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DrugStability:Updateandfutureplans.
TimHillsNottinghamUniversityHospitalsNHSTrust
OnbehalfoftheBSACWorkingPartyonDrugStability
BSACDrugStabilityWorkstream
• Updateofprogresssofar• PK/PDconsiderations• FlucloxacillinStabilityresults• MeropenemStabilityresults• Clinicalexperienceofbufferedcontinuousinfusions
2016andbefore• NationalOPATsurvey
– LackofavailabilityofinfusiondeviceswaslimitingOPATandeffectiveantimicrobialstewardshipinOPAT
• Literaturereview121articlesvsNHSQCstandards“YellowCoveredDocument”– Nostudyfullycompliant
JenkinsetalJAC2017
BSACDrugStabilityTestingProgramme
• BSAC-supportedprogrammewithindustrypartners
• Independentlyverified• Open-accessdrug-stabilitydata• Increasingtheopportunityandavailabilityfor
sterileproductionforuseinOPATservices• Stabilitytenderawarded
– Continuousinfusionflucloxacillin– Continuousinfusionmeropenem
PK/PDconsideration
Pre-ScopingStudy
• Assessingpotentiallystableconcentration/formulations
• Lowerstandardofscrutiny
MainStudy(YCD)
• Triplicatetesting• Body-worn32oC• Twoelastomericpumps• Shelf-lifeassignmentrequires95-105%concentration(90-105%ifdegradationproductsfullyunderstood)
BSACDrugStabilityTestingProgramme
Pre-ScopingStudy
• 10and50mg/ml• Unbufferedèunstableat24hr• Sodiumcitratebuffer0.3%pHcirca.7
Flucloxacillin-Results
SodiumCitrate0.3%BufferedFlucloxacillin
• Assignedshelflife13days2-8oCthen24hoursat32oCPoster:Hills,AllwoodetalBSACOPAT2017
Meropenem–6.25mg/ml
Poster:Hills,AllwoodetalBSACOPAT2017
Meropenem–25mg/ml
Poster:Hills,AllwoodetalBSACOPAT2017
CitrateBuffer
3Ca2+
Ca2+
- O-O-
O-Ca2+
Ca2+
6Na+
CitrateBuffer–potentialissues
Citrate-BufferedCIVbeta-lactams• 11patientepisodes
– Fluclox.8g/24hr(n=4)– Fluclox.12g/12hr(n=2)– Pip/taz13.5g/24hr(n=5)
• Arangeofinfectionsweretreated,– Discitis/spinalsurgicalinfection(n=4),– Lungabscess/empyema(n=2),– Neurosurgicalinfection,prostheticjointinfection,diabetic
foot,osteomyelitis,Enterobacterialpneumonia,bronchiectasis(n=1each).
• Extendedbloodstakenatleastonce
Monitoredbloodresults
• NopatientrequiredCIVinterruption• LowCa2+:1xderangedLFTs,1xLowVitaminD• 9from11“Cured”or“Improved”• Nofailuresduetobuffer
OtherCIVissues• Clampwasnotreleased–missedoneday• Patientcutlinewhilstgardening• Linebecame“stiff”èincompleteinfusion• Drugnotrunningthrough?insufficientwarmuptimeor?patienttampering
• Patientselectionimportant• Currentleadtimes• Localpreparation
BSACDrugStabilityTestingProgramme-2018
• Publicationwithopenaccessfromhttp://www.bsac-dsp.com/
• Agents– Piperacillin/tazobactam– ?Benzylpenicillin– Industrypartners
Whichcontinuousinfusionpipercillin/tazobactamwould/doyouuseinyourservice?
Votingoptionsforslido1.13.5g/24hour2.18g/24hour3.Bothoftheabove4.Either5.Neither6.Don’tknow/notsure
2016andbefore
• OPATsurveyresults• LiteraturereviewvsYCDstandards• AwardingofBSACtenderforLaboratorystabilitytestingin-linewithYCD
2017
• Jan-LiteraturereviewpublishedJAC• April-YCDupdate–32oC+/-1oCstandardforexternalbody-wornin-usestudies
• Resultsforbody-wornCIVflucloxacillinandmeropenem• Piperacillin/tazobactamagreedasnextcommissionedagentforstabilitytesting
2018
• Publicationinpeer-reviewedjournalsasopen-accesspublications,linksfromdrugstabilityprogrammewebsite
• Discussionswithindustryrefuturetesting
Acknowledgements• BSACOPATStandardsCommittee-Devices/DrugStabilityWork-stream– ConorJamieson(SandwellandWestBirminghamNHSTrust)
– AndrewSeaton(Glasgow)– MarkGilchrist(Imperial)– MarkSantillo(ChairNHSPharmaceuticalQualityAssuranceCommitteeandQCSouthWest)
– CarolyneHorner(BSACProgrammeManager)