MAUDE Adverse Event Report: GLADERMA Q-MED RESTYLANE-L; IMPLANT, DERMAL, FOR AESTHETIC USE

Lot Number 18037

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Ecchymosis (1818); Hemorrhage/Bleeding (1888); Inflammation (1932); Necrosis (1971); Skin Discoloration (2074); Obstruction/Occlusion (2422); Pallor (2468); Neuralgia (4413); Subcutaneous Nodule (4548); Swelling/ Edema (4577); Appropriate Clinical Signs, Symptoms, Conditions Term / Code Not Available (4581)

Event Date 01/08/2021

Event Type  Injury  

Manufacturer Narrative

Pharmacovigilance comment: the serious expected event of vascular occlusion and non-serious expected event of induration, swelling, bruising, discolouration at implant site and non-serious unexpected events of neuralgia and poor peripheral circulation were considered possibly related to the treatment.Serious criteria include the need for multiple medical interventions.The likely root cause for the events include intravascular filler injection leading to vascular occlusionand its manifestations.The case meets the criteria for expedited reporting to the regulatory authorities.Engineering evaluation: no corrective or preventive actions are deemed necessary based on the outcome of the performed investigations.Manufacturer narrative: routine investigations have been performed and provide sufficient information to assess the potential root cause and indicate a possible association to the treatment procedure.The reported lot number was valid and verified the reported product.The information in this case does not indicate a non-conforming product or malfunction.The performed investigations are therefore considered adequate and no additional investigations will be conducted.

Event Description

Case reference number (b)(4) is a spontaneous report sent on 04-feb-2021 by an other health professional which refers to a (b)(6) -year-old female patient.Additional information was received on 05-feb-2021 from same reporter.No information about medical history has been provided.The patient had no known allergies.The patient had microdermabrasion and chemical peels in the past.The patient had previously received treatment with restylane-l on (b)(6)-2020, restylane lyft with lidocaine on (b)(6) 2020, botox and dysport.Concomitant treatments included spironolactone [spironolactone], vitamin d [vitamin d nos], zinc [zinc], duloxetine [duloxetine] and birth control [contraceptives].The patient had not yet received the covid vaccine.She had no dental procedures or vaccines in the past 6-12 month and any illnesses in the month prior to her session.On (b)(6) 2021, the patient received treatment with 1 ml restylane-l (lot 18037), 0.4 ml to upper lip and 0.3 ml bilaterally to pyriform apertures with unknown injection technique and needle type.In the same session, the patient also received treatment with dysport [dysport] to 30 units to the glabella, 20 units to the forehead, 15 units to the crow's feet bilaterally, and 15 units to the chin and polydioxanone (pdo) threads to her cheeks.Same day, on (b)(6) 2021, the patient experienced swelling(implant site swelling) and bruising (implant site bruising) which was resolved before or by (b)(6) 2021.It was also reported that patient also had vascular occlusion(vascular occlusion) while injecting restylane-l into the lip.It was firm like cement/hardness(implant site induration).12 days later, on (b)(6) 2021, patient reported that she had sharp, shooting and throbbing pain/nerve pain(neuralgia) to her right upper lip that radiated to her right cheek, which our nurse described as nerve pain, which she thought had resolved the next day.On (b)(6) 2021, the patient reported a sharp pain between her nose and lip, extreme bruising to her right upper lip so that a nickel-sized area of the right upper lip was purple(implant site discolouration).She said the nerve pain came back and had worsened.The patient also had lack of circulation/sluggish blood flow(poor peripheral circulation), swelling, and her right upper lip was painful and thick.The patient stated that she feels like her lip is going to split open when she smiles.The upper lip was like cement and it was 2-3 times normal size.The nerve pain resolved by (b)(6) 2021 but there was very mild tenderness to the areas where blood flow is sluggish.The hcp treated patient initially with ibuprofen [ibuprofen] and then she was injected with about 2 vials of hylenex [hyaluronidase] per visit (around 12 vials of hylenex in total).On (b)(6), 2 vials of hylenex injected in the morning and another 2 vials that evening.On (b)(6), she was seen about 2-3 times and each time she received about 2 vials of hylenex.On (b)(6), 1.7 vials hylenex injected when she came into the office; another 2 vials of hylenex given to her at her home.Hcp stated that the the hylenex had resolved the lack of circulation when she saw the patient on (b)(6) 2021, but the patient still has sluggish blood flow to certain areas like the vermillion border, columellas and subnasal area.On (b)(6), 2.3 vials hylenex injected.Massaged the lip.The sluggish blood flow was to the right and left upper lip and right nlf.The patient's right upper lip still has bruising although it has lightened up and the swelling to the right upper lip was still there but was better.The lip was no longer hard as cement but the areas of hardness are still there and she still has tenderness to the areas where blood flow was sluggish.Outcome at the time of the report: vascular occlusion was not recovered/not resolved.Swelling was recovering/resolving.Bruising was not recovered/not resolved.Firm like cement/hardness was not recovered/not resolved.Sharp, shooting and throbbing pain/nerve pain was not recovered/not resolved.Lack of circulation/sluggish blood flow was not recovered/not resolved.Purple was not recovered/not resolved.

Manufacturer Narrative

Pharmacovigilance comment: the serious expected events of vascular occlusion, necrosis at implant site and non-serious expected event of induration, swelling, bruising, discolouration, inflammation, pallor, mass at implant site and non-serious unexpected events of neuralgia and poor peripheral circulation were considered possibly related to the treatment.Serious criteria include the need for multiple medical interventions.The likely root cause for the events include intravascular filler injection leading to vascular occlusion and its manifestations.The non-serious events of vascular injury and haemorrhage were considered unexpected, unrelated to the treatment.Likely root cause for the events include concomitant threading procedure, which might have contributed to other events also.The case meets the criteria for expedited reporting to the regulatory authorities.Engineering evaluation: no corrective or preventive actions are deemed necessary based on the outcome of the performed investigations.Manufacturer narrative: routine investigations have been performed and provide sufficient information to assess the potential root cause and indicate a possible association to the treatment procedure.The reported lot number was valid and verified the reported product.The information in this case does not indicate a non-conforming product or malfunction.The performed investigations are therefore considered adequate and no additional investigations will be conducted.

Event Description

Case reference number (b)(4) is a spontaneous report sent on 04-feb-2021 by an other health professional which refers to a 39-year-old female patient.Additional information was received on 05-feb-2021 from same reporter.The patient's medical history included suspected raynauds.The patient had no known allergies.The patient had microdermabrasion and chemical peels in the past.The patient had previously received treatment with jup to lips on (b)(6) 2018, (b)(6) 2019, restylane-l on (b)(6) 2020 to lips and on (b)(6) 2020 to chin, botox and dysport.Concomitant treatments included bcp, spironolactone [spironolactone], vitamin d [vitamin d nos], zinc [zinc], duloxetine [duloxetine] and birth control [contraceptives].The patient had not yet received the covid vaccine.She had no dental procedures or vaccines in the past 6-12 month and any illnesses in the month prior to her session.On (b)(6) 2021, the patient received treatment with 1 ml restylane-l (lot 18037), 0.4 ml to upper lip and 0.3 ml bilaterally to pyriform apertures using 25/40 cannula with unknown injection technique.In the same session, the patient also received treatment with dysport [dysport] to 30 units to the glabella, 20 units to the forehead, 15 units to the crow's feet bilaterally, and 15 units to the chin and 4 polydioxanone (pdo) threads to each side midface for a total of 8.Same day, on (b)(6) 2021, the patient experienced swelling(implant site swelling) and bruising (implant site bruising) which was resolved before or by (b)(6) 2021.It was also reported that patient also had vascular occlusion(vascular occlusion) while injecting restylane-l into the lip.It was firm like cement/hardness(implant site induration).12 days later, on (b)(6) 2021, patient reported that she had sharp, shooting and throbbing pain/nerve pain(neuralgia) to her right upper lip that radiated to her right cheek, which our nurse described as nerve pain, which she thought had resolved the next day.As per follow up assessment was that patient complained of new onset pain on upper lip which started on right side and on left side as well.Shooting pain down cheek.The patient also had small clear bump (implant site mass) on inner mucosa of upper right lip with bruise.The bump was soft, tender, normal temparature, mild throbbing.The patient was advised for rest, advil [ibuprofen], campho phenique [camphor, phenol] to numb which was started on (b)(6) 2021.No initiator.The patient stated that she rubbed lip for a while intermittently, random with score of 6/10.Skin appeared normal color, mild swelling observed to upper lip tubers, greater on right side, mild swelling noted at ergo and right lateral cheek.The patient had 2 separate issues, shooting pain down cheek due to nerve irritation started post thread placement and swelling, bruise, bump on lip due to filler placement which was still in healing process and could be filler or fluid.The patient was educated that she was not having a reaction.The symptoms she reported were not expected but not abnormal.The nerve pain will subside on its own, could take several weeks.The patient was asked to monitor pain/bump on lip and to alert if there were any changes, specifically swelling and/or increase in change and told patient that she would like to see bump in person next week if it does not go away over the weekend.The patient was advised to continue rest, ice and nsaid for inflammation(implant site inflammation) and pain.On 24-jan-2021, the reporter followed up with patient and stated that lip pain was not as bad and swelling looked good.The results were amazing so far.Then the patient was told to reach out to if anything changes.On (b)(6) 2021, the patient reported a throbbing sharp intense pain to upper lip area between her nose and lip, extreme bruising to her right upper lip so that a nickel-sized area of the right upper lip was purple(implant site discolouration).She said the nerve pain came back and had worsened.The patient also had lack of circulation/sluggish blood flow(poor peripheral circulation) to left lip and above especially middle of lip and subnasally, swelling, and her right upper lip was painful and thick.The patient stated that she feels like her lip was going to split open when she smiles.The upper lip was like cement and it was 2-3 times normal size.The nerve pain resolved by (b)(6) 2021 but there was very mild tenderness to the areas where blood flow is sluggish.The patient was injected with 2 vials of hylenex [hyaluronidase], first one was mixed with bicarbonate [sodium bicarbonate] and 1% lidocaine [lidocaine] and injected via cannula.Second vial was plain and injected with deposit to areas of blanching(implant site pallor) and tolerated extremely well despite the pain.Ice and etoh [ethanol] used, much better refill everywhere.Later that evening at 7pm patient back for follow up, the patient looked so much better and felt so much better after first round of treatment.Video was taken before and after, injected one vial hylenex mixed with a bit of lidocaine 1% and bicarbonate via needle directly into areas of blanchy.The patient was taking asa [acetylsalicylic acid] 650mg also massaging with hot pack.The 2nd vial hylenex vial was injected via 29 g directly into isolated areas, showed patient how to check capillary refill and would be followed up in morning.On (b)(6) 2021, the patient returned for 3rd round follow up after hylenex.The patient reported significant decrease in pain, was able to sleep, firmness was decreased.The patient had massaged, applied heat and took asa at home.Rated pain on score of 2/10.Area of induration size decreased.When performing capillary refill checks the following areas showed more than 3 refill, medial upper tuber at cupids bow, right lateral tuber.Remaining areas, including ergo and pyriform all showed less than 3 second capillary refill.Video was taken before and after.The patient was injected with one vial hylenex mixed with 0.3ml of lidocaine 1% and 0.1ml bicarbonate using 30g needle direct to areas of blanching.Injected 1.5 hylenex total.Advised to continue heat, massage and asa 650mg.The patient was asked to return for follow up on (b)(6) 2021 at 10am.On (b)(6) 2021, the patient came back for follow up, felt so much better, even a little better from yesterday.Sluggish capillary refill as seen in video both medial and lateral left ergo/ vermilion border, improved from yesterday.Area was warm and soft.No sluggishness in pyriform, nasolabial fold, or tip of nose.Wiped off with chlor preparation, used puracyn (no ice).Injected with 0.6mls hylenex mixed with 0.15mls of 1% lidocaine using 30 g needle into medial ergo/pks, lateral left ergo and tuber.Hcp assessed, sluggishness moved to depressor septi area, injected more hylenex at this spot.Reassessed, better capillary refill, took post video, applied arnica [arnica montana] or aquaphor [white soft paraffin].The patient was instructed to follow up tomorrow and advised to continue aspirin and heat/massage to the area.On (b)(6) 2021, the patient sent a video a few hours ago showing left upper lip and slight right upper lip mildly sluggish.The patient was asked again whether she had been sick, vaccinated, or around anyone with covid or dental procedures or any autoimmune disease.All was negative except hcp thought she had raynauds.Mixed 0.03 lidocaine 1% with one vial hylenex injected via 27g cannula into left upper lip area including ergotrid.The patient tolerated it okay using ice and squeeze balls.Video taken, one area appeared still only slightly slow.Injected additional 0.3 hylenex via 30g needle into left upper lip.Total 1.3.Area was massaged and also gave 650mg asa.Capillary refill looked good.Also nares and nose tip all refill was within normal limit.The patient was requested to send videos for follow up.The patient sent videos on saturday, sunday and monday and was looking great.Also patient sent pics that she took on (b)(6) 2021.She looked fine.There was never any sloughing or blisters.The worst thing was a dark giant bruise to her upper right ergo and that went away with hylenex.That could have possibly been an area that would have necrosed(implant site necrosis).Additional follow up information was received on 12-feb-2021.The physician reported that the adverse event was likely due to the thread insertions and not the filler injections based on pictures sent.His analogy was that the cogs in the threads caused trauma.The patient was fine after initial injection.During the thread insertion, the threads were passed across the infraorbital nerve bundle.Over time, this caused nerve irritation which then caused a tear to vein(vascular injury) and a bleed(haemorrhage) into the lip area.There was a demarcation line parallel to the vermillion noted in the images.Nerve and vessels were all together initially so infraorbital nerve, 9/10 rating on the pain and the lip felt thick because there was blood in it.Bruising was from the threads as the appearance was consistent with a vascular pattern and all timing wise.He also mentioned that there was no such thing as a compressive vascular event, either inject into a vessels or do not.Hyaluronidase also lets tissue expand and lets clots disperse.So the injector had already completed the necessary steps to help her patient recover.Outcome at the time of the report: vascular occlusion was recovering/resolving.Possibly been an area that would have necrosed was recovering/resolving.Swelling was recovered/resolved.Bruising was recovered/resolved.Firm like cement/hardness was recovering/resolving.Sharp, shooting and throbbing pain/nerve pain was recovering/resolving.Lack of circulation/sluggish blood flow was recovering/resolving.Purple was recovering/resolving.Bump was recovering/resolving.Inflammation was recovering/resolving.Blanching was recovering/resolving.Tear to vein was recovering/resolving.Bleed was recovering/resolving.Tracking list: v.0 initial v.1 fu received on 11-feb-2021 from the same hcp and on 12-feb-2021 from the physician.Events (necrosis at implant site, tear to vein, bleed, bump, inflammation and blanching) added.Patient medical history, concomitant medication, past filler, suspect device needle type, outcome, reporter causality and corrective treatment details were updated.

• Brand Name: RESTYLANE-L
• Type of Device: IMPLANT, DERMAL, FOR AESTHETIC USE
• Manufacturer (Section D): GLADERMA Q-MED; seminariegatan 21; uppsala, SE-75 228; SW SE-75228
• MDR Report Key: 11372178
• MDR Text Key: 242052560
• Report Number: 1000118068-2021-00005
• Device Sequence Number: 1
• Product Code: LMH
• Combination Product (y/n): N
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Distributor
• Type of Report: Initial,Followup
• Report Date: 03/03/2021

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 02/24/2021
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Expiration Date: 01/31/2023
• Device Lot Number: 18037
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: Yes
• Date Report Sent to FDA: 03/03/2021
• Distributor Facility Aware Date: 02/11/2021
• Event Location: Outpatient Treatment Facility
• Date Report to Manufacturer: 02/11/2021
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Treatment: BIRTH CONTROL (NOT SPECIFIED); BIRTH CONTROL (NOT SPECIFIED); DULOXETINE; DULOXETINE; DYSPORT; DYSPORT; SPIRONOLACTONE; SPIRONOLACTONE; VITAMIN D; VITAMIN D; ZINC; ZINC
• Patient Outcome(s): Required Intervention
• Patient Age: 39 YR