing, popping, chronic) and concern for 'increase erthrytema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that patient presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.The knee pain was associated with gait instability, joint swelling, some limping.Pain occurred at night with activity and intermittently.It occurred with weight bearing.Due to pain, patient was on a bad day on an average day.The problem limited patient to difficulty getting up from a chair, difficulty sitting, standing, walking, difficulty with recreational sports, using toilet (in and out of car).There was initially concern for possible hemarthrosis given that patient was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and patient's pain was thus attributed to a hypersensitivity reaction to the synvisc.On (b)(6) 2017, patient's x-ray knee left and right showed left greater than right djd, moderate arthritis, joint space narrowing and chondrocalcinosis, subchondral sclerosis/ subchondral cyst formation.She was started on empiric steroids of prednisone 40 mg qday x5 days (11/30-12/4).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, patient had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On (b)(6) 2017, the patient had left knee arthrocentesis.On (b)(6) 2017, x-ray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On (b)(6) 2017, the patient was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, gerd, lower anterior resection of rectum, urinary tract infection, major depressive disorder recurrent, insomnia.Patient endorsed groin pain on several occasions during hospitalization.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the patient's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On an unknown date in 2017, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknown latency, the patient experienced uti.Patient endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Patient was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date on (b)(6) 2017.Urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On (b)(6) 2017, the patient was discharged.As of on (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Patient had back pain that was killing her ever since and currently patient was in rehab.Post injection, the leg and knee swelled up and it looked like patient had an elephants leg.When patient was getting in and out of the car going to the bathroom it was still very painful.On an unknown date, the patient had left knee pain located on the inside of the knee and all over the knee (diffuse).The knee pain had been present for 4 years.The left knee pain occurred intermittently with activity, at night, and occurred with weight bearing.The knee pain was best described as aching, stabbing, associated with popping, throbbing, sharp, acute, and chronic and was associated with joint swelling, limping, bruising, and gait instability.The knee pain was 7 out of 10 on an average day, 10 out of 10 on a bad day, and 7 out of 10 currently.She had been treated with tylenol.Since an unknown date, the patient had difficulty sitting, difficulty with recreational sports participation, difficulty walking, difficulty getting up from a chair, difficulty standing, and using toilet, getting in and out of the car.X-rays of the left knee were ordered and obtained, demonstrating normal alignment.Visual inspection of the joint reveals bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue examination showed normal soft tissue.She did have bone-on-bone arthritis.On an unknown date in 2017, patient had mild effusion (effusion left knee) offered to aspirate and inject her knee and send this fluid off for evaluation but at this point she wanted to talk to her attorney about and decide if she wanted to aspirate inject this knee.On (b)(6) 2018, the patient's left knee was evaluated.The patient came in with continued complaints of pain in her left knee and her attorney came in and this brought with her that a tablet which is 1 of never heard of.This point though the also said that her cultures never grew anything.The patient was told that it was probably not infection of the pseudo-septic reaction to the synvisc now regular with arthritis.The knee was aspirated, obtained about 15 cc of serosanguineous fluid injected some depo-medrol marcaine was since office novasure but also defensive test as well as culture and cell count but did not think this was infectious in etiology and think this was all degenerative disease.The same day, lab test showed high total nucleated cell count (mononuclear cells high) with the value of 649/mcl (reference range: less than 150; mononuclear cells: 86.9%) (reference range: less than 75.0).The same day, culture test was done which showed no growth in aerobic and anerobic culture.On an unknown date, the patient had hand pain.The pain had been present for 5 months.The right hand pain was described as associated with clicking and associated with finger numbness and finger tingling.The right hand pain was 3 out of 10 currently.The right wrist and hand special tests: positive 'liners sign, positive durkan's compression test and positive pheten's test.Patient had carpal tunnel for 8 months or more.She had nerve testing in connecticut showing carpal tunnel.She had failed splinting.On an unknown date, patient had neck pain, involving the cervical spine.The cervical spine pain worsens with neck movement and worsens with lifting.The cervical spine pain is described as radiating, acute, and radiating into both hands and associated with shoulder pain, tingling, headaches, and numbness.The cervical spine pain is 10 out of 10 currently.On an unknown date, patient had musculoskeletal disorder, joint swelling, unsteady gait, headache, tremors, leg cramps, blurred vision.Pt.Was counselled about natural history of degenerative joint disease of the knee which typically has exacerbations and remissions.On an unknown date, pt had pain in her neck (down the left arm but this was resolved also distended feel well she does feels dizzy and weak some recommend she see an internist or even go to emergency room given the names of some disability meantime her neck is very stiff when asked to get in a collar which she has at home start on medial dosepak and work with therapist use warm soaks and x-ray showed marked degenerative disease of multiple levels.Action taken: unknown.Corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc; ceftriaxone, cefuroxime for utire commending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; not reported for back pain.Outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc, unable to move or walk or even talk, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain, depression; unknown for rest.A pharmaceutical technical complaint (ptc) was initiated with global ptc number: (b)(4).An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot: 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hospitalization for device malfunction, uti, effusion, left knee, unable to move or walk or even talk, pain was attributed to a hypersensitivity reaction to the synvisc, can't bend knee additional information was received on (b)(6) 2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Additional information was received on (b)(6) 2018 from patient.Gender of the patient was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Additional information was received on 16-feb-2018.Ptc investigation results were added additional information was received on (b)(6) 2018 from healthcare professional (case became medically conformed).Patient's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like patient had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Follow up information was received on 12-apr-2018.No new information was received.Additional information was received on (b)(6) 2018 from the healthcare professional.The additional events of weight bearing difficulty, leg cramps, difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation, limping, bruising, neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, total nucleated cell count high / mononuclear cells high were added with details.The medical history was added.Clinical course updated.Additional information was received on (b)(6) 2018.Medical history (osteoporosis) was added.X-ray results (knee) dated on (b)(6) 2017 were updated.Clinical course was updated.Text was amended accordingly.

Event Description

Based on additional information received on 30-mar- 2018, this case became medically confirmed.This unsolicited case from united states was received on 02-jan-2018 from patient.This case concerns a 84 year old female patient who received treatment with synvisc one injection and after unknown latency can't bend knee, unable to move or walk or even talk, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc, effusion, left knee, uti.Also, device malfunction was identified for the reported lot number.Patient had a hearing impairment.The patient was a firmer smoker.Relevant medical history included intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder, hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain., motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), osteoarthritis of left knee.Since an unknown date, the patient had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The patient denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections which she completed in (b)(6) 2014.It was reported that patient was given depo- medrol and lidocaine at the pes anserinus, left knee.The patient tolerated the procedure well and post injection instructions were reviewed.The patient was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics).Relevant concurrent conditions included wrist contusion, weakness of both hips, sensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism.Relevant concomitant medications included zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, cholecalciferol (vitamin d3), escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate(suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien).Patient's mother had diabetes type ii, patient's father had heart disease and ulcers.Patient's chronic polyarticular osteoarthritis with left knee involvement was complicated in (b)(6) 2017 by a fall on same knee, for which she received a series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On (b)(6) 2017, at 14:30 patient received treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Patient was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the patient started to develop a great deal of pain.The same day, patient's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h).The injection was given at 7:30 and at 2:30 patient was crying (latency: unknown).Patient could not be touched.Present to ed for significant pain and swelling left knee.Patient was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Patient had effusion, left knee.The same day patient's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the patient in an ambulance to the emergency room.During that time, one of the patient's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Patient was transferred to drh for admission for pain control and pt.Then the patient was in the hospital for a full week and then in rehab for a full week.Then patient had to stay at a friend's house.Patient had to take the auto train which was total agony the back was in and still was bothering the patient.It was the worst trip patient had in her life.Patient was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain and concern for 'increase erthrytema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that patient presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.There was initially concern for possible hemarthrosis given that patient was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and patient's pain was thus attributed to a hypersensitivity reaction to the synvisc.On (b)(6) 2017, patient's x-ray knee left and right showed left greater than right djd and chondrocalcinosis.She was started on empiric steroids of prednisone 40 mg qday x5 days (11/30-12/4).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, patient had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On (b)(6) 2017, the patient had left knee arthrocentesis.On (b)(6) 2017, xray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On 05-dec-2017, the patient was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, urinary tract infection, major depressive disorder recurrent, insomnia.Patient endorsed groin pain on several occasions during hospitalization.No external lesions noted and full mobility of the hip.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.No fracture of dislocation.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the patient's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On an unknown date in 2017, after unknown latency, patient was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Patient stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Patient was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Patient tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknown latency, the patient experienced uti.Patient endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Patient was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date (b)(6) 2017.Urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On (b)(6) 2017, the patient was discharged.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (patient was now able to bear weight).Also reported, that the patient had ivs in place.On an unknown date, after unknown latency, patient had back pain that was killing her ever since and currently patient was in rehab.Post injection, the leg and knee swelled up and it looked like patient had an elephants leg (latency: unknown).When patient was getting in and out of the car going to the bathroom it was still very painful.Patient was very upset and agitated.Action taken: unknown corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc; ceftriaxone, cefuroxime for uti recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; not reported for back pain outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc, unable to move or walk or even talk, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain a pharmaceutical technical complaint (ptc) was initiated with global ptc number: 51745 an investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hospitalization for device malfunction, uti, effusion, left knee, unable to move or walk or even talk, pain was attributed to a hypersensitivity reaction to the synvisc, can't bend knee additional information was received on 10-jan-2018 from patient.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Treatment start and stop date, dose and frequency of synvisc one was added.Corrective treatment for excruciating pain was added.Clinical course was updated and text was amended accordingly.Additional information was received on 15-jan-2018 from patient.Gender of the patient was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Event verbatim of knee was swollen as a basketball all the way down to foot/knee swelled up was updated.Event outcome of back pain was updated.Clinical course was updated and text was amended accordingly.Additional information was received on 16-feb-2018.Ptc investigation results were added additional information was received on 30-mar-2018 from healthcare professional (case became medically conformed).Patient's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like patient had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Clinical course was updated.Text was amended accordingly.Pharmacovigilance comment: sanofi company comment for follow up dated 30-mar-2018: this case concerns a patient who has received synvisc one injection from the recalled lot and later was hospitalized for having excruciating pain, left knee swelling, unable to walk and could not bend the knee.A temporal relationship can be established with the product administration.In addition, the concerned lot number has been identified to have malfunction by the company, hence, the causal relationship of the events to the product cannot be excluded.

Event Description

Device malfunction [device malfunction] pain was attributed to a hypersensitivity reaction to the synvisc/ fluid turbidity and mild leukocytosis found on joint aspiration suggest acute hypersensitivity/ pallergic reaction to synvisc [hypersensitivity reaction] ([knee pain], [swelling of l knee], [leg edema], [pain upon movement]) can't bend knee [joint range of motion decreased] unable to move or walk or even talk / unsteady gait / unsteadiness on feet [unable to walk] uti [uti] ([dysuria], [hesitancy]) effusion, left knee [effusion (l) knee] weight bearing difficulty [weight bearing difficulty] leg cramps [leg cramps] difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation [musculoskeletal disorder] back pain [back pain] limping [limping] bruising [bruising] neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting [neck pain] ([radiating pain], [shoulder pain], [tingling], [headache], [numbness], [neck stiffness], [dizzy], [weakness]) tremors [tremor] blurred vision [blurred vision] depression [depression] total nucleated cell count high / mononuclear cells high [lab test abnormal] increase erthrytema [erythema] warmth [feeling of warmth] bacteria [bacteria urine identified] clarity turbid [urine analysis] proteinua [urine protein, quantitative] blood 3+ [blood in urine] leukocytesur 3+ [urine leukocyte esterase positive] rbcua 189 [urine rbc increased] wbcua >900 [urine wbc increased] crp 7.13 [c-reactive protein increased] case narrative: based on additional info.Rec.On (b)(6) 2018, case became medically confirmed.This unsolicited legal case from united states rec.On (b)(6) 2018 from patient.This case concerns a 84 year old female pt who rec.Treatment with synvisc one injection, after unknown latency had weight bearing difficulty, leg cramps, musculoskeletal disorder, limping, bruising, had neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, can't bend knee, unable to move or walk or even talk/ unsteady gait/ unsteadiness on feet, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, effusion, left knee, uti, erythema, warmth, bacteria, blood in urine, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Also, device malfunction was identified for the reported lot number.Pt had a hearing impairment.The pt was a former smoker.Relevant medical history included osteoarthritis, osteoporosis, basal cell carcinoma, squamous cell carcinoma, gerd, mechanical valve replacement, intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (assessment: lumbar radiculitis).She experienced an acute flare-up of her right knee pain in her vacation.(history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder (4 glasses of wine), hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain, motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), acute exacerbation of osteoarthritis of left knee.Since an unknown date, the pt had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The pt denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections (lot 2h598n) which was given in superolateral approach using ultrasound guidance which she completed in aug-2014.It was reported that pt was given depo-medrol and lidocaine at the pes anserinus, left knee.The pt tolerated the procedure well and post injection instructions were reviewed.The pt was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics) (abdominal pain and nausea).Relevant concurrent conditions included wrist contusion, weakness of both hipensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism.Relevant concomitant medications included celecoxib (celebrex) for bilateral knee pain, escitalopram and zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, cholecalciferol (vitamin d3), escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate (suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien), warfarin, biotin, acetazolamide, acetaminophen (tylenol), bisacodyl (dulcolax), docusate (colace), polyethylene glycol (miralax), polyvinyl alcohol (liquitears).Pt's mother had diabetes type ii, pt's father had heart disease and ulcers.Pt's chronic polyarticular osteoarthritis with left knee involvement was complicated in jun-2017 by a fall on same knee, for which she rec.A series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On (b)(6) 2017, at 14:30 pt rec.Treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Pt was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the pt started to develop a great deal of pain.The same day, pt's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h), prothrombin time was 23.6(high), prothrombin 2 (high).The injection was given at 7:30 and at 2:30 pt was crying (latency: unknown).Pt could not be touched.Present to ed for significant pain and swelling left knee.Pt was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Pt had effusion, left knee.The same day pt's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the pt in an ambulance to the emergency room.During that time, one of the pt's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Pt was transferred to drh for admission for pain control and pt.Then the pt was in the hospital for a full week and then in rehab for a full week.Then pt had to stay at a friend's house.Pt had to take the auto train which was total agony the back was in and still was bothering the pt.It was the worst trip pt had in her life.Pt was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain (all over knee, on the inside; gradual insidious onset; sharp, stabbing, popping, chronic) and concern for 'increase erythema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that pt presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.The knee pain was associated with gait instability, joint swelling, some limping.Pain occurred at night with activity and intermittently.It occurred with weight bearing.Due to pain, pt was on a bad day on an average day.The problem limited pt to difficulty getting up from a chair, going downstairs, difficulty sitting, standing, walking, difficulty with recreational sports, using toilet (in and out of car).There was initially concern for possible hemarthrosis given that pt was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and pt's pain was thus attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc.On (b)(6) 2017, pt's x-ray knee left and right showed left greater than right djd, moderate arthritis, joint space narrowing and chondrocalcinosis, subchondral sclerosis/ subchondral cyst formation.She was started on empiric steroids of prednisone 40 mg qday x5 days (11/30-12/4).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, pt had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On (b)(6) 2017, the pt had left knee arthrocentesis.On (b)(6) 2017 lab results reported plt was 136 (low).On (b)(6) 2017, x-ray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On (b)(6) 2017, labs were plt 144(low), chloride 110, co2 was 22, glucose was 180 and calcium was 8.5.On (b)(6) 2017, some lab test showed results bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.On (b)(6) 2017 at 1506 hours, patient had a physical therapy session.She reported that she was doing well, however her left knee was still sore and swollen.Patient wanted to get out of bed and brush her teeth.Pt bed mobility and supine cga/mina+1 for lle.Patent ambulated cga using rw in room to sink patient was able to tolerate standing at sink with good standing balance while brushing her teeth, combing her hair and washing her face.Patient ambulated with equal step length and appeared to bearing full weight.On (b)(6) 2017, the pt was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, gerd, lower anterior resection of rectum, urinary tract infection, major depressive disorder recurrent, insomnia.Pt endorsed groin pain on several occasions during hospitalization.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the pt's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On (b)(6) 2017, lab results were calcium was 7.9 (low) and neutrophils percentage was 48.7 (low)on an unknown date in 2017, pt was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Pt stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Pt was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Pt tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknow latency, the pt experienced uti.Pt endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Pt was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date (b)(6) 2017.Urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On (b)(6) 2017, the pt was discharged.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (pt was now able to bear weight).Pt had back pain that was killing her ever since and currently pt was in rehab.Post injection, the leg and knee swelled up and it looked like pt had an elephants leg.When pt was getting in and out of the car going to the bathroom it was still very painful.On an unknown date, the pt had left knee pain located on the inside of the knee and all over the knee (diffuse).The knee pain had been present for 4 years.The left knee pain occurred intermittently with activity, at night, aggravated with walking, stair climbing and occurred with weight bearing.The knee pain was best described as aching, stabbing, associated with popping, throbbing, sharp, acute, and chronic and was associated with joint swelling, limping, bruising, and gait instability.The knee pain was 7 out of 10 on an average day, 10 out of 10 on a bad day, and 7 out of 10 currently.She had been treated with tylenol.Since an unknown date, the pt had difficulty sitting, difficulty with recreational sports participation, difficulty walking, difficulty getting up from a chair, difficulty standing, and using toilet, getting in and out of the car.X-rays of the left knee were ordered and obtained, demonstrating normal alignment.Visual inspection of the joint reveals bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue examination showed normal soft tissue.She did have bone-on-bone arthritis.On an unknown date in 2017, pt had mild effusion (effusion left knee) offered to aspirate and inject her knee and send this fluid off for evaluation but at this point she wanted to talk to her attorney about and decide if she wanted to aspirate inject this knee.On (b)(6)2018, the pt's left knee was evaluated.The pt came in with continued complaints of pain in her left knee and her attorney came in and this brought with her that a tablet which is 1 of never heard of.This point though the also said that her cultures never grew anything.The pt was told that it was probably not infection of the pseudo-septic reaction to the synvisc now regular with arthritis.The knee was aspirated, obtained about 15 cc of serosanguineous fluid injected some depo-medrol marcaine was since office novasure but also defensive test as well as culture and cell count but did not think this was infectious in etiology and think this was all degenerative disease.The same day, lab test showed high total nucleated cell count (mononuclear cells high) with the value of 649/mcl (reference range: less than 150; mononuclear cells: 86.9%) (reference range: less than 75.0).The same day, culture test was done which showed no growth in aerobic and anerobic culture.On an unknown date, the pt had hand pain.The pain had been present for 5 months.The right hand pain was described as associated with clicking and associated with finger numbness and finger tingling.The right hand pain was 3 out of 10 currently.The right wrist and hand special tests: positive 'liners sign, positive durkan's compression test and positive pheten's test.Pt had carpal tunnel for 8 months or more.She had nerve testing in connecticut showing carpal tunnel.She had failed splinting.On an unknown date, pt had neck pain, involving the cervical spine.The cervical spine pain worsens with neck movement and worsens with lifting.The cervical spine pain is described as radiating, acute, and radiating into both hands and associated with shoulder pain, tingling, headaches, and numbness.The cervical spine pain is 10 out of 10 currently.On an unknown date, pt had musculoskeletal disorder, joint swelling, unsteady gait, unsteadiness on feet, headache, tremors, leg cramps, blurred vision.Pt.Was counselled about natural history of degenerative joint disease of the knee which typically has exacerbations and remissions.On an unknown date, pt had pain in her neck (down the left arm but this was resolved also distended feel well she does feels dizzy and weak some recommend she see an internist or even go to emergency room given the names of some disability meantime her neck is very stiff when asked to get in a collar which she has at home start on medial dosepak and work with therapist use warm soaks and x-ray showed marked degenerative disease of multiple levels.On unknown date, pt experienced increase erthrytema and warmth.No further info.Provided.Action taken: unknown corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc; ceftriaxone, cefuroxime for utire commending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; ; not reported for back pain outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, unable to move or walk or even talk/unsteady gait/ unsteadiness on feet, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain, depression; unknown for rest a product technical complaint (ptc) was initiated on 30-mar-2018 for synvisc one.Batch number; 7rsl021, global ptc number: 51745 an investigation was initiated as a result of an unexpected increase in the number of labelled adverse events rec.From the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hsp for device malfunction, uti, effusion, left knee, unable to move or walk or even talk/unsteady gait/ unsteadiness on feet, pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, can't bend knee additional (add) information (info) rec.On (b)(6) 2018 from pt.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Add info rec.On (b)(6) 2018 from pt.Gender of the pt was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Add info rec.On (b)(6) 2018.Ptc investigation results were added add info rec.On (b)(6) 2018 from healthcare professional (case became medically conformed).Pt's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like pt had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Follow up info.Was rec.On (b)(6) 2018.No new info.Was rec.Add info rec.On (b)(6) 2018 from the healthcare professional.The additional events of weight bearing difficulty, leg cramps, difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation, limping, bruising, neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, total nucleated cell count high / mononuclear cells high were added with details.The medical history was added.Clinical course updated.Add info rec.On (b)(6) 2018.Med.History (osteoporosis) was added.X-ray results (knee) dated (b)(6) 2017 were updated.Clinical course was updated.Text was amended accordingly.Add info rec.On (b)(6) 2018 and (b)(6) 2018 (csd 07-jun-2018).Events of increase erthrytema, warmth, bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Lab results added.Clinical course was updated.Text was amended accordingly.Add info rec.On (b)(6) 2018.Med.History and concomitant medications were added.Text was amended accordingly.Add info on (b)(6) 2018.Concomitant medications were added.Event verbatim updated for unable to move or walk or even talk / unsteady gait to unable to move or walk or even talk / unsteady gait / unsteadiness on feet and pain was attributed to a hypersensitivity reaction to the synvisc/ fluid turbidity and mild leukocytosis found on joint aspiration suggest acute hypersensitivity/ allergic reaction to synvisc.Lab results were updated.Clinical course updated and text amended accordingly.Follow up info rec.On (b)(6) 2018 from lawyer.No new information.

Event Description

Device malfunction [device malfunction] pain was attributed to a hypersensitivity reaction to the synvisc/ fluid turbidity and mild leukocytosis found on joint aspiration suggest acute hypersenstivity [hypersensitivity reaction] ([knee pain], [swelling of l knee], [leg edema], [pain upon movement]) can't bend knee [joint range of motion decreased] unable to move or walk or even talk / unsteady gait [unable to walk] uti [uti] ([dysuria], [hesitancy]) effusion, left knee [effusion (l) knee] weight bearing difficulty [weight bearing difficulty] leg cramps [leg cramps] difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports particpation [musculoskeletal disorder] back pain [back pain] limping [limping] bruising [bruising] neck pain involving cervical spine / radiaitng, acute and cervical spine pain worsens with neck movement and worsens with lifting [neck pain] ([radiating pain], [shoulder pain], [tingling], [headache], [numbness], [neck stiffness], [dizzy], [weakness]) tremors [tremor] blurred vision [blurred vision] depression [depression] total nucelated cell count high / mononuclear cells high [lab test abnormal] increase erthrytema [erythema] warmth [feeling of warmth] bacteria [bacteria urine identified] clarityu turbid [urine analysis] proteinua [urine protein, quantitative] bloodu 3+ [blood in urine] leukocytesur 3+ [urine leukocyte esterase positive] rbcua 189 [urine rbc increased] wbcua >900 [urine wbc increased] crp 7.13 [c-reactive protein increased] case narrative: based on additional info.Rec.On 30-mar-2018, this case became medically confirmed.This unsolicited case from united states was rec.On 02-jan-2018 from patient.This case concerns a 84 year old female pt who rec.Treatment with synvisc one injection and after unknown latency had weight bearing difficulty, leg cramps, musculoskeletal disorder, limping, bruising, had neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, can't bend knee, unable to move or walk or even talk, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc, effusion, left knee, uti, erthrytema, warmth, bacteria, blood in urine, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Also, device malfunction was identified for the reported lot number.Pt had a hearing impairment.The pt was a former smoker.Relevant medical history included osteoarthritis, osteoporosis, basal cell carcinoma, squamous cell carcinoma, gerd, mechanical valve replacement, intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (assessment: lumbar radiculitis).She experienced an acute flare-up of her right knee pain in her vacation.(history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder (4 galsses of wine), hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain, motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), acute exacerbation of osteoarthritis of left knee.Since an unknown date, the pt had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The pt denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections (lot 2h598n) which was given in superolateral approach using ultrasound guidance which she completed in aug-2014.It was reported that pt was given depo-medrol and lidocaine at the pes anserinus, left knee.The pt tolerated the procedure well and post injection instructions were reviewed.The pt was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics).Relevant concurrent conditions included wrist contusion, weakness of both hipensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism.Relevant concomitant medications included celecoxib (celebrex) for bilateral knee pain, zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, colecalciferol (vitamin d3), escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate (suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien), warfarin, biotin, acetazolamide.Pt's mother had diabetes type ii, pt's father had heart disease and ulcers.Pt's chronic polyarticular osteoarthritis with left knee involvement was complicated in jun-2017 by a fall on same knee, for which she rec.A series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On (b)(6) 2017 at 14:30 pt rec.Treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Pt was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the pt started to develop a great deal of pain.The same day, pt's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h).The injection was given at 7:30 and at 2:30 pt was crying (latency: unknown).Pt could not be touched.Present to ed for significant pain and swelling left knee.Pt was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Pt had effusion, left knee.The same day pt's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the pt in an ambulance to the emergency room.During that time, one of the pt's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Pt was transferred to drh for admission for pain control and pt.Then the pt was in the hospital for a full week and then in rehab for a full week.Then pt had to stay at a friend's house.Pt had to take the auto train which was total agony the back was in and still was bothering the pt.It was the worst trip pt had in her life.Pt was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain (all over knee, on the inside; gradual insidious onset; sharp, stabbing, popping, chronic) and concern for 'increase erthrytema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that pt presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.The knee pain was associated with gait instability, joint swelling, some limping.Pain occurred at night with activity and intermittently.It occurred with weight bearing.Due to pain, pt was on a bad day on an average day.The problem limited pt to difficulty getting up from a chair, going downstairs, difficulty sitting, standing, walking, difficulty with recreational sports, using toilet (in and out of car).There was initially concern for possible hemarthrosis given that pt was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and pt's pain was thus attributed to a hypersensitivity reaction to the synvisc.On (b)(6) 2017 , pt's x-ray knee left and right showed left greater than right djd, moderate arthritis, joint space narrowing and chondrocalcinosis, subchondral sclerosis/ subchondral cyst formation.She was started on empiric steroids of prednisone 40 mg qday x5 days (11/30-12/4).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, pt had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On 30-nov-2017, the pt had left knee arthrocentesis.On 01-dec-2017, x-ray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On (b)(6) 2017 , the pt was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, gerd, lower anterior resection of rectum, urinary tract infection, major depressive disorder recurrent, insomnia.Pt endorsed groin pain on several occasions during hospitalization.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the pt's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On an unknown date in 2017, pt was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Pt stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Pt was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Pt tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknow latency, the pt experienced uti.Pt endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Pt was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date (b)(6) 2017.Urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On 09-dec-2017, the pt was discharged.As of 10-jan-2018, it was difficult to get in/out of car and use the bathroom (pt was now able to bear weight).Pt had back pain that was killing her ever since and currently pt was in rehab.Post injection, the leg and knee swelled up and it looked like pt had an elephants leg.When pt was getting in and out of the car going to the bathroom it was still very painful.On an unknown date, the pt had left knee pain located on the inside of the knee and all over the knee (diffuse).The knee pain had been present for 4 years.The left knee pain occurred intermittently with activity, at night, aggravated with walking, stair climbing and occurred with weight bearing.The knee pain was best described as aching, stabbing, associated with popping, throbbing, sharp, acute, and chronic and was associated with joint swelling, limping, bruising, and gait instability.The knee pain was 7 out of 10 on an average day, 10 out of 10 on a bad day, and 7 out of 10 currently.She had been treated with tylenol.Since an unknown date, the pt had difficulty sitting, difficulty with recreational sports participation, difficulty walking, difficulty getting up from a chair, difficulty standing, and using toilet, getting in and out of the car.X-rays of the left knee were ordered and obtained, demonstrating normal alignment.Visual inspection of the joint reveals bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue examination showed normal soft tissue.She did have bone-on-bone arthritis.On an unknown date in 2017, pt had mild effusion (effusion left knee) offered to aspirate and inject her knee and send this fluid off for evaluation but at this point she wanted to talk to her attorney about and decide if she wanted to aspirate inject this knee.On 29-jan-2018, the pt's left knee was evaluated.The pt came in with continued complaints of pain in her left knee and her attorney came in and this brought with her that a tablet which is 1 of never heard of.This point though the also said that her cultures never grew anything.The pt was told that it was probably not infection of the pseudo-septic reaction to the synvisc now regular with arthritis.The knee was aspirated, obtained about 15 cc of serosanguineous fluid injected some depo-medrol marcaine was since office novasure but also defensive test as well as culture and cell count but did not think this was infectious in etiology and think this was all degenerative disease.The same day, lab test showed high total nucleated cell count (mononuclear cells high) with the value of 649/mcl (reference range: less than 150; mononuclear cells: 86.9%) (reference range: less than 75.0).The same day, culture test was done which showed no growth in aerobic and anerobic culture.On an unknown date, the pt had hand pain.The pain had been present for 5 months.The right hand pain was described as associated with clicking and associated with finger numbness and finger tingling.The right hand pain was 3 out of 10 currently.The right wrist and hand special tests: positive 'liners sign, positive durkan's compression test and positive pheten's test.Pt had carpal tunnel for 8 months or more.She had nerve testing in connecticut showing carpal tunnel.She had failed splinting.On an unknown date, pt had neck pain, involving the cervical spine.The cervical spine pain worsens with neck movement and worsens with lifting.The cervical spine pain is described as radiating, acute, and radiating into both hands and associated with shoulder pain, tingling, headaches, and numbness.The cervical spine pain is 10 out of 10 currently.On an unknown date, pt had musculoskeletal disorder, joint swelling, unsteady gait, headache, tremors, leg cramps, blurred vision.Pt.Was counselled about natural history of degenerative joint disease of the knee which typically has exacerbations and remissions.On an unknown date, pt had pain in her neck (down the left arm but this was resolved also distended feel well she does feels dizzy and weak some recommend she see an internist or even go to emergency room given the names of some disability meantime her neck is very stiff when asked to get in a collar which she has at home start on medial dosepak and work with therapist use warm soaks and x-ray showed marked degenerative disease of multiple levels.On unknown date, pt experienced increase erthrytema and warmth.On (b)(6) 2017 , some lab test showed results bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.No further info.Provided.Action taken: unknown.Corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc; ceftriaxone, cefuroxime for utire commending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; ; not reported for back pain.Outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc, unable to move or walk or even talk, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain, depression; unknown for rest a product technical complaint (ptc) was initiated on (b)(6) 2018 for synvisc one.Batch number; 7rsl021, global ptc number: (b)(4).An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events rec.From the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hsp for device malfunction, uti, effusion, left knee, unable to move or walk or even talk, pain was attributed to a hypersensitivity reaction to the synvisc, can't bend knee additional info.Was rec.On 10-jan-2018 from pt.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Additional info.Was rec.On 15-jan-2018 from pt.Gender of the pt was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Additional info.Was rec.On 16-feb-2018.Ptc investigation results were added additional info.Was rec.On 30-mar-2018 from healthcare professional (case became medically conformed).Pt's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like pt had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Follow up info.Was rec.On 12-apr-2018.No new info.Was rec.Additional info.Was rec.On 09-may-2018 from the healthcare professional.The additional events of weight bearing difficulty, leg cramps, difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation, limping, bruising, neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, total nucleated cell count high / mononuclear cells high were added with details.The medical history was added.Clinical course updated.Additional info.Was rec.On 31-may-2018.Med.History (osteoporosis) was added.X-ray results (knee) dated 29-nov-2017 were updated.Clinical course was updated.Text was amended accordingly.Additional info.Was rec.On 01-jun-2018 and 07-jun-2018 (csd 07-jun-2018).Events of increase erthrytema, warmth, bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Lab results added.Clinical course was updated.Text was amended accordingly.Additional info.Was rec.On 21-may- 2018.Med.History and concomitant medications were added.Text was amended accordingly.

Event Description

Device malfunction [device malfunction] pain was attributed to a hypersensitivity reaction to the synvisc/ fluid turbidity and mild leukocytosis found on joint aspiration suggest acute hypersenstivity/ pallergic reaction to synvisc [hypersensitivity reaction] ([knee pain], [swelling of l knee], [leg edema], [pain upon movement]) can't bend knee [joint range of motion decreased] unable to move or walk or even talk / unsteady gait / unsteadiness on feet [unable to walk] uti [uti] ([dysuria], [hesitancy]) effusion, left knee [effusion (l) knee] weight bearing difficulty [weight bearing difficulty] leg cramps [leg cramps] difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports particpation [musculoskeletal disorder] back pain [back pain] limping [limping] bruising [bruising] neck pain involving cervical spine / radiaitng, acute and cervical spine pain worsens with neck movement and worsens with lifting [neck pain] ([radiating pain], [shoulder pain], [tingling], [headache], [numbness], [neck stiffness], [dizzy], [weakness]) tremors [tremor] blurred vision [blurred vision] depression [depression] total nucelated cell count high / mononuclear cells high [lab test abnormal] increase erthrytema [erythema] warmth [feeling of warmth] bacteria [bacteria urine identified] clarityu turbid [urine analysis] proteinua [urine protein, quantitative] bloodu 3+ [blood in urine] leukocytesur 3+ [urine leukocyte esterase positive] rbcua 189 [urine rbc increased] wbcua >900 [urine wbc increased] crp 7.13 [c-reactive protein increased] case narrative: based on additional info.Rec.On 30-mar-2018, case became medically confirmed.This unsolicited legal case from united states rec.On 02-jan-2018 from patient.This case concerns a 84 year old female pt who rec.Treatment with synvisc one injection, after unknown latency had weight bearing difficulty, leg cramps, musculoskeletal disorder, limping, bruising, had neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, can't bend knee, unable to move or walk or even talk/ unsteady gait/ unsteadiness on feet, back pain and had after unknown latency experienced pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, effusion, left knee, uti, erythema, warmth, bacteria, blood in urine, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Also, device malfunction was identified for the reported lot number.Pt had a hearing impairment.The pt was a former smoker.Relevant medical history included osteoarthritis, osteoporosis, basal cell carcinoma, squamous cell carcinoma, gerd, mechanical valve replacement, intermittent gradual progressive bilateral knee pain, asthma, hysterectomy, left knee pain, low back and right leg pain (assessment: lumbar radiculitis).She experienced an acute flare-up of her right knee pain in her vacation.(history of intermittent right sided low back pain radiating to the hip and thigh to the knee, muscle weakness (generalized), difficulty in walking, urinary tract infection, major depressive disorder recurrent, insomnia, alcohol use disorder (4 galsses of wine), hypovitaminosis d, constipation.Symptoms were aggravated with walking and improved with rest.She denied groin pain, motor weakness, paresthesias, bowel or bladder dysfunction or constitutional symptoms), acute exacerbation of osteoarthritis of left knee.Since an unknown date, the pt had pain on the medial aspect of her knee.Activity aggravated and improved with rest.The pt denied knee swelling.Locking or giving way.She feels this pain to be different than pain she was experiencing prior to her supartz injections (lot 2h598n) which was given in superolateral approach using ultrasound guidance which she completed in aug-2014.It was reported that pt was given depo-medrol and lidocaine at the pes anserinus, left knee.The pt tolerated the procedure well and post injection instructions were reviewed.The pt was allergic to ciprofloxacin hydrochloride (ciprofloxacin) (rash), oxycodone hydrochloride/paracetamol (acetaminophen w/oxycodone) (hallucinations), pantoprazole (off balance), sulfa (sulfonamide antibiotics) (abdominal pain and nausea).Relevant concurrent conditions included wrist contusion, weakness of both hipensory hearing loss, bilateral, pseudophakia of both eyes, primary hyperparathyroidism, onychomycosis, lumbago, inguinal hernia, generalized osteoarthrosis of hand, dry eyes, contusion of right knee, initial encounter, contusion of left knee, initial encounter, arthritis of left shoulder region, actinic keratosis, adrenal nodule, numbness and tingling in right hand, chronic atrial fibrillation, hypothyroidism, carpal tunnel syndrome (since 8 months or more).Relevant concomitant medications included celecoxib (celebrex) for bilateral knee pain, escitalopram and zolpidem tartrate (zolpidem) for depression and insomnia, digoxin for chronic atrial fibrillation, levothyroxine sodium (synthroid), levothyroxine sodium (levothroid) both for hypothyroidism, warfarin sodium (coumadin), digoxin (lanoxin), acetazolamide (diamox), aciclovir (zovirax), calcium ascorbate, colecalciferol (vitamin d3), vitamin c , vitamin b6, green power drink, digestive freedom plus, escitalopram oxalate (lexapro), magnesium sulfate/potassium sulfate/sodium sulfate (suprep bowel prep), metronidazole (flagyl), neomycin, nitrofurantoin (macrobid), zolpidem tartrate (ambien), warfarin, biotin, acetazolamide, acetaminophen (tylenol), bisacodyl (dulcolax), docusate (colace), polyethylene glycol (miralax), polyvinyl alcohol (liquitears).Pt's mother had diabetes type ii, pt's father had heart disease and ulcers.Pt's chronic polyarticular osteoarthritis with left knee involvement was complicated in jun-2017 by a fall on same knee, for which she rec.A series of synvisc injections.Failing this treatment, she scheduled an appointment to receive a synvisc-one injection from doctor while visiting a friend.On(b)(6) 2017 , at 14:30 pt rec.Treatment with intra- articular synvisc one injection (contaminated lot), at a dose of 6 ml, once (batch/lot number: 7rsl021, expiration date: not provided) in left knee for unilateral primary osteoarthritis, left knee.It was reported that the administering health care professional (hcp) withdrew fluid from her knee prior to injection, but she did not knew if they drew more fluid after the reaction.Pt was given a contaminated shot that put her in absolute agony.It was reported that at 1930, five hours after the injection, she experienced sudden onset of agonizing pain in her left knee.It was reported that the pt started to develop a great deal of pain.The same day, pt's wbc was 10.6, chloride was 111 (h), co2 was 16 (l), creatinine was 1.2 (h), inr was 2 (h), prothrombin time was 23.6(high), prothrombin 2 (high).The injection was given at 7:30 and at 2:30 pt was crying (latency: unknown).Pt could not be touched.Present to ed for significant pain and swelling left knee.Pt was evaluated by orthopedics in the ed, noted to have a knee effusion likely from inflammatory response from knee injection.Pt had effusion, left knee.The same day pt's review of the system was positive for hearing loss, palpitations, anal bleeding, gait problem and joint swelling.They put the pt in an ambulance to the emergency room.During that time, one of the pt's hearing aids was lost which cost a good amount of money to replace it.Recommendation was rice and pain control.Pt was transferred to drh for admission for pain control and pt.Then the pt was in the hospital for a full week and then in rehab for a full week.Then pt had to stay at a friend's house.Pt had to take the auto train which was total agony the back was in and still was bothering the pt.It was the worst trip pt had in her life.Pt was found by the dog-sitter and an ambulance was called around 19:30.Orthopedics consulted again left knee pain (all over knee, on the inside; gradual insidious onset; sharp, stabbing, popping, chronic) and concern for 'increase erythema and warmth".Her pain had waxed and waned and has gradually improved, although she was still unable to move her left leg.It was reported that pt presented with acute on chronic l knee pain (chronic 2/2 to osteoarthritis) following a joint injection of synvisc.The knee pain was associated with gait instability, joint swelling, some limping.Pain occurred at night with activity and intermittently.It occurred with weight bearing.Due to pain, pt was on a bad day on an average day.The problem limited pt to difficulty getting up from a chair, going downstairs, difficulty sitting, standing, walking, difficulty with recreational sports, using toilet (in and out of car).There was initially concern for possible hemarthrosis given that pt was therapeutically anticoagulated at the time of the injection.Orthopedics was consulted, recommending supportive care of elevation, immobilization, ice, and analgesia and was not concerned for infection.This was employed, with tylenol and prn hydromorphone as well as lidocaine patches used for pain control.Inflammatory markers including crp and procalcitonin were trended and were positive.Orthopedics elected to perform l knee arthrocentesis on 11/30, finding yellow turbid fluid that was not sanguinous with 9730 nucleated cells (88% neutrophils, 5% lymphocytes, no eosinophils), no uric acid or calcium pyrophosphate crystals.The findings of the tap were felt not to be suggestive of infectious etiology (or hemarthrosis) and pt's pain was thus attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc.On (b)(6) 2017 , pt's x-ray knee left and right showed left greater than right djd, moderate arthritis, joint space narrowing and chondrocalcinosis, subchondral sclerosis/ subchondral cyst formation.She was started on empiric steroids of prednisone 40 mg qday x5 days (11/30-12/4).Diclofenac gel topically was added to her pain regimen and hydromorphone was discontinued.Pt was consulted and recommended snf with pt vs home 24 hr safety with home health pt, recommended pt 3-5x/week.By time of discharge, pt had marked improvement in her ability to mobilize the l knee and her pain was well controlled on po medications.While systemic nsaids were not required for effective pain control in house, and were initially avoided given concern for potential hemarthrosis, she may be given prn oral nsaids for her knee pain.On (b)(6) 2017 , the pt had left knee arthrocentesis.On (b)(6) 2017 lab results reported plt was 136 (low).On (b)(6) 2017 , x-ray hip left showed moderate to advanced degenerative changes in the hips and x-ray lumbar spine showed advanced disc degeneration in the low lumbar spine with associated facet arthropathy, mainly due to the levoconvexity of the of the lumbar spine.On (b)(6) 2017 , labs were plt 144(low), chloride 110, co2 was 22, glucose was 180 and calcium was 8.5.On (b)(6) 2017 , some lab test showed results bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.On (b)(6) 2017 at 1506 hours, patient had a physical therapy session.She reported that she was doing well, however her left knee was still sore and swollen.Patient wanted to get out of bed and brush her teeth.Pt bed mobility and supine cga/mina+1 for lle.Patent ambulated cga using rw in room to sink patient was able to tolerate standing at sink with good standing balance while brushing her teeth, combing her hair and washing her face.Patient ambulated with equal step length and appeared to bearing full weight.On (b)(6) 2017 , the pt was admitted to the hospital with a diagnosis of muscle weakness (generalized), difficulty in walking, chronic atrial fibrillation, hypothyroidism, gerd, lower anterior resection of rectum, urinary tract infection, major depressive disorder recurrent, insomnia.Pt endorsed groin pain on several occasions during hospitalization.Plain films of the left hip and pelvis as well as lumbar spine revealed moderate to advanced degenerative changes {osteoarthritis) in both hips.There were also findings of generalized spondylosis, advanced disc degeneration in the lumbar spine with associated facet arthropathy.The groin pain was thus attributed to the pt's known l hip osteoarthritis with superimposed worsening due to fixed positioning in bed secondary to her knee complaint.On (b)(6) 2017 , lab results were calcium was 7.9 (low) and neutrophils percentage was 48.7 (low)on an unknown date in 2017, pt was unable to move or walk or even talk and knee was swollen as a basketball all the way down to her foot.Pt stayed in the hospital for 1 week and was in rehab for 1 week after hospital discharge.Pt was in excruciating pain and was still having bad knee problems, could not bend it and get in and out of a car (onset date: unknown).Pt tried to contact provider and was unable to reach him.Since an unknown date in 2017, after unknow latency, the pt experienced uti.Pt endorsed dysuria and hesitancy.Pvr was 70 ml.Ua was consistent with uti.Pt was started empirically on ceftriaxone and narrowed to cefuroxime 250 mg bid x5 days total treatment course with stop date (b)(6) 2017 urine culture grew gbs and e.Coli which was susceptible to cefuroxime.On (b)(6) 2017 , the pt was discharged.As of (b)(6) 2018, it was difficult to get in/out of car and use the bathroom (pt was now able to bear weight).Pt had back pain that was killing her ever since and currently pt was in rehab.Post injection, the leg and knee swelled up and it looked like pt had an elephants leg.When pt was getting in and out of the car going to the bathroom it was still very painful.On an unknown date, the pt had left knee pain located on the inside of the knee and all over the knee (diffuse).The knee pain had been present for 4 years.The left knee pain occurred intermittently with activity, at night, aggravated with walking, stair climbing and occurred with weight bearing.The knee pain was best described as aching, stabbing, associated with popping, throbbing, sharp, acute, and chronic and was associated with joint swelling, limping, bruising, and gait instability.The knee pain was 7 out of 10 on an average day, 10 out of 10 on a bad day, and 7 out of 10 currently.She had been treated with tylenol.Since an unknown date, the pt had difficulty sitting, difficulty with recreational sports participation, difficulty walking, difficulty getting up from a chair, difficulty standing, and using toilet, getting in and out of the car.X-rays of the left knee were ordered and obtained, demonstrating normal alignment.Visual inspection of the joint reveals bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue examination showed normal soft tissue.She did have bone-on-bone arthritis.On an unknown date in 2017, pt had mild effusion (effusion left knee) offered to aspirate and inject her knee and send this fluid off for evaluation but at this point she wanted to talk to her attorney about and decide if she wanted to aspirate inject this knee.On (b)(6) 2017 , x ray results for left knee were reported as normal alignment.Visual inspection of the joint revealed bone on bone, lateral compartment and decreased joint space, all compartments.Soft tissue exam showed normal soft tissue.On (b)(6) 2018, the pt's left knee was evaluated.The pt came in with continued complaints of pain in her left knee and her attorney came in and this brought with her that a tablet which is 1 of never heard of.This point though the also said that her cultures never grew anything.The pt was told that it was probably not infection of the pseudo-septic reaction to the synvisc now regular with arthritis.The knee was aspirated, obtained about 15 cc of serosanguineous fluid injected some depo-medrol marcaine was since office novasure but also defensive test as well as culture and cell count but did not think this was infectious in etiology and think this was all degenerative disease.The same day, lab test showed high total nucleated cell count (mononuclear cells high) with the value of 649/mcl (reference range: less than 150; mononuclear cells: 86.9%) (reference range: less than 75.0).The same day, culture test was done which showed no growth in aerobic and anerobic culture.On an unknown date, the pt had hand pain.The pain had been present for 5 months.The right hand pain was described as associated with clicking and associated with finger numbness and finger tingling.The right hand pain was 3 out of 10 currently.The right wrist and hand special tests: positive 'liners sign, positive durkan's compression test and positive pheten's test.She had failed splinting.On an unknown date, pt had neck pain, involving the cervical spine.The cervical spine pain worsens with neck movement and worsens with lifting.The cervical spine pain is described as radiating, acute, and radiating into both hands and associated with shoulder pain, tingling, headaches, and numbness.The cervical spine pain is 10 out of 10 currently.On an unknown date, pt had musculoskeletal disorder, joint swelling, unsteady gait, unsteadiness on feet, headache, tremors, leg cramps, blurred vision.Pt.Was counselled about natural history of degenerative joint disease of the knee which typically has exacerbations and remissions.On an unknown date, pt had pain in her neck (down the left arm but this was resolved also distended feel well she does feels dizzy and weak some recommend she see an internist or even go to emergency room given the names of some disability meantime her neck is very stiff when asked to get in a collar which she has at home start on medial dosepak and work with therapist use warm soaks and x-ray showed marked degenerative disease of multiple levels.On unknown date, pt experienced increase erthrytema and warmth.No further info.Provided.Action taken: unknown.Corrective treatment: empiric steroids of prednisone, left knee arthrocentesis, recommending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, pt for pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc; ceftriaxone, cefuroxime for utire commending supportive care of elevation, immobilization, ice, and analgesia, paracetamol (tylenol) and prn hydromorphone as well as lidocaine patches, diclofenac sodium (diclofenac) gel topically, depo medrol, pt for effusion, left knee, unable to move or walk or even talk, can't bend knee; ; not reported for back pain outcome: recovering/resolving for device malfunction, pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, unable to move or walk or even talk/unsteady gait/ unsteadiness on feet, effusion, left knee, uti; not recovered/not resolved for can't bend knee, back pain, depression; unknown for rest a product technical complaint (ptc) was initiated on (b)(6) 2017 for synvisc one.Batch number; 7rsl021, global ptc number: (b)(4).An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events rec.From the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation is completed, corrective and preventive actions would be implemented.Seriousness criteria: hsp for device malfunction, uti, effusion, left knee, unable to move or walk or even talk/unsteady gait/ unsteadiness on feet, pain was attributed to a hypersensitivity reaction to the synvisc/ allergic reaction to synvisc, can't bend knee additional (add) information (info) rec.On 10-jan-2018 from pt.Additional events of unable to move or walk or even talk, knee was swollen as a basketball all the way down to foot, back pain were added along with details.The event term can't bend knee/ get in and out of car was updated to can't bend knee/ get in and out of car and use the bathroom.Add info rec.On 15-jan-2018 from pt.Gender of the pt was added.Additional event of leg swelled up/ looked like i had an elephants leg and when getting in and out of the car going to the bathroom it's [still] very painful were added with details.Add info rec.On 16-feb-2018.Ptc investigation results were added add info rec.On 30-mar-2018 from healthcare professional (case became medically conformed).Pt's age was added.Lot number of suspect product was updated and indication was added.Additional event of pain was attributed to a hypersensitivity reaction to the synvisc was added and events of knee was swollen as a basketball all the way down to foot/knee swelled, leg swelled up/ looked like pt had an elephants leg, when getting in and out of the car going to the bathroom it was [still] very painful were updated as its symptoms.Event term of excruciating pain was updated to excruciating pain/ pain in the left knee, 10/10 pain and it was updated as symptom of pain was attributed to a hypersensitivity reaction to the synvisc.Additional events of effusion, left knee, uti, device malfunction were added.Medical history, past drugs, concurrent conditions and concomitant medications were added.Hospitalization dates updated.Follow up info.Was rec.On 12-apr-2018.No new info.Was rec.Add info rec.On 09-may-2018 from the healthcare professional.The additional events of weight bearing difficulty, leg cramps, difficulty sitting, difficulty getting up from a chair, difficulty standing, difficulty with recreational sports participation, limping, bruising, neck pain involving cervical spine / radiating, acute and cervical spine pain worsens with neck movement and worsens with lifting, tremors, blurred vision, depression, total nucleated cell count high / mononuclear cells high were added with details.The medical history was added.Clinical course updated.Add info rec.On 31-may-2018.Med.History (osteoporosis) was added.X-ray results (knee) dated 29-nov-2017 were updated.Clinical course was updated.Text was amended accordingly.Add info rec.On 01-jun-2018 and 07-jun-2018 (csd 07-jun-2018).Events of increase erthrytema, warmth, bacteria, clarityu turbid, proteinua, bloodu 3+, leukocytesur 3+, rbcua 189, wbcua >900 and crp 7.13.Lab results added.Clinical course was updated.Text was amended accordingly.Add info rec.On 21-may- 2018.Med.History and concomitant medications were added.Text was amended accordingly.Add info on 02-oct-2018.Concomitant medications were added.Event verbatim updated for unable to move or walk or even talk / unsteady gait to unable to move or walk or even talk / unsteady gait / unsteadiness on feet and pain was attributed to a hypersensitivity reaction to the synvisc/ fluid turbidity and mild leukocytosis found on joint aspiration suggest acute hypersenstivity/ allergic reaction to synvisc.Lab results were updated.Clinical course updated and text amended accordingly.Follow up info rec.On 02-oct-2018 from lawyer.No new information.Additional information received on 02-oct-2018 from lawyer.Concomitant medications and treatment were added.Medical history added.Clinical course updated.Text amended accordingly.

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Brand Name

SYNVISC ONE

Type of Device

MOZ

Manufacturer (Section D)

GENZYME BIOSURGERY (RIDGEFIELD)

1125 pleasantview terrace

ridgefield NJ 07657

MDR Report Key

7204643

MDR Text Key

97715243

Report Number

2246315-2018-00080

Device Sequence Number

Product Code

MOZ

Combination Product (y/n)

PMA/PMN Number

P940015

Number of Events Reported

Summary Report (Y/N)

Report Source

Manufacturer

Source Type

consumer,health professional

Remedial Action

Recall

Type of Report

Initial,Followup,Followup,Followup,Followup

Report Date

10/12/2018

1 Device was Involved in the Event

1 Patient was Involved in the Event

Is this an Adverse Event Report?

Yes

Is this a Product Problem Report?

Yes

Device Operator

Health Professional

Device Lot Number

7RSL021

Was Device Available for Evaluation?

Was the Report Sent to FDA?

Initial Date Manufacturer Received

01/02/2018

Initial Date FDA Received

01/18/2018

Supplement Dates Manufacturer Received

01/10/2018
01/15/2018
02/16/2018
03/30/2018
03/30/2018
03/30/2018
03/30/2018
03/30/2018
03/30/2018

Supplement Dates FDA Received

01/20/2018
01/30/2018
03/06/2018
04/20/2018
06/08/2018
06/14/2018
10/04/2018
10/11/2018
10/25/2018

Is This a Reprocessed and Reused Single-Use Device?

Patient Sequence Number

Patient Outcome(s)

Hospitalization; Required Intervention;

Patient Age

84 YR

Patient Weight

MAUDE Adverse Event Report: GENZYME BIOSURGERY (RIDGEFIELD) SYNVISC ONE; MOZ

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