MAUDE Adverse Event Report: GALDERMA Q-MED AB RESTYLANE SILK; IMPLANT, DERMAL, FOR AESTHETIC USE

Lot Number 15453

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

Patient Problems Abscess (1690); Cellulitis (1768); Erythema (1840); Unspecified Infection (1930); Inflammation (1932); Pain (1994); Deformity/ Disfigurement (2360); Swollen Lymph Nodes/Glands (4432); Easy Bruising (4558); Swelling/ Edema (4577); Appropriate Clinical Signs, Symptoms, Conditions Term / Code Not Available (4581)

Event Date 09/19/2018

Event Type  Injury  

Manufacturer Narrative

Pharmacovigilance comments: the serious expected events of abscess, inflammation, nodule, cellulitis, infection at implant site, and non-serious expected events of cutaneous contour deformity, bruising, warmth, pain, oedema, erythema at implant site and unexpected event of lymphadenitis were considered possibly related to the treatments.Serious criteria include the need for multiple medical interventions and permanent damage.Potential root causes for the reported events include injection procedure associated with inadequate aseptic technique leading to subsequent 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 nonconforming product or malfunction and to confirm this a batch record review will be requested.

Event Description

Case reference number (b)(4) is a spontaneous report sent on (b)(6) 2020 by a lawyer which refers to a (b)(6) year-old female patient.The patient's medical history included allergic to penicillin and sulfonamides and alcohol use.The patient had family history of high blood pressure, glaucoma, thyroid disease and high cholesterol.The patient had moles.Concomitant treatments included azithromycin [azithromycin] 250 mg tablet, bupropion hcl xl [bupropion hcl xl] 300 mg 24 hour tablet, extended release, clindamycin [clindamycin], fluconazole [fluconazole] 150 mg tablet, methylprednisolone [methylprednisolone] 4 mg tablets in a dose pack, mupirocin [mupirocin] 2 percent topical ointment, omeprazole [omeprazole] 40 mg capsule, delayed release, prednisone [prednisone] 20 mg tablet, spironolactone [spironolactone] 100 mg and 50 mg tablet, 1 tablet by mouth daily.Skin history included cosmetic treatments.The patient also received botox [botox] 20 units to the corrugator and procerus muscles and 24 units to the crow's feet area.The patient had previously received treatment with unspecified ha filler.Treatment was well tolerated by the patient and post-care was discussed.The procedure was completed without event and there was no post procedure bruising.Pre-treatment anesthetic was used and injection amount used mentioned as 4 cc.On (b)(6) 2018, the patient received treatment with 2 ml restylane defyne (lot 16042) to cheeks and jawline area, 1 ml restylane silk (lot 15453) to perioral area and 2 ml restylane lyft with lidocaine (lot 16114) to hands.Needle type and injection technique were unknown.Within one week, on unknown date in (b)(6) 2018, the patient began to experience pain(implant site pain) and edema/swelling/fluid(implant site oedema) in her face, as well as multiple hardened masses/indurated nodules(implant site nodule) on her face.The patient presented to emergency department, where a ct of the maxillofacial with and without contrast was performed.On (b)(6) 2018, the physician noted a complex mass in the left malar check region found measuring 1.3 x 2.1 cm.Fluidal edema was noted, and the injection of fillers was identified to be the considered cause.Specifically, three (3) facial abscess(implant site abscess) at the left molar cheek region, right nasolacrimal groove region and right pre-mandibular area were noted.Medium attenuated fluid related to filler injections at the contralateral areas were also noted.On (b)(6) 2018, the patient contacted to discuss the signs and symptoms of her injuries with the physician and was placed on a regimen of bactrim [trimethoprim/sulfamethoxazole] to reduce the infection/biofilm(implant site infection) and swelling.The patient also subsequently consulted a dermatologist and infectious diseases specialist, who switched her to doxycycline [doxycycline] 100 mg per oral every 12 hours as well as rifampin [rifampicin].On (b)(6) 2018, the patient was evaluated for the multiple abscesses on her face.The physician reviewed the ct scan, and at this point the patient had a 3 cm x 3cm warm, indurated, tense nodule in her right cheek, hard warm(implant site warmth) nodule on her left cheek, and two indurated warm nodules along her jawline approximately 2 cm from the jawline.After discussion it was recommended the patient undergo hyaluronidase injections to dissolve the filler that was creating the infection.On (b)(6) 2020, the entire face was wiped clean with alevicin twice and then several wheals of lidocaine with epinephrine [lidocaine w/epinephrine] were made to access the right cheek and the indurated areas in the lower face.After cleansing and anesthetizing the region, 150 units of hyaluronidase [hyaluronidase] and 1 ml were combined in a 3 ml syringe and injected into the palpable mass with a 27g, 1.5 inch needle.This was then repeated with another 150 units on hyaluronidase and another ml of lidocaine.This was then repeated a third time with yet another 150 units of hyaluronidase and another cc of lidocaine 1 percent.Pressure was kept on the mass and gently massaged.Over the next few minutes the hard nodule became fluctuant and began to leak out of the injection sites made by the 27g needles used to deliver the hyaluronidase.At that point, a sterile 18g needle and 3 ml syringe were inserted into the fluctuant mass to aspirate it's contents through a sterilized region of the skin inferio-lateral to the canthal fold.Approximately 1-1.5 cc of sero-sangeounous fluid was aspirated and another cc or so was expressed after aspiration through the aforementioned aspiration site.Pressure was held on the site while moved to the mandibular region of the face.The skin over the mandible was again cleansed with alevicin.Then, 150 units of hyaluronidase and 1 ml were combined in a 3 ml syringe and injected into the palpable mass with a 27g, 1.5 inch needle on the right side of mandible approximately 1 cm below the right oral commissure.This exact process was then repeated on the left side of the mandible.These areas were also intervened by a sterile 18g needle on a sterile 3 ml syringe through a cleansed port at the area of greatest induration.Both areas were aspirated.However, neither side produced an aspirate.Pressure was held and the last of the available hyaluronidase was injected into both sides another 75 iu into each indurated site.The procedure went without complication, the patient tolerated the procedure well and was asked to return to office in 48 hours for re-evaluation and potentially continued injection of the enzyme.On (b)(6) 2018, the patient was re-evaluated, and further hyaluronidase injections were given.At this point, the regions were noted to be pitting/divots/abnormal appearance (cutaneous contour deformity) with bruising(implant site bruising).However induration and fluctuation had resolved.No erythema or ttp.Next upper quadrant cheek appears to be a nodule in the inferior lateral space.Superior to the buccal fat pad.No erythema, no tenderness to palpation.The lower face had diffuse ttp, erythema(implant site erythema), induration and right submandubular lymphadenopathy, accompanied with diffuse warmth to palpation.The following procedure was performed.Prepped and cleaned area with alevicin.Injected 1 ml of lido 1% with epinephrine 1:100,000.Using a 3cc syringe and 27g needle, 600i iuof hyaluronidase was injected along with 1cc of 1% lidocaine.Area was massaged vigorously.The patient was instructed to use warm compresses and stayed overnight in a hotel near the doctor office.The bactrim was subsequently changed to doxycycline 100mg and rifampin 300mg.The nature of infection was discussed and future management with a plastic surgeon, dermatologist and infectious disease doctor.On (b)(6) 2020, on examination of right upper quadrant at the site of the previous nodule, area was healing.There was no induration.However, there was mild ttp and a nodule approximately 1x1cm in the medial aspect of the cheek, and approximately 1 cm below the medial canthal fold.Left cheek examination had no erythema, no ttp, with the exception of an inferior lateral nodule measuring approximately 2 cm long by 2 cm wide with no ttp or erythema.The lateral mandible was unremarkable.Upon palpation of the medial aspect of the chin was a 1 cm nodule below the oral comrnisure.There was induration varying 1 cm by 1 cm 1 cm.All illicit nodules were mild ttp to deep palpation.There was submandibular lymphadenopathy on the right side, left side was unremarkable.Neck exam was unremarkable.It was planned to continue with another 6 x 150 international units of hyalurondise in lower face and one in the left cheek nodule.The plan of care for patient was changed from rifampin to clarithromycin [clarithromycin] 300 mg orally bid and a prednisone [prednisone] burst and taper were recommended on (b)(6) 2018.On (b)(6) 2018, it was found that induration and nodules wer resolving.Still some densities along the jaw line but much less tense.Still awaiting cultures and sensitivities.No more injections were planned.Advised warm compresses.The patient would continue antibiotics and prednisone.On (b)(6) 2018, the patient presented to hcp office with a new nodule on her left chin and was injected with 300 iu hylenex [hyaluronidase].The patient was noted to be continuing to take doxycycline for 8 weeks.On (b)(6) 2018, the patient underwent a repeat maxillofacial ct with and without contrast.Edema was noted with deep cellulitis(implant site cellulitis) with reactive lymphadenitis (lymphadenitis).Immature abscesses collections were noted bilaterally in the pre-mandibular and submandibular areas, and further woke up was advised.On (b)(6) 2018, another round of hylenex and 2 ml kenalog [triamcinolone acetonide] was injected into the abscessed areas on patient face.Cannula was used.Patient tolerated the procedure well.On (b)(6) 2019, the patient was followed up with care with (b)(6) where filler infection was noted, and she was again injected with hylenex in three areas of her face and 1 ml vitrase [hyaluronidase] cheek and chin.On (b)(6) 2019, again 1 ml vitrase [hyaluronidase] was injected into patient face to dissolve the infected filler.On (b)(6) 2019, an injection of kenalog was utilized in chin, as well as botox [botulinum toxin type a] to try to reduce the pitting.On (b)(6) 2019, the patient was followed up with dermatology associates of atlanta, where the patient was noted to be concerned with the abnormal appearance of her cheeks and face.The use of flourouracil 5-fu was discussed as a possibility, as were direct prednisone shots into the cheeks.This was not proceeded with however, as it was noted to potentially cause mote divots/pitting in the face.Vitrase was injected to try to dissolve infectious process from filler.This was again performed on (b)(6) 2019 in cheek and chin.The patient continued to experience flare ups of abscesses on her face through the fall of 2019 and continued to take steroids to control flare-ups.She was advised not to have surgery to correct divots/pitting until the filler infection had become static.On (b)(6) 2020, the patient underwent surgery to correct the divots/pitting in her face caused by the restylane filler.She still had some noticeable pitting, and micro needling as well as possible subscision and fat transfer had been recommended to correct those deformities.Outcome at the time of the report: abscess was unknown.Infection/biofilm was unknown.Multiple hardened masses/indurated nodules was unknown.Pitting/divots/abnormal appearance was not recovered/not resolved.Inflammatory response was unknown.Deep cellulitis was unknown.Edema/swelling/fluid was unknown.Pain was unknown.Warm was unknown.Bruising was unknown.Erythema was unknown.Reactive lymphadenitis was unknown.

Manufacturer Narrative

Pharmacovigilance comments: 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.No potential quality issues have been identified in the manufacturing process of the specified batch.The batch is manufactured and released according to galderma quality management system.The information in this case does not indicate a nonconforming product or malfunction.The performed investigations are therefore considered adequate and no additional investigations will be conducted.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 nonconforming product or malfunction and to confirm this a batch record review will be requested.

Event Description

Case reference number (b)(4) is a spontaneous report sent on 28-dec-2020 by a lawyer which refers to a 68-year-old female patient.The patient's medical history included allergic to penicillin and sulfonamides and alcohol use.The patient had family history of high blood pressure, glaucom, thyroid disease and high cholesterol.The patient had moles.Concomitant treatments included azithromycin [azithromycin] 250 mg tablet, bupropion hcl xl [bupropion hcl xl] 300 mg 24 hour tablet, extended release, clindamycin [clindamycin], fluconazole [fluconazole] 150 mg tablet, methylprednisolone [methylprednisolone] 4 mg tablets in a dose pack, mupirocin [mupirocin] 2 percent topical ointment, omeprazole [omeprazole] 40 mg capsule, delayed release, prednisone [prednisone] 20 mg tablet, spironolactone [spironolactone] 100 mg and 50 mg tablet, 1 tablet by mouth daily.Skin history included cosmetic treatments.The patient also received botox [botox] 20 units to the corrugator and procerus muscles and 24 units to the crow's feet area.The patient had previously received treatment with unspecified ha filler.Treatment was well tolerated by the patient and post-care was discussed.The procedure was completed without event and there was no post procedure bruising.Pre-treatment anesthetic was used and injection amount used mentioned as 4 cc.On 12-sep-2018, the patient received treatment with 2 ml restylane defyne (lot 16042) to cheeks and jawline area, 1 ml restylane silk (lot 15453) to perioral area and 2 ml restylane lyft with lidocaine (lot 16114) to hands.Needle type and injection technique were unknown.Within one week, on unknown date in sep-2018, the patient began to experience pain(implant site pain) and edema/swelling/fluid(implant site oedema) in her face, as well as multiple hardened masses/indurated nodules(implant site nodule) on her face.The patient presented to emergency department, where a ct of the maxillofacial with and without contrast was performed.On 30-sep-2018, the physician noted a complex mass in the left malar check region found measuring 1.3 x 2.1 cm.Fluidal edema was noted, and the injection of fillers was identified to be the considered cause.Specifically, three (3) facial abscess(implant site abscess) at the left molar cheek region, right nasolacrimal groove region and right pre-mandibular area were noted.Medium attenuated fluid related to filler injections at the contralateral areas were also noted.On 17-oct-2018, the patient contacted to discuss the signs and symptoms of her injuries with the physician and was placed on a regimen of bactrim [trimethoprim/sulfamethoxazole] to reduce the infection/biofilm(implant site infection) and swelling.The patient also subsequently consulted a dermatologist and infectious diseases specialist, who switched her to doxycycline [doxycycline] 100 mg per oral every 12 hours as well as rifampin [rifampicin].On (b)(6) 2018, the patient was evaluated for the multiple abscesses on her face.The physician reviewed the ct scan, and at this point the patient had a 3 cm x 3cm warm, indurated, tense nodule in her right cheek, hard warm(implant site warmth) nodule on her left cheek, and two indurated warm nodules along her jawline approximately 2 cm from the jawline.After discussion it was recommended the patient undergo hyaluronidase injections to dissolve the filler that was creating the infection.On (b)(6) 2020, the entire face was wiped clean with alevicin twice and then several wheals of lidocaine with epinephrine [lidocaine w/epinephrine] were made to access the right cheek and the indurated areas in the lower face.After cleansing and anesthetizing the region, (b)(4) units of hyaluronidase [hyaluronidase] and 1 ml were combined in a 3 ml syringe and injected into the palpable mass with a 27g, 1.5 inch needle.This was then repeated with another (b)(4) units on hyaluronidase and another ml of lidocaine.This was then repeated a third time with yet another (b)(4) units of hyaluronidase and another cc of lidocaine 1 percent.Pressure was kept on the mass and gently massaged.Over the next few minutes the hard nodule became fluctuant and began to leak out of the injection sites made by the 27g needles used to deliver the hyaluronidase.At that point, a sterile 18g needle and 3 ml syringe were inserted into the fluctuant mass to aspirate it's contents through a sterilized region of the skin inferio-lateral to the canthal fold.Approximately 1-1.5 cc of sero-sangeounous fluid was aspirated and another cc or so was expressed after aspiration through the aforementioned aspiration site.Pressure was held on the site while moved to the mandibular region of the face.The skin over the mandible was again cleansed with alevicin.Then, 150 units of hyaluronidase and 1 ml were combined in a 3 ml syringe and injected into the palpable mass with a 27g, 1.5 inch needle on the right side of mandible approximately 1 cm below the right oral commissure.This exact process was then repeated on the left side of the mandible.These areas were also intervened by a sterile 18g needle on a sterile 3 ml syringe through a cleansed port at the area of greatest induration.Both areas were aspirated.However, neither side produced an aspirate.Pressure was held and the last of the available hyaluronidase was injected into both sides another 75 iu into each indurated site.The procedure went without complication, the patient tolerated the procedure well and was asked to return to office in 48 hours for re-evaluation and potentially continued injection of the enzyme.On 22-oct-2018, the patient was re-evaluated, and further hyaluronidase injections were given.At this point, the regions were noted to be pitting/divots/abnormal appearance (cutaneous contour deformity) with bruising(implant site bruising).However induration and fluctuation had resolved.No erythema or ttp.Next upper quadrant cheek appears to be a nodule in the inferior lateral space.Superior to the buccal fat pad.No erythema, no tenderness to palpation.The lower face had diffuse ttp, erythema(implant site erythema), induration and right submandubular lymphadenopathy, accompanied with diffuse warmth to palpation.The following procedure was performed.Prepped and cleaned area with alevicin.Injected 1 ml of lido 1% with epinephrine 1:100,000.Using a 3cc syringe and 27g needle, 600i iuof hyaluronidase was injected along with 1cc of 1% lidocaine.Area was massaged vigorously.The patient was instructed to use warm compresses and stayed overnight in a hotel near the doctor office.The bactrim was subsequently changed to doxycycline 100mg and rifampin 300mg.The nature of infection was discussed and future management with a plastic surgeon, dermatologist and infectious disease doctor.On (b)(6) 2020, on examination of right upper quadrant at the site of the previous nodule, area was healing.There was no induration.However, there was mild ttp and a nodule approximately 1x1cm in the medial aspect of the cheek, and approximately 1 cm below the medial canthal fold.Left cheek examination had no erythema, no ttp, with the exception of an inferior lateral nodule measuring approximately 2 cm long by 2 cm wide with no ttp or erythema.The lateral mandible was unremarkable.Upon palpation of the medial aspect of the chin was a 1 cm nodule below the oral comrnisure.There was induration varying 1 cm by 1 cm 1 cm.All illicit nodules were mild ttp to deep palpation.There was submandibular lymphadenopathy on the right side, left side was unremarkable.Neck exam was unremarkable.It was planned to continue with another 6 x 150 international units of hyalurondise in lower face and one in the left cheek nodule.The plan of care for patient was changed from rifampin to clarithromycin [clarithromycin] 300 mg oraly bid and a prednisone [prednisone] burst and taper were recommended on (b)(6) 2018.On (b)(6) 2018, it was found that induration and nodules wer resolving.Still some densities along the jaw line but much less tense.Still awaiting cultures and sensitivities.No more injections were planned.Advised warm compresses.The patient would continue antibiotics and prednisone.On 12-nov-2018, the patient presented to hcp office with a new nodule on her left chin and was injected with 300 iu hylenex [hyaluronidase].The patient was noted to be continuing to take doxycycline for 8 weeks.On (b)(6) 2018, the patient underwent a repeat maxillofacial ct with and without contrast.Edema was noted with deep cellulitis(implant site cellulitis) with reactive lymphadenitis (lymphadenitis).Immature abscesses collections were noted bilaterally in the pre-mandibular and submandibular areas, and further woke up was advised.On (b)(6) 2018, another round of hylenex and 2 ml kenalog [triamcinolone acetonide] was injected into the abscessed areas on patient face.Cannula was used.Patient tolerated the procedure well.On (b)(6) 2019, the patient was followed up with care with dermatology associates where filler infection was noted, and she was again injected with hylenex in three areas of her face and 1 ml vitrase [hyaluronidase] cheek and chin.On (b)(6) 2019, again 1 ml vitrase [hyaluronidase] was injected into patient face to dissolve the infected filler.On (b)(6) 2019, an injection of kenalog was utilized in chin, as well as botox [botulinum toxin type a] to try to reduce the pitting.On (b)(6) 2019, the patient was followed up with dermatology associates of atlanta, where the patient was noted to be concerned with the abnormal appearance of her cheeks and face.The use of flourouracil 5-fu was discussed as a possibility, as were direct prednisone shots into the cheeks.This was not proceeded with however, as it was noted to potentially cause mote divots/pitting in the face.Vitrase was injected to try to dissolve infectious process from filler.This was again performed on (b)(6) 2019 in cheek and chin.The patient continued to experience flare ups of abscesses on her face through the fall of 2019 and continued to take steroids to control flare-ups.She was advised not to have surgery to correct divots/pitting until the filler infection had become static.On (b)(6) 2020, the patient underwent surgery to correct the divots/pitting in her face caused by the restylane filler.She still had some noticeable pitting, and micro needling as well as possible subscision and fat transfer had been recommended to correct those deformities.Outcome at the time of the report: abscess was unknown.Infection/biofilm was unknown.Multiple hardened masses/indurated nodules was unknown.Pitting/divots/abnormal appearance was not recovered/not resolved.Inflammatory response was unknown.Deep cellulitis was unknown.Edema/swelling/fluid was unknown.Pain was unknown.Warm was unknown.Bruising was unknown.Erythema was unknown.Reactive lymphadenitis was unknown.

• Brand Name: RESTYLANE SILK
• Type of Device: IMPLANT, DERMAL, FOR AESTHETIC USE
• Manufacturer (Section D): GALDERMA Q-MED AB; seminariegatan 21; uppsala, SE-75 228; SW SE-75228
• MDR Report Key: 11181305
• MDR Text Key: 232591796
• Report Number: 1000118068-2021-00002
• 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: 02/05/2021

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: No Information
• Device Expiration Date: 02/28/2020
• Device Lot Number: 15453
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: Yes
• Date Report Sent to FDA: 02/05/2021
• Distributor Facility Aware Date: 01/22/2021
• Event Location: Other
• Date Report to Manufacturer: 01/22/2021
• Initial Date Manufacturer Received: Not provided
• Initial Date FDA Received: 01/15/2021
• Supplement Dates Manufacturer Received: Not provided
• Supplement Dates FDA Received: 02/08/2021
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Treatment: AZITHROMYCIN 250 MG TABLET; AZITHROMYCIN 250 MG TABLET; BOTOX; BOTOX; BUPROPION HCL XL 300 MG TABLET; BUPROPION HCL XL 300 MG TABLET; CLINDAMYCIN 300 MG CAPSULE; CLINDAMYCIN 300 MG CAPSULE; FLUCONAZOLE 150 MG TABLET; FLUCONAZOLE 150 MG TABLET; METHYLPREDNISOLONE 4 MG TABLET; METHYLPREDNISOLONE 4 MG TABLET; MUPIROCIN OINTMENT 2 PERCENT TOPICAL; MUPIROCIN OINTMENT 2 PERCENT TOPICAL; OMEPRAZOLE DR 40 MG CAPSULE; OMEPRAZOLE DR 40 MG CAPSULE; PREDNISONE 20 MG TABLET; PREDNISONE 20 MG TABLET; RESTYLANE LYFT WITH LIDOCAINE; RESTYLANE LYFT WITH LIDOCAINE; SPIRONOLACTONE 100 MG DAILY ORAL PILL; SPIRONOLACTONE 100 MG DAILY ORAL PILL; UNSPECIFIED ANESTHETIC; UNSPECIFIED ANESTHETIC
• Patient Outcome(s): Required Intervention
• Patient Age: 68 YR