MINISTRY OF PUBLIC HEALTH OF THE REPUBLIC OF BELARUS INSTRUCTION (patient information leaflet) for me i!al appli!

ation of NIMEFAST Description of the drug Trade name" Nimefa#t International nonproprietary name" Nime#$li e General description Nimefa#t (Nime#$li e)% &'' m() Bi!on*e+ ro$n ,#-ape ta.let# of li(-t,/ello0 !olor) Ingredients Ea!- ta.let !ontain#" A!ti*e moiet/" Nime#$li e &'' m(1 A$+iliar/ !omponent#" mi!ro!r/#talline !ell$lo#e% #o i$m #tar!- (l/!ollate (t/pe A)% ma(ne#i$m #tearate% po*i one% la!to#e) Dosage for Ta.let# !har acotherapeutic class" Ot-er antiinflammator/ an antir-e$mati! r$(#) Nime#$li e) Indications and usage treatment of a!$te pain# !a$#e ./ m$#!$lo#2eletal #/#tem in3$rie#% #oft ti##$e# in3$rie# an 0o$n #% inflammator/ i#ea#e# of t-e m$#!$lo#2eletal #/#tem (art-riti#% .$r#iti#% m/o#iti#)) #/mptomati! treatment of pain# !a$#e ./ o#teoart-riti#) primar/ /#menorr-eal) T-e e!i#ion !on!ernin( t-e pre#!ription of Nimefa#t #-o$l .e .a#e on t-e e#timation of in i*i $al ri#2 fa!tor# of a patient) Dosage and ad inistration S-o$l .e ta2en after meal) Before inta2e /o$ #-o$l i##ol*e a ta.let in 4',&'' ml of 0ater or !-e0 it $ntil !omplete i##ol$tion in t-e mo$t- !a*it/) T-e prepare #ol$tion m$#tn5t .e #tore ) A $#$al o#e for a $lt# amo$nt# to &'' m( t0o time# a a/) A ail/ o#e for t-e !-il ren from &6 to &7 /ear# ol amo$nt# to &'' m(% in !a#e of .o / 0ei(-t i# more t-an 8' 2( t-e o#e #-o$l amo$nt to &'' m( t0o time# a a/) T-e minimal t-erape$ti! o#e #-o$l .e pre#!ri.e in or er to e!rea#e po##i.le a *er#e rea!tion# to t-e r$() T-e ma+im$m perio of t-e nimefa#t inta2e #-o$l n5t e+!ee &4 a/#) Patient# #$fferin( from renal in#$ffi!ien!/ 0it- !reatinine !learan!e 9',7' ml:min% an el erl/ patient# on5t nee t-e e!rea#e of a nimefa#t o#e) Ad#erse reactions ;$rin( t-e a mini#tration of Nimefa#t t-e follo0in( rea!tion# are po##i.le" ner*o$# #/#tem" (i ine##% en!ep-alopat-/% #leepine##% -ea a!-e (Re/e5# #/n rome)1 e/e#" *i#$al impairment#1 re#pirator/ apparat$#% !-e#t% an me ia#tin$m" /#pnea% .ron!-io#pa#m1 (a#trointe#tinal i#t$r.an!e#" na$#ea% *omitin(% iarr-ea% #tool retention% meteori#m% (a#triti#% #toma!-a!-e% /#pep#ia% #tomatiti#% melena% (a#trointe#tinal tra!t $l!eration% (a#trointe#tinal .lee in( an perforation1 li*er" -i(- a!ti*it/ of tran#amina#e#% prolon(ation of .lee in( time1

-epato.iliar/ #/#tem" -epatiti#% f$lminant -epatiti# (in!l$ in( fatal o$t!ome)% !-ole#tati! 3a$n i!e1 .loo " anemia% eo#inop-ilia% t-rom.o!/topenia% le$2o!/topenia% a(ran$lo!/to#i#1 meta.oli#m an meta.oli! i#or er" -/per2aliemia1 p#/!-iatri! i#or er#" an+iet/% ner*o$#ne##% ni(-tmare#1 !ar io*a#!$lar #/#tem" ta!-/!ar ia% -/perten#ia% .loo pre##$re ifferential% r$#- of .loo 1 2i ne/# an $rinar/ tra!t#" /#$ria% -emat$ria% $rinar/ retention% oli($ria% inter#titial nep-riti#1 in i#po#ition% a#t-enia1 aller(i! rea!tion#" #2in er$ption% er/t-ema1 rarel$ < anap-/la!ti! #-o!2% $rti!aria% =$in!2e># e ema) If an/ of t-e a *er#e rea!tion# o!!$r# #top ta2in( t-e r$( an !on#$lt t-e o!tor) Contraindications -/per#en#iti*it/ to nime#$li e an ot-er !omponent# of t-e r$(1 -/per#en#iti*it/ to a!et/l#ali!/li! a!i an ot-er NSAI;# (in!l$ in( in pa#t me i!al #tor/)% in!l$ in( #$!- manife#tation# a# .ron!-ial a#t-ma% $rti!aria or r-initi#1 ero#i*e,$l!ero impairment# of t-e #toma!- an $o en$m in a!$te !on ition of t-e i#ea#e1 (a#trointe#tinal tra!t .lee in( in pa#t me i!al #tor/1 #erio$# .loo ,!lottin( i#or er# (pat-olo(/ of t-e -emo#ta#i# #/#tem !omponent#% for e+ample !oa($lopat-/% t-rom.o!/topat-/% an(iopat-/% !om.ine -emo#ta#iopat-ie#)1 #erio$# renal in#$ffi!ien!/ (!reatinine !learan!e i# le## t-an 9' ml:min)1 #erio$# impaire !ar ial f$n!tion1 li*er i#or er#% li*er impairment1 al!o-oli#m% r$( epen en!e1 -epatoto+i! rea!tion# to nime#$li e in pa#t me i!al #tor/% #im$ltaneo$# pre#!ription 0it- ot-er -epatoto+i! r$(#1 temperat$re ri#e an :or infl$en?a #/mptom#1 pre(nan!/ an la!tation1 !-il ren $n er &6 /ear# ol ) O#erdosage If an o*er o#e of nimefa#t i# ta2en% o*er o#a(e #/mptom#% t/pi!al for NSAI;# !an o!!$r% li2e t-e follo0in(" (i ine##% na$#ea% *omitin(% epi(a#tri! pain#% 0-i!- are re*er#i.le in !a#e of t-e #$pporti*e treatment) @a#trointe#tinal .lee in( !an o!!$r) T-ere are rare !a#e# of -/perten#ia an a!$te renal in#$ffi!ien!/) Anap-/la!ti! rea!tion# are po##i.le) Treatment" #/mptomati! an #$pporti*e% t-ere are no #pe!ifi! anti ote#) Hemo ial/#i#% a# 0ell a# artifi!ial i$re#i#% $rine al2ali?ation or -emoperf$#ion !an .e ineffe!ti*e .e!a$#e of -i(le*el ($p to AB%4C) of nime#$li e .in in( 0it- .loo protein#) It !an .e re!ommen e to for!e *omitin(% $#e a!ti*ate !ar.on (D',&'' () an o#moti! la+ati*e $rin( t-e fir#t 8 -o$r# after an o*er o#a(e) It5# ne!e##ar/ to !ontrol li*er an 2i ne/# f$n!tion#) !recautions T-e r$( #-o$l .e pre#!ri.e 0it- #ome pre!a$tion in !a#e of arterial -/perten#ion% impaire !ar ial f$n!tion% an pan!reati! ia.ete# of t/pe II) Ad inistration during pregnanc$ It5# not re!ommen e to ta2e t-i# r$( $rin( pre(nan!/) T-e $#e of nime#$li e !an .rin( -arm to 0omen5# fertilit/ an i#n5t re!ommen e to 0omen plannin( pre(nan!/ a# 0ell a# 0omen 0-o -a*e iffi!$ltie# in .e!omin( pre(nant or .ein( $n er e+amination !on!ernin( female #terilit/)

A# 0ell a# ot-er NSAI;#% 0-i!- in-i.it pro#ta(lan in #/nt-e#i#% nime#$li e !an !a$#e premat$re !lo#$re of an arterial $!t% p$lmonar/ -/perten#ion% oli($ria% oli(oanion% an in!rea#e ri#2 of .lee in(% $terine inertia an perip-eral e ema) Some !a#e# -a*e .een ete!te 0-en !-il ren of t-e 0omen% 0-o too2 nime#$li e $rin( la#t mont-# of t-eir pre(nan!/% -a renal in#$ffi!ien!/) Ad inistration during lactation It penetrate# into .rea#t mil2% t-erefore% i#n5t re!ommen e to .e ta2en $rin( t-e la!tation) Ad inistration %$ elderl$ people El erl/ patient# are li2el/ to e+perien!e a *er#e rea!tion# of NSAI;#% in!l$ in( (a#trointe#tinal .lee in(% 2i ne/#% -eart an li*er i#or er#) So% #$ita.le !lini!al monitorin( i# re!ommen e ) Special instructions T-e ri#2 of a *er#e rea!tion# to nime#$li e !an .e e!rea#e if a #-ort !o$r#e of me i!al treatment i# $#e an t-e r$( i# 0it- ra0n 0-en t-e t-erape$ti! a!tion i# a!-ie*e or .e!a$#e of it# ineffe!ti*ene##) Patient#% 0-o are #$.3e!t to li*er i#or er# (anore+ia% na$#ea% *omitin(% #toma!-a!-e% 0ea2ne##% $rine ar2enin() 0-ile ta2in( nime#$li e or 0-o -a*e a.normal in i!ator# of t-e li*er f$n!tion% #-o$l #top ta2in( t-e r$() S$!- patient# #-o$l n5t .e pre#!ri.e nime#$li e on!e a(ain) T-ere -a*e .een ete!te t-e !a#e# of li*er e#tr$!tion e*en after a #-ort inta2e of t-e r$() Con!$rrent $#e of ifferent NSAI;# i#n5t re!ommen e ) It5# re!ommen e to a*oi #im$ltaneo$# $#e of nime#$li e 0it- ot-er anal(e#i! r$() Patient#% 0-o (et a r$nnin( temperat$re or infl$en?a,li2e #/mptom#% #-o$l #top ta2in( t-e r$() ;$rin( t-e me i!al treatment $l!eration or (a#trointe#tinal .lee in( 0it- or 0it-o$t pre!e in( #/mptom# !an o!!$r in !a#e of t-e pre#en!e of @IT i#or er# in pa#t me i!al #tor/ or 0it-o$t t-em) Patient# 0it- 2i ne/# or -eart i#or er# #-o$l .e !aref$l% a# nime#$li e !an !a$#e 2i ne/# impairment) If 2i ne/# impairment o!!$r#% it5# ne!e##ar/ to 0it- ra0 t-e r$() Nimefa#t #-o$l .e !aref$ll/ $#e ./ t-e patient#% 0-o ta2e r$(#% 0-i!- e!rea#e .loo !lottin( or #$ppre## t-rom.o!/te a((re(ation) Ne*ert-ele##% nime#$li e !an5t .e !on#i ere an a!et/l#ali!/li! a!i #$.#tit$te for !ar io*a#!$lar prop-/la+i#) Nimefa#t !ontain# la!to#e an t-erefore i#n5t re!ommen e to t-e patient# 0it- rare (eneti! pro.lem of (ala!to#e intoleran!e% Lapp la!ta#e efi!it or mala.#orption #/n rome of (l$!o#e, (ala!to#e) It5# re!ommen e to a*oi #im$ltaneo$# $#e of nime#$li e 0it- al!o-ol) Effects on a%ilit$ to dri#e and use achines T-e patient#% 0-o -a*e (i ine## or #leepine## 0-ile ta2in( nimefa#t% #-o$l a*oi ri*in( an 0or2in( 0it- ma!-ine#% 0-i!- reE$ire# -i(- !on!entration of attention an a!!$rate !oor ination of mo*ement#) Drug interactions Pharmacodynamic interaction Farfarin an #imilar anti!oa($lant#% a!et/l#ali!/li! a!i " an in!rea#e .lee in( ri#2% t-erefore #im$ltaneo$# $#e 0it- nime#$li e i#n5t re!ommen e % an for t-e patient# 0it- #erio$# .loo !lottin( i# !ontrain i!ate ) If t-e $#e of #$!- !om.ination i# ne!e##ar/% t-e !ontrol of anti!oa($lant# a!tion i# reE$ire ) Pharmacodynamic/pharmacokinetic interaction with diuretics F$ro#emi e" if people are -ealt-/% nime#$li e e!rea#e# Natri$m an to a le## e+tent pota##i$m e+!retion in a tran#ient 0a/% e!rea#e# a i$reti! a!tion of f$ro#emi e) Sim$ltaneo$# $#e of nime#$li e an f$ro#emi e lea # to AUC e!rea#e (appro+imatel/ ./ 6'C) an t-e e!rea#e of total f$ro#emi e e+!retion% not !-an(in( it# 2i ne/# !learan!e)

Sim$ltaneo$# $#e of nime#$li e an f$ro#emi e reE$ire# pre!a$tion# if patient# -a*e 2i ne/# an -eart i#or er#) Pharmacokinetic interaction with other drugs Lit-i$m r$(#" t-ere i# information t-at NSAI;# e!rea#e lit-i$m !learan!e% 0-i!- lea # to t-e in!rea#e of lit-i$m !on!entration in .loo pla#ma an it# to+i!it/) T-erefore% 0-ile #im$ltaneo$# ta2in( of nime#$li e an lit-i$m r$(# it5# ne!e##ar/ to !ontrol re($larl/ t-e lit-i$m !on!entration in .loo pla#ma) Intera!tion of nime#$li e 0it- (li.en!lami % t-eop-/lline% 0arfarin% i(o+in% !imeti ine% an anta!i # (t-e !om.ination of al$min$m an ma(ne#i$m !onpo$n #) 0a# #t$ ie in *i*o) Clini!all/ important intera!tion# -a*en5t .een ete!te ) Nime#$li e in-i.it# CYP 6CA en?/me% t-erefore t-e !on!entration of t-e r$(#% meta.oli?e 0it- t-e -elp of t-i# en?/me% in .loo pla#ma !an in!rea#e 0-ile #im$ltaneo$# $#e 0itnime#$li e) Met-otre+ate" in!rea#e of met-otre+ate !on!entration in .loo #er$m an % t-erefore% it# to+i!it/) It5# ne!e##ar/ to .e !aref$l if nime#$li e i# a mini#tere le## t-an one a/ .efore or after met-otre+ate inta2e) C/!lo#porine" in!rea#e of !/!lo#porine nep-roto+i!it/ !an o!!$r 0-ile #im$ltaneo$# $#e 0itnime#$li e) Influence of other drugs on the pharmacological profile of nimesulide Re#ear!-e# in *itro -a*e #-o0e t-at tol.$tami e% #ali!/li! an *alproate a!i # for!e nime#$li e o$t of protein,.in in( #ite#) Ho0e*er% e#pite a po##i.le in!rea#e of nime#$li e !on!entration in .loo pla#ma% t-i# intera!tion oe#n5t -a*e a !lini!al importan!e) Storage conditions It #-o$l .e #tore at t-e temperat$re not -i(-er t-an 64GC in a ar2 r/ pla!e) Heep a0a/ from !-il renI S-elf life i# 6 /ear#) ;on5t $#e after t-e e+piration ate) Conditions of sales %$ phar acies Pre#!ription r$(#) !ac&age Description &' ta.let# in a .li#ter% ma e from pol/*in/l!-lori e an al$min$m film) Ea!- pa!2 !ontain# t0o or t-ree .li#ter# 0it- an in#tr$!tion for $#e) Infor ation a%out the anufacturer" JJJ (LLC) KR$.i2onL Belar$#% 6&'''6% Mite.#2% M) @or52o(o #tr% D6 B% tel:fa+" N9B4(6&6) 98,'D,6A