Herpes Simplex Virus Infection (1 of 9)

1 Patient presents w/ signs & symptoms suggestive of herpes simplex virus (HSV) infection

2 DIAGNOSIS No ALTERNATIVE Are clinical & lab ﬁ ndings DIAGNOSIS supportive of HSV infection?

Yes

Orolabial Genital HSV disease HSV disease

TREATMENT OF PRIMARY TREATMENT OF PRIMARY INFECTION INFECTION A Supportive measures A Supportive measures • Adequate hydration • Patient & sexual partner B Symptomatic therapy counseling • • Analgesic (oral) Saline bath • • Zinc preparations (topical) Wet compresses C • Increase ﬂ uid intake to dilute Antivirals urine Any one of the following: B • Aciclovir (oral or topical) Symptomatic therapy • • Penciclovir (topical) Analgesic (oral) • • Valaciclovir (oral) Anesthetic (topical) C Antiviral • To be administered within 7-10 days of the start of infection* Any one of the following: • Aciclovir (oral) • Famciclovir (oral) • Valaciclovir (oral)

Recurrence Recurrence TREATMENT © MIMSSee page 2 *Longer treatment duration for immunocompromised patients

Not all products are available or approved for above use in all countries. Speciﬁ c prescribing information may be found in the latest MIMS.

B161 © MIMS 2019 C B A C B EPISODIC ANTIVIRAL TREATMENT ANTIVIRAL EPISODIC Antivirals Antivirals Symptomatic therapy measures Supportive ofrecurrent for treatment Antiviral Symptomatic therapy • • • Any oneofthefollowing: • • • • • • • • Any oneofthefollowing: • infection HSV • • • Valaciclovir (oral) Famciclovir (oral) (oral)Aciclovir (topical) Anesthetic (oral)Analgesic Saline bath Patient counseling Valaciclovir (oral) Penciclovir (topical) (topical) Docosanol (oralAciclovir ortopical) the stageduring prodromal treatment tostart early It isnecessary Oral preparations preparations (topical) Zinc (oral)Analgesic TREATMENT

© D MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not B A effalone maybe symptoms control to ective treatment &supportive durationshorter ofsymptoms w/a severe less generally are infections Recurrent Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Symptomatic therapy measures Supportive Herpes SimplexVirus Infection(2of9) • • • • RECURRENT OROLABIAL HSV DISEASE HSV OROLABIAL RECURRENT Anesthetic (topical) Anesthetic (oral)Analgesic Saline bath Patient counseling TREATMENT OF & PREVENTION TREATMENT OF RECURRENT GENITAL DISEASE HSV B162 C E C Antiviral for short-term for short-term Antiviral Follow-up Antivirals SUPPRESSIVE ANTIVIRAL ANTIVIRAL SUPPRESSIVE • • Any oneofthefollowing: light) UV (eg stimulation intense known to prior treatment prophylactic • • • Any oneofthefollowing: Famciclovir (Oral) (Oral) Aciclovir Valaciclovir (oral) Famciclovir (oral) (oral)Aciclovir PREVENTION TREATMENT D © MIMS 2019

HERPES SIMPLEX HERPES SIMPLEX • • • • • • • • • disease HSV Genital • • • • • • • • • • • disease HSV Orolabial • • • Infection HSV Recurrent • Infection -Nonprimary First Episode • Infection HSV Primary - &higher rate infections ofcomplicationsMore severe inwomen: bilateral,likely w/lymphadenopathy tobe &presents symptoms &systemic isdiff genital infection Primary erent inthat extensive, recurrent prolonged, from more infection painful, itisoften pustulesorulcers) stages (vesicles, present may invarying be Lesions Fever,Systemic symptoms: pain abdominal myalgia, headache, &urethral discharge vaginal &tender lymphadenopathy inguinal dysuria, Pain,itching, symptoms: Local - Typically through contact usuallytransmitted sexual occurs inadults; - - - inmen: Infection - - - Disease duration: 2-4weeks Disease - HSV-2 genitalis butHSV-1 isusuallythe ofherpes cause may occur inupto⅓ duration: 2-3weeks Disease Fever,Systemic symptoms: fl malaise, myalgia, u-like symptoms lymphadenopathy Cervical inthe which may lesions chinDrooling about &neck bring Halitosis diffi causes Edema oforopharynx throat) (sore culty inswallowing - at the appear ofthe (cold border vermilion lips typically 3-5 lesions sores) buccal mucosa orlips &ulcerative vesicles palate, ontongue gingiva, Painful lesions asymptomatic May be shedding active viral through contact old;transmitted close whohave w/individuals commonlyOccurs most inchildren <5 years - HSV-2 by HSV-1 by orolabial caused Most are butmay caused lesions be also frequent w/time less &becomes severe Less febrile illness stress, immunosuppression, trauma, light, Usually UV eg brought factors triggering by about oflatent reactivation from virus Results HSV-2 respectively w/eitherInfection HSV-1 against HSV-1 antibodies or existing orHSV-2 whohave inindividuals previously toeithernot have HSV-1 antibodies orHSV-2 (HSV-2) whodo simplex (HSV-1) inindividuals virus-2 simplex orherpes w/either virus-1 1st infection herpes

or perineum thighs buttocks, skin &extragenital eg urethral or perianal areas clitoris, vagina, cervix, occur onvulva, Lesions contact 4-7days after appear lesions primary exposure, after weeks is2days-2 Incubation period than HSV-2HSV-1 recurrences &milder disease fewer tends tocause Painful lesions contain lesions Painful which alarge 3weeks are over particles excreted viral amount ofinfectious Lesions usually occur on the prepuce, glans penis, penile shaft; usuallyw/6-10vesicles shaft; penile usuallyoccur onthe prepuce,Lesions glanspenis, or fungi w/bacteria &superinfection orthighs),athy, infections disseminated perineum extragenital (buttocks, lesions sacralradiculop- myelitis, transverse meningitis, aseptic retentionSystemic syndrome, complications: Urinary Perianal infection & proctitis may be commonmen mayPerianal &proctitis be inhomosexual infection Systemic complications isreported meningitis rarely occur inmen, aseptic Extragenital areas eg buttocks, perineum orthighs aﬀ may be perineum buttocks, eg Extragenital areas ected © MIMS pustular, become that after Lesions soon painresolves ulcerative 72-96 hours; within &crusted tends tooccur more frequently w/HSV-1 thanRecurrent disease HSV-2 infection 1 Herpes SimplexVirus Infection(3of9) HERPES SIMPLEX VIRUS INFECTION B163

of new cases of new © MIMS 2019 HERPES SIMPLEX • • Patient/Parent Counseling • Virologic Tests • • Diff Diagnoses erential • • Tzanck Smear • • • Type-specifi Testsc Serologic • • • Prevention Suppressive treatment may incurhigher &inconvenience costs - Ifpatient ≥6episodes/year, has consider treatment suppressive - Episodic treatment treatment suppressive vs - treatmentDiscuss options relationships sexual transmission &perinatal antiviral treatments, recurrent episodes, the disease, Reduce patient’s &help them of patients anxiety educating onthe by tocope natural w/the infection history - Viral culture immunocompromised, oraneonate orispregnant, infection orsevere disease aCNS has & if patient are maydone atypical if lesions but lab be on distinctive lesions tests is usually based Diagnosis Herpes zoster, syphilis, candidiasis, hand-foot-&-mouth disease zoster, candidiasis, Herpes syphilis, reliably cannot emethod differentiate varicella-zoster from HSV virus lesions ruptured offreshly the the from from base scrapings A Tzanck preparation (Wright-Giemsa stain)may multinucleated show giant cells orintranuclear inclusions forrecurrent infections especially sensitivity lacks detection IgMantibody - recent suggests whileIgMantibody infection infection past indicates IgG antibody anogenital orolabial notdistinguish from Do infection complement immunosorbent (ELISA), assay Eg fi enzyme-linked Westernxation tests, blot isnotwell-defi HSV forcutaneous test adiagnostic role as butits Highlysensitive, ned - Test DNA forHSV - chain (PCR) reactions Polymerase HSV-1 &HSV-2 between discrimination Rapid butdonotallow - antigens HSV Detect - immunofl Eg tests, immunoperoxidase uorescence, immunoassay enzyme - Antigen tests detection - eff cytopathic culture show viral will Apositive replication characteristic ofHSV ect - - the partners number Limiting ofsexual - contact sexual recurrences Abstainingfrom or prodromes lesion during - Educate patient toprevent transmissionby: onhow - Understanding that asymptomatic viral shedding may Understanding transmission cause shedding that viral asymptomatic - - Using acondom may help transmission(notfoolproof) against toprotect -

• conjunctiva CSF, blood, or forculture: Skin,Sources mucocutaneous lesions, ofspecimens oropharynx stool, urine, Test HSV-1 &HSV-2 between itisrapid discrimination 7days), (within &allows ofchoice sensitive because evaluation &treatmentevaluation toseek todiagnosis 60days preceding prior from partner(s) sexual orformer partner sexual Informing - shedding, &transmission shedding, Taking viral asymptomatic recurrent genital antiviral lesions, daily suppressive therapy which decreases

Increase flIncrease uid intake todiluteurine © orifrecurrences are w/time symptomatic;however,infection, decreases shedding is more likely shedding to occur an w/ HSV-2 viral in the following 1st year Asymptomatic infection, MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Herpes SimplexVirus Infection(4of9) A SUPPORTIVE MEASURES SUPPORTIVE 2 DIAGNOSIS B164 © MIMS 2019 1 Various topical anesthetics are available. Please see prescribing information forspecifiVarious prescribing see are available. anesthetics Please topical c formulations inthe latest MIMS. • Tromantadine • • Penciclovir • • Docosanol • Cidofovir • above as -Same Aciclovir Topical erapy • orInosiplex Methisoprinol • • Foscarnet • • • Valaciclovir • • • Famciclovir • • • • • • Aciclovir Oral erapy • • Infection HSV Genital Recurrent • • Infection HSV Primary TreatmentGeneral Principles • • Preparations Zinc • Preparations Oral • • • (Topical)Anesthetics • • (Oral) Analgesics Derivative ofAmantadine w/ antiviral activity Derivative : t c ffe E Aciclovir ofactionas Same mechanism labialis time of recurrent herpes healing Decreases into cells the entry cell viral replication which membrane &viral prevents &HSV between plasma fusion Inhibits forAciclovir-resistant used May genital be infections Topical effi limited agent shown has cacy orstimulating cell-mediated immune process modifying by Antiviral activity forAciclovir-resistant inimmunocompromised used patients infections May mucocutaneous HSV be isnotrequired thymidine by &activation Foscarnet isvirostatic kinase - polymerase &DNA that analogue RNA isanoncompetitive inhibitorofviral Pyrophosphate oftransmission risk todecrease shown been Has possible frequency dosing orlesser oraladministration than after doses makinglower Aciclovir absorption better Has ofAciclovir, prodrug ester liver &intestine by toAciclovir L-valine rapidly metabolized Aciclovir ofactionas Penciclovir similarmechanism has higher bioavailabilityHas than Penciclovir &israpidly converted toPenciclovir inGIT, &liver blood ofPenciclovirFamciclovir isaprodrug frequent dosing requiring Bioavailability ispoor Topical agent effi limited has forgenital HSV,cacy hence notrecommended orcomplications isnecessary where disease hospitalization forsevere isusuallyreserved IV are eff both Oral &IV intreating HSV-1ective &HSV-2 toother ofthe spread cells virus further replication &stops viral Limits polymerase that analogue nucleoside DNA isacompetitive purine inhibitorofviral Acyclic 3months oftherapy anyleast to1 year effi toachieve cacy at requires treatment suppressive forfrequent recurrences (prophylaxis) ofgenital disease Long-term HSV or for5days asingle-day patient-initiated as given mayEpisodic treatment be forrecurrent genital disease HSV treatment &patientChoice schedule ofagent dosing preference oncost, depends however, notprevent recurrences does symptoms; infection treatment early ofprimary eff be antivirals can onset, ofsymptom 72 hours within If given &duration of severity inreducing ective ofsymptoms Shorten timeofresolution gel sulfate oxide/glycine Zinc cream, Eg Zinc Symptomatic relief ofulceration &inflammation inorolabial disease HSV In theory, butrarely may sensitization happens cause inpractice Symptomatic relief ofpain Dyclonine Lidocaine, viscous Eg Benzocaine, Symptomatic relief ofpain Eg Paracetamol, Ibuprofen

Decreases healing time of recurrent herpes labialis time ofrecurrent herpes healing Decreases © MIMS 1 Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Speciﬁ c prescribing information may be found in the latest MIMS. latest the in found be may information Speciﬁc prescribing Herpes SimplexVirus Infection(5of9) B C SYMPTOMATIC THERAPY ANTIVIRAL THERAPY B165 © MIMS 2019

HERPES SIMPLEX • • • • • • • • • Antiviral Suppressive erapy • • • Treatment Antiviral Episodic • TreatmentSupportive Alone Restart treatmentRestart ifhighrate ofrecurrences ofrecurrence frequency Interrupt treatment 6months-1 year toassess after Suppressive treatment may incurhigher &inconvenience costs It treatment suppressive torestart issafe&advisable inpatients whocontinue tohave significant infection - &frequency severity both shouldinclude 2recurrences toview Period ofassessment - ofrecurrences frequency &cessation toassess Annual isrequired oftherapy 1year evaluation after diagnosis incorrect resistance or therapy compliance, adjustments, during fordose shouldinvestigateOutbreaks forpoor need Full eff suppressive when intreatment isusuallyobtained ect for5days 80%&95%respectively by shedding &viral outbreaks clinical Reduces - shedding viral Antivirals symptomatic &asymptomatic suppress chance relief oftransmission & provide ofsymptoms ofrecurrences, frequency todecrease Used &inimmunocompromised patientsinfection, trimester, inthe lesions last pregnant patients w/herpetic problems duetothe patients w/ psychological prodromes, orpainful severe inpatientsRecommended (≥6episodes/year), w/frequent recurrent genital herpes 1-2days duration by Reduces ofsymptoms patients forHSV-infected whohave &infrequent recurrences mildsymptoms Best - Patient-initiated pre-prescribed therapy tobe that needs treatment eff alonemay be tocontrolective symptoms & supportive duration w/ a shorter of symptoms, severe less are generallyRecurrent infections self-limiting,

some outbreaksome the that orduring prodrome 1day within heralds onset oflesion possible as antiviralStart therapy soon as D © MIMS MANAGEMENT STRATEGIES FOR RECURRENT GENITAL HERPES Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Speciﬁ c prescribing information may be found in the latest MIMS. latest the in found be may information Speciﬁc prescribing Herpes SimplexVirus Infection(6of9) E FOLLOW-UP B166 © MIMS 2019

HERPES SIMPLEX HERPES SIMPLEX 1 Aciclovir combined w/ Zinc oxide is available. Please see prescribing information forspecifi prescribing see oxide isavailable. Please combined w/Zinc Aciclovir c formulations inthe latest MIMS. ( Acyclovir) Aciclovir Drug 1 Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products 250 mg/m 3mth-12 yr: Childn complete 10days oftotaltherapy at least oralantiviral therapy by to followed days oruntil improvement w/clinical 1hr8 hrly over x5-7 5 mg/kgIV Adults: For infection: severe are healed 12 hrly x4-5days oruntil400 mg PO lesions exposure): (eg stimulation UV due toknown infection recurrent against Prophylaxis healed dailyx4-5daystimes oruntil are lesions 5 200-400 mgPO infection: Recurrent 7-10 days dailyx 5times 15mg/kgPO <2 yr: Childn daily x5-10days 5times 200 mgPO >2 yr: &childn Adults infection: Primary disease: HSV Orolabial mth 12 hrly x6-12 dailyor400 mgPO to 5times 12 hrly 200 mgPO treatment: Suppressive 8-12 hrly x5days dailyor400 mgPO times 6hrly to5 200 mgPO infection: Recurrent patients mised to400 mg/day inimmunocompro-increased may be hrx5-10days; waking during daily 5times 200 mgPO infection: Primary disease: HSV Genital 10 mg/kg IV 8 hrly x10 days Childn <3mth:10 mg/kgIV 5 days placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Herpes SimplexVirus Infection(7of9) Dosage ANTIVIRALS (SYSTEMIC) Dosage Guidelines 2 IV 8 hrly x IV B167 • • Instructions Special • • • Reactions Adverse maintain adequate hydration avoided, injrapid shouldbe bolus 1 hr toavoid precipitation inkidney; Parenteral over IV administration slow by abnormalities electrolyte signifi hepatic or serious cant hypoxia, abnormalities, CrCl ),neurological impairment according (adjust dose to Use w/caution inpatients w/renal enzymes) Hepatic effrash); liver (elevated ect effDermatologic pruritus, (hives, ects acute renal GIeff failure); (N/V); ects BUN &creatinine, possible (increased phlebitis at inj site);Renal eff ects effIV: Local (inflects ammation & eff (N/V,ects diarrhea) effOral: CNS GIT headache); (malaise, ect wellGenerally tolerated Remarks © MIMS 2019 HERPES SIMPLEX Methisoprinol) ( Inosiplex, acedoben dimepranol Inosine Other ( Valacyclovir) Valaciclovir Famciclovir Drug Antivirals Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed divided into 4-6doses divided 100 mg/kg/day PO infections: Severe 6-8 hrly divided Adult 50 mg/kg/day PO &childn >5yr: 24 hrly 500 mgPO treatment: Suppressive 1 day or500 mg12 hrly x3days 12-24 hrly x 1-2 gPO infection: Recurrent To taken 7-10days be 1stdose taken 12hrsafter tobe 2nd dose 12hrly 12 hrly or 1000mgPO 2000 mgPO dose: Initial infection: Primary disease: HSV Orolabial 12 hrly 24 hrly or 250-500 mgPO 500-1000 mgPO treatment: Suppressive 3-10 days 12 hrly x 500 mgPO infection: Recurrent x 5-10days 12 hrly 500-1000 mgPO infection: Primary disease: HSV Genital 24 hrly 1.5 gPO infection: Recurrent 12 hrly Primary infection:250 mgPO disease: HSV Orolabial x 6-12mth 12 hrly :250 mgPO treatment Suppressive 5 days 12 hrly x 125 mgPO infection: Recurrent 8hrly x5days 250 mgPO infection: Primary disease: HSV Genital & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Herpes SimplexVirus Infection(8of9) ANTIVIRALS (SYSTEMIC)(CONT’D) Dosage Dosage Guidelines B168 • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse renal function, goutrenal orhyperuricemia function, Use w/ caution inpatients w/impaired &urine in serum Transient N/V, acidconc uric increased inchildnNot recommended forAciclovir As forAciclovir As inchildnNot recommended impairment inpatientReduce dose w/renal thrombocytopenia pain, fever, rarely granulocytopenia, hallucination,confusion, abdominal N/V,Headache, skinrash, dizziness, Remarks © MIMS 2019 1 Aciclovir combined w/ Zinc oxide is available. Please see prescribing information forspecifi prescribing see oxide isavailable. Please combined w/Zinc Aciclovir c formulations in the latest MIMS. (Acyclovir) Aciclovir Na Carbenoxolone Tromantadine Penciclovir Polidocanol Apply paste to dried lesions 3-5 times daily 3-5times lesions Apply todried paste Polidocanol Povidone-iodine Gargle undiluted 15-mL soln x 30 sec 2-4 x30sec 15-mLsoln Gargle undiluted Povidone-iodine Drug Drug 1 PREPARATIONS FORORALULCERATION &INFLAMMATION Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed daily or more often as needed needed as daily ormore often Apply 1%gelontoaff times 3-5 ected area disease: HSV Orolabial hrx4days waking during Apply onto 1%cream aff 2 hrly area ected disease: HSV Orolabial Recurrent times/day (3-4 hrly) x5-10days Apply 5%oint/cream onaff 5-6 area ected & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All lesion Apply gel 6 hrly >3 yr: on &childn Adults © MIMS required dailyas times Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please Herpes SimplexVirus Infection(9of9) Dosage Dosage ANTIVIRALS (TOPICAL) Dosage Guidelines B169 • Instructions Special • Reactions Adverse • Instructions Special • Reactions Adverse • Instructions Special • Reactions Adverse • • Instructions Special • • Instructions Special • Instructions Special or already brokenor already have when vesicles notuse formed Do Contact dermatitis continue until healed & infection ofHSV atStart 1stsign numbness Transient & burning stinging, page 7 See pruritus) erythema, burning, effDermatologic (transient stinging, ects digitalis glycosides digitalis orrenal &patients failure hepatic, on Use w/caution inpatients w/cardiac, in pregnancy Contraindicated suff other from ering illness membrane orwoundinpatients mucousUse w/ caution ininfected suture tosurgical subsequently closed wounds indeep used Not tobe of radioactiveiodine having specific treatment involving use therapy onLithium &those diseases, hyperthyroidism orany thyroid inptientsContraindicated w/ Remarks Remarks © MIMS 2019

HERPES SIMPLEX