Dear Mr Pollard Re Irene Ann PEARSON (Deceased) (your Ref: JSPIERJ01780-2015) Following your officer' $ phone call with Meera Pithia on 30th March 2016, this letter constitutes Takeda'$ response to the Regulation 28 report. Item @ With regard to your specific comment concerning the lack of clarity over heat exposure, we would like to bring your attention the fact that the first page of the Matrifen patient information leaflet displays a list of *Important you need to know about Matrifen transdermal patches'_ This comprises 7 bullet points highlighted in bold text; including 'do not expose the patches to a heat source (such as a bot water bottle) . Given the need to balance completeness with brevity and understandability in the compilation of patient information leaflets, our current view is that the information presented in the Matrifen leaflet adequately addresses the issue of expoging patches to heat sources However; we have reported this matter to Johnson and Johnson; who own the brand leader product Durogesic, and have requested that conduct & review to determine whether any changes are required to the product information a8 a Tesult of this incident: We are obliged to ensure that the product information leaflet for Matrifen is consistent with that for Durogesic. We can confirm that this incident has becn reported to the Medicines and Healthcare Products Regulatory Agency (MHRA) For your information, we can additionally confirm that the product information for Fentanyl patches (which include Matrifen) hag recently extensively reviewed by the MHRA to ensure the wamings are adequate. Item 2; With regard to your request for us to define 'prolonged' and *hot' Iam afraid we are not able to do this a8 we do not have sufficient data on heat exposure and fentanyl absorption t0 determine what an appropriate duration or temperature would be. Takeda UK Ltd. Building 3, Glory Park; Glory Park Avenue, Wooburn Green, Bucknghamshire HPIQ ODF United Kingdom Tel: +44(0} 1628 537900 * Fax: +44(0] 1628 526615 wvwwtakeda co uk Regittered ollice; Buldg dory Park, Clory Park Avenue. wonhum Grcen; Buckinghamstiire; HPIO ODr, United Xingdom Registcrcd h Englard Jnd Walc; No 3362860 things tbey been safety

Takeda Futthermore; since rate of absorption will vary by person, depending on dosage, age and body weight for example, giving advice in terms of exact duration and temperature would be inappropriate. Should you require any additional information regarding this rcport_please do not hesitate to contaci Deputy Safety Officer on

Dear Mr Pollard Re: Irene Anne Pearson (Deceased) am writing in response to your regulation 28 report forwarded to the Trust by Macmillan Cancer Care following the inquest into the death of the above named person: am grateful to you for highlighting your concerns and for providing me with an opportunity to respond: shall address each of your concerns in the order in which you raised them: heard evidence that the Macmillan Nurses had advised the deceased to take a bath when preparing to remove the 'exhausted' patch s0 as to aid removal: The toxicologist pointed out that even when due for change, the patch contains (and therefore can release) very considerable level of the The advice to use this method of removal would therefore seem to be inherently potentially dangerous: The Macmillan team have provided assurance that would not advise anyone to take a bath to aid removal of an exhausted or indeed to submerge the patch in water: In response to the information you have shared we have sent a 'Trust Alert' out to all hospital and community staff to ensure are reminded of this risk was told that the Macmillan Nurses will prescribe additional opiate pain control, but there seemed little or no Iiaison with the GP Practice as to the regulation of this: It is the practice of the Macmillan team when changing or prescribing medication to the relevant GP practice within 24 hours_ In terms of prescribing for Mrs Pearson, the following information (in italics) indicates the Iiaison which occurred from the Macmillan team to the GP practice: understand that on receipt; these faxes are scanned and attached to the GP records_
24.03.15 Dexamethasone 4mgs daily x28 tablets Cyclizine SOmgslml x10 ampoules Water for injection drug: they patch they fax

01.04.15 BuTrans 1Omcgs/hr x patches: One patch every 7 days Oramorph 1Omgs/smls x1OOmls 2.5-Smls pm Cyclizine for injection SOmgs/ml x10 Cyclizine S0mgs TDS x1o0
12.05.15 Fentanyl 25mcgs/hr 72hours x10 patches: Stop BuTrans patches
02.06.15 Benzydamine oral mucosal spray 3Omls x2 Increased Mirtazipine from 15mgs to 3Omgs
08.06.15 A letter was faxed to GP after Mrs Pearson's husband phoned the Macmillan team following a review by an Out of Hours GP who had increased the Fentanyl patch from 25mcgs to 5Omcgs: Mr Pearson confirmed that she was much better and not experiencing any side effects He was requesting more patches ad this request was included in the letter faxed to the GP to prescribe if he felt it appropriate
29.06.15 Request for Mirtazipine 1 x6O. Take 2 at night
01.07.15 Following visit from Macmillan nurse, the Fentanyl patch Was decreased from SOmcgs to 37mcgs and therefore 12mcgs Fentanyl patch was prescribed (x5). (i.e. 25mcgs plus 12mcgs)
07.07.15 Mrs Pearson was visited due to an increase in pain; Irene and her family informed staff that had increased the patch 37mcgs back to sOmcgs on the 06.07.2015 without seeking advice: We have clarified with the GP practice and the notifications of the above prescriptions completed by the Macmillan team were all received by the practice and scanned onto the patient records. We cannot find a record of the letter sent on 08.08.2015 as above; however we did find that this change of medication the Out of Hours GP was communicated to the practice_ hope that this response answers your concerns and provides you with the assurance that the Trust is committed to improving the quality of care we give to all our patients. Please do not hesitate to contact me if yourave any further questions regarding this matter: