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Tips & Pearls in the Treatment of Viral Eye Disease

J. James Thimons, O.D.,FAAOJ. James Thimons, O.D.,FAAO

Medical Director Ophthalmic Consultants of CT.Medical Director Ophthalmic Consultants of CT.

Clinical Professor, PCO, MCHPSClinical Professor, PCO, MCHPS

Epidemic Keratoconjunctivitis

EKCSerotypes 8,19 most typicalSeasonal Primarily bilateralyAtypical serotypes; Enterovirus 70

Clinical PresentationChemosis Injection InfiltratesAc/reaction?FBS

EKC

TreatmentsPalliative

• Cold compress• Tears• Tears

Interventional• Anti-inflammatory agents• Decongestants• Combination agents• Cidofovir• Betadine• Zirgan?

EKC

TreatmentsBetadine wash

Surgical DebridementSurgical Debridement

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EKC Betadine Protocol

Topical anesthetic x 2

Non Alcohol betadine applied to inferior/ superior cul de sacsuperior cul de sac

One minute wait

Rinse with artificial tears

Apply Topical steroids x 3-4 in post treatment period

EKC Betadine Protocol

Clinical “Pearls”Most effective if treated within 3 days of onset

Less effective in advanced casesLess effective in advanced cases

SPK incidence is close to 100%

Patients will complain of FBS 1-2 hours later

ZIRGANZIRGAN®®

((ganciclovirganciclovir ophthalmic gel) 0.15%ophthalmic gel) 0.15%

FDA approval 9/16/2009FDA approval 9/16/2009

Available in Europe under Available in Europe under the trade name the trade name VirganVirgan((LaboratoiresLaboratoires ThéaThéa) since) since((LaboratoiresLaboratoires ThéaThéa) since ) since 19961996

Purchased from Purchased from SirionSirion by by Bausch & Lomb 2010Bausch & Lomb 2010

Adenovirus Adenovirus Conjunctivitis and Conjunctivitis and keratoconjunctivitiskeratoconjunctivitis caused by caused by

adenoviruses are common and highly contagiousadenoviruses are common and highly contagious

Usually affect both eyes and may cause Usually affect both eyes and may cause epidemicsepidemics

Patients may have painful Patients may have painful conjunctivalconjunctivalmembranes and palpablemembranes and palpable preauricularpreauricularmembranes and palpable membranes and palpable preauricularpreauricularadenotherapyadenotherapy

ZirganZirgan is active in vitro against adenovirus asis active in vitro against adenovirus as11

TabbaraTabbara did a controlled randomized doubledid a controlled randomized double--masked clinical study of patients with adenovirus masked clinical study of patients with adenovirus keratoconjunctivitiskeratoconjunctivitis and found that and found that ganciclovirganciclovirsignificantly reduced both the duration of disease significantly reduced both the duration of disease and the incidence of and the incidence of subepithelialsubepithelial infiltratesinfiltrates22

1Crumpacker CS. Ganciclovir. N. Engl. J. Med. 335(10), 721–729 (1996).2.Tabbara K, Jarade E. Ganciclovir effects in adenoviral keratoconjunctivitis. [ARVO abstract 3111] (suppl), S579 (2001)

Adenovirus clinical trial Adenovirus clinical trial ((TabbaraTabbara, 2001), 2001)

Controlled randomized masked series of 18 Controlled randomized masked series of 18 patients with adenoviral patients with adenoviral keratoconjunctivitiskeratoconjunctivitis

Compared treatment with GCV ophthalmic gel Compared treatment with GCV ophthalmic gel 0.15% versus preservative0.15% versus preservative--free artificial tearsfree artificial tears

Mean time to recovery Mean time to recovery

Significantly shorter for Significantly shorter for ganciclovirganciclovir--treated treated patients: 7.7 days, in contrast to 18.5 days for patients: 7.7 days, in contrast to 18.5 days for those receiving artificial tears (P < 0.05) those receiving artificial tears (P < 0.05)

SubepithelialSubepithelial opacities opacities

Developed in 7 (77%) patients treated with artificial Developed in 7 (77%) patients treated with artificial tears, compared to 2 (22%) patients in the GCVtears, compared to 2 (22%) patients in the GCV--treated group.treated group.

Tabbara K, Jarade E. Ganciclovir effects in adenoviral keratoconjunctivitis. [ARVO abstract 3111] (suppl), S579 (2001).

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HerpeHerpess SimplexSimplex KeratitisKeratitisIncidence and Incidence and PrevalencePrevalence

Leading cause of corneal blindnessLeading cause of corneal blindness

Affects approximately 10 million people Affects approximately 10 million people worldwideworldwide

60% of the U S population shows evidence of60% of the U S population shows evidence of 60% of the U.S. population shows evidence of 60% of the U.S. population shows evidence of infection by age 5infection by age 5

95% of the population by age 1595% of the population by age 15

Approximately 1% of infected patients develop Approximately 1% of infected patients develop ocular outbreaksocular outbreaks

20,000 new primary cases are diagnosed in the 20,000 new primary cases are diagnosed in the U.S. each yearU.S. each year

28,000 recurrences a year in the U.S.28,000 recurrences a year in the U.S.

HerpeHerpess Simplex Simplex KeratitisKeratitis After primary infection, typically becomes latent in the After primary infection, typically becomes latent in the

trigeminal ganglion or corneatrigeminal ganglion or cornea

Stress, UV radiation, and hormonal changes can Stress, UV radiation, and hormonal changes can reactivate the virusreactivate the virus

Lesions are common in the Lesions are common in the immunosuppressedimmunosuppressed (i.e. (i.e. recent organ transplant or HIV patients)recent organ transplant or HIV patients)

Recurrences tend to occur in the cornea and Recurrences tend to occur in the cornea and uveauveaand may cause and may cause dendriticdendritic or geographic corneal ulcersor geographic corneal ulcers

DendriticDendriticulcerulcer

Geographic Geographic ulcerulcer

ANTI-VIRALS

CLINICAL APPLICATIONSACUTE VS CHRONIC INFECTION

PRIMARY LESIONSPRIMARY LESIONS

EPITHELIAL HERPES SIMPLEX

STROMAL HERPES SIMPLEX

HERPES ZOSTAR

HERPETIC IRIDOCYCLITIS

Oral Oral AntiviralsAntivirals IndicationsIndications

Infectious disease/ProphylaxisInfectious disease/Prophylaxis

Acyclovir (Acyclovir (ZoviraxZovirax))

Treatment 400mg 5x/d 1weekTreatment 400mg 5x/d 1week

Maintenance 400mg 2x/d Maintenance 400mg 2x/d gg

ValaciclovirValaciclovir ((ValtrexValtrex))

Treatment 500 mg Treatment 500 mg tidtid 1 week1 week

Maintenance 500 mg Maintenance 500 mg qdqd

FamciclovirFamciclovir ((FamvirFamvir))

Treatment 250 mg Treatment 250 mg tidtid 1 week1 week

Maintenance 250 mg Maintenance 250 mg qdqdBarron BA, Gee L, Hauck WW, Herpetic Eye Disease Study: A controlled trial of oral acyclovir Barron BA, Gee L, Hauck WW, Herpetic Eye Disease Study: A controlled trial of oral acyclovir for herpes simplex for herpes simplex stromalstromal keratitiskeratitis. Ophthalmology 101: 1871. Ophthalmology 101: 1871--1882, 1994.1882, 1994.

Effective against HSV and HZVTargets virally infected cells only Inhibits DNA synthesis – activated by a

virus-specific thymidine kinase then phosphorylated by host enzymes into its active form

Few side effectsNausea most commonDon’t use with diminished kidney function

Oral Oral AntiviralsAntivirals

Indications in Infectious HSVIndications in Infectious HSV

EndotheliitisEndotheliitis

IridocyclitisIridocyclitis

Primary Herpetic DiseasePrimary Herpetic Disease Primary Herpetic DiseasePrimary Herpetic Disease

ImmunocompromisedImmunocompromised patientspatients

Post Post keratoplastykeratoplasty

? All cases of Infectious ? All cases of Infectious

Epithelial Epithelial KeratitisKeratitis

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ANTI-VIRALS

SIDE EFFECTSRENAL FAILURE/ IMPAIRMENT

HYPERSENSITIVITY REACTIONSHYPERSENSITIVITY REACTIONS

FACIAL EDEMA

VISUAL HALLUCINATIONS

Topical Treatments for Herpes Topical Treatments for Herpes Simplex Simplex KeratitisKeratitis

6 topical ophthalmic 6 topical ophthalmic antiviralsantivirals have been or are have been or are currently used in the U.S. and Europecurrently used in the U.S. and Europe

11stst & 2& 2ndnd Generation Generation AntiviralsAntivirals IdoxuridineIdoxuridine (IDU)(IDU)

IododesoxycytidineIododesoxycytidine (IDC)(IDC)

VidarabineVidarabine ((AraAra--A)A)

TrifluridineTrifluridine (TFT): Approved in U.S. 1980(TFT): Approved in U.S. 1980

IDU, IDC, and IDU, IDC, and AraAra--A have been abandoned by A have been abandoned by clinicians due to high toxicityclinicians due to high toxicity

33rdrd Generation Generation AntiviralsAntivirals: more selective, less toxic: more selective, less toxic Acyclovir (ACV): Europe onlyAcyclovir (ACV): Europe only

GanciclovirGanciclovir (GCV): Europe and available in US in early (GCV): Europe and available in US in early 20102010

The Antiviral for the 21st Century

Zirgan 0.15% GelSirion PharmaceuticalsHSK 2 years and olderGanciclovir: Selectively targets replication ofGanciclovir: Selectively targets replication of

HSV DNA within corneal cellsDose: 5 x / day till lesion resolves then tid for one

weekToxicity:60% blur20% irritation5% Hyperemia

GanciclovirGanciclovir Structure and ActivityStructure and Activity

Synthetic nucleoside analog of 2′Synthetic nucleoside analog of 2′--deoxyguanosine deoxyguanosine 99--(1,3(1,3--dihydroxydihydroxy--22--propoxymethyl) guaninepropoxymethyl) guanine

In vitro activity:In vitro activity:

Mean effective dose for HSV1 and HSV2 in clinicalMean effective dose for HSV1 and HSV2 in clinical Mean effective dose for HSV1 and HSV2 in clinical Mean effective dose for HSV1 and HSV2 in clinical isolates is 0.23 µg/m1isolates is 0.23 µg/m1

Inhibitor of viral replication for Inhibitor of viral replication for HSV1, HSV2, HZV, EBV, CMV, HSV1, HSV2, HZV, EBV, CMV, adenovirus and HHV6 virusesadenovirus and HHV6 viruses

11 Inoue, et al. 1989. Comparative efficacy of three antiviral drugs in mice Inoue, et al. 1989. Comparative efficacy of three antiviral drugs in mice herpetic herpetic keratitiskeratitis. . JpnJpn J J OphthalmolOphthalmol, 33:125, 33:125--31.31.22 LocarniniLocarnini, et al. 1989. Inhibition of HBV DNA replication by , et al. 1989. Inhibition of HBV DNA replication by ganciclovirganciclovirin patients with AIDS. Lancet, 8673:1225in patients with AIDS. Lancet, 8673:1225--6.6.

ZIRGAN® Mechanism of ActionZIRGAN® Mechanism of ActionActivated GCV inhibits the Activated GCV inhibits the synthesis of viral DNA in 2 synthesis of viral DNA in 2 ways:ways:

(1) Competitive inhibition(1) Competitive inhibition

Activated GCV directlyActivated GCV directly Activated GCV directly Activated GCV directly inhibits viral DNA inhibits viral DNA polymerase, preventing polymerase, preventing viral replicationviral replication

(2) Chain termination(2) Chain termination

Activated GCV Activated GCV incorporates into viral incorporates into viral DNA, preventing DNA DNA, preventing DNA synthesissynthesis

GanciclovirGanciclovir Mechanism of ActionMechanism of Action Penetrates cell infected with the virusPenetrates cell infected with the virus

PhosphorylatedPhosphorylated within the cell to within the cell to ganciclovirganciclovirmonophosphatemonophosphate by a viral by a viral thymidinethymidine--kinasekinase

Affinity for viral Affinity for viral thymidinethymidine--kinasekinase allows for allows for specificity in its actionspecificity in its actionspecificity in its actionspecificity in its action

Activation continues due to several cell Activation continues due to several cell kinaseskinasesleading to formulation of leading to formulation of ganciclovirganciclovir triphosphatetriphosphate, , which:which:

Inhibits viral DNA polymeraseInhibits viral DNA polymerase

Incorporates into viral DNA preventing replicationIncorporates into viral DNA preventing replication

CastelaCastela N, N, VermerieVermerie N, N, ChastChast F, et al. F, et al. GanciclovirGanciclovir ophthalmic gel in herpes simplex virus rabbit ophthalmic gel in herpes simplex virus rabbit keratitiskeratitis::Intraocular penetration and efficacy. J Intraocular penetration and efficacy. J OculOcul PharmacolPharmacol. 1994;10(2):439. 1994;10(2):439––451451

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GanciclovirGanciclovir 0.15% (0.15% (ZirganZirgan™)™)Clinical Efficacy ResultsClinical Efficacy Results

Results from 3 randomized, singleResults from 3 randomized, single--masked, controlled masked, controlled multicenter clinical trials evaluating multicenter clinical trials evaluating ganciclovirganciclovirophthalmic gel 0.15% compared to acyclovir ophthalmic gel 0.15% compared to acyclovir ophthalmic ointment 3% patients with ophthalmic ointment 3% patients with dendriticdendritic ulcersulcers

GCV 0.15%GCV 0.15%N N = = 5757

ACV 3%ACV 3%N = 49N = 49

Clinical ResolutionClinical ResolutionBy Day 7By Day 7

41 (72%)41 (72%) 34 (69%)34 (69%)

WilhelmusWilhelmus KR. The treatment of herpes simplex virus epithelial KR. The treatment of herpes simplex virus epithelial keratitiskeratitis. Trans Am . Trans Am OphthalmolOphthalmol Soc. 2000;98:505Soc. 2000;98:505––532532

Colin J, et al. Colin J, et al. GanciclovirGanciclovir ophthalmic gel (ophthalmic gel (ZirganZirgan 0.15%) in the treatment of herpes simplex 0.15%) in the treatment of herpes simplex keratitiskeratitis. . CorneaCornea1997;16:3931997;16:393––399399

ZirganZirgan®® ((ganciclovirganciclovir ophthalmic gel) ophthalmic gel) 0.15% 0.15% vsvs Acyclovir 3%Acyclovir 3%

Safety Safety -- Most Common Adverse Effects Most Common Adverse Effects -- 4 studies 4 studies

GanciclovirGanciclovir 0.15%0.15% Acyclovir 3%Acyclovir 3%

Vision Blurred 93/161 (57.8%) 112/157 (71.3%)Vision Blurred 93/161 (57.8%) 112/157 (71.3%)

Eye Irritation 32/125 (25.6%) 55/119 (46.2%)Eye Irritation 32/125 (25.6%) 55/119 (46.2%)

PunctatePunctate KeratitisKeratitis 11/125 (8.8%) 19/119 (16.0%) 11/125 (8.8%) 19/119 (16.0%)

ConjunctivalConjunctival Hyperemia 7/125 (5.6%) 6/119 (5.0%) Hyperemia 7/125 (5.6%) 6/119 (5.0%)

WilhelmusWilhelmus KR. The treatment of herpes simplex virus epithelial KR. The treatment of herpes simplex virus epithelial keratitiskeratitis. Trans Am . Trans Am OphthalmolOphthalmol Soc. 2000;98:505Soc. 2000;98:505––532532

Colin J, et al. Colin J, et al. GanciclovirGanciclovir ophthalmic gel (ophthalmic gel (ZirganZirgan 0.15%) in the treatment of herpes simplex 0.15%) in the treatment of herpes simplex keratitiskeratitis. . CorneaCornea1997;16:3931997;16:393––399399

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HSK

DENDRITIC KERATITISWITH OR WITHOUT DENDRITE

DIFFERENTIAL DxDIFFERENTIAL DxVARICELLA-ZOSTAR

EPSTEIN -BARR

VACCINIA

THYGESON’S

HSK

IMPAIRED EPITHELIAL HEALINGANTIVIRALS

ANTIBIOTICSANTIBIOTICS

PRESERVATIVES

POST INFECTIOUS

SCL’s

HSK

CLINICAL FINDINGSACANTHAMOEBA

EPITHELIAL DEPOSITSEPITHELIAL DEPOSITS

MUCOUS PLAQUES

GEOGRAPHIC KERATITIS

STROMAL KERATITIS

NECROTIZING KERATITIS

Risk of Recurrence25% recurrence risk over two years after a

first episode of epithelial keratitisfirst episode of epithelial keratitisSecond episode has a 43% recurrence risk

Natural CourseLittle scarring first recurrencesScarring increases with increased recurrenceVascularizationStromal keratitis

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Oral acyclovir has not been demonstrated to be more effective than topical agents in the treatment of epithelial herpes keratitis

Long term oral acyclovir may reduce the recurrence of epithelial keratitis1p

Oral acyclovir, as part of the treatment of epithelial keratitis, does not reduce the risk of developing stromal keratitis2

1. Simon Al, et al. Long term oral acyclovir therapy. Effect on recurrent infectious herpes simplex keratitis in patients with and without grafts. Ophthalmology 1996;103:1404-5.

2. A controlled trail of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Arch Ophthalmol 1997;115:1196.

Herpetic Herpetic KeratitisKeratitis Prophylaxis Case Prophylaxis Case Series Series ((TabbaraTabbara, 2005), 2005)

Prospective interventional case series studied the use of Prospective interventional case series studied the use of topical topical ganciclovirganciclovir ophthalmic gel 0.15% for treatment and ophthalmic gel 0.15% for treatment and prophylaxis of herpetic epithelial prophylaxis of herpetic epithelial keratitiskeratitis

Evaluated the effects of treatment among 16 cases and Evaluated the effects of treatment among 16 cases and prophylaxis among 6 of those casesprophylaxis among 6 of those casesp p y gp p y g

Instillation once every 6 hours for 2 weeksInstillation once every 6 hours for 2 weeks

Complete resolution of herpetic Complete resolution of herpetic keratitiskeratitis noted in all ptsnoted in all pts

During followDuring follow--up, none of the 6 patients on prophylactic up, none of the 6 patients on prophylactic ganciclovirganciclovir developed a recurrencedeveloped a recurrence

3 of 10 patients without prophylaxis developed recurrences3 of 10 patients without prophylaxis developed recurrences

No ocular side effects were notedNo ocular side effects were noted

Tabbara K, Treatment of herpetic keratitis. Ophthalmology: 112, 9. pg 1640.

HSKDIAGNOSISCYTOLOGY

• SCRAPE - ACTIVE VESSICLES

• PAPANICOLAOU STAIN

• MULTINUCLEATED GIANT CELLS• MULTINUCLEATED GIANT CELLS

ANTIGEN DETECTION TESTS• IMMUNOFLOURESCENCE

• IMMUNOPEROXIDASE

• ENZYME IMMUNOASSAY

• DNA PROBE

• PCR

HSK

MANAGEMENT/EPITHELIAL DISEASEDEBRIDEMENT

ROSE BENGAL / LISSAMINE GREEN

DRUG THERAPY• TRIFLURIDINE

• IDOXURIDINE

• VIDARABINE

• ORAL AGENTS

• CIDOFIR

TREATMENT

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HSK

STROMAL KERATITISRULE OUT MICROBIAL DISEASE

VIROPTIC

ORAL AGENTS

CORTICOSTEROIDS

CYCLOSPORINE A

SURGERY• PKP

• CONJUNCTIVAL FLAPS

• TISSUE ADHESIVES

Oral acyclovir has demonstrated no benefit in the treatment of stromal keratitis1

Long term (one year) oral acyclovir reduces the risk of recurrent stromal keratitis2

1. Barron BA, et al. Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes stromal keratitis. Ophthalmology 1994;101:1871-2.

2.Acyclovir for the prevention of recurrent herpes simplex virus eye disease: Herpetic Eye Disease Study Group. N Engl J Med, 1998;339:300-6.

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If It wasn’t for Bad Luck I would have none at all!

DR a really nice 58 y/o white male presented with a 4 year history of recurrent HSK with stromal involvement.Medical Hx positive for Leukemia well

controlled until last 6 months.Patient complained of LOV x 6-7 days

progressing.Additionally patient demonstrated 50-60 lbs

weight loss since last visit.

Bad Luck

Clinical presentation showed:VA – FC @ 3 ft

2+3 Injection2+3 Injection

Ptosis 2mm

Discharge 2+

SLE: 7mm central lesion with staining. Peripheral white cell ring. AC 2+3 cell with posterior KP’s

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Bad Luck

Initial TherapyValtrex 1000 mg tid

Zymar qidZymar qid

HA 5% TID

Neosporin Ung TID

Follow up 24 hrs

Bad Luck

24 hour follow up:Patient c/o increased pain

VA; HM @ 3ftVA; HM @ 3ft

Lesion melting @ 1:00 with 60 % thinning

Increased white cell perimeter

1/8 chamber hypopyon

TX:?

Bad Luck!

Day two:No change!

Tx?Tx?

Day Three:Decreased white cell skirt

Hypopyon 90 % cleared

Decreased pain

The Non-Healing Eye

BC a 54 y/o white male was referred for evaluation of a non-healing corneal wound following abdominal surgery 6 and 2 weeks g g yearlier.

The patient was wheelchair bound and unable to ambulate, had suffered a 40 lb weight loss in two weeks and complained of severe LOV.

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The Non-Healing Eye

Clinical exam:

VA- LP OD , 20 25 OS ph no change

SLE: 9 mm area of confluent staining ODSLE: 9 mm area of confluent staining OD with 4+ edema. Anterior chamber 1+ cells.

Ta 19/ 13 mmHg

DFE: No view OD/ OS wnl

External: 3/5 / minimal reaction/ -MG

The Non-Healing Eye

One week after initial therapyVA 20/400

AC= trace cellAC trace cell

Corneal lesion 4 mm with stromal haze 2+

The Non-Healing Eye

Following therapy at 4 weeks the epithelial defect closed with residual hyperplasia.

VA- 20/50 ph 20/40+VA 20/50 ph 20/40+

BCL removed

Ta 26/20 mmHg

See Photo!

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The Non-Healing Eye

Next visit patient on Alphagan-P bid OD, PF qid, AT’s PRN.

Complains of Photophobia pain ODComplains of Photophobia, pain OD.

VA 20/ 30 OD ph 20 25-

Ta 38 /20 mmHg

SLE: 1+2 cell, Cornea as shown

DFE- Negative

The Non- Healing Eye

Patient did very well for 3 weeks, then returned with complaint of severe photophobia and redness.p p

Joint pain @ knee, shoulder and hip.

Urethritis returned x4 days

VA decreased , IOP 19mmHg, VF- Non specific loss

Meds: Cosopt 2/2, Alpha-P 2/2, PF qd

The Non-Healing Eye

Patient saw GMD was Diagnosed with Reiter’s ( Non STD) , secondary to “dirty” surgery.g y

Current meds Cosopt 2/2, AP 2/2, PF 4/0

VA 20 30+ ph 20/20-

SLE : see photo

Ta 15 mmHg

VARICELLA ZOSTAR-KERATITIS

PRIMARY INFECTIONCHICKEN POX

VACCINATION RECOMMENDED BYVACCINATION RECOMMENDED BY AMERICAN ACAD of PEDIATRICS

RECURRENT INFECTIONOPHTHALMIC INVOLVEMENT 10-255

OPHTHLAMIC ZOSTAR > OVER AGE 60

UNDER 40 50% IIMMUNOCOMPRIMISED

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HZK

HZKV1, V2, V3

CONJUNCTIVACONJUNCTIVA

CORNEA

MUCOUS PLAQUE

DECREASED CORNEAL SENSATION

ENDOTHELEITIS

HZK

STROMAL KERATITISBASIC FEATURES

• IMMUNOGENIC RESPONSE

CLINICAL FEATURES• DISCIFORM

• SUPPERATIVE

• MIXED

TREATMENT

A New Potent Topical Steroid

Background Information and Clinical Experience

Dose Uniformity – Durezol verses Generic Prednisolone Acetate

Suspension

600

700

800

m

Inverted, not shaken (generic pred)

Upright, shaken (generic pred)

Inverted, not shaken (Durezol)

Upright shaken (Durezol)

0

100

200

300

400

500

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19Time (Days)

% L

abel

Cla

im Upright, shaken (Durezol)

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HZK

TREATMENTORAL AGENTS

• ACYCLOVIR 800 mgg

• FAMVIR 500 mg

• VALTREX 1000 mg

• SORIVUDINE

• VRIVUDIN

Adults – Zostavax

Children – Varivax

Relationship between them