MAUDE Adverse Event Report: BIOCOMPATIBLES U.K. LIMITED LC BEAD; EMBOLIC AGENT SINGLE USE IMPLANTABLE MEDICAL DEVICE

Model Number MI 70-150

Device Problem Insufficient Information (3190)

Patient Problems Hair Loss (1877); Test Result (2695)

Event Type  Other  

Event Description

This is an initial report received on (b)(4) 2014 from a hospital pharmacist.The report is regarding a (b)(6) female pt who developed systemic side effects of alopecia and prolonged neutropenia post chemoembolization.The procedure was undertaken using lc bead (b)(4) (batch# v10627) loaded with 100mg irinotecan.The date of procedure and precise time to onset of the adverse event was not reported.It was however confirmed that the onset of the events was a few days after the procedure and therefore the patients stay in hospital was not prolonged.Genetic testing was undertaken as a result of the adverse events and the pt was found to have ugt1a1 deficiency.No further info was provided regarding pt outcome, the severity of the neutropenia or the treatment of the adverse events.Further info has been requested.

Manufacturer Narrative

Lc bead loaded with irinotecan was used in the treatment of this pt however lc bead is not indicated for use with drugs.The device has not been sent to the mfr for evaluation, however, a batch review will be performed against the lot number which has been provided.Medical assessment: this report is regarding a pt subsequently identified as having ugt1a1 deficiency who developed systemic side effects of alopecia and prolonged neutropenia post chemoembolization with debiri.Very little info has been provided apart from that the adverse events presented a few days post treatment.Whilst it is most likely the event was caused by exposure to irinotecan in this susceptible pt, and unlikely that the systemic reaction was caused by a device malfunction, there is very little info provided to assess the casuality of these systemic like effects of inrinotecan.The severity of the neutropenia was not confirmed and therefore this event is conservatively assessed as reportable.

Manufacturer Narrative

Case comment: neutropenia, alopecia and off label use are considered unlisted according to lc bead current reference safety info.In line with the author's assessment, the company considers that neutropenia and alopecia are not related to the administration of lc beads, but rather related to a pt with undiagnosed homozygous ugt1a128 7/7 allele mutation who received irinotecan.This single case report does not modify the risk benefit balance of lc bead.The company is continuously monitoring all respective reports received and, based on cumulative experience, will re-evaluate the available on an ongoing basis.The btg's final medical assessment concluded that whilst the most likely cause of the event was exposure to irinotecan in a susceptible pt and unlikely that the systemic reaction was caused by a device malfunction, there is very little info provided to assess the causality of these systemic like effects of irinotecan.The severity of the neutropenia was not confirmed, the event was therefore conservatively assessed as reportable.All requirements for reporting were met.No corrective and preventive action (capa) plan has been identified as a result of this rca.The investigation is summarized within the report, no further investigations are required.The potential contributory factors were investigated and assessed as part of this complaint.The potential root cause was identified as a previously unidentified pt genetic disorder ugt1a1 which is known to exacerbate the expected systemic side effects of irinotecan solution.No device failure, trend in a type of incident or unexpected risk to pt or users health has been identified, no field safety corrective action or product recall is required.Batch record review did not identify any issues or non-conformances during the mfg or packaging processes of lc bead lot v10627 that could affect product quality, safety and efficacy.The inspection of the retain sample did not find any abnormalities in the product appearance.A review of the relevant operators training confirmed that operators were appropriately trained.

Event Description

Grade 4 neutropenia.Grade 2 alopecia.Off-label use.F/u info was received on (b)(4) 2014 and on (b)(4) 2014.This literature case report was published in annals of pharmacotherapy by cruz j et al, entitled "the power of genes: a case of unusually severe systemic toxicity after localized hepatic chemoembolization with irinotecan-eluted microspheres for metastatic colon cancer." the articles refers to an 80 y/o female subject undergoing therapy with lc bead (polyvinyl alcohol microspheres) mixed with irinotecan on post-operative day 69 after hemicolectomy.A dose of 100 mg irinotecan was loaded into 70-150-um lc beads to treat residual sites of metastatic disease.The pt's medical history included early-stage breast cancer more than a decade prior to the event; mild dementia; colonoscopy; iron deficiency anemia; near-obstructing cecal mass which was diagnosed as stage iv colon cancer (pt3pn2apm1a); metastases to liver, laparoscopic, robotic-assisted right hemicolectomy and partial hepatectomy; and postoperative deep venous thrombosis of the lower extremity.The concomitant medications included sodium ferric gluconate for iron deficiency anemia and enoxaparin for deep venous thrombosis.On an unspecified date, a pt underwent debiri-tace to treat the residual sites of metastatic disease.The procedure was well tolerated.The pt was discharged to home the day after the procedure.One week later, during a f/u appointment, the pt was noted to be neutropenic without a fever.The absolute neutrophil count was 400/mm3 (grade 4).Neutropenia persisted for 24 days after the procedure.In addition, she developed grade 2 alopecia approx 3 weeks after the procedure.These events were noted as severe systemic toxicity.A complete genomic analysis was done which revealed a homozygous mutation ugt1a128/77.A score of 7 on the naranjo algorithm indicated that the identified reaction had a probable causal relationship to debiri-tace therapy.The pt was not hospitalized for the event.The events of neutropenia and alopecia subsequently resolved completely.The authors considered the event of neutropenia and alopecia as related to debiri-tace therapy with irinotecan chemotherapy in a pt with ugt1a1 polymorphism but not to lc bead (polyvinyl alcohol microspheres).The authors noted, "the toxic effects of irinotecan are well understood.Pts with genetic polymorphisms of genes encoding for the enzymes ugt1a1 may have increased incidence of irinotecan-associated toxicities because of decreased clearance of the active metabolite sn38 via the glucuronidation pathway.To date, there have been limited publications describing systemic adverse events following tace or debiri-tace and, based on a thorough literature search, none following these procedures in pts with ugt1a1 polymorphisms.Based on the scoring results of the naranjo algorithm (7), we are confident in attributing the observed reaction to the pt's genetic polymorphism.".

• Brand Name: LC BEAD
• Type of Device: EMBOLIC AGENT SINGLE USE IMPLANTABLE MEDICAL DEVICE
• Manufacturer (Section D): BIOCOMPATIBLES U.K. LIMITED; weydon lane; farnham business park; farnham, surrey GU9 8 QL; UK GU9 8QL
• Manufacturer (Section G): BIOCOMPATIBLES UK LTD; weydon lane; farnham business park; farnham, surrey GU9 8 QL; UK GU9 8QL
• Manufacturer Contact: farnham business park; weydon ln; farnham, surrey GU9 8-QL ; 252732732
• MDR Report Key: 3878142
• MDR Text Key: 4461362
• Report Number: 3002124545-2014-00014
• Device Sequence Number: 1
• Product Code: HCG
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: K094018
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional,health professional,litera
• Reporter Occupation: Pharmacist
• Type of Report: Initial,Followup
• Report Date: 06/04/2014

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 06/13/2014
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Model Number: MI 70-150
• Device Lot Number: V10627
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 09/05/2014
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Unknown
• Patient Sequence Number: 1
• Treatment: IRINOTECAN
• Patient Outcome(s): Other
• Patient Age: 80 YR