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

Lot Number 7RSL021

Device Problems Microbial Contamination of Device (2303); Device Contamination With Biological Material (2908)

Patient Problems Arthritis (1723); Nausea (1970); Pain (1994); Myalgia (2238); Arthralgia (2355); No Code Available (3191)

Event Date 11/21/2017

Event Type  Injury  

Event Description

This unsolicited case from united states was received on 21-dec-2017 from a patient this case concerns a (b)(6) female patient who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation and knee had locked/ left knee was locked; after unknown latency could not bend the knee, not able to bear weight on it and blood sugar raised to over 400.Also, device malfunction was identified for the reported lot number.No concomitant medications was provided.Patient had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The patient stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The patient estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The patient has type 2 diabetes and hypertension.The patient has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The patient has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The patient stated she had no allergy to chicken, eggs, feathers, or bird protein.Patient was allergic to penicillin.Patient had hip replacement surgery.The patient had no other injections into her knee at the time of the synvisc-one injection.On (b)(6) 2017, the patient initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain.On the same day, five hours after the synvisc one injection, patient could do nothing but cry, patient could not even move.On the same day, few hours after injection, patient had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the patient mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.Patient called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Patient could not get any relief.Patient had to contact personal physician who could only suggest icing and elevating until patient could get back to the ortho doctor.It was reported that patient knee had swollen to a size as large as a baby's head, patient could not move and had to resolve to walk on crutches for 8 days.Patient had pain, swelling, fever and discomfort suffered, disabled patient and had patient in tears for over 5 days.On an unknown date 2017, latency unknown, patient was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the patient estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, patient returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to patient existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On (b)(6) 2017, the patient received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, patient could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The patient stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the patient was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the patient had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why patient got the synvisc-one injection on (b)(6) 2017.Patient was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.The patient estimated that her left knee pain today ((b)(6) 2017), as she went into her orthopedic doctor's office, was about a 5, when patient tried to put weight on it.The doctor's office did give patient a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The patient stated that the doctor's office said that as of today, at this time, the left knee does not look infected.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The patient stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the patient said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the patient cannot apply the topical gel whenever she has left knee pain.The patient mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.Action taken: unknown for cortisone corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; not reported for rest events.Outcome: recovering for all events.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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation pharmacovigilance comment: sanofi company comment dated 21-dec-2017: this case concerns a patient who has received synvisc one injection from the recalled lot and later experienced joint inflammation with inability to walk.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

This unsolicited case from united states was received on (b)(6) 2017 from a patient this case concerns a 70 year old female patient who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation and knee had locked/ left knee was locked, nausea (latency: 0 day); after unknown latency could not bend the knee/ inability to move leg/knee (left), not able to bear weight on it and blood sugar raised to over 400.Also, device malfunction was identified for the reported lot number.Patient had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The patient stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The patient estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The patient has type 2 diabetes and hypertension.The patient has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The patient has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The patient stated she had no allergy to chicken, eggs, feathers, or bird protein.Patient was allergic to penicillin (rash) and oxycodone hydrochloride/paracetamol (percocet) (severe stomach pain).Patient had hip replacement surgery.The patient had no other injections into her knee at the time of the synvisc-one injection.Concomitant medications included clopidogrel bisulfate (plavix) for stroke and aneurysm, levothyroxine sodium (levothyroxine), ezetimibe/simvastatin (vytorin), sitagliptin phosphate (januvia) and metformin hydrochloride (metformin) for blood sugar control.On 21-nov-2017, the patient initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain and for arthritis relief.On the same day, five hours after the synvisc one injection, patient could do nothing but cry, patient could not even move.On the same day, few hours after injection, patient had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the patient mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.The same day, the patient had excruciating pain and discomfort, had inability to move left leg and knee, extreme swelling, redness, nausea, heat in left leg, cramping, pain which lasted for over 6 days, patient was miserable.Patient called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Patient could not get any relief.Patient had to contact personal physician who could only suggest icing and elevating until patient could get back to the ortho doctor.It was reported that patient knee had swollen to a size as large as a baby's head, patient could not move and had to resolve to walk on crutches for 8 days.Patient had pain, swelling, fever and discomfort suffered, disabled patient and had patient in tears for over 5 days.On an unknown date 2017, latency unknown, patient was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the patient estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, patient returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to patient existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On 27-nov-2017, the patient received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, patient could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The patient stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the patient was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the patient had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why patient got the synvisc-one injection on 21-nov-2017.Patient was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.The patient estimated that her left knee pain today (22-dec-2017), as she went into her orthopedic doctor's office, was about a 5, when patient tried to put weight on it.The doctor's office did give patient a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The patient stated that the doctor's office said that as of today, at this time, the left knee does not look infected.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The patient stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the patient said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the patient cannot apply the topical gel whenever she has left knee pain.The patient mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.On 28-dec-2017, the patient underwent blood work, echogram and ekg.As of 27- feb-2018, the patient was still had swelling and periodic pain with stiffness.Action taken: unknown for cortisone corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; crosne gel, cortisone injection for could not bend the knee/inability to move leg/knee (left); insulin lispro (humalog) for blood sugar raised to over 400; not reported for rest events outcome: unknown for device malfunction and nausea; not recovered/ not resolved for could not bend the knee/inability to move leg/knee (left); recovering for all events a pharmaceutical technical complaint was initiated with global ptc number: 51579 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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation; could not bend the knee/inability to move leg/knee (left) follow up was received on 15-jan-2018.Global ptc number was added.Additional information was received on 27-feb-2018 from a patient.Outcome for the event of device malfunction was updated as unknown.Event term could not bend the knee/inability to move leg was updated to could not bend the knee/inability to move leg/knee (left), the event was updated as serious and its corrective treatment was added.Corrective treatment for the event of blood sugar raised to over 400 was added.Redness was added as symptom for the event of inflammation.Additional event nausea along with details was added.Past drug and concomitant medications were added.Pharmacovigilance comment: sanofi company follow up comment dated 27-feb-2018: this case concerns a patient who has received synvisc one injection from the recalled lot and later experienced joint inflammation with inability to walk, along with weight bearing difficulty, joint range of motion decreased, joint lock, and nausea.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

Device malfunction [device malfunction].Couldn't even move [unable to walk].Could not bend the knee/inability to move leg/knee (left) [joint range of motion decreased].Inflammation/l knee for pain/inflammation [joint inflammation] ([knee pain], [swelling of l knee], [discomfort in joints], [stiff joint], [joint warmth], [joint effusion], [radiating pain], [joint disorder], [joint noise], [redness]).Frozen leg [limbs stiffness].Not able to bear weight on it [weight bearing difficulty].Knee had locked/ left knee was locked [joint lock].Nausea [nausea].Blood sugar raised to over 400 [blood sugar increased].Tear of meniscus of knee [tear of lateral cartilage or meniscus of knee, current].Muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh [generalised muscle aches].Overweight [overweight].Pretibial 1+ [pretibial edema].Crepitus [crepitations].Pain ellicted by motion/pain at initiation of movement [pain upon movement].Tenderness of the greater trochanter/ tenderness of femoral condyle [bone tenderness].Hip pain/mildly sore [pain in hip] ([stiffness hip], [hip swelling]).Case narrative: this case is related to (b)(4) (same patient).Based on the information received on (b)(6) 2018 from a medical doctor, this case became medically confirmed.This unsolicited legal case from united states was received on (b)(6) 2017 from a patient this case concerns a 70 year old female patient who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation/l knee for pain/inflammation and knee had locked/ left knee was locked, nausea (latency: 0 day); after unknown latency could not bend the knee/inability to move leg/knee (left), not able to bear weight on it and blood sugar raised to over 400, frozen leg, tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter/ tenderness of femoral condyle and hip pain/mildly sore.Also, device malfunction was identified for the reported lot number.Patient had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The patient stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The patient estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The patient has type 2 diabetes and hypertension.The patient has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The patient has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The patient stated she had no allergy to chicken, eggs, feathers, or bird protein.Patient was allergic to penicillin (rash) and oxycodone hydrochloride/paracetamol (percocet) (severe stomach pain).The patient had hip arthroplasty on (b)(6) 2017).Patient had hip replacement surgery on (b)(6)2017).The patient had no other injections into her knee at the time of the synvisc-one injection.Patient had also suffered from intervertebral disc degeneration, menopause, cataract, diverticulum, hypothyroidism, hypertension, onychomycosis, cardiac murmur, joint dislocation and thyroid disorder.She was also reported to have small intestine surgery.She also had gall bladder surgery.She had also undergone to the procedure of tonsillectomy, adenoidectomy and bunion operation.Concomitant medications included clopidogrel bisulfate (plavix) for aneurysm and cerebrovascular accident, levothyroxine (levothyroxine), ezetimibe, simvastatin (vytorin), metformin (metformin) for blood glucose abnormal, sitagliptin phosphate (januvia), acetylcarnitine (acetylcarnitine), coenzyme q10 (coenzyme q10), diclofenac (diclofenac), ciprofloxacin (ciprofloxacin), clonidine hcl (clonidine hcl), repaglinide (repaglinide), tramadol (tramadol), dexamethasone, tobramycin (tobramycin and dexamethasone ophthalmic suspension), diclofenac sodium, misoprostol (diclofenac/misoprostol), fish oil (fish oil), metoclopramide (metoclopramide), hydrochlorothiazide, telmisartan(telmisartan/hydrochlorothiazide), ranitidine (ranitidine) and vitamin d3 (vitamin d3).Patient is a non-smoker and non-tobacco user.Patient had a history of ankle/foot surgery (dec-2011), abdominal surgery (dec-2009), knee surgery (apr-2006), wrist/hand surgery (mar-1990), hip surgery (feb-1956).Concurrent conditions included localized, primary osteoarthritis of the pelvic region and thigh, osteoarthritis of knee, right hip pain, right knee pain, muscle weakness on (b)(6) 2017), antalgic gait on (b)(6) 2017), poor posture on (b)(6) 2017), poor posture on (b)(6) 2017), tear of meniscus of knee.Patient had a family history of diabetes mellitus (mother), kidney disease (sister), osteoarthritis, disorder of thyroid gland.On (b)(6) 2017, the patient initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain and for arthritis relief.On the same day, five hours after the synvisc one injection, patient could do nothing but cry, patient could not even move.On the same day, few hours after injection, patient had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the patient mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.The same day, the patient had excruciating pain and discomfort, had inability to move left leg and knee, extreme swelling, redness, nausea, heat in left leg, cramping, pain which lasted for over 6 days, patient was miserable.Patient called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Patient could not get any relief.Patient had to contact personal physician who could only suggest icing and elevating until patient could get back to the ortho doctor.It was reported that patient knee had swollen to a size as large as a baby's head, patient could not move and had to resolve to walk on crutches for 8 days.Patient had pain, swelling, fever and discomfort suffered, disabled patient and had patient in tears for over 5 days.On (b)(6) 2017, it was reported that patient suffered from lot of discomfort.On an unknown date 2017, latency unknown, patient was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the patient estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, patient returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to patient existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On (b)(6) 2017, the patient received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, patient could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The patient stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the patient was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the patient had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why patient got the synvisc-one injection on (b)(6) 2017.Patient was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.On (b)(6) 2017, she reported to have mild soreness and stiffness.The patient estimated that her left knee pain today on (b)(6) 2017), as she went into her orthopedic doctor's office, was about a 5, when patient tried to put weight on it.The doctor's office did give patient a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The patient stated that the doctor's office said that as of today, at this time, the left knee does not look infected.She also reported muscle aches, muscle weakness and arthralgias/joint pain.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The patient stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the patient said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the patient cannot apply the topical gel whenever she has left knee pain.The patient mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.On (b)(6)2017, the patient underwent blood work, echogram and ekg.On (b)(6) 2018, patient went to hospital and reported about the stiffness and swelling in her right hip and thigh.She continued to have tenderness and stiffness in the right hip and thigh.On (b)(6) 2018 at 09:30 am, the patient visited hospital for her follow-up for left knee pain, her vitals on admission were: blood pressure was 114/70 (units and reference range: not provided) and pulse was 75bpm (reference range: not provided).Patient was improving with moderate left knee pain but there was no change in symptoms.Patient reported no fatigue, no fever, no night sweats, no significant weight gain, no significant weight loss and no exercise intolerance.Patient reported no dry eyes, no irritation, and no vision change.Patient reported no hearing loss, no difficulty hearing and no ear pain.Patient reported no frequent nosebleeds and no nose/sinus problems.Patient reported no sore throat, no bleeding gums, no snoring, no dry mouth, no mouth ulcers, no oral abnormalities, and no teeth problems.Patient reported no chest pain, no arm pain or exertion, no shortness of breath when walking, no shortness of breath while lying down, no palpitations and no known heart murmur.Patient reported no cough, no wheezing and no shortness of breath.Patient reported no abdominal pain, no vomiting, normal apetite, normal stools, no diarehea, no coughing up blood, and no constipation.Patient reported no incontinence, no difficulty urinating, no blood in urine, no frequency, no increased frequency, and no change inn bowel control.Patient reported no abnormal moles, no jaundice, no eczema and no rashes.Patient reported no loss of consciousness, no weakness, no seizures, no dizziness, no headaches, and tolerant of heat or cold.Patient reported no muscle aches, no muscle spasms, no arthralgias/joint pain, no joint swelling and no back pain.Patient reported no depression, no mania/anxiety, no sleep disturbances, feeling safe in relationship and no alcohol abuse.Patient reported no fatigue.Patient reported no swollen glands and no bruising.Patient reported no runny nose, no sinus pain/pressure, no itching, no hives and no frequent sneezing.On physical examination, it was found that the patient was overweight, patient had right and left pretibial edema, and varicosities, tenderness of the lateral patellar facet and it was revealed that the there was a crepitus in the right patellofemoral knee joints.On passive range of motion left: normal, flexion normal, pain elicited by motion.On (b)(6) 2018, x-ray of the left knee (anteroposterior view and lateral view) showed the evidence of osteoarticular abnormality but no fracture and no dislocation; severe bilateral degenerative joint disease with loss of space and large spurs.On (b)(6) 2018.Patient presented with tenderness of lateral joint line, tenderness of lateral femoral condyle.On the same date, it was also observed that she experienced tenderness of popliteal fossa and tenderness of biceps femoris condyle.During the examination of knee patient was observed with weakness, instability, swelling/redness and popping and clicking.As of on (b)(6) 2018, the patient was still had swelling and periodic pain with stiffness.On an unknown date (after unknown latency; 4 hours post injection) the patient began experiencing symptoms including frozen leg, swelling, redness for 8 days.The patient had pain and went back to the healthcare professional.On 15-mar-2018, she presented with muscle aches, arthralgias/joint pain and joint swelling.While the physical examination, she was found with pretibial 1+.She was also observed with tenderness of the lateral patellar facet.She also examined with tenderness of the lateral patellar facet.She was also observed with crepitus.During primary knee joint examination, patient was suffering from pain ellicted by motion.On (b)(6) 2018, patient when presented in the medical care facility, she complained about knee soreness and stiffness.As of on (b)(6) 2018, it was reported that the patient wanted to know the name of the bacteria in the synvisc-one recalled lot for her records.Action taken: unknown for cortisone.Corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; crosne gel, cortisone injection for could not bend the knee/inability to move leg/knee (left); insulin lispro (humalog) for blood sugar raised to over 400; not reported for rest events.Outcome: unknown for frozen leg, device malfunction, nausea, tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter and hip pain/mildly sore ; not recovered/ not resolved for could not bend the knee/inability to move leg/knee (left); recovering for all events.A pharmaceutical technical complaint 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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation; could not bend the knee/inability to move leg/knee (left) follow up was received on 15-jan-2018.Global ptc number was added.Additional information was received on (b)(6) 2018 from a patient.Outcome for the event of device malfunction was updated as unknown.Event term could not bend the knee/inability to move leg was updated to could not bend the knee/inability to move leg/knee (left), the event was updated as serious and its corrective treatment was added.Corrective treatment for the event of blood sugar raised to over 400 was added.Redness was added as symptom for the event of inflammation.Additional event nausea along with details was added.Past drug and concomitant medications were added.Additional information received on 12-mar-2018 from a medical doctor.Hospital follow-up visit details were added.Labs of date on (b)(6) 2018 were added.Medical history, concurrent conditions were added.Concomitant medications acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3) were added.Clinical course was updated.Text was amended accordingly.Additional information was received on (b)(6) 2018 from the patient.Additional event of frozen leg was added along with details.Clinical course was updated.Text was amended accordingly.Additional information was received on 08-oct-2018 from the healthcare professional.Concomitant medications were added.For inflammation updated to inflammation/l knee for pain/inflammation.Events of tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter and hip pain/mildly sore were added.Medical history of the patient updated.Events of intervertebral disc degeneration, menopause, cataract, diverticulum, hypothyroidism, hypertension, onychomycosis, heart murmur, joint dislocation, gall bladder surgery, tonsillectomy, adenoidectomy and bunion operation were added in medical history.Clinical course updated, and text amended accordingly.

Event Description

Based on the information received on (b)(6) 2018 from a medical doctor, this case became medically confirmed.This unsolicited case from united states was received on (b)(6) 2017 from a patient.This case concerns a 70 year old female patient who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation and knee had locked/ left knee was locked, nausea (latency: 0 day); after unknown latency could not bend the knee/ inability to move leg/knee (left), not able to bear weight on it and blood sugar raised to over 400.Also, device malfunction was identified for the reported lot number.Patient had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The patient stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The patient estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The patient has type 2 diabetes and hypertension.The patient has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The patient has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The patient stated she had no allergy to chicken, eggs, feathers, or bird protein.Patient was allergic to penicillin (rash) and oxycodone hydrochloride/paracetamol (percocet) (severe stomach pain).Patient had hip replacement surgery ((b)(6) 2017).The patient had no other injections into her knee at the time of the synvisc-one injection.Concomitant medications included clopidogrel bisulfate (plavix) for stroke and aneurysm, levothyroxine sodium (levothyroxine), ezetimibe/simvastatin (vytorin), sitagliptin phosphate (januvia), metformin hydrochloride (metformin) for blood sugar control, acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3).Patient is a non-smoker and non-tobacco user.Patient had a history of ankle/foot surgery ((b)(6) 2011), abdominal surgery (dec-2009), knee surgery ((b)(6) 2006), wrist/hand surgery ((b)(6) 1990), hip surgery ((b)(6) 1956).Concurrent conditions included localized, primary osteoarthritis of the pelvic region and thigh, osteoarthritis of knee, right hip pain, right knee pain, muscle weakness (03-nov-2017), antalgic gait (03-nov-2017), poor posture (03-nov-2017), poor posture (03-mar-2017), tear of meniscus of knee.Patient had a family history of diabetes mellitus (mother), kidney disease (sister), osteoarthritis, disorder of thyroid gland on 21-nov-2017, the patient initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain and for arthritis relief.On the same day, five hours after the synvisc one injection, patient could do nothing but cry, patient could not even move.On the same day, few hours after injection, patient had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the patient mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.The same day, the patient had excruciating pain and discomfort, had inability to move left leg and knee, extreme swelling, redness, nausea, heat in left leg, cramping, pain which lasted for over 6 days, patient was miserable.Patient called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Patient could not get any relief.Patient had to contact personal physician who could only suggest icing and elevating until patient could get back to the ortho doctor.It was reported that patient knee had swollen to a size as large as a baby's head, patient could not move and had to resolve to walk on crutches for 8 days.Patient had pain, swelling, fever and discomfort suffered, disabled patient and had patient in tears for over 5 days.On an unknown date 2017, latency unknown, patient was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the patient estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, patient returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to patient existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On 27-nov-2017, the patient received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, patient could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The patient stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the patient was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the patient had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why patient got the synvisc-one injection on 21-nov-2017.Patient was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.The patient estimated that her left knee pain today (22-dec-2017), as she went into her orthopedic doctor's office, was about a 5, when patient tried to put weight on it.The doctor's office did give patient a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The patient stated that the doctor's office said that as of today, at this time, the left knee does not look infected.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The patient stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the patient said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the patient cannot apply the topical gel whenever she has left knee pain.The patient mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.On 28-dec-2017, the patient underwent blood work, echogram and ekg.On 08-feb- 2018 at 09:30 am, the patient visited hospital for her follow-up for left knee pain, her vitals on admission were: blood pressure was 114/70 (units and reference range: not provided) and pulse was 75bpm (reference range: not provided).Patient was improving with moderate left knee pain but there was no change in symptoms.Patient reported no fatigue, no fever, no night sweats, no significant weight gain, no significant weight loss and no exercise intolerance.Patient reported no dry eyes, no irritation, and no vision change.Patient reported no hearing loss, no difficulty hearing and no ear pain.Patient reported no frequent nosebleeds and no nose/sinus problems.Patient reported no sore throat, no bleeding gums, no snoring, no dry mouth, no mouth ulcers, no oral abnormalities, and no teeth problems.Patient reported no chest pain, no arm pain or exertion, no shortness of breath when walking, no shortness of breath while lying down, no palpitations and no known heart murmur.Patient reported no cough, no wheezing and no shortness of breath.Patient reported no abdominal pain, no vomiting, normal apetite, normal stools, no diarehea, no coughing up blood, and no constipation.Patient reported no incontinence, no difficulty urinating, no blood in urine, no frequency, no increased frequency, and no change inn bowel control.Patient reported no abnormal moles, no jaundice, no eczema and no rashes.Patient reported no loss of consciousness, no weakness, no seizures, no dizziness, no headaches, and tolerant of heat or cold.Patient reported no muscle aches, no muscle spasms, no arthralgias/joint pain, no joint swelling and no back pain.Patient reported no depression, no mania/anxiety, no sleep disturbances, feeling safe in relationship and no alcohol abuse.Patient reported no fatigue.Patient reported no swollen glands and no bruising.Patient reported no runny nose, no sinus pain/pressure, no itching, no hives and no frequent sneezing.On physical examination, it was found that the patient was overweight, patient had right and left pretibial edema, and varicosities, tenderness of the lateral patellar facet and it was revealed that the there was a crepitus in the right patellofemoral knee joints.On passive range of motion left: normal, flexion normal, pain elicited by motion.On 08-feb-2018, x-ray of the left knee (anteroposterior view and lateral view) showed the evidence of osteoarticular abnormality but no fracture and no dislocation; severe bilateral degenerative joint disease with loss of space and large spurs.As of (b)(6) 2018, the patient was still had swelling and periodic pain with stiffness.Action taken: unknown for cortisone corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; crosne gel, cortisone injection for could not bend the knee/inability to move leg/knee (left); insulin lispro (humalog) for blood sugar raised to over 400; not reported for rest events outcome: unknown for device malfunction and nausea; not recovered/ not resolved for could not bend the knee/inability to move leg/knee (left); recovering for all events a pharmaceutical technical complaint was initiated with global ptc number: 51579 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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation; could not bend the knee/inability to move leg/knee (left) follow up was received on 15-jan-2018.Global ptc number was added.Additional information was received on 27-feb-2018 from a patient.Outcome for the event of device malfunction was updated as unknown.Event term could not bend the knee/inability to move leg was updated to could not bend the knee/inability to move leg/knee (left), the event was updated as serious and its corrective treatment was added.Corrective treatment for the event of blood sugar raised to over 400 was added.Redness was added as symptom for the event of inflammation.Additional event nausea along with details was added.Past drug and concomitant medications were added.Additional information received on 12-mar-2018 from a medical doctor.Hospital follow-up visit details were added.Labs of date 08-feb-2018 were added.Medical history, concurrent conditions were added.Concomitant medications acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3) were added.Clinical course was updated.Text was amended accordingly.Pharmacovigilance comment: sanofi company follow up comment dated 12-mar-2018: this case concerns a patient who has received synvisc one injection from the recalled lot and later experienced joint inflammation with inability to walk, along with weight bearing difficulty, joint range of motion decreased, joint lock, and nausea.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

Based on the information received on 12-mar-2018 from a medical doctor, this case became medically confirmed.This unsolicited case from united states was received on 21-dec-2017 from a patient.This case concerns a 70 year old female patient who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation and knee had locked/ left knee was locked, nausea (latency: 0 day); after unknown latency could not bend the knee/ inability to move leg/knee (left), not able to bear weight on it and blood sugar raised to over 400, frozen leg.Also, device malfunction was identified for the reported lot number.Patient had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The patient stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The patient estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The patient has type 2 diabetes and hypertension.The patient has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The patient has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The patient stated she had no allergy to chicken, eggs, feathers, or bird protein.Patient was allergic to penicillin (rash) and oxycodone hydrochloride/paracetamol (percocet) (severe stomach pain).Patient had hip replacement surgery (b)(6) 2017).The patient had no other injections into her knee at the time of the synvisc-one injection.Concomitant medications included clopidogrel bisulfate (plavix) for stroke and aneurysm, levothyroxine sodium (levothyroxine), ezetimibe/simvastatin (vytorin), sitagliptin phosphate (januvia), metformin hydrochloride (metformin) for blood sugar control, acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3).Patient is a non-smoker and non-tobacco user.Patient had a history of ankle/foot surgery ((b)(6) 2011), abdominal surgery ((b)(6) 2009), knee surgery ((b)(6) 2006), wrist/hand surgery ((b)(6) 1990), hip surgery ((b)(6) 1956).Concurrent conditions included localized, primary osteoarthritis of the pelvic region and thigh, osteoarthritis of knee, right hip pain, right knee pain, muscle weakness (b)(6) 2017), antalgic gait ((b)(6) 2017), poor posture ((b)(6) 2017), poor posture ((b)(6) 2017), tear of meniscus of knee.Patient had a family history of diabetes mellitus (mother), kidney disease (sister), osteoarthritis, disorder of thyroid gland on (b)(6) 2017, the patient initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain and for arthritis relief.On the same day, five hours after the synvisc one injection, patient could do nothing but cry, patient could not even move.On the same day, few hours after injection, patient had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the patient mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.The same day, the patient had excruciating pain and discomfort, had inability to move left leg and knee, extreme swelling, redness, nausea, heat in left leg, cramping, pain which lasted for over 6 days, patient was miserable.Patient called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Patient could not get any relief.Patient had to contact personal physician who could only suggest icing and elevating until patient could get back to the ortho doctor.It was reported that patient knee had swollen to a size as large as a baby's head, patient could not move and had to resolve to walk on crutches for 8 days.Patient had pain, swelling, fever and discomfort suffered, disabled patient and had patient in tears for over 5 days.On an unknown date 2017, latency unknown, patient was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the patient estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, patient returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to patient existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On (b)(6) 2017, the patient received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, patient could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The patient stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the patient was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the patient had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why patient got the synvisc-one injection on (b)(6) 2017.Patient was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.The patient estimated that her left knee pain today ((b)(6) 2017), as she went into her orthopedic doctor's office, was about a 5, when patient tried to put weight on it.The doctor's office did give patient a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The patient stated that the doctor's office said that as of today, at this time, the left knee does not look infected.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The patient stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the patient said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the patient cannot apply the topical gel whenever she has left knee pain.The patient mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.On (b)(6) 2017, the patient underwent blood work, echogram and ekg.On (b)(6) 2018 at 09:30 am, the patient visited hospital for her follow-up for left knee pain, her vitals on admission were: blood pressure was 114/70 (units and reference range: not provided) and pulse was 75bpm (reference range: not provided).Patient was improving with moderate left knee pain but there was no change in symptoms.Patient reported no fatigue, no fever, no night sweats, no significant weight gain, no significant weight loss and no exercise intolerance.Patient reported no dry eyes, no irritation, and no vision change.Patient reported no hearing loss, no difficulty hearing and no ear pain.Patient reported no frequent nosebleeds and no nose/sinus problems.Patient reported no sore throat, no bleeding gums, no snoring, no dry mouth, no mouth ulcers, no oral abnormalities, and no teeth problems.Patient reported no chest pain, no arm pain or exertion, no shortness of breath when walking, no shortness of breath while lying down, no palpitations and no known heart murmur.Patient reported no cough, no wheezing and no shortness of breath.Patient reported no abdominal pain, no vomiting, normal apetite, normal stools, no diarehea, no coughing up blood, and no constipation.Patient reported no incontinence, no difficulty urinating, no blood in urine, no frequency, no increased frequency, and no change inn bowel control.Patient reported no abnormal moles, no jaundice, no eczema and no rashes.Patient reported no loss of consciousness, no weakness, no seizures, no dizziness, no headaches, and tolerant of heat or cold.Patient reported no muscle aches, no muscle spasms, no arthralgias/joint pain, no joint swelling and no back pain.Patient reported no depression, no mania/anxiety, no sleep disturbances, feeling safe in relationship and no alcohol abuse.Patient reported no fatigue.Patient reported no swollen glands and no bruising.Patient reported no runny nose, no sinus pain/pressure, no itching, no hives and no frequent sneezing.On physical examination, it was found that the patient was overweight, patient had right and left pretibial edema, and varicosities, tenderness of the lateral patellar facet and it was revealed that the there was a crepitus in the right patellofemoral knee joints.On passive range of motion left: normal, flexion normal, pain elicited by motion.On (b)(6) 2018, x-ray of the left knee (anteroposterior view and lateral view) showed the evidence of osteoarticular abnormality but no fracture and no dislocation; severe bilateral degenerative joint disease with loss of space and large spurs.As of (b)(6) 2018, the patient was still had swelling and periodic pain with stiffness.On an unknown date (after unknown latency; 4 hours post injection) the patient began experiencing symptoms including frozen leg, swelling, redness for 8 days.The patient had pain and went back to the healthcare professional.As of (b)(6) 2018, it was reported that the patient wanted to know the name of the bacteria in the synvisc-one recalled lot for her records.Action taken: unknown for cortisone corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; crosne gel, cortisone injection for could not bend the knee/inability to move leg/knee (left); insulin lispro (humalog) for blood sugar raised to over 400; not reported for rest events outcome: unknown for frozen leg, device malfunction and nausea; not recovered/ not resolved for could not bend the knee/inability to move leg/knee (left); recovering for all events a pharmaceutical technical complaint was initiated with global ptc number: 51579 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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation; could not bend the knee/inability to move leg/knee (left) follow up was received on 15-jan-2018.Global ptc number was added.Additional information was received on 27-feb-2018 from a patient.Outcome for the event of device malfunction was updated as unknown.Event term could not bend the knee/inability to move leg was updated to could not bend the knee/inability to move leg/knee (left), the event was updated as serious and its corrective treatment was added.Corrective treatment for the event of blood sugar raised to over 400 was added.Redness was added as symptom for the event of inflammation.Additional event nausea along with details was added.Past drug and concomitant medications were added.Additional information received on 12-mar-2018 from a medical doctor.Hospital follow-up visit details were added.Labs of date (b)(6) 2018 were added.Medical history, concurrent conditions were added.Concomitant medications acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3) were added.Clinical course was updated.Text was amended accordingly.Additional information was received on 24-apr-2018 from the patient.Additional event of frozen leg was added along with details.Clinical course was updated.Text was amended accordingly.Pharmacovigilance comment: sanofi company follow up comment dated 24-apr-2018: the follow-up information received does not alter the overall case assessment.The patient experienced joint inflammation with inability to walk, along with weight bearing difficulty, joint range of motion decreased, joint lock, and nausea after the administration of recalled lot of synvisc one.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

Device malfunction [device malfunction] , couldn't even move [unable to walk], could not bend the knee/inability to move leg/knee (left) [joint range of motion decreased], inflammation/l knee for pain/inflammation [joint inflammation] ([knee pain], [swelling of l knee], [discomfort in joints], [stiff joint], [joint warmth], [joint effusion], [radiating pain], [joint disorder], [joint noise], [redness]), frozen leg [limbs stiffness] , not able to bear weight on it [weight bearing difficulty] , knee had locked/ left knee was locked/locking up [joint lock] , nausea [nausea] , blood sugar raised to over 400 [blood sugar increased] , tear of meniscus of knee [tear of lateral cartilage or meniscus of knee, current], muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh [generalised muscle aches] , overweight [overweight] , pretibial 1+ [pretibial edema] , crepitus [crepitations] , pain ellicted by motion/pain at initiation of movement [pain upon movement], tenderness of the greater trochanter/ tenderness of femoral condyle [bone tenderness] , hip pain/mildly sore/ mild soreness/ tenderness right hip [pain in hip] ([stiffness hip], [hip swelling]).Case narrative: this case is related to (b)(4) (same pt (patient)).Based on the information received on 12-mar-2018 from a medical doctor, this case became medically confirmed.This unsolicited legal case from united states was received on 21-dec-2017 from a patient.This case concerns a 70 year old female pt who received treatment with synvisc one and cortisone after 5 hours of receiving synvisc one injection, couldn't even move; after few hours had inflammation/l knee for pain/inflammation and knee had locked/ left knee was locked/ locking up , nausea (latency: 0 day); after unknown latency could not bend the knee/inability to move leg/knee (left), not able to bear weight on it and blood sugar raised to over 400, frozen leg, tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter/ tenderness of femoral condyle and hip pain/mildly sore/mild soreness/ tenderness at right hip.Also, device malfunction was identified for the reported lot number.Pt had been receiving synvisc one injections over the past five years with other orthopedic doctors and facilities and have never had any reactions or experienced anything like this.The pt stated that she has had synvisc-one injections in her left knee previously, 5 or 6 injections of synvisc-one, going back approximately 5 years, about once a year, and it has helped her left knee pain.The pt estimated the pain in her left knee prior to synvisc-one, on a scale of 0 to 10 with 0 no pain and 10 the worst pain, as about a 5 or 6.The pt has type 2 diabetes and hypertension.The pt has had an aortic aneurysm for over 20 years, and it was being monitored regularly by her doctor for size, and they were likely to operate if or when it gets too big.The pt has an artificial right hip now, and a pin in a toe on her left foot because of a bunion years ago, but no other prosthetic devices in her body.The pt stated she had no allergy to chicken, eggs, feathers, or bird protein.Pt was allergic to penicillin (rash) and oxycodone hydrochloride/paracetamol (percocet) (severe stomach pain).The pt had hip arthroplasty ((b)(6) 2017).Pt had hip replacement surgery ((b)(6) 2017).The pt had no other injections into her knee at the time of the synvisc-one injection.Pt had also suffered from intervertebral disc degeneration, menopause, cataract, diverticulum, hypothyroidism, hypertension, onychomycosis, cardiac murmur, joint dislocation and thyroid disorder.She was also reported to have small intestine surgery.She also had gall bladder surgery.She had also undergone to the procedure of tonsillectomy, adenoidectomy and bunion operation.Concomitant medications included clopidogrel bisulfate (plavix) for aneurysm and cerebrovascular accident, levothyroxine (levothyroxine), ezetimibe, simvastatin (vytorin), metformin (metformin) for blood glucose abnormal, sitagliptin phosphate (januvia), acetylcarnitine (acetylcarnitine), coenzyme q10 (coenzyme q10), diclofenac (diclofenac), ciprofloxacin (ciprofloxacin), clonidine hcl (clonidine hcl), repaglinide (repaglinide), tramadol (tramadol), dexamethasone, tobramycin (tobramycin and dexamethasone ophthalmic suspension), diclofenac sodium, misoprostol (diclofenac/misoprostol), fish oil (fish oil), metoclopramide (metoclopramide), hydrochlorothiazide, telmisartan(telmisartan/hydrochlorothiazide), ranitidine (ranitidine) and vitamin d3 (vitamin d3).Pt is a non-smoker and non-tobacco user.Pt had a history of ankle/foot surgery ((b)(6) 2011), abdominal surgery ((b)(6) 2009), knee surgery ((b)(6) 2006), wrist/hand surgery ((b)(6) 1990), hip surgery ((b)(6) 1956).Concurrent conditions included localized, primary osteoarthritis of the pelvic region and thigh, osteoarthritis of knee, right hip pain, right knee pain, muscle weakness ((b)(6) 2017), antalgic gait ((b)(6) 2017), poor posture ((b)(6) 2017), poor posture ((b)(6) 2017), tear of meniscus of knee.Pt had a family history of diabetes mellitus (mother), kidney disease (sister), osteoarthritis, disorder of thyroid gland on (b)(6) 2017, the pt initiated treatment with intra-articular synvisc one injection, at a dose of 6 ml once (batch/lot number: 7rsl021 and expiry date: 31-may-2020) for left knee pain and for arthritis relief.On the same day, five hours after the synvisc one injection, pt could do nothing but cry, pt could not even move.On the same day, few hours after injection, pt had the injection about 11:00 am and by 4 pm she could not move or bend the knee, and the knee was swelling, and at the height of the swelling it was about as big as a baby's head, and the pt mentioned in her email.The left knee was hot, and if it had a fever in it.It was knee had locked and the pain was unbearable.The same day, the pt had excruciating pain and discomfort, had inability to move left leg and knee, extreme swelling, redness, nausea, heat in left leg, cramping, pain which lasted for over 6 days, pt was miserable.Pt called the doctor's office that same evening trying to seek help, but of course, they had closed and tried the next day.Pt could not get any relief.Pt had to contact personal physician who could only suggest icing and elevating until pt could get back to the ortho doctor.It was reported that pt knee had swollen to a size as large as a baby's head, pt could not move and had to resolve to walk on crutches for 8 days.Pt had pain, swelling, fever and discomfort suffered, disabled pt and had pt in tears for over 5 days.On (b)(6) 2017, it was reported that pt suffered from lot of discomfort.On an unknown date 2017, latency unknown, pt was not able to bear weight on the knee and had to use crutches, and the left knee was "locked" and she could not bend it.After the synvisc-one injection, the pt estimated the pain as "past 10" or about 12, and it was so severe that it woke her up at night and she cried from the pain.When the offices re-opened after the holiday, pt returned to the doctor/pa and received a cortisone injection (form, route, dose and frequency: not reported) to relieve the inflammation and swelling, which unfortunately, raised my blood sugars to over 400 causing more trauma to pt existing situation.It was reported that the swelling subsided, the pain still exist and over the past week evidence of swelling and stiffness was returning.On (b)(6) 2017, the pt received a corticosteroid injection in the knee for swelling, which helped, and by 8 or 9 days after the synvisc- one injection, pt could bend her left knee again for the first time.The corticosteroid injection did increase her blood glucose up over 400, and then recently her blood glucose has been too low, so her type 2 diabetes has been affected, and after the corticosteroid injection she urinated clear urine frequently for 3 days.The pt stated that she no longer needs crutches and only has to use a cane, as of today.Of note, the pt was recovering from right hip replacement surgery at the time she got the synvisc-one injection.Because it was the right hip that was replaced, the pt had just gotten to where she was using a cane after the hip surgery, and the stress that favoring the right hip put on her left knee caused it to be stiff, and that was why pt got the synvisc-one injection on (b)(6) 2017.Pt was using a cane in her left hand after the right hip replacement, and now she was using a cane in the right hand for her left knee swelling and pain.O on (b)(6) 2017, it was reported that pt continues to have hip stiffness but minimal hip pain.On (b)(6) 2017 , pt did not have hip pain but continues to had mild soreness and stiffness.On (b)(6) 2017, she reported to have mild soreness and stiffness.The pt estimated that her left knee pain today ((b)(6) 2017), as she went into her orthopedic doctor's office, was about a 5, when pt tried to put weight on it.The doctor's office did give pt a brace for her left knee today, but she has not had time to see how that would help with pain or walking.The pt stated that the doctor's office said that as of today, at this time, the left knee does not look infected.She also reported muscle aches, muscle weakness and arthralgias/joint pain.Today, the inflammation of the left knee was better, there was still some swelling of the right side of her left knee, and that area was tender.A topical spray was used to numb the injection site on the knee.The pt stated she experienced no fever, no vomiting, and to her knowledge has not received immunosuppressants.No fluid was withdrawn from the left knee, no blood work was done, and no cultures have been performed.Treatment of the left knee reaction, in addition to the corticosteroid injection, has been rest and the use of a generic voltaren topical gel, which the pt said she has to be careful using, and her primary care doctor told her not to use it more than twice a day, because of a potential interaction with her blood thinner, so that the pt cannot apply the topical gel whenever she has left knee pain.The pt mentioned that every now and then she has a shooting pain from the left knee up to her left thigh.On (b)(6) 2017, the pt underwent blood work, echogram and ekg.On (b)(6) 2018, pt appointment went well.Pt had to continued physical therapy for twice per week for 4 weeks as par medical doctor request.Pt reported no hip pain just stiffness and weakness.Pt did not have hip pain throughout the treatment.Pt continued to have tenderness and stiffness at right hip and thigh.Pt would continue to progress as per poc to improve hip range of motion and strength.Pt also had stiffness and swelling in her right hip but no hip pain.On (b)(6) 2018, pt went to hospital and reported about the stiffness and swelling in her right hip and thigh.She continued to have tenderness and stiffness in the right hip and thigh.On (b)(6) 2018 at 09:30 am, the pt visited hospital for her follow-up for left knee pain, her vitals on admission were: blood pressure was 114/70 (units and reference range: not provided) and pulse was 75bpm (reference range: not provided).Pt was improving with moderate left knee pain but there was no change in symptoms.Pt reported no fatigue, no fever, no night sweats, no significant weight gain, no significant weight loss and no exercise intolerance.Pt reported no dry eyes, no irritation, and no vision change.Pt reported no hearing loss, no difficulty hearing and no ear pain.Pt reported no frequent nosebleeds and no nose/sinus problems.Pt reported no sore throat, no bleeding gums, no snoring, no dry mouth, no mouth ulcers, no oral abnormalities, and no teeth problems.Pt reported no chest pain, no arm pain or exertion, no shortness of breath when walking, no shortness of breath while lying down, no palpitations and no known heart murmur.Pt reported no cough, no wheezing and no shortness of breath.Pt reported no abdominal pain, no vomiting, normal appetite, normal stools, no diarrhea, no coughing up blood, and no constipation.Pt reported no incontinence, no difficulty urinating, no blood in urine, no frequency, no increased frequency, and no change inn bowel control.Pt reported no abnormal moles, no jaundice, no eczema and no rashes.Pt reported no loss of consciousness, no weakness, no seizures, no dizziness, no headaches, and tolerant of heat or cold.Pt reported no muscle aches, no muscle spasms, no arthralgias/joint pain, no joint swelling and no back pain.Pt reported no depression, no mania/anxiety, no sleep disturbances, feeling safe in relationship and no alcohol abuse.Pt reported no fatigue.Pt reported no swollen glands and no bruising.Pt reported no runny nose, no sinus pain/pressure, no itching, no hives and no frequent sneezing.On physical examination, it was found that the pt was overweight, pt had right and left pretibial edema, and varicosities, tenderness of the lateral patellar facet and it was revealed that the there was a crepitus in the right patellofemoral knee joints.On passive range of motion left: normal, flexion normal, pain elicited by motion.On (b)(6) 2018, x-ray of the left knee (anteroposterior view and lateral view) showed the evidence of osteoarticular abnormality but no fracture and no dislocation; severe bilateral degenerative joint disease with loss of space and large spurs.On (b)(6) 2018, the pt did not had any hip pain.On (b)(6) 2018.Pt presented with tenderness of lateral joint line, tenderness of lateral femoral condyle.On the same date, it was also observed that she experienced tenderness of popliteal fossa and tenderness of biceps femoris condyle.During the examination of knee pt was observed with weakness, instability, swelling/redness and popping and clicking.As of (b)(6) -2018, the pt was still had swelling and periodic pain with stiffness.On an unknown date (after unknown latency; 4 hours post injection) the pt began experiencing symptoms including frozen leg, swelling, redness for 8 days.The pt had pain and went back to the healthcare professional.On (b)(6) 2018, she presented with muscle aches, arthralgias/joint pain and joint swelling.While the physical examination, she was found with pretibial 1+.She was also observed with tenderness of the lateral patellar facet.She also examined with tenderness of the lateral patellar facet.She was also observed with crepitus.During primary knee joint examination, pt was suffering from pain ellicted by motion.On the same day, the pt presented to doctor with left knee pain and swelling.She further reported that her knee had not been the same since the (b)(6) 2017 knee injection.Pt was concerned that the cortisone injection would cause her blood sugar to rise.Pt left knee pain was 7./10 and then decreased to 5/10 but the knee was very stiff.On (b)(6) 2018, pt when presented in the medical care facility, she complained about knee soreness and stiffness.On (b)(6) 2018, the pt examination revealed the knee pain was 7/10 and the knee was locking up.As of (b)(6) 2018, it was reported that the pt wanted to know the name of the bacteria in the synvisc-one recalled lot for her records.Action taken: unknown for cortisone.Corrective treatment: icing and elevating for knee had locked/ left knee was locked; icing; elevating;cortisone; brace; diclofenac potassium (voltaren) topical gel for inflammation; crutches; cane for couldn't even move; crosne gel, cortisone injection for could not bend the knee/inability to move leg/knee (left); insulin lispro (humalog) for blood sugar raised to over 400; not reported for rest events outcome: unknown for frozen leg, device malfunction, nausea, tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter; recovered for hip pain/mildly sore/mild soreness/ tenderness at right hip ; not recovered/ not resolved for could not bend the knee/inability to move leg/knee (left); recovering for all events a pharmaceutical technical complaint was initiated with global ptc number: 51579 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 was completed, corrective and preventive actions would be implemented.Seriousness criterion: required intervention for device malfunction, couldn't even move, inflammation; could not bend the knee/inability to move leg/knee (left).Follow up was received on 15-jan-2018.Global ptc number was added.Additional information was received on 27-feb-2018 from a pt.Outcome for the event of device malfunction was updated as unknown.Event term could not bend the knee/inability to move leg was updated to could not bend the knee/inability to move leg/knee (left), the event was updated as serious and its corrective treatment was added.Corrective treatment for the event of blood sugar raised to over 400 was added.Redness was added as symptom for the event of inflammation.Additional event nausea along with details was added.Past drug and concomitant medications were added.Additional information received on 12-mar-2018 from a medical doctor.Hospital follow-up visit details were added.Labs of date (b)(6) 2018 were added.Medical history, concurrent conditions were added.Concomitant medications acetylcarnitine, ubidecarenone (coq-10) diclofenac sodium (diclofenac topical gel), diclofenac/misoprostol, fish oil, metoclopramide hydrochloride (metoclopramide), ranitidine, colecalciferol (vitamin d3) were added.Clinical course was updated.Text was amended accordingly.Additional information was received on 24-apr-2018 from the pt.Additional event of frozen leg was added along with details.Clinical course was updated.Text was amended accordingly.Additional information was received on 08-oct-2018 from the lawyer.Concomitant medications were added.Verbatim for inflammation updated to inflammation/l knee for pain/inflammation.Events of tear of meniscus, muscle aches/tenderness of the hip flexor muscles/tenderness of the piriformis/increased tenderness along her right thigh, overweight, pretibial 1+, crepitus, pain ellicted by motion/pain at initiation of movement, tenderness of the greater trochanter and hip pain/mildly sore were added.Medical history of the pt updated.Events of intervertebral disc degeneration, menopause, cataract, diverticulum, hypothyroidism, hypertension, onychomycosis, heart murmur, joint dislocation, gall bladder surgery, tonsillectomy, adenoidectomy and bunion operation were added in medical history.Clinical course updated, and text amended accordingly.Additional information was received on 06-nov-2018 from lawyer.Verbatim of hip pain/mildly sore/mild soreness/ tenderness at right hip and knee had locked/ left knee was locked/ locking up was updated.Outcome of knee had locked/ left knee was locked/ locking up was updated to recovered.Clinical course was updated and text amended accordingly.

• Brand Name: SYNVISC ONE
• Type of Device: MOZ
• Manufacturer (Section D): GENZYME BIOSURGERY (RIDGEFIELD); 1125 pleasantview terrace; ridgefield NJ 07657
• MDR Report Key: 7203267
• MDR Text Key: 98167337
• Report Number: 2246315-2017-00592
• Device Sequence Number: 1
• Product Code: MOZ
• Combination Product (y/n): Y
• PMA/PMN Number: P940015
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: consumer,health professional
• Remedial Action: Recall
• Type of Report: Initial,Followup,Followup,Followup,Followup
• Report Date: 11/30/2018
• 2 Devices were Involved in the Event: 1 2

1 Patient was Involved in the Event

• Date FDA Received: 01/18/2018
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 05/31/2020
• Device Lot Number: 7RSL021
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: No
• Date Manufacturer Received: 04/24/2018
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Treatment: ACETYLCARNITINE (ACETYLCARNITINE),; ACETYLCARNITINE (ACETYLCARNITINE),UNKNOWN; ACETYLCARNITINE(CON.) - START; ACETYLCARNITINE(CON.) - START; CIPROFLOXACIN (CIPROFLOXACIN),; CIPROFLOXACIN (CIPROFLOXACIN),UNKNOWN; CLONIDINE HCL (CLONIDINE HCL),; CLONIDINE HCL (CLONIDINE HCL),UNKNOWN; COENZYME Q10 (COENZYME Q10),; COENZYME Q10 (COENZYME Q10),UNKNOWN; COENZYME Q10(CON.) - START; COENZYME Q10(CON.) - START; DICLOFENAC (DICLOFENAC),; DICLOFENAC (DICLOFENAC),UNKNOWN; DICLOFENAC(CON.) - START (ONGOING); DICLOFENAC(CON.) - START (ONGOING); DICLOFENAC/MISOPROSTOL (DICLOFENAC SODIUM, MISOPRO; DICLOFENAC/MISOPROSTOL(CON.) - START; DICLOFENAC/MISOPROSTOL(CON.) - START; DICLOFENAC/MISOPROSTOL,UNKNOWN; FISH OIL (FISH OIL),; FISH OIL (FISH OIL),UNKNOWN; FISH OIL(CON.) - START; FISH OIL(CON.) - START; JANUVIA (SITAGLIPTIN PHOSPHATE),; JANUVIA (SITAGLIPTIN PHOSPHATE),UNKNOWN; JANUVIA(CON.); JANUVIA(CON.); JANUVIA(CON.); LEVOTHYROXINE (LEVOTHYROXINE),; LEVOTHYROXINE (LEVOTHYROXINE),UNKNOWN; LEVOTHYROXINE(CON.); LEVOTHYROXINE(CON.) - START; LEVOTHYROXINE(CON.) - START; METFORMIN (METFORMIN),; METFORMIN (METFORMIN),UNKNOWN; METFORMIN(CON.); METFORMIN(CON.) - START; METFORMIN(CON.) - START; METOCLOPRAMIDE (METOCLOPRAMIDE),; METOCLOPRAMIDE (METOCLOPRAMIDE),UNKNOWN; METOCLOPRAMIDE(CON.) - START; METOCLOPRAMIDE(CON.) - START; PENICILLIN(PREV.); PENICILLIN(PREV.); PERCOCET(PREV.); PERCOCET(PREV.); PERCOCET(PREV.); PLAVIX (CLOPIDOGREL BISULFATE),; PLAVIX (CLOPIDOGREL BISULFATE),UNKNOWN; PLAVIX(CON.); PLAVIX(CON.) - START; PLAVIX(CON.) - START; RANITIDINE (RANITIDINE),; RANITIDINE (RANITIDINE),UNKNOWN; RANITIDINE(CON.) - START; RANITIDINE(CON.) - START; REPAGLINIDE (REPAGLINIDE),; REPAGLINIDE (REPAGLINIDE),UNKNOWN; SYNVISC ONE(PREV.); SYNVISC ONE(PREV.); SYNVISC ONE(PREV.); TELMISARTAN/HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZI; TELMISARTAN/HYDROCHLOROTHIAZIDE,UNKNOWN; TOBRAMYCIN AND DEXAMETHASONE OPHTHALMIC SUSPENSION; TOBRAMYCIN AND DEXAMETHASONE OPHTHALMIC SUSPENSION; TRAMADOL (TRAMADOL),; TRAMADOL (TRAMADOL),UNKNOWN; VITAMIN D3 (VITAMIN D3),; VITAMIN D3 (VITAMIN D3),UNKNOWN; VITAMIN D3(CON.) - START; VITAMIN D3(CON.) - START; VYTORIN (EZETIMIBE, SIMVASTATIN),; VYTORIN (EZETIMIBE, SIMVASTATIN),UNKNOWN; VYTORIN(CON.); VYTORIN(CON.) - START; VYTORIN(CON.) - START
• Patient Outcome(s): Required Intervention; Disability
• Patient Age: 70 YR
• Patient Weight: 99