SPE~IAl

'

PATIENT POPULATIONS: Eklarly lfntJ RanaVHep..lie

~:Increased plasma concentrallonl ot Paroxetina OCC\If In

lllderly~andlnlhoNsubfec/lwitto-re renaJimpalrmenfotin

' I '

lhoM wi1l1 Npaflc

PAROXETINE

.lrment. but the fll'l9"

of I)Uilml

oonoantratiool

~lhlt ofhNI!hyadults~.

r,..,_,

INDICATIONS:
ol: ""-i-r DepraaiNe tlPi80dH. Obaelli8
Compulalvl Disotder. Panic Oisordaf wilt! and without agoraphobia.
SociiiAnxleryDilon:lei'IISOCillphobla. GtMrlliMd~Oiaordar .

Potl-tr.umalicStrasaOIIOfder
COMPOSITION
DOSAGE & METHOD OF ADMINISTRATION: II ill recommended lhal
PMOulina il ~ter.d~daily~nlhamoroingwithlood. The tablet

Elldiiii'JOIWdfllmcoat.alblcllcon/aklt:~lngredient

Pal0lleline(alhydrochlorielatwmihydrala) 20mg.

shouldbtiswalloweclra!hetlhanc:Nwed. M.;rx~~:Tha
r~doMil20mvdaity. lngeneral. ~ ln ~M~tienls

~~ Sodlumstardlgtyoolate, ~.

sta11a att.r one WMil bui!TIIy ooly becoma I'VIdenllrom the second wMk
or lhenlpy. AI wiltillllltntidapreasant ITll!dlcinal pn:lducl$, dosage should

c:ak:i\lmhydfogenpholphatl, ~---le. ~

"""'"'

be~ltfldsdjulladltnec:.saarywithirl3104WMklof initiation ot

PHAAMACEUTICALFORM: F'llmcoaledlablets

lherllpyancithefMfler u judgedcllnieallyapprop1at. lnsoma patlents,

PHARMACOLOGICAl. PROPERTIES

uploamuimumol50mga.dl.ylr! IOmg llepl~lolhapatient'l

r~. Pa6ants with~ lhoUd be tra.a.lad tor e suf!bant
pe-riod or at 1aut 6 mon~ to ltOIUr81hatltley .,.. tra.a. !rom IYfi'IP/OfTIS

Pharmacodynamics: ~nlrloi/Jdiot!;

wlltllnlufllcianl~to20mg,!he<IOaemaybeWMM<IgraOO&IIy

Paroxetineiaapolltnland

IMcthoeiMibilol'of~(s-HT. IMftllofm)I.IPiakeand"'
anti6eoprnuntaetionandalf~inlhelrHlmlnloi'OCO

Social

AnW~y dlsorder/Soeial Phobia, Geoenll AnWly Diaordaf, PQill~umalil::

Straa1 Diaorderlnd Panic Oilordlr il lhougM loblr.lltedto!tl spt~Cifoc

inhibition of 5-HT ~~e In bfaln ~Uf'OMI. Paroxe tine is chemically
unrelated lo lhlllicydic. tetrac,dic and~ avallabla antQeprnsarus.
Pamxeline has low allinity lor muscamic cholinergic reotptOrS and
animal studle1 h8YI lndicl!ld only -~ anllcholinergic: propartles. In
ICOOfdlnoawlththis~action.inYIIrosll.ldlnhawindicaled/tlal.

In contrast to tricyc!lc aofideprHsanta, Paroxeline l'las ~~~~~ alfDty lor

llphl t ,alpha2~bltll~, tlopamine(02),5-HT11ike.s- .
~histamine (H1) ~:This 1ac1t of inleraction with poe!

HT2

lynaptie~in'ii!ro la suballlltlatedbylnvhoollllll:liaawhic:tl

dlmooltra/81ack of CNS deprltSianl and hypotensiYa properties.

PhlmiiiCOdynamic EffecU: Paroxaline does 1101 lmpeir psyd'lolnotor
function and 0011 nol p~MnUetelha daprenao/allactl of ltNinol. Ae with
olharMiec11v115-HTuptakainhibitors, ParoxalinacaU$tlllo l yrnp(OmSol
altCIISIIva 5-HT raceplof stimulation when ~ to anlmall

:::U~J;;:Ero=:W:::~~~~wa~k=

at doMa g.nat"al/y .OOV. those raquifed to lnNbH !o1iT uptake. The

IICtlvalingptopertleaarenol "~lalfiiM.Iika' in nature. Animalstudln
indicnt.lhltPatQx~inellwalllolaratedbylhacart!iovaiCUiarlystam.

Pa roxetina producM 1'10 ~ slgniflcanl c:t~anges in blood preNllre,

heanrateandECOaflet~tohnlthysutljec3. St.udin

indiCate that, lncontraatroantiOepressantsll'ltlichlnhiOilthe vplllka of

nor~ltnalina.ParGJtetinahnarnuchreducedpropansltylo~lt\a
~tillypeMeNiYeetlectaotguanethidiM.Inlhetreatmentol'depntsllve
d~re.Paroetineexhlbltleornperablaefficacytol!andan:l

antldepr~NfltS. Thefa ll allosoma~lhai Paro.wtinemaybeof

lherapeu\lc value in pa~ who ha'l'l !ailed to respund to ttandlrd

therapy. Morning oo.lng_With Paro~atlne u not haw~ Qelnm.n\111
~ on ltittler_ltle QUIIity or c2uration of al&ep. Morvov.,. patients are
lil<.ety to expenenca improYed sleep u they respond 1o Part1~.tine
theffiiP)'.

CltiHWveCompufslveOIJorr1ar:Tha~dola ii 4Qmgde~y.

Patiatlts lhould lltart on 20 rnw'clly and the OoM may ba ncr.u.d

gradually In tO mg increments to lha rlfXlfiWMOdld doN. II afte r IOITie
Wftbonthar~dcelnlufficienl~ia-toma
patientsmaybenelitlfotnhlvinglhelrdose~Soedgraduallyuptoa

muimum of 60 ~day. Petiatlla lltittl OCO ahould be ll"nled !Of a

auf!lciant period to -ura lhlt ttwy 111. ll"ee lrom symptoms. This period

mayba..-.tmonlhlor-longrar.
Pl.flicl1isorlr:Tha
I"8COfTII'nfJildose II 40 mg daily. Pa'**Sihould be slarted on tO
lfl9'dayandlhedoNgradllaJtyirocrei:Mdin 10mgslaplaccor6ngl0tna
patient's rnpon&e up to the f800ll"II"IWI'IdoM. Aiowinitlalat.rtingdose
is ~ to mlnimi5e the pohlntisl worwn1og of panic
sympiDmll~.whlchlsgE!Mfl.llyrecognlsl!dloooeurll'ly ln the

lru.lmlntotlhisdiaorder.llellriiOrflltWHkaonlher8COri"WTlai"Kidose
iNufficleni111Sp0nMisiM!'I.amepatlanls may'*-rottrom haYing their
~ ~eued gradually up to a maximum ol60 rngfclly. Patients owith
Plfllcdisotdershooldbetrea~edlor_a~periodtolfiiUr81hat they

atelreelrom s )'fT1lloms. This peflod mayba.MYeflll months orewl"l

looger. SociallllJIIetytisordai'/ socialphobii: TIIareootnmendaddoseis
20 mg daily. II attar 10m11 weeks on tha racornrnandt <1oM inlulflQenl
r-.ponse il ~Mn somct patients may benefit lfom haYing their dose
lncluNd gradually in 10 mg 11~ up to a maxlmumol50 lf9'day. Longtenn UN lhould be regu/llty avalua~ec;t. o.n.raJiMd lfiJ6ety rJ~srW:
The~ doN Ia 20 rng daily. 11 a l l e r - .,..q on lha
r~dolelnlufficlttnl~iiiM!'Isomapatien'- may
be~lllromhavinglhairdoMnc...~grldulltylrl10mg atepsuptoa

rrwomum of 50 mg/01~.

Loog-~ ..,.. should be regularly avalualad.

Po.t-lrar.II'TIItlc stress ~The recomrnanded doN i1 20 mv daily. II

attereomeweeklonlhe~doMinsufficiantreJpor~N IIHetl

some patlenta maybenel~ rrom ~ ltMrirOON incrMHd gr~lly in

10 mgst~upto a ~ol50ff9dlly. long-termUMihouldbe

reguiar1yealuatad. ~ln/oii7Miiori: WI!hlkawals~-on

~llonol Plrtlli&Me: Abruptdiloontinuallonshould be avoided.
The taperpi\He regimen used in clincaltriallinYolo.'8doec.reaalngthe
f:kliydoHby IOrngatW'HIIIyinlerwhi. ll lniOierable 1ymp10maoccor
lollollllrlg a GecrHM In lha dose or upon lbconiW!uation ot traalment.
then fftUfNng the pravioualy prescribed dose may be conaldetad.
~.thaph~lleianmayiXllllnueGec:rHslnglhedoN. bula!a

more gradu8l rate.

Special~:

Elderly. Increased plasma

concenlr-'ionlorParo~etinaoca~rinelderlysubjec:U. buttharangeol

concentnn.iorolov.naps wilhlhatobMrv..:! in )'OUOglr iU()jecU.Dosiog

shoukl_cornrnance_attnaadu!lstartingdoN. Increasinglhedoaemighlba
uselul~somctplberltl, butlhall'lllrirPiumCioMihouldnole~4Qmg
dlify. Ctlltlr.,liDd~a(7- 17)'NrsJ; Paroxetlneshouldnol be

UMdlorthelffl.trnantofchildrllllll'ld8dolucentiiScontrolledciW!ical
trials ha'l'l lound Patt~xetirla to be a111ociated wttt1 increaMd risk for
s~ behavlourandhostillty. lnackfition.in lhnltrilllelflc:acyhalnol

been acquatety demonttrated. CNbwn fl(l<~ 1 yeara: Tha VM o1

Paroxllina has nol been lltudlad in chkSren lesl lhan 1 ye111. Paroxetlne
should not be Ulld. ulong uaatetyandetlieleyln ltlilagagrouphl.,.
not bHn _aslabli&hed. ~lk: /mpllinl'wnl: lncrANd plasma
corw::entralionl ot partlllelina OOcot in palilrnts wlltl aavere renal
~ (~titWw ciH~ '"' 1'-tl 30 mVminJ. or In lhoN with

Theretor., ao..g.shouldbaratticr< /Oihe lower

end ol 1M dosaga range. Conlra/ndbllions: Known hyperHnaitiYity 10
hepalir:~r.

Paroutirle or anyollhea~~.ParOllelina iloontraindicaledln

combination with monoamine oU:IaN inhibitor~ {MAOis). In eliCeplionll

~.linezolld{ananliblotlcwl"lich isarWI!f"l.iblenonMiective

MAOt)_~be gi'ten ln ~tlonwithParoxebnaproW:ladlhat thara

aralacililoeslorcloeaobaervationofl~ofaetOlOflirllyndromeand

~olbloodprHsure. TraaiiTNir1lwi/JfM,_.,ineca'lbainil;.l8d;
rwo~ alter6tcontlnuationof an il'rliverslbla MA<>t, or M least 24hre

att.r diloontlnualion ot 1 rewtlible MAOt (e.g. modobemida, !inalolid).

At leulonewttekshould...,..._.~disconlinuatlonotParoetne
lnd~llon ollhapy with any MAOI. Paro~ine shoukl not be U6tld in

OOITibinallon \l!l!thlhioriclaz!ntt, baeaute. as wittlolherelruglwtlittllnhlbit

tha hoepllllc enzyme CYP450 206. Paroxetina can ataYall pl. .ma lavtlls
of lhlortcSallne. Adn1if\istration ollhiMdazlne -'one can lead to QTc
intervalproli:JnQIItlon wilhassoclatedMriousvarMevlararrtlythn1ieiUC:tl
a110r88dell:le ~las, andsuddendnth. ParOlletina should no1 be used

incorrCllna1ionWittlplmozlde.
SlOE EFFECTS: Soma of IN acrv.t. . d1ug reactiOnllillted below may
decreasa in intaneity and trequancy wilh continued tr. .tmant .nd do not
~laadloCIIS8IIIoflottharapy. AdWr"Ndrugreactioi'Waralitlad
belowbyl}'ltemOtganclallandlreQuaney. F,..quencjallfa ~:

Yerycommon(J.1110), c:orrwnon (J.I/100, <1110), uncomti'IOII ( J.ln .ooo,

<11100), rara { J,l/10,000, .::1/1,000). very rare (<1110.000). Including
llollted rep'll'tl:. Blood MJd i)omphatic ayal~ dilorcrf: Uocommon:
lbnomlal b~Mciint. predominantly of lt1a skin lnd rnuc:cM.II membrlnas
{moally ecx:hymolil). VfKY rare: ~.tiM1\II'II!t system
dlsordere: Vary rare: allefvlc reactions (lnctuOing urticaria and
angioedema). Endocrine diaorditrs: Vary rare: 1yndrome ollnloppropna/8
efrti.diuretic hormone ..cration (S IAOH). Mftlbolilm and nu1ri1ion
d!so~Ue1'11: Conmon: lncteasll ln cholallllfollewls, decteaMd appetile
Rar: trypoNil"IMiia. HyponetrMmia hu bean reporWd preOotninanlly
In
pallertta and is IOI"natfmaldua 10 a)'Odrome of iuppropriata
anll-diuratic hormone IMICfetion (S IAOH). Psychialrif; ~:

""'!tl)'

~:IOITV10ience. ~. agitation,lbnonnalclreM'JI(~

nigtllmarn). Uncommon: contusion. hlnucinationl. Rare: manic

raac:lionf,ll\llktfy. lteperMlMiilltlon, panicai!IICb,aka1hlsia. Frequency
not known: sulciiMI idaa.tlon and 5Ukil:lat beha'l'lour. ea- of suicldel
Ktntion and suk::iGal behaviours nave been ~during Pai'Ollalina
thefapy or nrly after treatment diecontinuatlon, These aymploms may
alsobeduetolhaundellylng<iiiHN. Hervouasyst~~mtlsordars:

=::--~r~~iR~

Nfl:lklrWI syndrome. (symptOmll may Include agitl'llon, oonlution,

dllphoraai.. halluC~naUons, hyparrellellll, myoclonus, lhl'f'erlng,
~and~). Reportsofeldrapyramidatcbofdafindullng

oro-lacill dyalonil haw been recMied in pllioantl somati'nas WiUl

=-~dttorda~:o,~blu= ~.c:::.=

~=v~~~~:::..~~

tachyearOia, Rare: bfadyeardia. Vasculllr rliaon;/Ms: Uncommon:

transient incraa...s or decraallt in blood pressura ~tural
~Transiarlt~orcorea-olbloodpr. . . . hava
been reporled lolowing hUtment with PatOlletlne, ~WJally in paOenls with
pre...xlsting hypartenMln or anxiety. Ra1plratory. thontclc arod
lnlidlallt:inal dllol'del"s: Conmon: yawning. c;..,~ ~:
Very oonwnon: ' * -,Common: ~. dlarrtlon. vomitng, dry
moulh,Very rare: gasttOinlestirvJ bleeding. ~~ry ~:
Rare: alevallon ot hepalic enzymes. Very rare: hepatic eYente (suet\ a 1
hepatitis, sometimes anociatad with )eurldice lllldlor llwlr !allure).
Elevation ol hepl.lic .ozymea haw bMn raportld. POIIt-nwtoLallng raport1
olhepatic.....,... (.uchashepalitls,sometimesassociatedl'f'llhjaurldiea

arrd/orliYer lailura)haYaallobNnreceivedveryTal'ety. Dilcontinuatlonol

Paroxellnashouklbe~red illherals prolongadelavallonolti..,..

function lflt ....ms. Skin ar>rf aueootatl110<141 na- dlaort~ers. Common;

~. ~:!:;:a.:="~~e~-=
UJ'II'IIIy lnconllnanc:e. Reproductive8f'/entfWJLlt"IMfrli1trrMJ:VIfY

~:~=-=~~

arlhrllgla.myalgia, Epldemiologicalstudiel, mairllyconducledlnpatienll

50 yean ol age and dder, show en incaalld risk ot bona traclurft; in
patienta r.ceMng SSAII and TCAJ. The mechanllm leading 10 lhil rtsk is
unknown. Genanlllhorder lod adrninlstnallon lila OCJnditiorq: COmmon:
asthenia. body weight gU-i: Verr ra re: pa~t oedema. WMdrlllfal
~'""on dhoconlinUallon of Paroxettne trealment: Common:
~- ~_dlll\llbaocn.aleepdistllltJoanco8a.aruriaty, headllche.

~: agitl.liOn. NI,IIN., u.mor. confusion. 1-allng. emotional

instability. visual disturbances. palpltatlonl. cNarrnoea. irrilebllify.
~tlono!Parollna fparticulartv..t~anabrupt) ccrrmontyleadl

10 withdrawal symptomS. Diutoeu, MnSOry dl$b,ubances (induding

pataHthHil, alec:tric ~hod~: sensatiOnllnd tinMull, s~eap disturbances
(iocludiog lnl.,... <name). agitalion or IINIIaty. MUSN, tremor,
conl\lllon.~':tlng, l'lelldectle, dOantloaa,palpltationl,amotlonll

lnalabilly. irritabilily, and visual dlln.lrbancH na..... bNn 111p011ed.

GenaraBv thall went~ a re mild 10 ITIOI:Iarate and a re Nlf.timiling.
hoWeVer. In tome pe.tienlllhey may be s.....,. lfWJ/or prolonged. It is
lheratorloiMMd !hl.t when Paroatine treatment II no longer r~
griO.Ial ~lion by doN tapering should beearril!dout. ArNerH
IMinls frr:Im,PHdia~cfnical I'Nis:The lollowlog l<t'I'II'M--. _,e
obllf"'''d:

~suicidal relltedbeha'iiourl[n;ludingsuicide

~~~~~~~rna::~~
~ trl&la or~

wilt\

Ma;or DepAtuiYe Olsordar. lncreased

l"lo5tilityoccurredpa~rly lnchlldren wiVIoblessl'lac:ornpulsive

~. ande!lpliSatty~nyounger ctl!ldral'llnslhan 12yeanolage.
AddilionaleYII"Itllhlt-a-ara: Oect&IIMI'dlflPIIIile, ~.

iSWHtng, hyperkinasia,agitatlon, emotlonallabiliry(inctuclingctyingand

~Jiuctuallons), blaedingflletedld\leraeevents. predominanltyoflhe
skinand~~. E_,.aiMI\altel'dlsoontinuationlleperlrlg
ot Pllrtllletina lf~: amoliGnall&blllly (~ cryltl(J. mood lluctuationa,
~harm. llllcicllllhoughllandattemptadauidOa).netV'O\.IIrliU,
diZZ~s. nausea and abtlominal pain. OverdoN: S)"'''l))ION Mid Signs:

A lll'lde I'NI'9ir\ otsatety II avidant from avall&bla ovardoN Information on

Paroetina. Exparianoe of Part1~atlne in ovardoH has indicated that. in
addition to ! ' - 1ymp10m1 mentioned In "Uodnlrable Ellects ~.
lever end irwolunt;lry muacle conlri!ICtionl haYe been rapMid. Pau.nts
hlvegane<llllyreooveredwl!houlaerious MqUelea......,..nendoMsof

up to 2000 mg have been taken lioN. Event.~ tuch IS com.a or ECG

c::hangaahlveoecui0n811ybMnreportedand, veryrerely lllllh tetal

outcome, but generdy when PatOlfeb was taken In CO!ltJnellon wilt!

other ps)'Chotropic drugs, wilt! or without ak:otlol. TtNtmenl: No apecillc
anlkklle II known. The ll"M1rr*" lhould COillist o1 tt-. general
emplo'fed in the mAI"IIQIIMI"II ol O'l'lfdoae with any
antidapfft.aallt. Adminietra1ionol20-30gactiYatedcharcoaii'Niybl

mNSUI'M

con~ifpouiblewiltllnfewhourlalterOYartlolainlakeiO

dacr-absorptionofParoxellna. Supportiveca;rewith lrequent

moniiOr1ng of villi &lgna and c:.rlul obNrvation is Indicated. Pallant
maoagement lhould baas clinically Indicated.
DRUG INT_EAACTION: SerofMerpic drl~Qs: All with oth SSAI1, coadministration with . .rmooergic dr\lgl may lead to an locldanca oi5HT
anociated eltecla . Caution lhoukl be advlaad and a doser clinical
monitoring Is r~ when MI'Otonefgic 0'\lgl (IUCtl as L-lrypiOphan.
lriptana, lrlllladol, linazolid, SSFUs, lithium, pethidine and St John's Wort
- Hyperk:\lm perloraturn -tnP~rationl) are comblroed wilh Paroxetina.
Ca ution llallo ad'vtMd with lantenyl UMd in genaral afllleslhHia or in lhe
tru ttnefl! ofchronlcpain. Concotnitanti.IM ofParoxatlneand MAOisls
contrlllndlcal~ because ollhe riU of serotonin S)'fldrome. ~:
lncrea.ed ptrn0.1:1da levels ot on -aoe 2.5 limn hiiYe been
~!rated in~ 1/UdyolaeinglalowtbN pknozlda (2 rng) when
COI.dl'tlinlllerld with 60 rng Pai"OQtine. This may bl a.plained by the
known CYP206 iriOibii"O<Y prope1tin ol Pan>l!llline. Due 10 tha flllmlW
therapeutic Index ot pimo:dde anditl known ability to prolong QT Interval.
concomi..nt UM ol pimolida and PatOlletine is COI'llraindiclted.
ORUO METABOLISING ENZYMES: The metabolism and
phlrmaooklneticiJ ol Paro~atina may be allected by the induction or
inhibition ol drug malaboblng 8~'\Z)'JT~ft. When P110xetina is to be co~terad WiUl a ~ drug metabolising eneyma irnbilor.
con~tionshouklbagr.oen to uaiogParoxatloaOOMi at ltlelowefeod

ollhe range. Noinlllaldougaadjustmenl lriconllidefed,_51.ry wtlen

~drugllto beco-adminis1era.wilhknownc:trug metabolilinglif\ZYn1tl

induoers (e.g. carbamazeplna, rif~. ptlenobalbital. proenytoin) or

wilh ~mpranallitl rilona'lil'. Any Pero.ome ~adjustment (either

alter initiation or folowirlg disconUnualion ot an enzyme lnWcer) should
be g uid ed_b clinical fleet ( tolera b ility a nd a lllc acy) .
F~v~r!rttonaYir: . Coedminilltrationolkllamprena'lil'/ rltonavir

700'100 mg ~daily wilh PatOlfetine 20 rng daily in healtt!r volun!Mrt

for 10 dl'fl significantly decteased plasma te'f'lllt o1 P.-oxetina br
lppfO~imelely 55%. The pluma.lavelsot losa~/ritonaYirdumg
coadminillrlltlonof Partlllatina-allmilllriOrelereoceyl.luesololher

::=~r!!':~~:oo00dl~lt.=':'etta::

tongterm ooadminlatratlon of PlrOlleh and loN~vir/rilonavir

exceeding 10 days. Procyclidlna: Oa;ty administration of Paroxellne
lncrtNIIIS algniflcanllythapluma lavelaolprocydidine. K an~-d!olinerglc
efl~a,.

aeen.

tnactoseofprocydidlneshould t~ereduced.

Antteonvulaants : carbama~plne. phenytoin. sodium va lproate.

Corocomllant admlniltration u nol . . , to lhow any eltect on
phlrrnacokinliticlctyrwnicprolilalnapileplicpatlanti. CYP.2p6 ~Vllbitory
po!encyofparox~ina: Atwilholhefantidapraasan!a:. lncludlngother

SSRII. P110xe~ inhibits lhe hepatic cytoc.hrome P.50 enzyme

CYP206. . Inhibition of CYP206 may lead to lncreasad plasma
oonc:ent~a/lonS of CC)ol.drninlsterld ciNgl mellbolleed by llis enzyme.
ThaN include ~ tricyclic anlidapreaaants (a .g . clomipramine,
nortrtptyt~. and dtlsipraml~)_. phanolhiu ine neuroteptics (e.g.
perphena.zine and 'lhlorld.allne). rilperldone, atomoxetlne, certein Typa
ICM!Iarlfnmlcs(a.g. propalenonaandftecllrlide) andmetoprolol. lt ls
not recommended lo 11M Paroxetina in combination with meklprtllol when
givenincardiac ioluffiderlcy, beeluseollhenai'I'OWihe~lil::lncle ol
~inthlsindicallon. !M7t0llfwl;ilapn>drug requlriflgmetabolic

actlvabon by CYP206. lrltlibillon o1 CYP206 by Paroxetina' mey lead 10

reduc::ed pl. .ma concantra!lona ot a n .cll'l'l mallbolite and hence
rettuoe<~ aflk:acy oltamoxllen. aspecidy In lilllenslve fllll.llbollser. 1111
recommendad that preacriOefl consider uslrlg a n alte rnall
antiOapressant with min!rrlal CVP206 actMry. AJcohol: A wilt\ other
paychotropic drug~ patienta ahould bei<MMdto avoid a1oot101 UN While
taking Paroxetlne. Oral andcoagu4anls: A ptwmaoodynlrnlc intefactlon
betWeen Paroxlilirle and oral antieoaogulentl mayoocur. Conoomitant use
otParoxetine andOilllanllcoegulanllcanlead iO a nirocreased
antlcoegvlent actMty and haernont\egic tlsk. Therefore. paroxetine
lhoUkl be UMd with wutlon In patients llllho are trMted with or.c
anticoagulants. NSAIOs and ac.tylsalicyiC ICid, and othef lnliplatelat
agents:A phi~ Interaction betwetHl Partllfellne and
NSAID&IacetytsaNcyllc ICid I'NIY occur. Concomitant uae or Paroetinll
and NSAIOslacatyllallcylic: add can lead 10 en Increased~
rislc. Caution it a<Msad in patients taking SSRI'I . CQfiCOITIIIanlly with oral
anticoagulants, Orugsllnowntoalleclplaleiet fuoctlonorlncre&se tiskol
blaeding {e.g. alypicalartlipaychoticasuc:nasclozaptna, phenolhllzines,
most TCA'I, IC8tyllllicylic acid, NSAIO's. COX-2inhibilofl) u ..ell as in

palienlawl/tlahit~ofblaedlngdilon:larsorconditionawnicnmay

predispoae to biNding. D<ugs allecllng gutric PH: In villi:) data haYe

shown that dinocllltion of Paroxetina lrom the oral suspension 11 PH
depaodlnl. Ther~e. ONga that_llter gallric PH (SUCh u antacid Orugs.
proton pump Inhibitors or hlstam~na H2reoeplor aru.egoroilts) may allact
plai!TiaParoxatineooncentrationl inpauentallldngthaOflltuSpanaion.
PRECAUTIONS & WARNINGS: Trealment with Plrtllletine should be
~iated cautioull)' two WMI<s anar terminating trHtment with an
""~lll'llbla MAOI or24 houort: alter lei'l"nlnating trealmettl will\ a rVI!f'llbla

MAO inhibitor. Dosage of PatOlfelina should be r.crea..d graduaJy Wil

anopllmal responN iareactled. UN i1 childtelandadolncfof1tJ UIICtiK 18
)'Nil" olage: Prtl~atlne should not ba used in the liNiment of ctliklran
lnd adole!IC'IIlt umar the age of 1a ~ure. Suicidarllated behaviours
(suicide _attempt lnd IUiddal lhougtltt), & hostility (pradomlnanlly
aggrMSIOI'l, oppoaitional behaviour and anger) - e mora lraqoentty
observed in clinical trials among children and adoleacents trnted With
~lldepre111nts compared to lhoM treated wiltl plecebo. II, bUed on
ctink:al need, a(lac;slon to treatilnawrlhatell lal<en: !tie patient should
becarelullymonltored lorlhe appearatiCII ofiUiciclllly!'l'lptCiml.ln
addition. ~term safety date in chiklrerl and adolescents ooocemlng
growth, maturation. and cogni/MI and betll'l'loural development are
/aclfring. Suic/del~fflougl!l$orefinicMIIOfNI'ling: Oepresslon is
~tad~ an II'ICI'H Sid risll. ol ~ h:Jugt\tl, Mit harm and

=~=~~tad~i:y':~~lhe~

_,kl or mora ollfMtmllnt, patoenta should be closely monitored unt~

SUChllnpfovaman!OCOJI"S.It isgenetatcllnlcale~periencalhettha risllor
sUicide may iocfMsa in the early stage~ of ltiCIOYefY. Other pri)'thialric

cordtionslorwhiehPai'Olle/inaarepreiCflbedcanalsobeassociatad

~~:=~~ma:':,..-:!o::."r~=

pnteeutlona obsenlad when lrl!ating patlants with major depras:slve

<border ahoVId lharelore be oblerwd -..t~en trNIIng patlenta with ouwr

peychialricdlsorderi. Pitientswilti ahlslotyolsok::iderellled.....ms,or

/hooNextliblllngasignilicantdegraaolsuicidalideatlonprioriO
c:ommencaomanl ol trN!menl are known 10 ba llljfH!ef risk of suicidal
/houghtl orsull::ida al\ampll.andshouldrecaivecarefulmonltoring during
llHimao(. A malaan~~/ylll of pLacabooonlrole ditllcll trials ol
anlidepre~ drugs In ldull patientS wiltl psychiatric disorders showed
lfl incrMsed nak ol suicidal bahil'liour wiltl antidapfananll compa.rect 10
pYc:llboin~ lutlhll125yeareold. Ciose~ otpatiant4

Helictlbaderpyloriinlflc:tion). and after surgety (wgotorny. gastrectomy)

The PH dapenOency should b1 liMn into account wt1an chlngir.g
Paroutine formulallon (e .g.lhe plllmi.Paroxetine c:onc:1tration may
decraaseatterchangioglromlabletto oralauspension inpalienll wi1ha
high gastric PH). Caution lltherelote racorT\ITIII'Id In pe.lienls when
INtiallng or ancNng treatment with drug~ incfeaaiog ~~~~ PH. DoN
adjuStmentI'Niybenaceasarylnuchlitualionl. kltlflllCiionwilll
latr'IOlliten: Peroxetine may IHd to reducad ettieacy ot tamo~llen. 11 is
recommended that prescribers conkler usil'lg an a uamative
antldeprHIIIlt 'llrilh minimal CYP206 IICUvity. Wlttldrltw81 1)'11l)foms
MCW!Orl~oiPIIroxlillnetraatmant: Wilhdrawai*Yfflploms

when traatmant 11 dlscontnued are common, pa rticularly il

dllcontirlultionlslbrupt. ln cllniCII trials advefse eYenb llll"lon
traatmentdiecontinuationOCCIJIT8din30%olpa~trealadwith

ParOlleline OCJn"lf)llred to 20% ot patients treated w11t1 piKebo. The

~ofwiltldrawatsyn..,tomtlsnollhe$81T11Uihadrugbeing

addictive or dapendeoce producing. The 1'1111 of withdr-111 syn'lfllomS

maybedapendentonse....,.llfactorsincludingtheduralion and<k!Mot
lher~ and the rate ot OOH reduction. DiuinHI. sensory dlsturbllnoes
[f!lduding paraeslhesla, elactric shoe!<. senulions and linnilusJ. ~a~eep
diall.l~ (lndudlng~ drnma), agitationora<Wet)', fllluse&,

~~~=tY. s;::m1.

=d=

~:=e.

par::::;
f"liPor/li'd. G-ray ltllse s~mptoms ara mild to moderate, ' - " " In
soma patlantl they may be savlfe in Intensity. They usually occur wilhln
thaflrlt lewdaysolclsccntlnuing trN.tment, but lhera hil.,.baan'I'IIY rare
raports ollluch ~inplberltswhohiYeinadven.enttymiiMda

ctosa. GenetaUy lheM symptoms are

M ltlimltlng lnd usudy r..otve

within 2 _..,, !hough In IOml indillldl.>als they INIY be prolonged (2-3

monthl or mora). II il tharafore adViMd /hat Parollllfine should be
~ ta.pere(l whendiiC:ominuing lllNitmenl OYef a period of Meral
wvekl or monlhl. acoordingtotha patients needs.

and In panicullr lhoN at high rille sh<U:f ac:oompall)' drug therapy

npecially in early tr8ilbTient and IOIIOwing dose ct~angea. Palilt!\11 (and

PREGNANCY ANO LACTATION: FMildy: Some dinic:allludie5 hive

~regiverlol~tients) lhoutdbe~lltloutlhaneed!Omonitorlorany

Shown lhel SSRII flnciu!Sing. Paroxlllne) may allact 'P8fYn qualit)'. This

ctinicalworwoong, 5uicidalbehaviourorthoughtlandUOUI4.I&Ichangelin
behaviour and to leek medical acMce immediately il these symptoma
present. Aka~ydlomofor reatfe&lneN:The uaeof PIJOJIIilirle has
beanauoclatl!dwithlhedeveloprnentof akathlsia. wtalcttlschlracterized
by an_Inner 181\H ol ri!SIIessness and paychomo/01" egilation s.udl 11 an
inabilitytosilorstandstiltuaualtyasiOCillldwithsubjecMOist,.lt. Thls
ilmoatlikalytoocourVI'ilhin lhalirst lew-ksottrealrnlnf. lnpatiants
who de~ these symptoms, lnc:feulng the 00se may ba datrirnl!nlal
Saroronm Syndrome!Naurolep/IC Ms~n/ Syndrottre: On rare
occuionl davelopl'llent of a urotonln ayndrome or neurol!!pllc malignant
syndrome--like avanb may occur in aiiOCietion with Crntmant o1
Paroxetina. particullrlywhengi'l'll'lineombinalionwllt!othef Mfotonefiic
andlof ~lc drugs. At theN~ mayrasull in potentially
~lettweetening oondit~. liN iment with PlfOJCetine should bl
diseon6no.iedil_audl _e vents (c:t\aractariaedbydua!IKioiSymp!Ornlsuch
ashypar1hem1ie. rlgidlly,_myoclonvs. aulonomlclnstebllily wlthposllble
rapid IU::tua~ ol Yltal llgns , rroet111l lltltus changes inc:lucSing
OOf'lfulion, lrrilability. eKtreme agitation progralling 10 delirium and coma)
occur and s,upport~Ya 1ymptomatie treatmeo1 stlould be Initiated.

effect appear$ to bl reversible lolowing discontinuation of treatment

Thesestudies navenolel<lrl'lined impactonlertili!)'bul.c:hangesinaperm
qualitymay altectlertilityin$0!Tllmen. Pragnllncy:Some ~

:a=~~~!~{!~~~~,~~~or::::i

I!IIIOCiated witt~ the 1.111 ol PatOlfatine ~ the tirst tr'imestel'. The

~it unknown. Tha dl.ta s uggest lhatlha riskol'hiYing anlnlant
with 1 c.rdioascullr Oelect !allowing maternal Paroxetine aJII)OIUfl is
less lhln 2/100 eompared 'lrith an expected ralli lor soch detects o1
approximately 11100 n the vene.ral population. Paroxatina should only be
UMd dufing pragoancy When llrictly indlcaled. The prescrGing physician
will nNd 10 ~ lha 09(ion of a hematiYe h'eatmants in women who a re
pregoronl or are planning lo blcome pregnant ~~ ~lion
.nould be avotded ~ring prltgfllncy. Neonates should be obaiiV1Id il
ITII~em&l use ol Perouline continUiil infO the tatet ~~ages ot pregnancy,
partlcularty thalhln:l 11'1mN!er. The /oll(lw;ng symptomsmayoocurin lh8
neonate after matamal P!V~etinll use ~ Later sllgn o1 pregnancy:
~'O<Y. dlsueu. cy~~~. apnoea, M<es, temperawr. Instability,
leedi!"lg dilficully, YOmillflll, hypoglycaernla, hypaflonill, hypotonia.

Partllt8tineshouldnotbe~ in combinatlonwithllrOIOflinpre<:urlorS

hyparrallellia. ~. jilterineu, .iNitability, lelhargy, constantcrytng,

o~~an)
to the riM of lll'olonergic
ayodroma. Mania;AIWIIh allan~PifOl(etinashouldbelllld

sorMolenCe and difficulty In $leaping. Thata symp~ornt; OCM.IId be dua to

(sucto as lll'yplophaf!.

ca.

'II'ICtl caution In patients wttn a hiltory ot mania. Paro~etina ehou4d be

dilcorolinued In IllY patient entering 1 maolc phase. RI<Wihepitic
~ Caulion is eoornml!l1ded if! patients with savere renal
III1PIIm"lentorlntho6e~~ticlmpllrment. Oiabetes: tnpatil!nlswilh
~. trNtment with an SSAI may alter glycMmic conlrol. Insulin

arrd/or oral hypoglycaemlcdosagamay need to be~. Epilepsy: As

wilt\ oiflerlfllideprellants. Paroxetine llhouldbe usedwilhcautlonin
patients Mlti epilepsy. s.tzures: OYer.~! the indl:lenceol aeiwra1 1s len

~inirr::;::,:~:, :.=:-.::-~~c~~~
cllrolcal exparienca of tha concurrent adrnirnb'atlon ot Paroxetina with
ECT. GIBUCCII'I"le: u wiltl other SSAII. Pl.rOllatlna can eauN mydriasis
andlthOuldbelllld wilh caution in patienll wilhnarTOWanglaglai.ICO!TIIor
hllloty ol gtaUOOITIII. C.!diM:Condil'ions:The\IIUII pr:autionallhould be
observed in !)llients with cardiac conditions . Hypot!arreml:
Hyponatraemla hu bean reported rarely, predomirwllly in tha alderly
Caution lhould allobe a x81'tiaed in thole patients at riak of
l"lyponatr_,ja e .g. lrom oonoom'tane medications and cintlolis. The
hyponatraemla generany flersvs on diiCOOiinulllon of Paro~elinii.
Ha~: Thera heve been reports o1 cutaneous blel!<llng
llbnormatitias such IS $CChYfllOMI 81"1(1 purpura Wllh SSRis . Other

eilherserotoroerglc .~or~lls)"TlliimS. In ama;or;tyol

~lhe~tiOnSIMI9iflmmediatelyorsoon (<24hours) aller

dali'l'lry. Epicjemlological cllla hl1 auggllted that the UM ol SSRII in

pragroancy. partlcularty in lata pregnancy. may haw an incrNHd risll of
perslttentpt*nonaryhypertenionollhe~ (PPHN)

The obsefvl!d n.tl was approUnately 5 cun per 1000 pregnandel. In

thaoenaral poputallon llo2C&Maof Pf'HN periOOO pregnanOeaoocur
Animel lll.dM sno.ed reproduc:tille lolllcity, but did not Indicate~
hlrml~eflectswilhraspecltopragnancy. arMiryonai.IJoetllldellelopmenl,

panurition or postnatal <SeYaloprrlent . LMMtion. Sm.ai amounts of

Paroxatine. ara ettreled into breast milk. In publbhad ltudiel, Mnm
('.(lnOifltra llonlinbrl!astlad lnlantswereundatectabla (<2no'ml)or'l'lty
low (<4r'l!iml). andnosignl ol drugetlectawerli oblervedlnlhese
~~noeltecbaraentielpted.breaslfeadingcanbe

S TORAGE: Storain a cool dryplac.ebelow lO"C .

Kaep outol raacholchiltlrlfl.

.......

PACKAGE: Canon box containing 2 blisters each o110 tablets and Inner

~manlfestatjonse.g. gast<Ointestinal~ ha.,_

been reported. Eldertypallents may beat an increased risk. Caution if;

advlsed in palientstaklngSSRI's~ wilhoralancieoagutanta.

drugs known to allact platelel: lundion orolher drugs that may lncreaN

rtlllofbll!l!ding {e .g. atyplcalantipaycholica such asctozl!lpine,

phenolhial:lnes. most TCAs . ecetytsaicylic add. NSAIO'e . COX2
intlibllors)u wellasinpallentsVI'ilhahlslotyof bleeding(bordersot
~wl"lichmayprediaposaiOblliedng. Drugsa/factingQBSlricPH:
In pat.enls rec11ivll'lg oral s uapenslon. tha Paro~eline plasma

concentration fTII bl inftuaoced by gastric PH. tn vitro dala haw stooon

lhallflacl6ciiiiVironrnenlilr~edlor reln" ollheiCiiYedn.rglfom

thesuapenslon, l"lenceabaorpllonrnay bereducadinpatients wilheNgll

gastllcPHor~lortlydria . .uch asalllirtliUMof cartain<Srugs (a ntacid
~- ~- H2rec.p!Or ~.protOn

pump inhlbilors). In

EVA

'

cerlllnCSiiMN IIItH(e.g. atropNcguttllil. pemicious~.chronic

C1312.00/02/00