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AdverseEvents
Adverse effects include headaches, depression, and increased liver enzymes. Patients may also
experienceGIsymptomsandrashes.
Interactions
The effect of acyclovir and valacyclovir is increased in patients taking foscarnet. Acyclovir and
valacyclovirmayincreasetheconcentrationsoftizanidine,clozapine,andzidovudine.Famciclovirdoes
not have any significant drug interactions. Patients on antiviral therapy should not receive the live
attenuatedzostervaccine(Zostavax)or varicella virusvaccine.Patientsshouldbe offantiviraltherapy
forgreaterthan24hourspriortoreceivingthosevaccinesandshouldnotreceiveantiviraltherapywithin
14daysofreceivingthevaccine.Thisisbecauseantiviralswilldecreasetheefficacyofthevaccine.
Acyclovir
TheprototypicalantiviralagentacycloviractsbyinhibitingviralDNAreplication.Thedrugworksonly
incellsinfectedbyHSV.Adisadvantageoforalacyclovirisitslowbioavailabilityof10%to20%and
needforfrequentdosing.
The recommended acyclovir dosage for an initial and recurrent HSV-1 orolabial disease in both
immunocompetentandimmunocompromisedpatientsis 400mgorallythricedailyfor5to10days(see
Table13.7). Immunocompromisedpatientsshouldcontinuetherapyuntil completeresolutionoflesions
has occurred. Suppressive therapy may be initiated for patients with severe or frequent recurrent
infections,althoughbenefitis minimal(Chietal.,2015).Theregimenforprophylaxisis acyclovir400
mg orally twice daily. The need for prophylaxis should be regularly assessed. Pediatric dosing of
acyclovirinHIV-exposedor-positivepatientsis20mg/kgfourtimesdaily,withamaximumdoseof400
mg,fourtimesdailyfor5 days.For immunocompetentpediatricpatientsrequiringchronic suppressive
therapyforsevereandfrequentrecurrences,thedoseofacyclovirshouldbe10mg/kgthricedaily,witha
maximumdailydoseof1g/d.Thisshouldbereevaluatedannually.
TherecommendeddosagefortreatingVZVinfectionsinimmunocompetentchildrenis20mg/kgorally
fourtimesdailyfor5days,withamaximumdailydoseof3.2g.ForpediatricpatientsexposedtoHIVor
whoareHIVpositive,itisrecommendedtoextendtreatmentdurationto7to10daysanduntil48hours
afterthelastnewlesionforms.Adultdosingis800mgorallyfivetimesdailyfor5to7daysanduntilall
lesionshavedried.Forcomplicatedcasesrequiringhospitalization,IVtherapyiswarranted.
Famciclovir
Famciclovirisapro-drugthatismetabolizedtoitsactiveform,penciclovir.Thedoseoffamciclovirfor
herpeslabialisis1,500mgonceforimmunocompetentpatients.Itisbesttostarttherapywithin1hourof
thefirstsignofinfectionifthepatienthasprodromalsymptoms.InpatientswithHIV,therecommended
doseoffamcicloviris500mgbymouthtwicedailyfor5to10days.
Inuncomplicatedvaricellainfection(chickenpox),theregimenisfamciclovir500mgbymouththrice
dailyfor5to7daysinaHIV-infectedpatient.Forherpeszoster,thedoseis500mgbymouththricedaily
for7days.ForpatientswithHIV,thisregimencanbeextendedto10daysorlongeriflesionshavenot
completelyhealed.
Valacyclovir
Valacyclovir is a pro-drug of acyclovir and is converted rapidly. First-pass metabolism converts
valacyclovirtoacyclovir,withapproximately55%bioavailability.Forherpeslabialis,therecommended
dose in immunocompetent patients is 2 g by mouth twice daily for 1 day. For severe and frequently
recurringinfections,suppressivetherapywithvalacyclovir500mgto1gbymouthdailycanbeinitiated
andperiodically reassessed. Inimmunocompromised patients, the recommended dose is 1 g bymouth
twicedailyfor5to10daysanduntillesionsarecompletelyhealed.Suppressivetherapycanbeinitiated
incaseofsevereandfrequentrecurrences.Thedoseis500mgbymouthtwicedaily.
Foruncomplicatedandmildvaricella(chickenpox)infection,therecommendeddoseis1gbymouth
thricedailyfor5to7daysanduntillesionshavecompletelycrustedover.Therecommendedregimenfor
herpes zoster infection is valacyclovir 1 g by mouth thrice daily for 7 days. Inimmunocompromised
patients,treatmentdurationcanbeextendedto10daysorlongerifthereisslowresolutionoflesions.
SalicylicAcid
Salicylicacidisakeratolyticagentthatmaybeusedforcommonandplantarwarts.Itisavailableover
thecounterandinavarietyofstrengthsforspecifictypesorsitesofverrucae.Itcomesinvariousdosage
forms including plaster, collodion-like vehicle, and karaya gum-glycol plaster vehicle. Usually, 17%
salicylicacidisusedtotreatsmalllesions.Apatchproductthatis40%salicylicacidplasterisusefulfor
largelesionsandcanbecuttofitthewart.Comparedtonotreatment,salicylic acidcureswartsfaster
(Loo&Tang,2014).
Dosage
For salicylic acid that comes in a collodion-like vehicle, a drop should be applied on the wart and
allowedtodry.Whenusingthekarayagum-glycolplastervehiclepreparation,thewartshouldbeinitially
flattenedgentlywithapumicestone.Adropofwarmwatershouldthenbeappliedtothewart,andthe
plastershouldbeappliedatbedtimeandkeptonforatleast8hours.Itshouldberemovedwhenawake;
this processcancontinuenightlyuntil thewartisremovedfor upto12 weeks.Salicylicacidpatches
comeinplasterstrengthsrangingfrom12%to40%.Theplastershouldbecuttofitthewartandlefton
for48hours.Thiscanberepeateduntilthewartisremovedforupto12weeks.Therearevariousoverthe-counterproductswithsalicylicacid,andpatientsshouldbecounseledonreadingandfollowingthe
directionsofuseonthepackage.
Contraindications
Topical therapy is contraindicated in patients with diabetes mellitus or impaired circulation and on
moles,birthmarks,orunusualwartswithhairgrowth.Somesystemicabsorptioncanoccur,andtherapy
shouldbeavoidedinpatientswithsalicylatehypersensitivity,includingthosewithanaspirinallergy.The
mostcommonadverseeffectisskinirritation,whichcanbesevereenoughtodiscontinuetreatment.
SelectingtheMostAppropriateAgent
Whenselectingan agent, it is necessarytoconsider ease ofcompliance, cost, andefficacy profile of
medication. For warts, most patients will seek treatment for cosmetic purposes, and treatment with
salicylicacidwillworkformostcommonandplantarwarts.Wartslocatedonthefaceorneck,suchas
filiformorflatwarts,mayneedtoberemovedbyadermatologist.Thisprocedureiscommonlydonein
theoffice.Mostwartscurethemselvesovertime,especiallyintheimmunocompetenthost.
First-LineTherapy:HerpesSimplexVirusType1
Herpeslabialisistypicallyself-limitingwithouttreatment.Forpatientswithrecurrentorsevereherpes
labialis, oralantiviraltherapywithacyclovir,famciclovir,or valacyclovirshouldbe initiated.Topical
antiviraltherapymaybeprescribedformildcasesinimmunocompetentpatients,althoughsymptomsmay
onlybe reducedby a day,whichmaynotbe worththe expenseof thetreatment.Immunocompromised
patientsshouldbetreatedwithoralantiviraltherapy.Costistypicallyadecidingfactorinwhichagentto
select.Mostinsuranceswillcovervalacycloviroracyclovir,butmosttopicalantiviralpreparationsare
notcoveredandexpensive.
Evidence for suppressive therapy suggests that topical antiviral preparations are ineffective in
preventingrecurrencesandshouldnotbeusedfor thatpurpose. Oralantiviralsuppressive therapycan
preventrecurrences,althoughthebenefitisminimal(Chietal.,2015).
First-LineTherapy:Varicella-ZosterVirus
Systemictherapyisusedonlyinpatientswithcomplicateddisease,childrenwithchronicpulmonaryor
cutaneous disease or taking inhaled corticosteroids or long-term salicylate therapy,or anyone healthy
abovetheageof12years.Itisprescribedonlyiftherashhasbeenpresentforlessthan24hours,asthat
iswhenitwillworkbest.
First-LineTherapy:HerpesZoster
Systemicantiviraltherapycanbestartediftheherpeszosteroutbreakislessthan72hoursindurationor
longerthan72hoursbutwithnewlesionsappearing,thepatientbeingolderthanage50,orthepatient
being immunosuppressed. Therapy consists of systemic therapy with acyclovir, famciclovir, or
valacyclovir.Mostoften,valacyclovirisprescribedtopatientswithinsurancecoverageasitistypically
covered andhasa lessfrequentdosingschedule (Figure13.2). For patients withoutinsuranceorwith
insurancethatdoesnotcovervalacyclovir,acyclovirwouldbeacheaperalternative.Patientswhohave
receivedastemcelltransplantoranytransplantonanti-rejectionmedicationorthosewhoareshowing
signsofextracutaneousinfectionshouldbehospitalizedandmanagedwithIVacyclovir.Theycanfinish
therecommended14-daycourseofantiviraltherapywithoralacyclovir,famciclovir,orvalacyclovir.
Oralanalgesics,suchasacetaminophen,aspirin,andnonsteroidalantiinflammatorydrugs,arehelpful
inpaincontrol.Patientswithneuropathicpain,commonlyassociatedwithshingles,mayneedmedication
targetingneuralgiaprescribed,suchasgabapentinorlidocainepatches.
First-LineTherapy:Verrucae
For commonwarts,topical salicylicacid ina 17% concentrationisused;itis applied at bedtime for
approximately 8 to 12 weeks or until the wart has healed. For plantar warts, a 40% salicylic acid
preparationisusedinplasterorpatchformthatiscuttothesizeofthewartandappliedatbedtime.
Thepreparationremainsinplacefor24to48hours.Whenremoved,theareaisrubbedwithapumice
stonetoremove dead whitekeratin.Thiscanbe repeatedforupto12weeksoruntilthewartisgone
(Figure13.3andTable13.8).
FIGURE13–2TreatmentalgorithmfortheHerpeszostervirusinfectionmanifestedasshingles.
Second-LineTherapy:Verrucae
Ifpatient-appliedtherapyfails,cryotherapy,carbondioxidelasertherapy,orpulseddyelasertherapycan
beperformed.Pulseddyelasertherapyseemstohavetheleastadverseeffectsassociatedwithitwhen
comparedwithotherlasertherapies(Nguyenetal.,2016).
MonitoringPatientResponse
Follow-upevaluationofHSVinfectionisnotrequiredifthesymptomsresolve.Forpatientswithherpes
zoster,follow-upisrecommendedifpainorsymptomshavenotresolved.
Innon-anogenitalHPVinfections,multipletreatmentsmaybenecessary.Patientsshouldunderstandthe
importance of follow-up beyondthe initial wart removal,becausethevirus may remain. Patients may
needweeklytreatmentuntilthewartiseradicated.
FIGURE13–3Treatmentalgorithmforcommonwarts.
TABLE13.8
RecommendedOrderofTreatmentforNon-anogenitalInfectionwithHumanPapillomavirus
Order Agent Comments
Firstline Salicylicacid Usedasfirst-lineagenttotreatanywartnotonfaceAvailableOTC
Secondline Cryotherapyorlasertreatment Referpatienttospecialist
OTC,overthecounter.
PatientEducation
LifestyleChanges
Educatingthepatientabouthygiene,precipitatingfactors,andpreventionisimperative.Viral infections
arespreadbyskincontact,sopatientsneedtorecognizetheimportanceofwearinggloveswhenapplying
medicationsandofthoroughhandwashing.Skin-to-skincontactshouldbe avoided. Patientswithwarts
shouldbeinformedthattheymayrecur.
ComplementaryandAlternativeMedicine
Capsaicin cream can be used for pain control in herpes zoster, although data on its efficacy are
insufficient.Teatreeandeucalyptusoilhavebeenreportedtohaveactivityagainstherpessimplex.Use
ofalternativemedicationshaveverylimiteddataandshouldnotberoutinelyrecommended.
SpecialPopulations
VZV infections during pregnancy are extremely rare and can cause fetal abnormalities. If a pregnant
womanisinfected,varicellazosterimmunoglobulinandantiviraldrugsshouldbeconsidered.
Prevention
There are no vaccinations for the prevention of HSV-1 infections. Patients should be counseled on
preventingtransmissiontoother people by not sharingdrinks and avoidingkissing withactive herpes
labialislesions.
VaccinationreducestheincidenceofVZV infections.Thevaricellavaccineisatwo-dose seriesthat
canbegivenafter12monthsofbirth.Therehasbeensignificantdeclineintheincidenceofchickenpox
sincethevaricellavaccinationprogramper theCenters forDiseaseControl andPrevention.There are
twodifferentvaccinationsforthepreventionofherpeszosterandpostherpeticneuralgiainadults.Live
zostervaccine(Zostavax)isasubcutaneousone-timeinjectiongiventoadultsovertheageof60years,
and since it is a live attenuated vaccine, it cannot be given to immunocompromised individuals.
Recombinantzoster vaccine (Shingrix) is the preferredshingles vaccine dueto itsbetter efficacyand
longer-lasting effect (Dooling et al., 2018). The vaccine is given as two doses 2 to 6 months apart
intramuscularlyinadultsolderthantheageof50years.
CASESTUDY1
B.H.isa72-year-oldmanwhopresentsforevaluationofseveralpainfulredbumpsonhisleftside.
Thepainradiates aroundto hischest.Therashresemblesblistersthatarejustforming.Henoticed
themyesterday,andmoreareforming.Hislaboratoryresultsareallnormal,andhiscreatinineis0.8
mg/dL.Hehasprescriptioninsurance(LearningObjectives2and3).
Diagnosis:HerpesZoster
1.What,ifany,riskfactorsdoesthispatienthavefordevelopingherpeszoster?
Answer:Patient'sagesuggeststhathehasbeeninfectedwithvaricellaasachild.
2.What,ifany,drugtherapywouldyouprescribe?Why?
Answer:Prescribevalacyclovir1,000mgthriceadayfor7 daysbecauseitiseasiertocomply
withthan5timesdailydosing.
3.Discusspatienteducationandpreventivemeasuresbasedonhishistoryandthetherapy.
Answer: Avoid contact with people while lesions are still wet especially with
immunocompromised individuals. Side effects ofvalacyclovirincludegastrointestinal (GI)upset
and headache. Seek medical attention if altered mental status occurs as valacyclovir can have
central nervoussystem (CNS)effectsinolder adults. Report anyneuropathic painas additional
treatmentmayneedtobe prescribed. Get vaccinatedonce healed, preferablywith the two-dose
seriesShingrex.
CASESTUDY2
M.R.isa66-year-oldwomanwithdiabetesmellitus.Sheisobeseandhasdifficultycaringforherself.
Shepresentswithanon-purulenterythematousareaonherleftlowerlegthatbegan2weeksagoasan
insectbite.Theareawasitchybutnotpainful.Shehashadanintermittent,low-gradefeverforthepast
weekbutotherwise feels well. Shestates thattheredness hasgotten worse,andthere isnow mild
swelling inher lower leg near the lesion. Her onlymedicationis insulin,andshe hasno allergies
(LearningObjectives1and3).
Diagnosis:Cellulitis
1.Whatsignsandsymptomsdoesthispatienthavetosuggestcellulitis?
Answer:Non-purulenterythematousareathatstarted after aninsectbite.Itchy,intermittentlow-
gradefeversaresuggestiveofbacterialinfection.
2.Whatdrugtherapywouldyouprescribe?Why?
Answer: Dicloxacillin or cephalexin. These agents are recommended for patients with mild to
moderate cellulitis, where the most likely pathogens include beta-hemolytic Streptococcus (i.e.,
groupAStreptococcus).
3.Discussspecificpatienteducationbasedontheprescribedtherapy.
Answer:
1. Counselthepatienttocompletetheentirecourseofmedicationeventhoughsymptomsofinfection
mayimprovequickly.
2. Direct the patient tocontacthis or herprovider ifsigns andsymptomsof infection do notget
betterorbecomeworseinthenext48to72hours.Thereshouldbenospreadingoferythema.
3. Educatethepatientonthesignsandsymptomsofanallergicreactionandtoreportanyallergy
symptomstotheprescriberorapharmacist.
4. GIupsetmayoccur;patientcantakewithfoodtominimizethisadverseeffect.Diarrheamayalso
occur.
4.Whatwouldbethechoiceforsecond-linetherapy?
Answer:
1. If the patient has a life-threatening allergy to penicillins and cephalosporins, an acceptable
alternativeantibioticforcellulitisisclindamycin.
2. Ifthepatientreceivesapenicillinorcephalosporinantibioticandsymptomsofinfectiondonot
improveor worsen,thepatientmayrequireadmissiontothehospitalandintravenousantibiotic
therapywithvancomycin.
5.Whatover-the-counteroralternativemedicationswouldbeappropriateforM.R.?
Answer:
1. Elevationof the affected limb and minimal weight bearingshould be recommended to reduce
swellingandpreventinfectiouscomplications.
2. Mildpainrelieverscanberecommendedasneeded,thoughcoolsterilesalinedressingscanbea
usefulalternative.
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