ED Ill 0 N
`
`2011
`
`PHYSCANS'
`DESK
`REFERENCE®
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`ISBN: 978-1-56363-780-3
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`AMN1010
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`
`ACZONE • ALLERGAN/.599
`
`VIGAMOX® solution should not be injected subconjunc~­
`va).!y, ll<!r' shoUld it be _jntroduced directly into the, antt))."ipr
`Chamber of the eye.·
`·
`In patients rece~ving systemically administered quinoloQ.es,
`including moxifioxacin, serious and occasionally fatal hyper-
`lactic) reactiQD~ have been reported,
`sensitivit
`-
`.
`st dose. Some reactionir were accom·''
`some' foil
`u1ar 'collapse, Joss of consciousness, an-
`paoied by
`gioedema (including laryngeal; pharyligeal or faci31 edema),
`airway !ll?strnction, dyspnea, urticaria,_ and itching. If an 91-
`lergic reaction to moxif!oxacin occurs, discontinue use 0~ the
`drug. St>ljous acute liy'persensitivib',reactions may requ!re
`in:>JD.~t#~te ~inerglln,cy' treatment. Ol!:ygen ~d amyay JUan(cid:173)
`agement should be administered as clinica1ly indicated.
`PREcAUTiONS
`General: .As.with other anti-infectives; prolonged use may
`result in overgrowth of non-susceptible organisms, includ(cid:173)
`ing-fungi. If superinfection occurs, discontinue use and in(cid:173)
`stitute alternative therapy. Whenever clinical judgment die~.
`tates, the patient should be examined wjth tqe aid ·of
`magoification, S\!Ch as slit-lamp biomicroscopy, arid, where
`appropriate, fluorescein staining; Patients should be ad- -
`vised not to w'e¥ cont!J-Ct lenses if they have signs and
`symptoms of bacterial conjunctivitis.
`lnformation'for Patients: Avoid contaminating the applica(cid:173)
`tor tip with material from the eye, fingers or other source.
`Systemically~.' administered·
`quinolones\ i:'ini:luding
`moxif!oxacin have been associated with hypers~nsitivity
`reactions" even following a single dose. Discoiitinue use im(cid:173)
`mediately and contact your physician at the first sign of a
`rash or allergic- reaction.
`Driig'liiteractioris: Drug-di\ig interaction studies'liave not
`been conducted with VIGAMOX® solu~ioQ.. l1f ~ipro studi,e~
`indicate. th~~ l,llmoiflqx'!-~!n does. not in:4ibit, CyP~M.
`CYP2D6, CYP2C9, CYP2C19, o:r CYP1A2 'indicating that
`mqXiiloxaciQ.' i~ Un!ikely to alter the pharmacokmetic5 .of
`drU~§ _metaboli~ed by.f.J:i.el'\' ~yto<;~m:,P45~ ,!socymes: .
`.
`CarJilnogenesis, Mutage.nesis,r.I01pa•rment .of Fer:t1hty:
`~ng~term studies in~als 'to d.~termine the ~cill,ogenic
`potential of moxifloxacin have not bee~ performed_. .l;lo-iY;(cid:173)
`ever, in 'an accelerated study with initiatotp and promoters,
`mo~oxacili was npt carc4J,ogenic in r~ts follo¥!'-g_ t;l' to j~
`'reeks of oral dosing at 500 mglkg/day (apprp=.ately
`21,700 times tlie higheSt 'recommended tptal <;laily'li,uffian
`ophthalmic dose for a 50' kg person, pn' a m!lfkg li~sisl. ~ .,
`M;oxifloxapfu 'l'as I).ot mutagenic in four -J;lacteriSJ.: s>train~
`u~ed_in theAines.S,almo'!ella r~':'i':"ion 1\s~ay ... ~M~J:totjle~
`qujl)olones, • th,e positi,ve
`response observ'ed
`. with
`moxifioxacin· in sb!ain TA 102 u.sing the same asS1J.Y may, he
`due,to'tlie inhibltiori of DNA !&rase. Moxllloxacfu was not
`mutai:eili~ in the'Ci:IOIHGPRT mammalian cell g~ne- muta(cid:173)
`tion issay . .An eqni,yocalrj!sult 'Yas obtain~d ~ th_e same a.s:
`say when v79 cel]s were ·use1l. Moxif\o1<8cin was clastOgenic
`~J)le v79 ~lu:o!p.p~ol):l~ iiiJerr!!tion,BJ?say,but.it did not in(cid:173)
`dn~• upscl)ed,qled ;D:NA ~ynthesis .in. cultured :.;at heP,ato(cid:173)
`cytes. There W!JS.n<i~v:l.de~ce ofgen.ot,(\~~Jty in.ri(~q in a;;r¢.:
`cronuC!ens test or a dOtyinant lethal test in mice. "
`.
`-
`¥oxi11oxacu;__Jl.?.'Q.' no ed:~ct on, ferlilit)i.~in,;9.~f a,pdjibPi,J!l
`rats at oral doses as high as 500 mglkg/day, approx,unately
`211?00 times the highest reCommended to,~,~,f,~·.·~.'ln
`oplitlialJni.c .dose. ,At· 500 mglkg,orally .there,\'{<ire;~ijghp ef(cid:173)
`feets on ·spetmc 'morphology,Chead-tail sepailition) ;il:l 'm.ile
`latsand on tliereSijpjJ.s' CyCle 'fr~_fenlaie rf:ltS'\~·: ~"">.! ·
`Pr~gnan,cy; T~"i''ogpni~ ~Effects., .· ·"' · ·
`,
`,
`.;
`Pr,egrla~cy Cljhmory Cj 11Jo~oxa9ifi '!Vas. _not ~ratoge,ci,c
`w4en administered to preg'nant,ra,ts duri)lg organog\\Desis
`at.~r41 dos..S as high as 500,Di~glday,_(a,Ppr:oxill).ately
`~~ 700 tirl).es the hig\\~st T'/,?llll':"e:!'-d'l\!; ,~otal dall;y hum~
`opht~.Uinic, dose); however, decreased 'fetal body weights
`and slightly q!jlayed fetal sk~letru; dev~lopment, wer~ 'qb,
`served. There w\'~ no ~)vidence· oftei:atoge'nicity when, preg:~
`nan! Cjnomol~ monkeys wei~ gi.,;~n oral d.oses as,hlgh1as
`100 ,ri.glkgJQ.ay:(~pjito#.jii{te)y t,,_390 tin:\.~~ "tile highest' r'l~­
`ommended tot~r <iilll.Yj, h~in) o,P,h~palll).~c. dos~)., ~-.in::
`creased incidence of smaller fetuses· was observed at
`lOOmg/kglday.
`· '''ci.l "··., ...
`'"
`Sinre there· are .no adequate and well-cohtrolled studies in
`pregnant women, VIGA!\iOX®.'solution.Should'be used.dur~
`ingpregnancy only if the potential benefit just!fi~s the po1
`tential risk to the fe~s. .
`. .
`· .
`.. ·
`, ,·.
`, .
`: ·
`flursinjj Motl:ler~:· 'Mo;irlfloxacln hils' not been .. nuiafllired in
`1uJnali nlilK;''allli'.J,lgn it'can ])\, presufned to be excreted in
`:mill!:? -:lC:autii:ni' shoufd t be"' e
`~· when
`'
`X® sol\iiton is ri:tlminiStered to a
`~ otilei-.
`iJge~- 'Tlid'safety iihif'illfectivlmess o~ . . _. oxi!!!
`.dutioif iii i&il:nts hE!ibw\:i year of age •have not been estaJic
`lished. There 'is1'no 'evide'nce that the ophtlillllhlc' adlirinis:
`t!ittion of VIGAMOX® .solution h_!)s ·any effect' on ·weight
`i'.J~ringjoints! even th~ugh· oral' admjnistration of some
`qninolones has been shown to ca.use arthropathy in imma-
`\i1reahirilals.
`,., ,
`Glllatri~ U5e: ·No 'overall difference a, in s~ety and eifec(cid:173)
`biiness have been observed• between, elderly' anti youngen
`pilients.
`.
`
`ADVERSE REACTIONS
`The most freq~ently reported ocular adverse. events were
`conjunctivitis,;decreased visual acnity, dry eye, keratitis, oc(cid:173)
`ular discomfort, ocular hyperemia, ocular pain, ocular pru(cid:173)
`ritus, subconjunctival hemorrhage, and tearing. These
`events occurred in approximately 1-6% of patients.
`l'f on ocular adverse -events reported at a rate· of 1-4% were
`'fever, increased cough, infection, otitis media, pharyngitis;
`·rash, and-rhinitis.
`DOSAGE AND ADMINISTRATION
`Instill on~ drop ifl the aire~ted eye 3 tinle;·a day for~7 ~ays.
`HOW SUPPLIED
`.
`VIGAM.OX® solution is •upplied .!ls_a stEtrile ophthalmi,~ so,
`lution in Alcon's DROP-TAINER® dispensing system con(cid:173)
`sisting of a natural low density polyethylene bottle and diS(cid:173)
`pensing plug and tan polypropylene closure: Tamper
`evidence is .. provided with a shrink band around the closure
`and neck area of the package.
`3 mL in' 4 mL bottle - NDC 0065-4013-03
`Storage: Store at 2~C-25'C (36'F-77'F).
`Rx Ouly
`Manufactured by
`Alcon ~aboratpries, Inc.
`Fort Worth, Texas 76134 USA
`'Licen&ed to. Alcon; 1nc. bY Bayer Health Care 1<\G.
`'U.S. PAT. NO. 4;990,5li; 5,607,942; 6, 716,830.
`: © 2003-20Q6, 2008~CO!l, fuc. , .
`
`All~.rgaQ, Inc.:' ..
`2525 DUPONT DRIVE
`P.O. BOX-19534
`IRVINE,, CA 92623-9534
`
`OPHTHALMIC PRODUCT~,
`_For i!iformation on Allergan, fuc.; prescription, OTC, and
`ophthalmic products, coiiimlt the £hjsicians' Desk''Refer(cid:173)
`ehce®'tfor Oplithd!mo{ogy. For li~rature, service' items; or
`s:!mple material, contact Allergari directly. See a coniplete
`listing of products' in the•ManUfacturers' Index section of
`this 'book.·
`· •
`''
`.-
`
`~
`
`-!l·
`
`·'
`ACZONE®
`(dapsdnel
`qel;5%
`HIGHUGHTS. OF~ PRESCffiBING INFORMATION
`These highlfghts di:i' riot inciude all the Jnforimitioii' needed
`to use ACZONE®·safelyabd eff'el:ttvely.'See full prescribjrig_
`information for ACZONE®. . .
`sr->
`ACZONE® (dapsone) Gel, 5o/ci'~.
`FO; topic'al Lise "qni·y
`' + ~/
`1 v·~>
`~ '''""C
`lnitiaf'IJ.S. 'Ai>inoval: 1955'
`.
`'
`INDICATIONS'AND:USAGE "
`ACZONE® Gel!s indicated for the t&pic,il treatment'of'a,ch'e
`vulgaris (1),
`.
`,, •
`.
`·
`·
`'
`·
`· •.
`:·
`----~DOsAGEAND'ADMllUSTRATION-· ----.i
`• Apply twii:e daily (2):. .
`.. .
`. '
`'0 '
`.
`• Apply approximate!Y;a ,Pea-sized'amount'of ACZONEI!!'
`-Gel, 5%; .in a thlit 'layer to ilie a,cM alfected,area (2):· I,: ..
`•' rr there. is no iiD.provem:ent after 12 weeks, ~atment with
`ACZONE®·Gel, 5%, shOuld oe rjias'sessed'(2).
`' "
`For topical- use· ouly!'''Not fdr . oral,' optltlialniiC', or
`intravaginal use''(2).11 ,s
`·~Ti, f~· 7.~. ~~ .4e~s-
`---DOSAGE.FQRMSAND STRENGTH~'- . •
`ACZONE® (dapsone)oGel, 5%;;is supplied- in 'the, following'
`sizetulies:r, >
`~ ~ • ?
`:o'
`···Professional Sample~ t3· grain laminate tube (3).
`• Cpmmercially: 30 and ·60 graindaininate tubes l3).
`-----,-~-.-tCO~ICATION:.~,...._-~~
`None.
`__
`WARNOONGSANDPRECA~ONS~'~"-~~
`Hamatologinal .,·Effects:.!/Some"· .subjects J.,wi,th · .. G6PD
`deficiency u~ing ,ACZQNE® ·Gel de1.'eloped4 -lalioratory
`~I:Ianges:suggestive 96 mild<hemolysis.•.(5,IHC8.6)
`·
`The following me seen <Withroral' dapSorle treatme.nt:
`·
`• Hematological Effects (5.1)~
`• Peripheral Neuropathy (5.2).
`~ Skin Reactions (5.3):;"'' ·
`.1-l'
`.. . . ~
`-
`.
`''ADVERSE REACTIONS:.'
`Most commori adv'erse reactions (incidence .. ""' .J 0%). are
`oifuiess/peeling;c<;lryness andr erythema <at the, application
`· l :
`' .,. £
`site .(6):
`'•»
`To repor,t SUSPECTED -ADVERSE. REACTIONS,, contact
`Allergan at 1,800..433.-8871 or FDA at.1,800,FDA-1088· ol:
`www.fda.gov/medwatch.
`.o
`"'
`
`~~---DRUG 'INTERACTION~~---'­
`~ 'Trimethoprim/sulfamethoxazole. (TMP/SMX) increases
`the level of dapsone and its metabolites. (7.1)
`• T~pical benzoyl peroxide used, .at- the '!laine. time as
`ACZONE® may result in tempomry local.yellow or orange
`..
`skin. discoloration. (7 .2)
`--.-.-USE IN SPECIFIC POPlJLAITIONS~--""'
`G6PD Deficiency (8.6).
`.,
`;
`See 17 for PATIENT COUNSELING INFORMATION
`and FDA.approved patient"labeling. , ·
`, ,
`
`Revised: 03/2009
`..;
`FULl. PRESCRIBING INFORMATION: .CONTENTS*
`1
`INDICATIONSANB-USAGE·
`2 DOSAGE ANnADMINISTRAT.ION
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS '"'
`...
`5 WARNINGS AND PRECAimONS '
`· 5.1 :.)l~JUatpjogical'1)ifrect~ . ,., . . '
`5 .. 2 Pen,Pheral Neuropathy ·:
`5:3 Skin
`'
`. . '
`.
`6 ADVERsEREACTIONS
`. .
`6;1. , Cl_inical Trials Experie,nce
`6.2 Experience With Oral Use of Dapsone '·
`7 DRUG INTERACTIONS
`' .. ..
`.
`7.1 Trimethopr:im-Sulfametllpi¢zole
`7.2 - TOpical Behloyl Nl-~liali ·
`7.3
`:Qrug,II).terac\)ons,\\'ith Ora!_ Dapsone
`8 USE IN SPECIFIC POPULATIONS'
`'
`8.1 Pregnancy
`8.3 Nursing Mothers,
`8.4 Pediatric Use ·
`: 8.5 dhl1'atric Use·
`,
`'8.6. · ,G6PD Deficienc\>:. ·
`'
`, r.
`10 OVERDOSAGE
`11 DESCRiPTION . \ .
`!2 cillticAL PifARMAQOLOGY
`12.1. ,Mechanism of Action
`12.3 Pnarlnai:okinetics '
`12.47 Microbiolbgy
`·
`l3 N;ONq:.~QAL T()XICOLOGY
`.
`13,;1 .Car$ogen~sis, Mutagen!Jsis, Impaii'Jl!f!mt' of
`, ,
`Fertili,ty
`,
`.
`14 CLINICAL STUDIES
`16 HOW Sl:JPPLJED/STORAGE ~iiANJ)~G'
`17 PATIENT COUNSELING INFORMATION
`''
`17.1 Information for Patients
`' ...
`' '
`·
`. i t.2 . .F.DA-Approved Pa;tient Labefuig
`,
`,
`.
`;sections-or subsections omitted from, the full pr7"cribing
`·
`·
`information are not listed.
`
`'
`
`,··
`
`.
`
`-
`
`"
`
`FULL PRESCRIBING INFORMATION
`1
`·INDICATIONS AND USAGE
`ACZONE® Gel,-5411,' i~ iiu:licated for the topical treatment of
`acnevul'~,' · .,,
`·
`2
`·DOSAGE AND ADMJNIS['RATION
`For , topical use ouly. Not' for oral, , ophthalmic, or
`~tr8.v8ginal use.·
`~ 1
`~
`~,,, , • ~~,
`After. the skin",;Bgently \viis he d. a~d If!lttecj. 'drY,; apply
`approximately a {lea-sized amount of•ACZONE® 'Gel; 5%; in
`a thin layer to-theacne affected areas twice· dailY. 'Riili'fu
`ACZONE® Gel, 5%;'gently and completely. ACZONE®:Gel,
`5%; is gritty with 'Vfsible drug substance partiCles. Was'h
`hands'after application of ACZONE® dei, ·5%:
`· '
`•,
`If there is'no improvement after 12 weekS, treatment Witli
`Jl,CZI;JNE® .!}el, 5')'0, should be re~sessed,
`· ·
`DOSAGE FORMS .AND STRENGTHS
`3
`ACZONE® (dapso~) Gel, 5%,-is-supylied in the fpllowing
`size tubes:
`':c
`-- -.
`'
`J~-
`• .:. ··:
`1
`• Professional Sample: S gram laminate tube
`• Comrriercially: 30 and 60 grain laminate' (i,WBs'
`4
`CONT;RAINDICA1'10NS
`None.
`5- W~GSANDPRECAUTIONS
`5,.1
`HemafQlogical Effects
`Oral dapsone" q,~atment · has produced d.ose-rei~terl
`hemo~ysis ~d hemolytic I!D~mia.I:Qdiyidu!lls:;vith gl_ilcilise-
`6-phosphate dehydrogenase ·(G6PD) deficiency ,are, more
`prone .to,lwmolysis w;ith the use of c.extain.drugs: .G6:PJ) de(cid:173)
`ficion~y is niost prevalen~ in populations of Africi!D, .. s~l1th
`Asian, Middle Eastern and Medite,rranean ancestry.
`There was no evidence of clin!~!!Jly, o:ele'(.an!< hemplysis J)J;
`anemia in patients treated with ACZONE® . Gel, 5%,
`including patients whow~.re .G6PD deficient. Some subjects
`with G6PD ·deficiency 'using;A'CZONE®.<'iel developed
`laboratory Changes suggestive of mild,neniolysis:C .
`' ;,,
`If signs and symptoms suggestive of hemolytic anemia
`oCcur, ACZONE® ,G!!l;· 5% should be discontinued:
`ACZONE® ,Gel, 5% should not be y.sed in patients wb_o are
`takingioral dapsoneoi:antiinalarlal-medii:ations because o£
`the potential for hemolytic reactions. Combination· of
`
`-Visit PDR,~et';to register for, Product SafetY Alerts arid to do1ilrnload.;inobi/ePDR~~ free to.U.S. prescribers·
`
`3
`
`

`

`For th.e Jates:t • PDR product information; visit'PDRmet :£
`. . -·. '};-
`. ,"-.(.
`.. ,.,
`,
`ACZONE®.,
`Vehicle
`.. ··:.
`1
`--~··~,_,,_, ~----'---'-:..__-+-~--·:,.:·-(N_=~l--,-81-..9)_'-JC~'-"'-;::,;_,..:..:t-·....;_;;_:..__rr·.N-:'=-.-:1,:6-:6-'-0)_;., ~~_,:• \'.
`, . . Modera~e ~ev~~e · ~l
`:Mild
`Application Site Event
`:Moderate .•
`:Seyere
`.Mild.
`t
`,.:1~
`· tl'o/o;
`9%
`<;1% .. •
`5%
`9%·
`• •·.
`Erythema ,
`-----------------~~~-~-+--~~~~·~~~~~~~~~~~
`'· . 4,'%
`~'i% -~
`•'
`, 1 14%
`11'1h:,
`3%
`.. ,
`<l.'J!>
`Dryneaa
`Oiline~s/Peeling
`~~~~·~,; ' Jj
`<1'/P-
`15%
`' ' . ,"~t
`. ...
`'
`6%'
`
`.-'
`
`13%
`
`6%
`
`··
`
`_.- ,--
`
`.,,',
`
`,
`
`0
`
`'j "'~,
`<-
`:·"/;j ., •
`Table 3-:Mean Hemoglobin, Bilirubin, and Reticulocyte Levels inAcne Subjects with G6PD,Deficiency.in ACZOI\IE®/ ,;·
`Vehicle Cross-Over Study·
`
`I
`
`HemoglObin (g/dL)
`
`Bilirubin (mgld¥)
`
`Reticulocytes (%)
`
`Pre-treatment
`2 weeks.
`12 weeks,..
`Pre-treatment
`.2·w~eks
`12-wceks
`Pre:t!eatment·
`2-weeks · "
`12
`
`r p
`r
`!
`
`600/.ALLERGAN 4t AC~GNE
`
`ACZONE® Gel, 5%;. With triineth:opri:inlsulfamethoxazole
`(T:MP/SMX)·'niay incr.ease ·the· likelihood of heniolysis·'in
`patients with G6P[! deficiencY.
`. ·'
`5,2
`• Periph,eral Neuropathy ·
`Peripheral -rieuropatjly (motor Joss •and ·muscle' weakness)
`ha5 been reported with oral dapsone" treatment. No events
`pf peripheral•\neurofiathy we're obserVed in clinical tri"'ls
`with topical ACZOI)lE® Gel, 5% treatment.
`· '
`· ·,
`s.s :. -skin · · · ·
`· · ·
`Skin reactions (toxic epidermal necrolysis, 'eryth~m'a4'niillti­
`foritie'; n'torbilliforril and scarlatiniform reactions, bullous
`and .. exfoliative .. , dermatitis, erythema . norlosum, .-and
`urticaria) have b'eeh reported ivith•oral aapS'oi\e-treatment.
`These t:ypes or'skin, reactions'were iiot observed.iti,.clmical
`trials wftli topical ACZ0-1\111® Gel, 5% treatment.
`ADVEiiSE-REACTIO~S.
`.6
`. ;:;
`. •• ,
`.
`Clinical Studies Experience
`6.1
`Because clinical trials ·are conducted lmdet'.presc'rihed
`conditions, adverae reaction 'rates oliser-Veil' m: the cli:riical
`trials of a drug cannot be directly:coinpared .tO ~ates in the
`clinical trials of another drug ;~p,d may; no~ reflectthe rates
`observed ih practice.
`.
`. •
`.... ,; .
`"
`' :
`Serious adv~rse r~actio~s. rlip.o~d. ~ pfit~~t,s treate'd"with
`ACZONE® Gel, 5%, durmg clinical tnals mcludeu but were
`. ~
`not linlited to the following: : ·"
`' :· •
`, :
`·
`• Nervous systein!Psychia'tri'c .-,Suicide attempt, tonic
`.clonic movements.
`.'··
`,
`·
`, · ~ . " · ·
`.
`• Gastromtestin'ai ,..' Abd~ki;al 'phln,' .'severe vonriting,
`pancreatitis.
`;· · .~., 0~' ••
`··~"-~ •• , •
`~ '
`~ •
`,
`.. ' .'
`•
`.
`• Other - Severe pharyngitis
`,
`In the Clinical trials, a .total ofl2 out of 4032 patientS )"ere
`reported to have depressitm (3 'of 1G60'~eitt'ed With vebicle
`and 9 of 23.72 treated with AczoNE®,,Gei;. 5%). Psychosis
`was reported in 2 of 2372 patien~itt.iate(l ~th ACZONE®
`Gel, 5%, and .in 0 of 1660 patients treated \yith,vehicle,
`.
`C.ombffi.ed contact sensitization/irritation, studies:. )'i'itl)
`ACZONE®' Gel, 5%, in 253 healthy"sulijecl:s j-esiiltedin at
`least 3 s,ubjects with moderllte' ei-Y,thema. ACiZON!O® Gel,
`5%,, ~d not induce phototdxicitj' ot pl\otililleiizy in' humfin
`, • -v - • ,,'
`,
`.
`dermal safety studies.
`. ,
`, :, ,
`.1\~ZONE~ Ge], 5%, was :e~'::t).iiated fof;:12. y,i~eli:s in four
`controlled 'sttidies for· local cutaneous eV,ents fn 1819
`patients. The most ·common events ,rep'titied from these
`studies inclnd" oiJiness/peeJing;,liryn!JSS, and' erythema.
`:These altta ,;;e' 'snowri :by ,severij;,y iil Table 'i below:, .
`'
`[See t;wle attop ng!ii;] ·
`. · '.
`. _ : "' · ·' , · ·: :·
`The a~verse reacti9~ o.cci:irrl.n!i'i'n at le~_f1% 'of patients in
`either. ar!!l in the (our :~el)i~l~J' contrj)lled · s~udies .are
`· · ~~-.,._•' ·, :
`p'ri!Se:(tted in Table 2.
`·
`· ·
`' ::
`·
`..
`
`•
`
`"
`
`• •
`
`• ,:,
`
`· , . '
`
`: ~
`
`ACZONE®
`N';if31llh
`
`Xe~cle,..
`.N~1660
`
`1·
`
`' •>'
`
`:Rbere are no· adequate and well controlled stUdies
`preg~
`nant women .. Dapsone has been,shown-.to·havetan embr,yu'
`cidal .effect in:r,ats· and rabbit!! wheit adfuinisteted orally in
`dos!¥'·of '{5 mglkg/day :ahd;:r~O;jniJkg/diiy (approl<hftatelY
`800 and 500 times' the systemic exposure observed in·bu~
`man 4'em.iles a'S''a'result.iif use'of·the maximum re'com-
`mended tbpical. · dose., has_ed-on·AUC crimparisotis},.respec'
`tivelY.··The!!e efl'ects·were: prooalily, seconqacy.:to maternal
`toxicity. ACZONE!W,Gel, 5%, Sho.uld beused.Q.uring;preg>
`nancynnlyifthepotentialbenefitjustiiiasthepotenliialrisk
`tothemtns.
`•
`,:·
`,
`,•;_,,, :
`, ·
`8.3
`'l'llursing Mothers
`: ~..
`_.
`Although systemic absorption of dapsone following topical
`• ,
`·
`On11 ~tie~t treateil~:AcmNE® Gel in the~IWC:\1. trlal:l
`applicatioticDfACZONE®.Ghll591J,as hliniolhlrelative tP oral
`~d • .f~t;iai , swellinl[' .which · led to :discontinuation o{ ~roe radminiatration1 it isJmowri that dapsO!)o is ex-
`creted.:m hunilui·milk, B~ause- o£ the •potenliiaH'ot oral·
`, >
`, ,,. ,; · , . •
`meiliJ;Irliqn.
`.
`In:-41ddition,.486. patients were. evaluated:in .a 12 month
`dapsone tb-~US!l advet'Sc reactions in lllll'tling infants;•a·dQ..
`safety, study. ~.adverse event profile in thiS study ·wllll
`cision.Shotrld \le'b:ti!M whether :to disctmtinuanursing·or to
`emuistent Wi.tll!:tl!at -!'lbservJld itt the• :vehicle:.controTied
`disCimtinlle·ACZONEl!ll Gel, li%, taking-into aceourilith!" iin-
`; Studiei;c.,:..
`'
`pm-tsnca \>f the drug to the moth~··
`' • > ·
`.l '"..
`
`Phai-Yngltis
`
`-.1"1-"~ . .-
`r 'iii '
`;, ..
`·
`· ·
`, ·,
`J_o,jn,·.t.J3.P,}:.'am.·_·_,.· .. ·,·.· ••. ·' •• ~ ,-, '•', ·;'' ho
`~-"'·"-'-'c.;.!;··::..-~:..:_"'"""'· . .,;;,;;: •"·:,.,.:·_.:.::;_.:::J ···~,:..:_-~4:..:_:.....:..::;..,;____;
`4% ."·
`:. ""'·
`IlJ<adac!i'e·Nos'
`'-' . ',
`. .
`,,.,
`.>?'"'
`
`7"
`
`IMPORTANT NOTICE:,Upda1ed drug•informatloii is.sent bitmonthly via :the ~R<~~' L!P.date lnsert;'For'.mcmff,1fy em!iJt·upCfitt~, re!;,IJ!;ter <11 POR.net.
`
`Each gram bf ACZONE\!!1 Gel, 5%,
`daps\lna;:USPAn: a' gal <)f.l·caroomer 1lB·~[tlietliy1eru• l!fJ
`mO!lll'ethyl ethe\',·.NF; rnetliylpamben, !'IJ!';:so>tUum
`ide, NF; and purified Water, USP.
`
`Experience. with Oral Us~ of Dapso~~~"' , . · ..•
`6.2
`Although JlOt observed in the:·cliniciil triiils,w;ith.~CZONE®
`Gel (topical dapsone) serious adverse reactions have been
`rejmrted 'with oral use of dapsone, including agranulocyto(cid:173)
`sis, hemolytic anemia, perij:Jher~ neuropathy (motor loss
`and muscle weakness), and skin, reactiol\s (t():idc epitl,ermai
`necrolysis, erythema multiforme, ·m~rbilliforril 'and sciirla(cid:173)
`tiniform reautions, bullouS and exfoliative dermatitis, ery(cid:173)
`thema nodosum, and urticaria).
`DRUG INTERACTIONS · '
`7
`.
`,
`.
`7.1_
`, Trimethopri'n:sul~~,>_!netlu>xazole_
`:A;dr~g,drug i:J;tt~r(;lction stufly evlj)ua,ted th.e.&ffect ofthe use,
`ofACZ9~_E® .Gel, 5%, ·W combinatiori, with d_oubll) strengt!>
`q69 ;:ing/800 mg) · •tl'hJlethopr{t!l'sulfalllethoxaz0le (T:MP/
`S:MX),.})uring, co-aqmixiistratign, syste@c Jevels· of TMP
`>i:qd SMX were essentially unchan~. Howeverf le;vels of
`dapsone imd its metsbolites increased in the presence of
`Tl\:IP/SivlX. Systemic exposirre '(AUC0_1;) of daP.sone and
`N-acetyl-dapsone (NAD) were increased by about>40%'ahd
`20% respectively in presence of T:MPiSMX. Notably, sys(cid:173)
`temic exposure (AUC0,d of dapsone hydroxylanlin'e (DHA)
`was more than doublE)11 in,the,p!:e~_e!J-,~e 9f:I':MP/8MX: J'lxpo(cid:173)
`s)lre from, fue proposed topic.U dose is about 1% pftnat frmn
`the 1oo'mg o.;~L dose: e;ven $1uiniO::ad.ministerea with
`TMP/SMX:
`' .. . ···.· · .
`. -~-:. ' . ,'
`' 1'
`lll%
`:Application Site•Reaction 'NOS''.c:
`:· · .
`.
`·'TopicafBimzoyli>eroxide . .c . .r
`: ··
`,
`.. ·
`•
`7.2
`'
`'
`'6"'-,-;,
`. , ., ,
`·,·
`'' _,
`·
`-
`·
`"
`·
`•
`·
`·
`' - · ·
`··
`·17%
`Application Site-·Dcyness
`,. :
`'lbpi~l a?plica~iori o~:ACZONE® p~l f?liO":~d },>Y. benzoy~
`-.-----,.-=----,..-,.-,...,...--,-+-,.,-,.---:-!--· ..,...,··.,.· _
`14%,
`.(\pP,lic.atipn. s_itil!Jr,y!;~,-e,'m
`- .... :....:.·:....:.:....:.....,.+:..,-,--:....:.-:,;j-..,·-· _· -"~ r~ry loi:al yello'Y m;;opange !liS,color'\t,ion ofJ:he.sJdn and fa-
`pero:odemst!bJectswithacn:evulgans.resultedm.atempo-,
`.. 'a.,
`· ·
`,
`,13%_,_·
`,
`,
`A.ppii.Satlq~ Sit~B~g ,
`'lial~ajr (r~porj;~d 6Y. 7;o.ut of9~ subjechl in a, clmicalst~J,dy)
`... ...
`• ,_:l_%
`:
`2_}o
`.'
`.. ,,
`' - , ,
`.' .,
`·'
`•'''
`\Vith resolution in 4 to 57 aays,
`'
`,
`'' '
`,,;'
`. ).:;& ;~· : ·"
`A{pllclfi~,f Sit~ p~\;,;~
`7,3 _ Qrug:!IJtera~ipns "l'l~h;f:lr~I,,Da~sone " ..
`.· _
`, .
`Certain concomitant· medications (su~h .. ~sji~aJllpii\, :g~ti­
`convul§ants; St .. John's wort) may hicrease'the formation of
`cfapso'ne'ii~droxyiiilnfue, .ametab.olite ol'd.ipsom) 'a~soci.i.ted
`With nenioiY,.is. W1tli oral daps&n~:lr~at;n'eni,,f~)i<f i.ci<ffiU-
`tagornats such as pyrimetliamme have -been llOttl~ to' poiisi-
`bly increase tli'e'ilkelih~oil'orhen:atologl.c re~c<i<iiiS:. .,._
`8 psE nfsi>:Ecl'F~c POPQLAiif>NS,
`Pregn'<lncl('·'';--· ... ·:.··r,,·,::' ..... :
`T~ratog~nlc:Eifects:: Pregn;;.,cy C~t~g~ry e ._
`
`1%
`~ ;' F\, 5%
`Nasoph~gitis'
`;6%
`-,-.,-,.,...~-,.,~_.,.,:....:.-,:..~,.....-~-'k=~-:-:--+-..--:--~-,-;:
`llp~.e~ ae~piratorir 'h-a~tl:nr: ,. " ' 3% '
`:.a%
`~--',-,"···-,'-··,.,-·',-·------+----h,...,---,
`•-.;:,
`..
`-,·'
`.. ,_.i%''
`_s,.:.in_u'-s_i,..ii_s_N_o_s_· ____ _ .::;.,;..:..:_~· ..:' .:.2:..91_•-'--+-.:..·--~
`1%
`1%-
`I'nl!u<mza
`
`81-
`
`.
`
`4
`
`

`

`1
`I
`
`Complimf.lll~ry,CME for PDR-Iisted:products at PDR. •e'
`
`ACZONE • ALLERGAN/601
`
`CLINICAL PHARMACOLOGY ·
`.·Me<l>a,.r m·,Ji Action
`, 12.1
`The meci ·" •: .m of action of dapsone gel in treating acne
`··:C:· ·
`· ,.
`Vtilgans.:is not.lmown.
`• .
`'
`..
`12,3
`·
`Pharmacokinetics
`.
`-•abel study compared th2 pharmacokinetics of
`'
`p
`dapsone ~.1\CZONEI!lo·J.le•. 5%, (110 :':: 60mglday)·was
`i twice daily (NBSA 22.5%) for 14 days (n=18) with a
`!l!>!illi
`sing! 100 'mg' dose of irral dapsone administered to a ;;tJb(cid:173)
`p:Oup of patients (;,.;.1()) in a crossovei' de~ign. On Dey 14.
`ihe mean da~sone AUC0.~ b was 41p·:± 2!24ng•h/mLfor
`ACZON!\".f Gel, 5%, whereas:! ·lowing a ~gfu 100 mg dOll<!
`of oral dapsohe the A.Ui:J~ was 52;64~ ±'26'~2~ n~~b/
`mL. E:xposum. after !Jte mill dose of 100 mg, (W'pso\'\e WIJ!! ap(cid:173)
`pioxilxia@ly 100 ,,tiinP.i;' ~ut.lr t~an :airet .. the t~!~.'11
`ACZONE® Gel, 5% 1lose, twice a day. .
`,
`. '. .
`. ,
`iaa l!J!lg,tlmn safety study Of .AC?;o!\(E® Gel, 5% tre'&tmen;
`periodic.blood BL • •. pies were coUected up to 12 .x:non.ths .to
`•jeternrln<' ,systemic ~xpo;1ure llf dapsone and ,its metabolites
`'ill,• pj)r0xim•· tely ,500: patients. Base<! n the·· me.asurn)lle
`dapsone concentrations frorn 408 patients {M