chlamydia

SantenPharmaceuticalCo.,Ltd.1

Revid:October2005(4thversion,ren

mentofthePharmaceuticalAffairsLaw)871319

-Broad-spectrumantibacterialophthalmicpreparation-

Tarivid®

ophthalmicointment

DesignateddrugandPrescriptiondrug

Caution:Uonlypursuanttotheprescriptionofaphysician,etc.

CONTRAINDICATIONS(TARIVIDOphthalmicoint-

mentiscontraindicatedinthefollowingpatients.)

Patientswithahistoryofhypernsitivitytotheingredient

ofthisdrugoranyquinoloneantibiotics.

DESCRIPTION

BrandnameTarividophthalmicointment

ActiveingredientOfloxacin

Contentpergram3mg

InactiveingredientPurifiedlanolin,whitepetrolatumand

liquidparaffin

Productdescription

Lightyellow,odorless,sterileophthal-

micointment

INDICATIONS

SusceptiblestrainsofStaphylococcussp.,Streptococcussp.,

Streptococcuspneumoniae,Enterococcussp.,Micrococcussp.,

Moraxellasp.,Corynebacteriumsp.,Klebsiellasp.,Serratia

sp.,Proteussp.,Morganellamorganii,Providenciasp.,Hae-

mophilusinfluenzae,Haemophilusaegyptius(Koch-Weeksba-

cillus),Pudomonassp.,Pudomonasaeruginosa,

Burkholderiacepacia,Stenotrophomonas(Xanthomonas)

maltophilia,Acinetobactersp.,Propionibacteriumacnes,and

Trachomachlamydia(Chlamydiatrachomatis).

Blepharitis,dacryocystitis,hordeolum,conjunctivitis,mei-

bomianitis,keratitis(includingcornealulcer),andaptic

treatmentduringaperioperativeperiodforocularsurgery.

DOSAGEANDADMINISTRATION

Usually,applyintheaffectedeye(s)3timesdaily.

Thedosagemaybeincreadordecreadaccordingtothepa-

tient’ssymptoms.

eralrule,thedurationofadministrationofthisdrug

shouldbelimitedtotheminimumperiodrequiredforthe

treatmentofthepatient’scondition,aftersusceptibilityofthe

microorganismtothedrughasbeenconfirmed,inorderto

preventtheemergenceofdrug-resistantmicroorganisms.

ationoftreatmentforconjunc-

tivitiscaudbyChlamydiatrachomatiswiththisdrug

shouldbe8weeksasastandard,andthereafterthisdrug

shouldbeadministeredwithcare.

PRECAUTIONS

eReactions

Adverreactionstothisdrugwerereportedin14(0.59%)

of2,360patientvaluatedatbeforeapprovalandDrug

oradverreactionswereitchy

nsationofeyelidin3patients(0.13%),swellingofeyelid

in3patients(0.13%),blepharitisin2patients(0.08%),

conjunctivalhyperaemiain2patients(0.08%),eyepainin

2patients(0.08%),andrednessofeyelidin2patients

(0.08%),etc..[Attheendofthere-examinationperiod]

1)Clinicallysignificantadverreactions(rarely:

<0.1%,occasionally:5%>≥0.1%,andnospecific

designation:≥5%orincidenceunknown)

Shock,anaphylactoidreaction:Sinceshockandana-

phylactoidreactionmayoccur,patientsshouldbe

ymptomssucharythema,

rash,dyspnoea,decreadbloodpressure,andeyelid

oedema,erved,administrationshouldbe

discontinuedandappropriatemeasuresshouldbe

taken.

Storage

Storeatroomtemperatureinatight

container.

Expirationdate

Indicatedonthepackageandtube.(3

years)

ApprovalNo.

(62AM)1012

DateoflistingintheNHIreimburmentpriceAugust1987

DateofinitialmarketinginJapanSeptember1987

DateoflatestreexaminationDecember1994

DateoflatestreevaluationSeptember2004

DateoflatestapprovalofindicationJune1989

2SantenPharmaceuticalCo.,Ltd.

2)Otheradverreactions

Ifadverreactionsareobrved,appropriatemeasures

suchasdiscontinuingadministrationshouldbetaken.

Incidence

unknown

5%>

≥0.1%

<0.1%

HypernsitivityRash,urticariaItchingBlepharitis(eyelid

redness/oedema,

etc.),eyelidder-

matitis

OphthalmicConjunctivitis

(conjunctival

hyperaemia/

oedema,etc.),

cornealdisorder

suchaskeratitis

superficialdif-

fu

⎯⎯

ingPregnancy,DeliveryorLactation

Thisdrugshouldbeudinpregnantwomenorwomen

whomaypossiblybepregnantonlyiftheexpectedthera-

peuticbenefitsoutweighthepossiblerisksassociatedwith

treatment.[Thesafetyofthisdrugduringpregnancyhas

notbeenestablished.]

tionconcerningU

Routeofadministration:Ophthalmicuonly.

PHARMACOKINETICS

oncentrations1)

Whenanappropriateamountofthisdrugwasappliedto

theeyes16timevery30minutesinhealthyadultvolun-

teers,thebloodconcentrationsofofloxacinwere0.009

µg/mLorless30minutesafterthelastapplication.

cularpenetrationinanimals

(albinorabbits,dogs)

Afterasingleapplicationofabout40mgofTARIVID

Ophthalmicointmenttotheeyesofnormalalbinorabbits,

thedruglevelinthebulbarconjunctivaandthesclera

reachedtheirpeaksof9.72and1.61µg/g,respectively,at

k

levelsofofloxacinintheaqueoushumorandthecornea

were0.69µg/mLand4.87µg/g,respectively,at1hourand

thereafterdecreadrapidly.2)

Whenonedropof0.3%ophthalmicsolutionoflevoflox-

acin,anopticalisomer(l-form)ofofloxacin,wasapplied

totheeyesofbeagledogs4timesdailyfor2weeks,the

concentrationsofthedrug24hoursafterthelastadmini-

strationwere39.4µg/gintheiris/ciliarybodyand12.3

µg/ginthechoroid/retinalpigmentepithelium,indicating

thattheconcentrationswerehighinthemelanin-containing

therhand,thetransferofthisdrug

totheretinaexcepttheretinalpigmentepitheliumwas

slight.3)

CLINICALSTUDIES4)-7)

cybydiagnosis

TheeffectivenessratesofTARIVIDOphthalmicointment

bydiagnosisinclinicalstudiesconductedon126patients

withexternalocularinfectionsaresummarizedbelow.

DiaEffectivenessrate*(%)

[“effective”orbetterevaluations]

Blepharitis

Hordeolum

Dacryocystitis

Conjunctivitis**

Tarsadenitis

Keratitis

Cornealulcer

Conjunctivitiscaudby

Chlamydiatrachomatis

100.0%

87.5%

85.7%

96.0%

100.0%

100.0%

100.0%

97.7%

(6/6)

(7/8)

(6/7)

(48/50)

(1/1)

(5/5)

(13/13)

(42/43)***

Note)*Patientswithmultiplediaswerecountedas

onecaperdia.

**Excludingtrachoma

***Includingunpublisheddata

cybymicroorganismsusceptibletoofloxacin

Theeffectivenessratesintheabove126patientsclassified

bythecausalmicroorganismarelistedbelow.

MicroorganismEffectivenessrate*(%)

[“effective”orbetterevaluations]

Staphylococcussp.

Streptococcussp.

Streptococcuspneumoniae

Enterococcussp.

Micrococcussp.

Corynebacteriumsp.

Pudomonassp.

nosa

Burkholderiacepacia

Stenotrophomonas

(Xanthomonasu)maltophilia

Haemophilusinfluenzae

Moraxellasp.

Serratiasp.

Klebsiellasp.

Providenciasp.

Trachomachlamydia

(Chlamydiatrachomatis)

93.1

100.0

75.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

97.7

(54/58)

(12/12)

(3/4)

(2/2)

(1/1)

(13/13)

(10/10)

(3/3)

(1/1)

(4/4)

(5/5)

(6/6)

(1/1)

(2/2)

(1/1)

(42/43)**

Note)*Whenmultiplecausalmicroorganismswere

detectedinapatient,eachmicroorganism

wascountedasoneca.

**Includingunpublisheddata

PHARMACOLOGY

ismofaction

OfloxacinisconsideredtoinhibitDNAsynthesisofbacte-

ectisbactericidal,andbacteriolysis

isobrvedattheMICs.8)Ofloxacinhasalsobeenrecog-

nizedtodestroytheelementarybodyofChlamydiatra-

chomatisinitsgrowthcycle.9)

SantenPharmaceuticalCo.,Ltd.3

cterialactivity

Ofloxacinexertsabroad-spectrumpotentantibacterialac-

tivityagainstmicroorganismscausingocularinfections,

includingGram-positivebacteria(Staphylococcussp.,

Streptococcussp.[niae],Micrococcus

sp.,Corynebacteriumsp.,etc.),Gram-negativebacteria

(Branhamellacatarrhalis,Pudomonassp.[includingP.

aeruginosa],Haemophilussp.,Moraxellasp.,Serratiasp.,

Klebsiellasp.,Proteussp.,Acinetobactersp.,etc.),and

Anaerobicbacteria(Propionibacteriumacnes,etc.).8)

OfloxacinalsohasantibacterialactivityagainstChlamydia

species,includingChlamydiatrachomatis.10)Itisrecog-

nizedthatChlamydiaspecieshardlyacquireresistanceto

ofloxacin.11)

PHYSICOCHEMISTRY

Nonproprietaryname:Ofloxacin(JAN,INN)

Chemicalname:

(3RS)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-

1-yl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxyl

icacid

Molecularformula:C

18

H

20

FN

3

O

4

Molecularweight:361.37

Structuralformula:

anditnantiomer.

Description:

Ofloxacinoccursaspaleyellowishwhitetolightyellowish

whitecrystalsorcrystallinepowder.

Itisfreelysolubleinaceticacid(100),slightlysolublein

water,andveryslightlysolubleinacetonitrilandinetha-

nol(99.5)

AsolutionofofloxacininsodiumhydroxideTS(1in20)is

opticallyinactive.

Itisgraduallycoloredbylight.

Meltingpoint:about265