Mavilor 5 mgNebivolol

COMPOSITION: EaChtablet contains 5.45 mg of Nebivolol hydrochk)ride equivalent to 5 mg of Nebivolol.Inactive: Lactose monohydrate, croscarmellose sodium, pregelatinized starch, mk:tocrystaline cellulose. magnesium stearate, potysomate 80, sodium lauryl sulphate.

PHARMACEUTICAL FORM: Tablet

IN OleA liONS: Hypertension. Treatment of essential hypertension. CtvoNc heart faiure (CHF). Treatment of stable mild and moderate chronic heart failure in addition to standardtherapies in ekierty patients> 70 years.

POSOLOGY AND METHOD OF ADMINISTRATION: The tablet should be swallowed _ a suffident amount of liquid (e.g. one glass ofwaler) with '" without meals.

HYPERTENSION: AJIJJJJ;. Tho dose osone tablet (5 mg)daily, preferably at the sarno lime of tho day The blood pressure lowering effect becomes _.1Iar 1-2_ of_mento.:cas.on.Iy. the _ """"' • ..-:hod rrit _ 4_.CombiOfUoa with qtfiw' .czftloow1wpstw fqt(JCs' Beta-bkx:kers can be used alone or c:::oncornitat- with 0Ihet antihypertensive agents. To date, an addi50naI ~ef.8ct has been observed CXW'f 5"lJ 1$ c::ombI'led wid"l hydroc:hk:lrothiazide 12.5-25 mgPatients with renal ufficiency: ., ~,.-a the recornrnenr»d star'Wlg dose is 2 5 mg daiy. tf needed, the daJy dose may be incraasad to 5 mg.Patients with hepatic insufficiency: Data In peeru ~ II"IIUf!ir::ie or impend Wet fln::bon are limited. Therefore the use of NebivoIoI in these patients is oontra..fndK:ated.~~"!'f~~($~ts=:e~rsex~:: ~ =.If needed .•.• daily dose may be Increased to 5 mg. However, in view of the limited experience in patients

Childran .ad .dqlascents· The safety and efficacy 01NetIM:*JI., 9d jess than 18~ have net been es&abIished. Therefore, use in children and adolescents is not recommended.

f£Zfgffaeee:abe~~~~f!:retre=~~~~ ••• _:~~~itir::, •• ::r~.:=~~~~~~;::abe~~~~~=~~~~n~:~~:~~~=~8~;a~'!~For those patients receivi"9 cardiovascu!ar drug therapy ~ ..:.or digom and/or N:E. rilibikn.nu qioteosin II antagonists, dosing of these drugs should be stabilized duringthe past two weeks prior to Initiation of NebNoIoI ~ The tIi'IOIJdbe done ac::c:cning to the steps at 1-2 weekly intervals based on patient tolerability. 1.25 mg NebivoIoI,to be inaeased to 2.5 mg NebivoIoI once daiy, then to 5 m; once •• -= to 10 mg once _ The ~..::cmmended dose is 10 mg Nebivo4oI once daily. Initiation of thefapy and everydose increase shoutt be done under OW~ d •• CIVet a penod d.leaSt 2 hcu:s Ie ..-.n that the dinical status (especially as regards b600d pressure, heart rate,c::ondudion ~ S91I oI~ d ~ 0c:cuTenc:e 01adveBe.....ts ma)' ~ •• patients being treated with the maxlroom recommended dose. If necessary,I'1e dose ~ ar aiIo be ~ ~ .-c _lCJPI'OP'iate 0uTIg Iw -.abon pta. =- 01worsening 01 the heart tan 01 inIDIerance it is recommended at torab:::e ne oc. d ar ax. ~ =- of....-e ~ _ ~ fare wiIh ac::uIe p&*nonary oedema. can:icIgeBc: sIloc*., ~

,. M__ ~ ~. ::re~ .'1CIl~tobes&Jpped sn::e-= . ~ ~lh:IUdbe ~l'T1Idto~ ••• ~ JP:2 toe. -=--rd ac. _ niw:iJaIyaa,....Bi 'l""'I!R: ISno

GREATER-"'" '::FE- I\lT01I805) ~.e.u.dNebMJkll"thesepa:B'ltSlSnot~.''' __ '''''-':'JeP8DC 1lSI.II'fioIn::.e 1'her!ftIre the use of ~ in these pabents IS c:ontra-cdcated.

~ dOSeaqusnent ••~ sn:::e ~." maxmum toIeraIec ~.IS indrw:tu.ly adjusted.Cbfldcva .ad ldoIuetoC$ - The..., an::.-"IcIcy of ~., d'ildren aged less ••• • years have fI:II been esta~ Therefore, use in children and adolesoents is not recorrvneoded.

CONTRAINOICA TIONS: HypersensitJvtt COthe actNe substance or to any 01 h exapients. l.Ner insufficiency Ofwer function impairment. Acute heart failure, cardiogenic shock orepisodes of heart failure decompensatIOn requiting tv. inotroptc therapy. •In .ddition, as with other betil-blocking agents, N~Ivo'OJ is contnllndlc.red in: s.ck sinus syndrome, includilg sino-atrial block. Second and third degree atrioventricular block(without a pacemaker). History of bronchospasm and bronchial asthma. Untreated phaeod'uomocytoma. Metabolic aadosis. Bradycardia (heart rate < 60 bpm prior to start of therapy).Hypotension (systolic blood pressure < 90 mmHg). Severe peripheral circulatory distufbances .

••.•---5iPECb1lt: W"RNINOS AN~AtlTIONS ~ORUSE~ng"W8=="a="preceutiOnS===""":;"1O =="re"'ne"'",;;;ic"'a"'n""Iagonists=;;:'=in,, __==~------------iAnnsfttglt- ConWluabon 01 beta bkx:kade reduoes the nsk of arrhyttvnIas during induction and I'1IlJbation. If beta bIcx:bde is I'1ier'Noied fl pn!piObOn b SU'QE!I'Y. the bet&-adrenefgic

~~~~~~~depfession.The~C3f1beprotec:lldagalf'tSl¥ag&--=:IIOra ~~d~

~:J~~~ -a:.e:.-a -'e~~~~~a ~ •• =:~ sa=le to~~ 01 a"QIRI:ec:IOI'& 3ecrw:lse,........- ~rdia: If the putSe ~ 2tJps beloW 5O-55.:a- _,.. or ~ •• aresugges;t'i'lecl orm,ca-...a ~ .OIl!~

Betidctawpic 'n1moaWs sboutd br uswt rtrh qgt;ipr? .--.rs with penpta"aI orcua:Jry disorders (RayaJd's mse.se or ~ ~ ~l asaggravatIOn IX these dlsordecs may oc::a.r: ., paaena ~ .......-.::ular bkl<:k, ~ cI negatIVe effect d ~ 00 conducIon wne •.•paIients pmzmetaI"sangina due to unopposed alpha-receptor mediated oorona-y anary ••asoc:tA••••••• , beta-adrene:rgJ ir'CIgOnIS:S may ecease the and dlnbc:wl of arJgIIOaIanacks. CombInation of NebMJklfwith calcium channel antagonists of the verapamil and dlltiazem type, wiIh Qass I anbarTtlythn'II Qugs, and centrally ac::r-g.mhypertensive drugs is generally not recommended.MetabollclEadocdaologlca'- Nebivolol does not affect glucose levels diabetic patients c:..t! snouti be taken., ~ however, as NebivoklI may mask certain symptomsof hypoglycaemia (tachycardic, palpitations). Beta-adrenergic blocking ~ ~ ~ ploms in hype ~ withdrawal may tntensify symptoms.~ In patients with chronic obstructive pulmonary disorders. troJId be used with ~ _....,. a::nstJidion may be aggravated ..Qtlmc; Pabents with a history of psoriasis should take beta-adr"enel7c ..,. caNIU :::cnsideration. B_ •••••• ...agcnsts may naease the sens&tJWy k) aIergensand the severiy 01 anaphytactic reacbons. The initiation of c::hr'orE ~ neceSSItates .•.."'eiIIm8nl ~ should not be done~ &ness dearty indicated_ ThIs medic:inaJ product contains ~ :mbiems of ~ ....a;::o-Iac:I 0I!IIaencya~.""'1i •~ shc:U:i rot taR NebNalot lnteraction with other medc:rw ~ ....-raction.

PHARMACODYNAMIC I TERACTION: The -.g antagon;sts ••

COMB TlONS OT RECOMMENDED: Class 1._ ~"'''" ,cibenzoline ~on~~imemaybepotentiatedand negaowe~ :...::ar.channel ~d ~ on~and~c:onduc:IIon.lntravenousadministration of~ 10 .nment may lead IOprt:JfoIn::I ~":~bIodL~aetp •••• lSiwes cIord1e,~, moxoridine, methyldopa, 1Wnerwiine) acting an~ c:i'ugS rr.., worsen ~ ••••.• D¥ a 08CnIIIIe ., N c:w.-aI~~:t".m:~~~u:~~~s':w,w:=n:~~~~~:/~ ~tl~~:r=,~~~:!:s~=:;"~tedconcomitant use of beta-adrenergic antagonists and anaesthetics may attenuate ret\u: and mcre.aJijl the nsk of 1lyPQtenslOn As a general rule avcld sudden WIthdrawal ofbeta-blOCker treatment. The anaesthesist should be informed when the patientls ~ HecwIdoL~~=:r:t(=~~t.=~'MIh~P&a::~~~;: ~~==.==~:,raJtoo~ad~~:ra:.=:

COMBINATIONS TO BE CONSIDERED: ovr- _ .......-,..,,,., .........,••••••, condudm _ CIincaI trials with Nebivol<> have not shown any dinicalevidence of an •.•teraction. ~ does I'ICt r:i ~ ~~ ~ type (all'bipl'le: tebIp'le. laOdipine, nifedipine, nicardipine, nimodipine,

~ca~~~ r. __ol~~::===~e::J~~~:~~~drugs (NSAtD). no eftec:t Cf'Itie ::.:0:: ~ .-..::: ~ ::aac:::ntIIlI use may ~ II8Ic:: r:l ~ antagonists. Beta-adrenergicagent5may!eedk)I.RXlOO!IIeC"'= *"" ~ •••• ~ice1fecls(nsad ~~and~bIoc:t~PHARMACOKlNETlC _ co-ad.........., __ .-.zyo:J< ...,.,.., ••••••••.•••~...: -=-:.-. .--= ..~riskofexc:essM! ~...:IaclieWeea. doneccreno:-=. _:::t ..-..; - d 'Gaftedthepla ~ ~ .~ .,..,.

!'I!r..-x sq-;ty~ -~ ~-=-~..-eca _ =- I=-7*'D a'dtt i::Ieiu;~ ~

-.-:I .....,...~ 2-. 6as •.•~..::1~.;JDOB'5 .-=-'f 08ta'~ ~XJCII!G_ ~sf'IcU:j netbeusedcbl1;l ~

~ ~ !lD:l:icMr..:l roetaIQI'CJIIIC'ftU:l oe.~ =-ed ellasOOPf19W'lCYCI'Ni:Jeus,::.:..-,~ d~and~ara~a:::!Ie~ Ihaksl3days.

• ~ rID ~ • not Itnc:Mor1whether this • excreted iIr*J Most ~ partICIAarty lipophilic:~ WI'!8C. ~. extett. Therefore breast IS not rec:ar-rwnoeo ~ ~ dNetwdol

heoM::IoI5mgdoest'lOlatlec:l~""'_"''''''~-''' ~.....=or. ..,.::e.~~==-~aa::~~==~=::that

UNDESIRABLE EFFECTS: -".-a .. for __ and CHF because ofdiff......". in'" background diseases• Hypertension: The adverse rudIons reported, whiCtt •• ., most 01•• case. d c ~Ie ntensity, are tabulated t.:.. classified by system 0f98I1 dass and ordered by frequency.• Immune system disorders: Not known, anglOf"l8urotic oedema, hyp~ ••••• '"

.---~ ••• yCtltatrte dfs-order'!: lJncommon: Nightmares, depressiOn.• Nervous system disorders: Common: headache, dizziness, paraeII:J!SII.. Very rare: syncope.• Eye disorders: Uncommon: imparred vision.• Cardiac disorders: Uncommon: I::ndycartka, heart failure, slowed AV ~V-bIock.• Vascular disorders: Uncommon: hypotension, (increase of) intern..n ClaJdicatioo.• Respiratory, thoracic and mediastinal disorders: Common: c:ppnoea. Uncommon: bn::lnc:t'Iospa.• Gastrointestinal disorders: Common: constipation, nausea,~. Uncommon: dyspepsa, 1aIuence, vomiting.• Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash eryd'Iematous. Vety rare: I)SCIr8$iS aggra vated.• Reproductive system and breast disorders: Uncommon: 1rl1pCII8OCe.

• General disorders and administration site conditions: Common: tiredness. oedema. The toIowIng adverse reactions have also been reported with some beta adrenergicantagonists: hallucinations, psychosis, confusion, coIdIcyanotic extremities Raynaud phenomenon, dry eyes, and ocukHnucocutaneous toxicity of the practoiol-type.• Chronic heart failure.: Data on adverse readioosil.CHF patientsare.available.frnm.oneplacabo-- trialmdmg l061-patient&.~NebM:IIoIend 1061 petientstekingplaoebo. kl:.""~=~~'".:~~~=~=~~~~:~~~~tr!~::n~~l°:,i~~r~~f~d~~~~a'ff~~:~~:~f~c!:!~~u~=5"(~~81~a;tN~b~~~to~~f :~~~~~~O:~f~~I~S:I::~~~~e=1~~~rN~~\?e~~~~~~r.~~7~~~n~~ci~~:I~:==~f~2~f&!=~~tie~~r:ci~~~~• Overdose: No data are a..••ailable on overdosage with Nebi ..••olol.• Symptoms: Symptoms of overdosage with beta·blockers are: bradycardia, hypotension, bronchospasm aIIC acutecardiac insufficiency.·Treabnent:In case of overdosage or hypersensitivity, the patient should be kept under dose supervision ar.:t be nated in an tntensiYe care ~ B;ood gb::OSe •••••• snotAd be

~bu~~~:u~n~r~s~~~~e~J~~~t~~~tnc~:-:~~..,c:n;::~~.--.dMiicHpIasrna.'pIa:srr1a subsbtutes..:t.' necessary. c::atec:t'Iotal_oes The ~ effect can be counteracted by sIow~ ~ oIsopret'1Mneh)ldroc:t*Jnoe ...-.g=.~~r!:oouce Of~s&aning~~ct"=~1~er.a~r::t.~~~~sro:rt!"~wiIhnone hcu'_ to be foIowed -4 r1!IQI.Jftd--by a"I .v. II"IfusIoncI gkX:agon exnme cases of treall'nenkeMtant bradycan:faa, a pac:emakef may be 1lS8fted.

PHARMACOLOGICAL PROPERTIES: Pharmacodynamic propwfJeS: PIIonnacotlHm!peuti<: gnqo: Beta bIoddng _, selective. __ ;sa racemale of two enantiomers,

~~:=:t=~~~~~~~~~~·L~~~.~~~~-:cr==~~a==pressure at rest and during exercise, both in normotensive subjects and •.• ~ patJenls. The antihypertensM: efIed is maintained during chronic treatment At therapeutic doses, NebivoIoI isdevoid of alpha-adrenergic antagonism. During acute and chronic treatment ~ in hypertensive patients S)'SII!ImC vascular resistance is decreased. Despite heart rate reduction, reduction in

~~:mcx;::!~~~.al~h=S:~~r:~=~~~=='~!~=;:~~~~~4~=?:=ts~=tt'::~~=~tshasPharmacokine~perties: BothNebivolol eoantiomers ara rapidly abscxbed •• oral administratIOn. The al:Jsorr*on ofNebivolol is not affected by food; Nebivolol can be given with or without meals.

~:~.!~:Pt~are=i~':wrttt:~~=-:=~·~-:a~~t~~~&~:=~ro::X:tiv~~~~~~~u:r~=~~~~~~~=:s~~in fast metabolisers and is virtualy ~ Il sk7.JtmetaboIsers. At steady state and.11e same dose level, the peak pIIsna concentration of unchanged NebivoIoI is about 23 times higher i'I poor metaboisersthan in extensive metaboisers. 'Nhen ~ cWg plus adrIe metaboItes are c::a&dered, the dtferenc:ein peak pIa:s;;:ra~ is 1.3 to 1.4 fdd_ Becauseoltha vanaDon., raiesol ~ fiedoseal __ alwaysbe~lDtho __ al"'_poor_Iherefore_ •••••• """doses.""" aI _•••••.••••••.• _ Ohoon .•• __ ....,. •••• J.5_k>rger ••••••n-. piasma~aI •• ~ •• *I*1tq>er_Ior •• SRRR___ hsdlfJetencel5~ •.•1ast_........"..hal-hesoflheh~ofbothenantiometsawnge24hcus,iRlaelibtUtwlCeaslDng ., __ metaI::IoiIeB.~plasma 1e¥eIs., most stqed:s (fast mMaboisers) are r-=hed wiIm 2A.1'Ic:u5 b NebMJk:iIand •••• a few days for the~. ~ ~ are ~ belween 1 ana JO~~of~~rO~~~~ ~~~~~nttyDoundm~.~.~~159!1 ...1."'~_SRRR~and97.9%b

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