Läkemedelsverkets Farmakovigilansdag

Transcription

1 Läkemedelsverkets Farmakovigilansdag PRAC : Pharmacovigilance Risk Assessment Committee Kommittén för säkerhetsövervakning & riskbedömning av läkemedel Farmakovigilansdagen maj 2018 Ulla Wändel Liminga, PhD Ämnesområdesansvarig farmakologi/toxikologi; PRAC delegat 1 The PRAC Structure, responsibilities & tasks Some figures Transparency Public hearing Summary of presentation Recent referral procedures Examples PRAC Workplan Observera att bilderna är presentatörens tolkning och avspeglar den information som fanns tillgänglig vid presentationstillfället. 1

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3 Läkemedelsverkets Farmakovigilansdag Agenda items Signals at PRAC signals 700 discussions Outcomes update of Product information 50% routine PhV / monitor within PSUR 36% ongoing end % referral 4% update RMP 2% PASS < 1% Observera att bilderna är presentatörens tolkning och avspeglar den information som fanns tillgänglig vid presentationstillfället. 3

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5 Läkemedelsverkets Farmakovigilansdag View of risks of using valproate during pregnancy, incl child? Agreement risks undeniable, well characterised. Seriousness & impact on those affected powerfully & movingly conveyed Views on current risk minimisation measures? Improved information resources developed after PRAC review 2014; BUT not reaching right people at right time Hoped for strengthening of risk minimisation not seen Other measures to reduce valproate risks during pregnancy? Many proposals e.g. Visual reminder on package Always dispensed in appropriate package + adequate risk info Alert in prescribing / dispensing software Regular reviews for all women on long term valproate Record women appropriately counselled Development of professional education More coordinated care services at national level Public awareness (tools for campaigns) 9 Valproate referral outcome Contraindicated in girls / women of child bearing potential unless pregnancy prevention programme followed assessment of each patient s potential for becoming pregnant pregnancy tests before starting & during treatment as needed, counselling risks & need for effective contraception whole treatment at least annual review of ongoing treatment by specialist new risk acknowledgement form Not used unless alternative treatments not suitable Visual warning on package (boxed text / pictogram) Educational materials for patients & prescribers MAHs undertake further studies 10 Observera att bilderna är presentatörens tolkning och avspeglar den information som fanns tillgänglig vid presentationstillfället. 5

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7 Läkemedelsverkets Farmakovigilansdag Hydroxyethyl starch (HES) Ongoing referrals low adherence to restrictions aimed at reducing risks of kidney injury and death (Art 107i), SE PRAC CoRapp, triggered by SE Ulipristal acetat (Esmya) risk of rare, serious liver injury (Art 20), SE PRAC Rapp; PRAC Rec May 18 Quinolone and fluoroquinolone long lasting effects mainly affecting musculoskeletal and nervous systems (Art 31) Radium (223Ra) dichloride (Xofigo) increased risk of death and fractures reported in an ongoing clinical trial (Art 20) Methotrexate risk of dosing errors (Art 31) 13 Paracetamol modified release Review B/R of modified & prolonged release paracetamol [MR] triggered by Sweden July 2016 Paracetamol + tramadol combo included in review; not IR Case reports & retrospective PK & clinical analysis* indicate recommended risk assessment of suspected poisonings inadequate standard treatment protocol with antidote NAC insufficient to manage overdoses with Alvedon 665 mg MR Overdoses w. Alvedon 665 mg MR causing hepatic injury, despite timely treatment, reported PRAC review Several rounds of questions, incl. re examination. Two ad hoc expert meetings BE PRAC Rapp, SE PRAC CoRapp, Re examination PRAC Rapp HR, CoR PL * Salmonson H, et al. Clin Toxicol 2016;54:424 (Abstract 124) 14 Observera att bilderna är presentatörens tolkning och avspeglar den information som fanns tillgänglig vid presentationstillfället. 7

8 Läkemedelsverkets Farmakovigilansdag Paracetamol modified release Review of all data submitted PRAC concluded Benefit/risk balance negative: Highly variable PK profile of overdoses with MR paracetamol formulations, uncertainties related to quantity & formulation that patient has ingested increase challenges in effective RMM for paracetamol toxicity Tramadol safety profile additional challenges for RMM Proposed RMM to reduce risk for overdose (education, communication, restricting availability) insufficient to minimise intentional / accidental overdoses hepatic injury following MR overdose not sufficiently effective/ reliable Majority recommendation in PRAC and CMDh Sept / Dec 2017 EC decision February HES (hydroxyethyl starch) HES: synthetic colloids used for plasma volume expansion 2012/2013: PRAC referrals due to large RCTs showing increased mortality, renal impairment in patients with sepsis, or being critically ill Contraindicate e.g. sepsis, critically ill etc Conditions : Studies in approved indication; drug utilisation studies (DUSs) Autumn 2017: DUSs show continued use in contraindicated patients SE trigger 107i referral (urgent safety review) in October 2017 Non adherence to revised product information e.g % non adherence to contraindications (9 % of patients exposed to HES critically ill, 5 8% of patients renal impairment, 3 4 % sepsis) Use in CI patient populations associated with scientifically well established risk for serious harm including mortality. Estimations in EU approx million patients exposed yearly Sweden seriously questioned if benefit/risk balance of these medicinal products remains favourable 16 Observera att bilderna är presentatörens tolkning och avspeglar den information som fanns tillgänglig vid presentationstillfället. 8

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