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ClinicalPearlsUNMHPharmacyResidents
JessicaLewis-Gonzalez,PharmDValentinPacuraru,PharmDAmre Elmaoued,PharmDSienaMeador,PharmDNgoc-YenPham,PharmD
ManagementofAdverseEffectsofPD1/PDL1Inhibitors
JessicaLewis-Gonzalez,PharmDPGY-1PharmacyResidentUniversityofNewMexicoHospitals
Objectives
¡ Pharmacist§ EvaluateandassessthemanagementofadverseeffectsofthePD1/PDL1inhibitors
¡ Technician§ Identify managementofadverseeffectsofthePD1/PDL1inhibitors
Wait…whichdrugsarethoseagain???
¡ PD1Inhibitors§ Pembrolizumab(Keytruda)
§ Nivolumab(Opdivo)
¡ PDL1Inhibitors§ Atezolizumab(Tecentriq)§ Avelumab(Bavencio)§ Durvalumab(Imfinzi)
• TheseareIVcancerchemotherapymedicationsthatareadministeredmostcommonlyintheoutpatientsettingatinfusioncenters.
Whyisthisimportanttoyou?
AdverseEventstobeAwareof:
¡ Immunerelatedadverseevents§ Dermatologic§ GI§ Hepatic§ Endocrine§ Otherlesscommoninflammatoryevents
Postcow.JourClin Onc.2015.
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GradingofAdverseEvents¡ PerCommonTerminologyCriteriaforAdverseEvents(CTCAE):
NIH,NCI.CommonTerminologyCriteriaforAdverseEventsV.5.0.2017.
TreatmentofAdverseEvents(InGeneral)
¡ Grade1:Mild,asymptomatic§ Management:Observation,interventionnotneeded
¡ Grade2:Moderate§ Management:Localornoninvasiveinterventionindicated§ Willlikelyneedlow-doseoralprednisone/methylprednisoloneandmaybe
abletocontinuetreatment¡ Grade3:Severalormedicallysignificantbutnotimmediatelylife-
threatening§ Management:Stopimmunotherapy,hospitalizationindicated,highdose
prednisone/methylprednisolone¡ Grade4:Life-threateningconsequences
§ Management:Urgentintervention,willpermanentlystopimmunotherapy¡ Grade5:DeathrelatedtoAE
NIH,NCI.CommonTerminologyCriteriaforAdverseEventsV.5.0.2017.
Derm AdverseEvent- MaculopapularRashGrade Hold
ImmunotherapySteroids Antihistamine Other
1 Moderate-potencytopical
Topicalemollient
2 Consider holding High-potency topicalAND/OR
low-dose prednisone/methylprednisolone
Topicalemollient
3/4 High-potency topical+low-dose prednisone/methylprednisolone(increasedoseifno
improvement)
UrgentDermConsult
NCCN.ManagementofImmunotherapy-RelatedToxicities(Version1.2018).
GIAdverseEvent- Diarrhea/ColitisGrade Hold
ImmunotherapySteroids Permanently DC Other
1 Considerholding Loperamide,hydration
2 IVmethylprednisolone
1mg/kg/day
3(considerresumingafterresolution)
IVmethylprednisolone
2mg/kg/day
ConsiderInpatientSupportiveCare
4 IVmethylprednisolone
2mg/kg/day
ConsiderInpatientSupportiveCare
(NCCN).ManagementofImmunotherapy-RelatedToxicities(Version1.2018).
HepaticAdverseEvent- AcutePancreatitis
Grade HoldImmunotherapy
Steroids Permanently DC Other
1 ConsiderGastroenterology
Referral
2 Low-doseprednisone/
methylprednisolone
3/4 High-doseprednisone/
methylprednisolone
(NCCN).ManagementofImmunotherapy-RelatedToxicities(Version1.2018).
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Low-dosevsHigh-dosesteroids¡ Low-dosecorticosteroidsforgrade2:
§ prednisoneormethylprednisolone0.5–1 mg/kg/day¡ High-dosecorticosteroidsforgrade3and4:
§ prednisoneormethylprednisolone1–2 mg/kg/day¡ Taperingoffsystemiccorticosteroidsover4–6 weeksafter
symptomshaveresolvedtoGrade1or2
Rudzki,JD.MemoSpringer.2018.
Summary¡ Whenitcomestoimmune-relatedadverseeventswithcheckpointinhibitors– Steroidsareyourfriends!§ Topical§ Low-dose§ High-dose
¡ WhenpatientspresenttothehospitalonaPD-1/PDL-1inhibitorwithanacuteevent:§ Considerdrugasapotentialcause§ Gradethereaction(ifcausedbydrug)§ Treatbasedongrading
ApproachtothePatientwithNausea&VomitingandQTcProlongation
ValentinPacuraru,PharmDPGY-1PharmacyResidentUniversityofNewMexicoHospitals
LearningObjectives
Pharmacists• DefinetheextentofQTcprolongingeffectofseveralN/Vmedications.
Technicians• IdentifythefivemostcommonlyuseddrugsforN/VthatimpactQTc.
QTcProlongationandriskofTorsades dePointes
Torsades
https://pedemmorsels.com/prolonged-qtc/
DefiningQTcProlongationQTc ValuesbyAgeandSex(ms)
1– 15y/o AdultMales AdultFemales
Normal <440ms <430ms <450ms
Borderline 440– 460ms 430– 450ms 450– 470ms
Prolonged >460ms >450ms >470ms
• >500ms
ClinicallySignificantQTcProlongation
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TorsadesdePointesRiskFactors¡ FemaleSex¡ Hypokalemiaand/orHypomagnesemia¡ Bradycardia¡ RecentCardioversion¡ StructuralHeartDisease¡ DigoxinTherapy¡ BaselineQTProlongation¡ RapidIVinfusionofQTprolongingmedications¡ PharmacokineticInteractions
LiM.PT.2017LinYL.Pharmacoepidemiol DrugSaf.2009
RiskScoringOptionTisdale RiskScoreRiskFactor Points QTc Interval RiskStratificationAge>68 1 RiskCategory RiskScoreFemaleGender 1
Low <7LoopDiuretic 1Potassium<3.5mEq 2QTc >450onAdmit 2
Moderate 7– 10AcuteMI 22+QTc Prolonging Drugs 3Sepsis 3
High >11HeartFailure 3OneQTc ProlongingMed 3
Maximum RiskScore 21TisdaleJE.CanPharmJ2016
ApproachingNauseaandVomiting
Gastroparesis
Infectious
MedicationInduced
ElectrolyteorFluidAbnormality
GIObstruction/Inflammation
GERD
DiabetesRelated
TreattheUnderlyingEtiologyFirst
CommonInpatientMedicationsforNauseaandVomiting
Ondansetron
Promethazine
Prochlorperazine
MetoclopramideHaloperidol
Trimetho-benzamide
Olanzapine
AlternateAgentsforNausea&Vomiting
Dexamethasone• BestdataforPONVandCINV• SideeffectslimituseinsimpleN/V
InhaledIsopropylAlcohol• PromisingEDdataincludingsuperioritytoondansetron
Benzodiazepines• Mostappropriateforwithdrawal,anxiety,andanticipatoryrelatednausea
AprilMDetal.AnnEmerg Med2018BeadleKL.AnnEmerg Med.2016
Haloperidol
D2ReceptorAntagonist
PublishedevidenceofQTc prolongationrangingfrom8ms –
35ms
Multiplepublicationsof
torsadogenesis andcardiacdysrhythmia
IM,IV,Sol,andTab
Wenzel-seifert K.Dtsch Arztebl Int.2011Vannoord C.JClin Psychopharmacol.2009
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Ondansetron
Serotonin-3ReceptorAntagonist
PublishedevidenceofQTcprolongation
rangingfrom4ms –32ms
Fewpublishedcasesoftorsades or
dysrhythmia,butassociatedhighIVdoses(32mg)
IV,IM,Sol,Tab,ODT,andPOFilm
Brygger L.ExpertOpin DrugSaf.2014Poluzzi E.PLoS ONE10.2015
Promethazine
H1andD2ReceptorAntagonist
PublishedEvidenceofQTc prolongation
Lowtorsadogenicpotential
IM,IV,PR,Sol,andTabavailable
JoSH..Pharmacol Res.2009Owczuk R.Anaesthesia.2009
Metoclopramide
D2ReceptorAntogonist
PublishedevidenceofQTcprolongation
Fewpublishedcasereportsof
cardiacdecompensation
IV,IM,Sol,Tab,andODT
SmithHS.AnnPalliat Med.2012SmithHS.AnnPalliat Med2012ChouCCChangGungMedJ2001Ellidokuz E.AlimentPharmacol Ther.2003
Prochlorperazine
D2ReceptorAntagonist
PublishedevidenceofQTc
prolongation,particularlyinvitro
Fewcasereportsofprochlorperazinecontributingtoan
arrhythmia
IM,IV,PR,Sol,andTab
Aström-lilja C.Pharmacoepidemiol DrugSaf.2008
Olanzapine
D2ReceptorAntagonist
PublishedevidenceofQTc prolongation
Fewcasereportsoftorsades withIVformulation
PO,IM,andIVformsavailable
Czekalla J.JClin Psychiatry.2001SuzukiY.HumanPsychopharmacology.2011LamYWF.BrownUniversityPsychopharmacology.2015
Trimethobenzamide
D2ReceptorAntagonist
NopublishedevidenceofQTcprolongation
Nopublishedevidenceof
torsadogenesis
POandIMformsavailable
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RankingTorsadogenicRisk
7)Trimethobenzamide
6)Prochlorperazine
5)Metoclopramide
4)Olanzapine
3)Promethazine
2)Ondansetron
1)Haloperidol
Isbister GK.BrJClin Pharmacol.2013
FinalThoughts
• Noonesizefitsallanswer
• QTc prolongation≠ torsadogenic risk
• Additionalriskfactorsareimportant
• Risk/Benefitisapatientspecificdecision
• Medicationchoiceshouldbebasedonrisk/benefit,patientspecificcharacteristics,androute
AlternativeUsesofHaloperidol
Amre Elmaoued,PharmDPGY-1PharmacyResidentUniversityofNewMexicoHospitals
Objectives
¡ Pharmacists:§ Evaluatesomealternativeusesofhaloperidol
¡ Technicians:§ Identifysomeoff-labelusesofhaloperidol
Haloperidol- D2Antagonist
¡ 1stgenerationAntipsychotic(a.k.a.TypicalAntipsychotic)
¡ FDAIndication:§ Psychosis§ Schizophrenia
¡ TypicalDosing:0.5-2mgtwo- threetimesdaily
MechanismofAction
PsychopharmacologyInstitute.(n.d.)
Haloperidol- Characteristics
PsychopharmacologyInstitute.(n.d.)
D2 Activity High
5HT2Activity Medium
MuscarinicActivity
Low
Alpha-1adrenergicActivity
Low
AntihistamineActivity
Low
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IMLactateforIVBriefPsychRatingScale
Baseline 4Hours 24Hours
Diazepam 28.5 11.4 6.3
Haloperidol 30.5 3.8 8
¡ Lerneret.al.(1978):§ Randomized40patientsto
haloperidolordiazepam§ BothreceivedviaIVroute
¡ FDAWarning(2007):§ IncreasedriskofQTc
prolongationhasbeenseen§ Studiesareshowinglower
dose,<2mg,noincreasedQTc
¡ Bothequallyeffectiveantipsychotics¡ Doses
§ Haloperidol=15mgstart. 10mgq1hr.Totalaverage~20-35mg§ Diazepam=10-15mgstart.5-10mgq1hr.Total~30-40mg
¡ MorewithdrawalassociatedwithhaloperidolDuprey M.S,Int CarMed.2016Lerner,Y.AmofPsy.1979Hatta,K. JClin Psy. 2001
Off-LabelUses• Intractableheadaches• Agitation/RapidTranquilization• Nausea/Vomiting
• Intractablehiccups• ChoreaofHuntingtondisease• DeliriumintheICU• Obsessive-compulsivedisorder
IntractableHeadaches
¡ Comparedhaloperidol5mgIVvs.metoclopramide10mgIV§ EmergencyDepartment,N=64
▪ 31haloperidol▪ 33metoclopramide
¡ Allpatientswerepretreatedwithdiphenhydramine25mg
¡ VASmeasured0,20,40,60,80min
Gaffigan,M.E.,JEmerg Med.2015
Agitation/RapidTranquilization
¡ Dose:haloperidollactate2.5mg-10mgIM
Ostinelli,E.G.etal.CochraneDatabaseSyst Rev.2017
Nausea/Vomiting
¡ UsualDose:0.5mg- 2.5mgQDorBID¡ Studiedin:
§ Cancer§ PalliativeCare§ Post-OperativeNauseaandVomiting
Nausea/VomitingResponse Complete
ResponsePartial Response NoResponse Failure
Patient-ratedDay2(n = 33)
8 12 10 3
Patient-ratedDay5(n = 23)
7 10 2 4
Observer-ratedDay2(n = 29)
8 15 4 2
Observer-ratedDay5(n = 19)
6 9 3 1
AdaptedfromHardy,J.R.,etal.JPainSymptomManage.2010.
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Nausea/VomitingResponse Response
(CR + PR)n/N(%)Response
(AllPatients) n/N(%)Patient-ratedDay2(n = 33) 20/33(60) 20/42(47)
Patient-ratedDay5(n = 23) 17/23(74) 17/42(40)
Observer-ratedDay2(n = 29) 23/29(79) 23/42(54)
Observer-ratedDay5(n = 19) 15/19(78) 15/42(35)
AdaptedfromHardy,J.R.,etal.JPainSymptomManage.2010.
SideEffects
TRANSLATESTOExtrapyramidalSideEffects
VeryHigh
AnticholinergicEffects
VeryLow
HypotensiveEffects
VeryLow
SedatingEffects VeryLow
D2 Activity High
5HT2Activity Medium
MuscarinicActivity
Low
Alpha-1adrenergicActivity
Low
AntihistamineActivity
Low
SideEffects- QTc Prolongation
RISKFACTORS CONSIDERATIONS
¡ BaselineECG¡ IfgivingIVhaloperidol,monitor
ECGclosely¡ Discontinuemultiplemedications
withQTcprolongation¡ QTc >500msà consideredrisk
forTdP§ >450msformalesà considered
prolonged§ >470msforfemales
Unmodifiableriskfactors Potentiallymodifiableriskfactors
FemaleGender Hypokalemiaorseverehypomagnesaemia
IncreasingageBradycardia
GeneticallylongQTsyndromeFamilyhistoryofsuddendeathHistoryofpreviousdrug-inducedQTprolongation
>1QTcprolongingmedication
Medsthatcauseelectrolyteabnormalitiesormaycauserenalorhepaticdysfunction
Structuralheartdisease/LVdysfunction
Starvationorobesity
Impairedeliminationduetorenalorhepaticdisease
HighdrugconcentrationsduetooverdoseorrapidIVadministration
RapidUpdate:RecentlyApprovedAntimicrobials
SienaMeador,PharmDPGY-1PharmacyResidentUniversityofNewMexicoHospitals
Objectives
¡ Pharmacist:§ Discusstheroleofrecentlyapprovedantimicrobialtherapies
¡ Technician:§ Identifyrecentlyapprovedantimicrobialtherapies
Baxdela™delafloxacin
https://jamanetwork.com/journals/jama/article-abstract/2646700
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FDAApprovedIndications
¡ Fluoroquinoloneforthetreatmentofacutebacterialskinandskinstructureinfections(ABSSSI)inadults≥18yearsold
Baxdela™(delafloxacin)[packageinsert].2017.
K.pneumoniae
P.
aeruginosa E.coli
E.faecalis
CertainStaphylococcus
spp.
CertainStreptococcus
spp.
Dosing¡ Bymouth
§ 450mgtabletevery12hours§ Notrenallyadjusted§ Withoutregardtofood
¡ IntravenouseGFR Dose Interval≥30 300mg 12hours15-29 200mg 12hours
<15ordialysis Notrecommended,consider switchingtotablet
Baxdela™(delafloxacin)[packageinsert].2017.
Warnings/AdverseEffects
¡ BlackBoxWarnings§ Tendinitis/tendonrupture§ Peripheralneuropathy§ Centralnervoussystemeffects§ Exacerbationofmuscle
weaknessinmyastheniagravis¡ Contraindication
§ Hypersensitivity¡ Warnings
§ C.difficile-associateddiarrhea§ Drug-resistantbacteria
¡ AdverseReactions§ Nausea(8%)§ Diarrhea(8%)§ Headache(3%)§ Transaminaseelevations(3%)§ Vomiting(2%)
¡ Requiresamedicationguide
Baxdela™(delafloxacin)[packageinsert].2017.
PlaceinTherapy
¡ Limitedbenefitoverotherfluoroquinolonesbutmore
expensive
¡ MostskinandskinstructureinfectionsarecausedbyGram
positivebacteria
¡ Gramnegativecoverageisnotusuallyindicated
Vabomere™meropenem/vaborbactam
http://www.vabomere.com
FDAApprovedIndications
¡ Carbapenem+β-lactamaseinhibitorforthetreatmentofcomplicatedUTI,includingpyelonephritis,inadults≥18yearsold
Vabomere™(meropenemandvaborbactam)[packageinsert]2017.
K.pneumoniae
Enterobactercloacaespp
E.coli
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Dosing¡ Intravenous
¡ Onlycompatiblewithnormalsaline¡ Alldosesareadministeredover3hours
eGFR Dose Interval Minimum diluent
≥50 4 gm 8 hours 250 mL30-49 2gm 8 hours 125mL15-29 2gm 12hours 125mL
<15 or dialysis 1gm 12hours 70 mL
Vabomere™(meropenemandvaborbactam)[packageinsert].2017.
Warnings/AdverseEffects
¡ Contraindication§ Hypersensitivity(1.8%)
¡ Warnings§ Seizures§ OtherCNSexperiences§ Neuromotor impairment§ Reducedvalproic acidlevels§ Thrombocytopenia§ C.difficile-associateddiarrhea§ Drug-resistantbacteria
¡ Adverseeffects§ Headache(8.8%)§ Phlebitis/infusionreactions
(4.4%)§ Diarrhea(3.3%)§ Nausea(1.8%)§ Transaminaseelevations
(1.8%)§ Pyrexia(1.5%)§ Hypokalemia(1.1%)
Vabomere™(meropenemandvaborbactam)[packageinsert].2017.
PlaceinTherapy
¡ Carbapenem-resistantenterobacteriaceae (CRE)
¡ DoesNOThaveimprovedefficacyagainstmultidrugresistant
Pseudomonasspp.orAcinetobacterspp.
¡ Limitedbydosingandadministrationrequirements
Solosec™secnidazole
https://www.solosec.com
FDAApprovedIndications
¡ Nitroimidazoleforthetreatmentofbacterialvaginosisinwomen≥18yearsold
Solosec™(secnidazole)[packageinsert].2017.
Bacteriodesspp.
Gardnerellavaginalis
Prevotella spp. Mobiluncusspp.
Megasphaera-liketypeI/II
Dosing
¡ Singledoseof2grams(1packet)¡ Sprinkleoverapplesauce,yogurt,orpudding¡ Consumewithin30minutes¡ Donotcheworcrunchthegranules¡ Maybefollowedwithaglassofwater¡ DoNOTdissolveinanyliquid
Solosec™(secnidazole)[packageinsert].2017.
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Warnings/AdverseEffects
¡ Contraindication§ Hypersensitivity
¡ Warnings§ Vulvo-vaginalcandidiasis(9.6%)
§ Riskforcarcinogenicity§ Drugresistance
¡ Adverseeffects§ Headache(3.6%)§ Nausea(3.6%)§ Dysgeusia(3.4)§ Vomiting(2.5%)§ Diarrhea(2%)§ Abdominalpain(2%)§ Vulvovaginalpruritus(2%)
Solosec™(secnidazole)[packageinsert].2017.
PlaceinTherapy
¡ Onlysingle-dosetreatmentforbacterialvaginosis
¡ Beneficialforpatientswithadherenceconcerns
¡ Maybeusefulinhospital-ownedoutpatientclinics
SHINGRIX™ZosterVaccineRecombinant,Adjuvanted
https://www.shingrix.com/index.html
FDAApprovedIndication/Dosing
¡ Forthepreventionofherpeszosterinadults≥50yearsold¡ Twovaccineseries,2to6monthsapart¡ 0.5mLinjectedintramuscularly¡ 2vialsperinjection¡ Keeprefrigerated,donotfreeze
Imagefromgsksource
Warnings/AdverseEffects
¡ Contraindication§ Severeallergicreactiontoanycomponentorafterapreviousdose
¡ Localreactions§ Pain(78%)§ Redness(38.1%)§ Swelling(25.9%)
¡ Generalreactions§ Myalgia(44.7%)§ Fatigue(44.5%)§ Headache(37.7%)§ Shivering(26.8%)§ Fever(20.5%)§ GIsymptoms(17.3%)
SHINGRIX™(ZosterVaccineRecombinant,Adjuvanted)[packageinsert].2017.
PlaceinTherapy
¡ AdvisoryCommitteeonImmunizationPractices(ACIP):§ Vaccinateallimmunocompetentpatients≥50yearsold
§ Recombinantherpeszosterispreferredoverthelivezostervaccine
§ Adultspreviouslyvaccinatedwiththelivezostervaccineshouldbe
revaccinatedwithShingrix
Dooling KL,etal.RecommendationsoftheAdvisoryCommitteeonImmunizationPracticesforUseofHerpesZosterVaccines.
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PreventionofHepatitisBreactivationinpatientsreceivingRituxantherapy
Ngoc-YenPham,PharmD.PGY-1PharmacyResidentUniversityofNewMexicoHospitals
LearningObjectives
¡ Pharmacists:§ FormulateanappropriaterecommendationtomanagepatientswithHepatitisBwhorequireimmunotherapymanagementwithRituxan
¡ Technicians:§ IdentifythetherapiesusedtomanagepatientswithHepatitisBwhorequireimmunotherapymanagementwithRituxan
Rituxan(rituximab)
IndicationsMonoclonalantibody
Boxedwarnings
Non-HodgkinLymphomaChronicLymphocytic
Leukemia(CLL)Rheumatoidarthritis
Vasculitis
Anti-CD20directedonB-lymphocytes
InfusionreactionMucocutaneousReactionsHepatitisBReactivationProgressiveMultifocalleukoencephalopathy
Rituxan(rituximab)[prescribinginformation].
HepatitisBVirus(HBV)Serology
§ IgMantibodytoHBVcoreantigen§ Indicatesrecent/acuteHBV
infectionin≤6months
§ HBVsurfaceantigen§ IndicatesapersonisinfectiousHBsAg § AntibodytoHBVsurfaceantigen
§ IndicatesimmunityAnti-HBs
§ IgGantibodytoHBVcoreantigen§ Markerofpastorcurrent
infectionwithHBV
IgMAnti-HBc
§ TotalantibodytoHBVcoreantigen
§ IndicatesexposuretoHBV
§ CorrelateswiththelevelsofHBVvirusparticles
§ MarkerofHBVreplicationandinfection
§ HBVeantigen§ MarkerofHBVreplication
andinfectionHBeAg
Anti-HBc
IgGAnti-HBc
HBVDNA
RiskfactorsforHBVreactivation(HBVr)
¡ HBV-DNAlevel
¡ Anthracyclines/steroiduse
¡ Transplantation
¡ Presenceoflymphoma
§ Malegender
§ LackofHBsantibody
§ HBsAgpositive
§ Presenceofprecore mutant
Tsutsumi Y.WorldJHepatol.2013.
Prophylacticantiviraltherapy
ProphylacticantiviraltherapyOrmonitoring
Monitoring
High
Moderate
Low
ManagementofHBVreactivationScreenpatientsbefore
immunosuppressivetherapy
HBsAg+Anti-HBc +
HBsAg-Anti-HBc +
HBsAg-Anti-HBc-
CheckHBVDNA
AssessRisk
HwangJ,NatRevGastroenterolHepatol.2014.Perrillo R.Gastroenterology.2015.
Pattullo V.ClinMolHepatol.2016.
vaccinations
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RiskStratificationforHBVrRiskGroups HBVr drugestimatesHigh-riskgroups(>10%) B-celldepletingagents
- Rituximab- OfatumumabAnthracyclinederivatives- Doxorubicin- EpirubicinCorticosteroidstherapy≥ 4weeks(prednisone20mg)
Mediumriskgroup(1%- 10%) TNF–α inhibitorsCytokinesandintegrininhibitorsTyrosinekinaseinhibitors
Low-riskgroups(<1%) Azathioprine,6-mercaptopurineMethotrexateIntra-articularcorticosteroids
Perrillo R.Gastroenterology.2015.HwangJ,NatRevGastroenterolHepatol.2014.Pattullo V.ClinMolHepatol.2016.
ProphylacticAntiviraltherapyResistance
ClassBoxedwarning:lacticacidosisandseverehepatomegalywithsteatosis,acuteexacerbationofHBVupondiscontinuation
Lamivudine Lowbarriertoresistance
Mutationandresistance
Entecavir Higherbarrierofresistance
Renaldoseadjustments
Tenofovir Higherbarrierofresistance
Renaldoseadjustmentsnephrotoxicity
HanS.JAmBoardFamMed.2015.LamperticoP.JHepatol.2017.
Concerns
ProphylaxisversusPre-emptivetherapyReference) Antiviralsvs
controls(n)Antiviraltiming Reactivationrates
Lauetal.(2003)
lamivudinevspre-emptivetreatment
1weekbeforechemotherapyordeferreduntilserologicalevidenceofHBV
0%verus53%(P=0.002)
Hsu etal.(2008)
lamivudinevspre-emptivetreatment
Onday1ofchemotherapyanduntil2monthsafterorstartedontreatmentifALTlevels>1.5xULN
11.5%versus56%(P=0.001)
Huang etal.(2013)
entecavirvspre-emptivetreatment
Beforechemotherapyto3monthsafteroratthetimeofHBVreactivation
Atmonths6,12,and180%,0%,and4.3%intheETVprophylacticgroupversus8%,11.2%,and25.9%(P=.019)
LauG.Gastroenterology.2003.HsuC.Hepatology.2008.HuangY.JClinOncol.2013. Prophylaxis>pre-emptivetherapy
Durationoftherapyandmonitoring
LoombaR.Gastroenterology.2017.HwangJ.JOncolPract.2015.Pattullo V.ClinMolHepatol.2016.
Guideline Duration MonitoringAGA 2-4weekspriortoinitiationand6-12
monthsafterlastdoseLFTsandHBsAglevels:every3monthsuntil6monthsafterlastdose
EASL ReceivingRituxan:atleast18monthsaftercessationoftherapyImmunosuppressivetherapy:atleast12months
Duringprophylaxis:LFTsandHBVDNAevery3to6months
Afterwithdrawal:LFTandHBVDNAatleast12monthsafter
ASCO Upto12monthsaftercessationoftherapy
HBVDNAandALTlevelsevery3monthsduringtherapy
AGA:AmericanGastroenterologicalAssociation,EASL:EuropeanAssociationfortheStudyoftheLiverisaEuropean,ASCO:AmericanSocietyofClinicalOncology
Conclusions
¡ ProphylaxistreatmentwithnucleotideanalogsisrecommendedinpatientswithmoderateorhighriskofHBVr
¡ InstitutionscreeningtoolsshouldincludeHBsAg,anti-HBc,andHBVDNAtoassesstheriskofreactivationpriortotheinitiationofRituxan
ThankYou