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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