Etoricoxib Brown 60 mg Filmdragerad tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

25-05-2021

Produktens egenskaper Produktens egenskaper (SPC)

20-04-2018

Aktiva substanser:
etoricoxib
Tillgänglig från:
Brown & Burk IR Limited
ATC-kod:
M01AH05
INN (International namn):
etoricoxib
Dos:
60 mg
Läkemedelsform:
Filmdragerad tablett
Sammansättning:
etoricoxib 60 mg Aktiv substans; laktosmonohydrat Hjälpämne
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 2 tabletter; Blister, 5 tabletter; Blister, 7 tabletter; Blister, 10 tabletter; Blister, 14 tabletter; Blister, 20 tabletter; Blister, 28 tabletter; Blister, 30 tabletter; Blister, 49 tabletter; Blister, 50 tabletter; Blister, 84 tabletter; Blister, 98 tabletter; Blister, 100 tabletter
Bemyndigande status:
Godkänd
Godkännandenummer:
55640
Tillstånd datum:
2017-09-26

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

31-03-2020

Produktens egenskaper Produktens egenskaper - engelska

31-03-2020

Läs hela dokumentet

Bipacksedel: Information för användaren

Etoricoxib Brown 30 mg filmdragerade tabletter

Etoricoxib Brown 60 mg filmdragerade tabletter

Etoricoxib Brown 90 mg filmdragerade tabletter

Etoricoxib Brown 120 mg filmdragerade tabletter

etoricoxib

Läs noga igenom hela bipacksedeln innan du börjar ta detta läkemedel. Den innehåller information

som är viktig för dig.

Spara denna information, du kan behöva läsa den igen.

Om du har ytterligare frågor, vänd dig till läkare eller apotekare.

Detta läkemedel har ordinerats enbart åt dig. Ge det inte till andra. Det kan skada dem, även om de

uppvisar sjukdomstecken som liknar dina.

Om du får biverkningar, tala med läkare eller apotekare. Detta gäller även eventuella biverkningar

som inte nämns i denna information. Se avsnitt 4.

I denna bipacksedel finns information om följande:

Vad Etoricoxib Brown är och vad de används för

Vad du behöver veta innan du tar Etoricoxib Brown

Hur man tar Etoricoxib Brown

Eventuella biverkningar

Hur Etoricoxib Brown bör förvaras

Förpackningens innehåll och övriga upplysningar

1.

Vad Etoricoxib Brown är och vad de används för

Vad är Etoricoxib Brown?

Etoricoxib Brown innehåller den aktiva substansen etoricoxib. Etoricoxib tillhör en grupp läkemedel

som kallas selektiva COX-2-hämmare. Dessa tillhör en familj av läkemedel som kallas icke-steroida

antiinflammatoriska läkemedel (NSAID).

Vad används Etoricoxib Brown för?

Etoricoxib Brown minskar smärta och svullnad (inflammation) i leder och muskler hos personer över

16 års ålder med artros, reumatoid artrit, ankyloserande spondylit och gikt.

Etoricoxib Brown används även för korttidsbehandling av måttlig smärta efter tandkirurgi hos

personer över 16 års ålder.

Vad är artros?

Artros är en sjukdom i lederna. Den orsakas av gradvis nedbrytning av brosk som dämpar benändarnas

kontakt med varandra. Detta orsakar svullnad (inflammation), smärta, ömhet, stelhet och

funktionsnedsättning.

Vad är reumatoid artrit?

Reumatoid artrit är en långvarig inflammatorisk sjukdom i lederna. Den orsakar smärta, stelhet, svullnad och

en minskande rörlighet i de leder som drabbas. Den kan även orsaka inflammation i andra delar av kroppen.

Vad är gikt?

Gikt är en sjukdom med plötsliga, återkommande attacker av mycket smärtsam inflammation och rodnad i

lederna. Det orsakas av inlagringar av mineralkristaller i leden.

Vad är ankyloserande spondylit?

Ankyloserande spondylit är en inflammatorisk sjukdom i ryggrad och stora leder.

Etoricoxib som finns i Etoricoxib Brown kan också vara godkänd för att behandla andra sjukdomar som inte

nämns i denna produktinformation. Fråga läkare, apotek- eller annan hälsovårdspersonal om du har

ytterligare frågor och följ alltid deras instruktion.

2.

Vad du behöver veta innan du tar Etoricoxib Brown

Ta inte Etoricoxib Brown:

om du är allergisk mot etoricoxib eller något annat innehållsämne i detta läkemedel (se avsnitt 6)

om du är allergisk mot icke-steroida antiinflammatoriska läkemedel (NSAID), inklusive

acetylsalicylsyra och COX-2-hämmare (se Eventuella biverkningar, avsnitt 4)

om du för närvarande har magsår eller blödningar i magen eller tarmarna

om du har en allvarlig leversjukdom

om du har en allvarlig njursjukdom

om du är eller skulle kunna vara gravid eller om du ammar (se ‘Graviditet, amning och fertilitet’)

om du är under 16 år

om du har en inflammatorisk tarmsjukdom, såsom Crohns sjukdom, ulcerös kolit eller kolit

om du har högt blodtryck som inte är under kontroll efter behandling (kontakta din läkare eller

sjuksköterska om du är osäker på om ditt blodtryck är tillräckligt kontrollerat)

om läkare har konstaterat att du har problem med hjärtat, inklusive hjärtsvikt (måttlig eller svår),

kärlkramp (bröstsmärta)

om du har haft en hjärtattack, bypass-kirurgi, perifer artärsjukdom (dålig cirkulation i ben eller fötter

på grund av snäva eller blockerade blodkärl)

om du har haft någon form av stroke (inklusive mini-stroke, transitorisk ischemisk attack, TIA).

Etoricoxib kan ge en lätt ökad risk för hjärtattack och stroke och bör därför inte användas av de som

redan har haft hjärtproblem eller stroke.

Om du tror att något av detta gäller dig, ta inte tabletterna innan du har rådfrågat din läkare.

Varningar och försiktighet

Prata med läkare eller apotekare innan du tar Etoricoxib Brown om:

Du tidigare har upplevt blödningar i magen eller magsår.

Du är uttorkad, till exempel på grund av långvariga kräkningar eller diarré.

Du upplever svullnad på grund av vätskeretention.

Du tidigare har haft hjärtsvikt, eller någon annan typ av hjärtsjukdom.

Du tidigare har haft högt blodtryck. Etoricoxib Brown kan öka blodtrycket hos vissa människor,

speciellt vid höga doser, och din läkare kommer vilja kontrollera ditt blodtryck då och då.

Du tidigare har haft lever- eller njursjukdomar.

Du behandlas för en infektion. Etoricoxib Brown kan maskera eller dölja feber, vilket är ett tecken på

infektion.

Du har diabetes, högt kolesterol eller röker. Detta ökar din risk gällande hjärtsjukdom.

Du är en kvinna som försöker bli gravid.

Du är äldre än 65 år gammal.

Om du inte är säker på om påståendena här ovanför gäller dig,

prata med läkare innan du tar Etoricoxib

Brown

för att se om detta läkemedel passar dig.

Etoricoxib Brown fungerar lika bra hos äldre som hos yngre vuxna patienter. Om du är över 65 år gammal

kommer läkare vilja följa upp dig på ett lämpligt sätt. Ingen dosjustering är nödvändig för patienter över 65 år.

Barn och ungdomar

Ge inte detta läkemedel till barn och ungdomar under 16 år.

Andra läkemedel och Etoricoxib Brown

Berätta för läkare eller apotekare om du tar, nyligen har tagit eller kan komma att ta andra läkemedel,

inklusive receptfria läkemedel.

Speciellt om du tar något av följande läkemedel kan din läkare vilja övervaka dig för att kontrollera att dina

läkemedel verkar ordentligt när du börjar ta Etoricoxib Brown:

blodförtunnande läkemedel (antikoagulantia), såsom warfarin

rifampicin (ett antibiotikum)

metotrexat (ett läkemedel vid rubbningar i immunsystemet som ofta används vid reumatoid artrit)

ciklosporin eller takrolimus (läkemedel som används för att undertrycka immunförsvaret)

litium (ett läkemedel som används för att behandla vissa typer av depression)

läkemedel som används för att behandla högt blodtryck och hjärtsvikt som kallas ACE-hämmare och

angiotensin-receptorblockerare, t.ex. enalapril och ramipril samt losartan och valsartan

diuretika (vätskedrivande medel)

digoxin (ett läkemedel mot hjärtsvikt och oregelbunden hjärtrytm)

minoxidil (ett läkemedel mot högt blodtryck)

salbutamoltabletter eller oral lösning (ett läkemedel mot astma)

p-piller (kombinationen kan öka risken för biverkningar)

hormonersättningsterapi (kombinationen kan öka risken för biverkningar)

acetylsalicylsyra, risken för magsår är större om du tar Etoricoxib Brown samtidigt med

acetylsalicylsyra.

acetylsalicylsyra för förebyggande av hjärtattacker eller stroke:

Etoricoxibtabletter kan tas samtidigt med acetylsalicylsyra i

låga doser

. Om du för närvarande tar

lågdos acetylsalicylsyra för att förebygga hjärtattacker eller stroke bör du inte sluta ta

acetylsalicylsyra innan du rådfrågat läkare

acetylsalicylsyra eller andra icke-steroida antiinflammatoriska läkemedel (NSAID):

ta inte

höga doser av

acetylsalicylsyra eller andra antiinflammatoriska läkemedel medan du tar

Etoricoxib Brown

Etoricoxibtabletter med mat och dryck

Effekten av Etoricoxib Brown kan uppnås snabbare om de tas utan mat.

Graviditet, amning och fertilitet

Graviditet

Etoricoxib Brown ska inte tas under graviditet. Om du är gravid eller tror att du skulle kunna vara gravid,

eller om du planerar att bli gravid, ta inte tabletterna. Om du blir gravid, sluta ta tabletterna och rådgör med

läkare. Kontakta läkare om du är osäker eller behöver mer råd.

Amning

Det är okänt om Etoricoxib Brown utsöndras i bröstmjölk. Om du ammar, eller planerar att amma, rådgör

med läkare innan du tar Etoricoxib Brown. Om du tar Etoricoxib Brown ska du inte amma.

Fertilitet

Etoricoxib Brown rekommenderas inte till kvinnor som försöker bli gravida.

Körförmåga och användning av maskiner

Yrsel och sömnighet har rapporterats hos vissa patienter som tar Etoricoxib Brown.

Kör ej bil och använd inte maskiner eller verktyg om du känner yrsel eller sömnighet.

Du är själv ansvarig för att bedöma om du är i kondition att framföra motorfordon eller utföra arbeten som

kräver skärpt uppmärksamhet. En av faktorerna som kan påverka din förmåga i dessa avseenden är

användning av läkemedel på grund av deras effekter och/eller biverkningar. Beskrivning av dessa effekter

och biverkningar finns i andra avsnitt. Läs därför all information i denna bipacksedel för vägledning.

Diskutera med din läkare eller apotekspersonal om du är osäker.

Etoricoxib Brown innehåller laktos

Om du av läkare fått veta att du inte tål vissa sockerarter, kontakta läkare innan du tar detta läkemedel.

3.

Hur man tar Etoricoxib Brown

Ta alltid detta läkemedel enligt läkarens anvisningar. Rådfråga läkare eller apotekspersonal om du är osäker.

Ta inte mer än den rekommenderade dosen för din sjukdom. Din läkare kan emellanåt vilja diskutera din

behandling. Det är viktigt att du använder den lägsta dosen som får din smärta under kontroll, och du bör

inte ta Etoricoxib Brown under längre tid än vad som är nödvändigt. Detta är för att risken för hjärtattacker

och stroke kan öka efter långvarig behandling, speciellt vid höga doser.

Det finns olika styrkor tillgängliga för detta läkemedel och beroende på din sjukdom kommer läkaren att

skriva ut tablettstyrkan som passar dig.

Den rekommenderade dosen är:

Artros

Den rekommenderade dosen är 30 mg en gång dagligen. Vid behov kan dosen ökas till maximalt 60 mg en

gång dagligen.

Reumatoid artrit

Den rekommenderade dosen är 60 mg en gång dagligen. Vid behov kan dosen ökas till maximalt 90 mg en

gång dagligen.

Ankyloserande spondylit

Den rekommenderade dosen är 60 mg en gång dagligen. Vid behov kan dosen ökas till maximalt 90 mg en

gång dagligen.

Akuta smärttillstånd

Etoricoxib bör endast användas under den akuta smärtperioden.

Gikt

Den rekommenderade dosen är 120 mg en gång dagligen vilket enbart bör användas under den akuta

smärtperioden, begränsat till max 8 dagars behandling.

Smärta efter tandkirurgi

Den rekommenderade dosen är 90 mg en gång dagligen, begränsat till max 3 dagars behandling.

Personer med leverproblem

Om du har en mild leversjukdom bör du inte ta mer än 60 mg dagligen.

Om du har

måttlig

leversjukdom bör du inte ta mer än

30 mg dagligen

Användning hos barn och ungdomar

Etoricoxib Brown bör inte tas av barn och ungdomar under 16 år.

Äldre patienter

Ingen dosjustering är nödvändig för äldre patienter. Som med andra läkemedel ska försiktighet iakttas hos

äldre patienter.

Administreringssätt

Etoricoxib Brown ska sväljas. Ta tabletterna en gång om dagen. Etoricoxib Brown kan tas med eller utan

mat.

Om du tar fler Etoricoxib Brown än vad du ska

Du bör aldrig ta fler tabletter än vad läkaren rekommenderar. Om du fått i dig för stor mängd läkemedel eller

om t.ex. ett barn fått i sig läkemedlet av misstag kontakta omedelbart läkare, sjukhus eller

Giftinformationscentralen (tel. 112) för bedömning av risken samt rådgivning.

Om du glömmer att ta Etoricoxib Brown

Det är viktigt att ta Etoricoxib Brown så som läkaren har ordinerat dig. Om du missar en dos, återuppta ditt

vanliga schema följande dag. Ta inte en dubbel dos för att kompensera för den glömda tabletten.

Om du har ytterligare frågor om användningen av detta läkemedel, fråga läkare eller apotekare.

4.

Eventuella biverkningar

Liksom alla läkemedel kan detta läkemedel orsaka biverkningar, men alla användare behöver inte få dem.

Sluta ta Etoricoxib Brown och kontakta omedelbart läkare om du får något av följande symtom (se

Vad du behöver veta innan du tar Etoricoxib Brown avsnitt 2):

andfåddhet, bröstsmärta eller svullna fotleder, om de uppstår eller förvärras

gulaktighud eller gulaktiga ögon (gulsot) - dessa är tecken på leverproblem

allvarlig eller ihållande magsmärta eller svart avföring

en allergisk reaktion – vilket kan innefatta hudproblem såsom sår eller blåsor, eller svullnad i

ansikte, läppar, tungan eller halsen som kan leda till andningssvårigheter

Frekvensen av eventuella biverkningar som anges nedan definieras enligt följande:

Mycket vanliga (kan förekomma hos fler än 1 av 10 användare)

Vanliga (kan förekomma upp till 1 till 10 användare)

Mindre vanliga (kan förekomma hos upp till 1 av 100 användare)

Sällsynta (kan förekomma hos upp till 1 av 1000 användare)

Mycket sällsynta (kan förekomma hos upp till 1 av 10 000 användare)

Följande biverkningar kan uppstå under behandling med Etoricoxib Brown:

Mycket vanliga:

magont

Vanliga:

torr tandhåleinflammation (inflammation och smärta efter utdragen tand)

svullnad i benen och/eller fötterna på grund av vätskeansamling (ödem)

yrsel, huvudvärk

hjärtklappning (snabb eller oregelbunden puls), oregelbunden hjärtrytm (arytmi)

förhöjt blodtryck

väsande andning eller andfåddhet (bronkospasmer)

förstoppning, väderspänning (mycket tarmgaser), gastrit (inflammation i magsäcken), halsbränna,

diarré, dyspepsi/magbesvär, illamående, kräkningar, inflammation i matstrupen, munsår

ändrade blodvärden avseende levern

blåmärken

svaghet och trötthet, influensaliknande symtom

Mindre vanliga:

gastroenterit (inflammation i magtarmkanalen som involverar både magen och

tunntarmen/maginfluensa), övre luftvägsinfektion, urinvägsinfektion

ändring av laboratorievärden (minskat antal röda blodkroppar, minskat antal vita blodkroppar, minskat

antal blodplättar)

överkänslighet (en allergisk reaktion inklusive nässelfeber som kan vara så allvarlig att omedelbar

läkarvård krävs)

ökad eller minskad aptit, viktökning

ångest, depression, nedsatt mental skärpa; att se, känna eller höra saker som inte finns

(hallucinationer)

smakförändringar, sömnsvårigheter, domningar eller stickningar, sömnighet

dimsyn, irritation och rodnad i ögonen

ringningar i öronen, yrsel (känsla av att snurra när man är stilla)

onormal hjärtrytm (förmaksflimmer), snabb hjärtrytm, hjärtsvikt, känsla av åtstramning, tryck eller

tyngd över bröstet (kärlkramp), hjärtattack

blodvallning, stroke, mini stroke (transitorisk ischemisk attack), allvarlig höjning

av blodtrycket, inflammation i blodkärlen

hosta, andnöd, näsblod

gaser i magen eller tarmen, förändrade tarmvanor, muntorrhet, magsår, magsäcksinflammation som

kan bli allvarlig och kan leda till blödning, irriterad tarm, inflammation i bukspottkörteln

svullnad i ansiktet, hudutslag eller kliande hud, hudrodnad

muskelkramp/ryckning, muskelsmärta/stelhet

förhöjd kaliumnivå i blodet, ändrade blod- eller urinvärden avseende njurarna, allvarlig njurpåverkan

bröstsmärta

Sällsynta:

angioödem (en allergisk reaktion med svullnad av ansikte, läppar, tunga och/eller hals vilket kan

orsaka andnings- eller sväljsvårigheter som kan vara så allvarliga att omedelbar läkarvård

krävs)/anafylaktiska/anafylaktoida reaktioner inklusive chock (en allvarlig allergisk reaktion som

kräver omedelbar läkarvård)

förvirring, rastlöshet

leverproblem (hepatit)

låga natriumhalter i blodet

leversvikt, gulaktig hy och/eller gulaktiga ögonvitor (gulsot)

allvarliga hudreaktioner

Rapportering av biverkningar

Om du får biverkningar, tala med läkare eller apotekspersonal. Detta gäller även biverkningar som inte

nämns i denna information. Du kan också rapportera biverkningar direkt (se detaljer nedan). Genom att

rapportera biverkningar kan du bidra till att öka informationen om läkemedlets säkerhet.

Läkemedelsverket, Box 26, 751 03 Uppsala. Webbplats: www.lakemedelsverket.se.

5.

Hur Etoricoxib Brown bör förvaras

Förvara detta läkemedel utom syn- och räckhåll för barn.

Används före utgångsdatum som anges på kartongen. Utgångsdatum är den sista dagen i angiven månad.

Inga särskilda förvaringsanvisningar.

Läkemedel ska inte kastas i avloppet eller bland hushållsavfall. Fråga apotekspersonalen hur man kastar

läkemedel som inte längre används. Dessa åtgärder är till för att skydda miljön.

6.

Förpackningens innehåll och övriga upplysningar

Vad Etoricoxib Brown innehåller

Den aktiva substansen är etoricoxib. Varje filmdragerad tablett innehåller 30, 60, 90 eller 120 mg etoricoxib.

De övriga ingredienserna är:

Kärna: Mikrokristallin cellulosa, vattenfritt kalciumvätefosfat, kroskarmellosnatrium, laktosmonohydrat,

hydroxipropylcellulosa, magnesiumstearat.

Filmdragering

30 mg, 60 mg och 120 mg: Hypromellos, laktosmonohydrat, titandioxid, triacetin, indigokarmin (E132) och

järnoxidgult(E172).

90 mg: Hypromellos, laktosmonohydrat, titandioxid och triacetin.

Hur Etoricoxib Brown ser ut och innehåll i förpackningen

Etoricoxib Brown finns tillgängliga i fyra styrkor:

30 mg: Blå-gröna, äppelformade, bikonvexa filmdragerade tabletter märkta på ena sidan med ‘30’ och den

andra sidan blank, ca 6,4 mm i längd och 6,2 mm i bredd.

60 mg: Mörkgröna äppelformade, bikonvexa filmdragerade tabletter märkta på ena sidan med ‘60’ och den

andra sidan blank, ca 7,4 mm i längd och 7,1 mm i bredd.

90 mg: Vita, äppelformade, bikonvexa filmdragerade tabletter märkta på ena sidan med ‘90’ och den andra

sidan blank, ca 8,5 mm i längd och 8,3 mm i bredd.

120 mg: Ljusgröna, äppelformade, bikonvexa filmdragerade tabletter märkta på ena sidan med ‘120’ och

den andra sidan blank, ca 9,3 mm i längd och 9,1 mm i bredd.

Förpackningsstorlekar:

30 mg, 60 mg, 90 mg och 120 mg:

Förpackningar med 2, 5, 7, 10, 14, 20, 28, 30, 49, 50, 84, 98, 100 filmdragerade tabletter.

Det är inte säkert att alla förpackningsstorlekar kommer att marknadsföras.

Innehavare av godkännande för försäljning

Brown & Burk IR Limited

22 Northumberland Road,

Ballsbridge, Dublin 4,

Irland

tillverkare

Misom Labs Ltd,

Malta Life Sciences Park,

LS2.01.06, Industrial Estate,

San Gwann, SGN 3000,

Malta

Lokal företrädare:

Brown & Burk AB

Skeppsgatan 19

211 11 Malmö

Sverige

Detta läkemedel är godkänt i EEA-länderna med följande namn:

UK: Etoricoxib 30mg/ 60mg/ 90mg/ 120mg film-coated tablets

SE: Etoricoxib Brown 30mg/ 60mg/ 90mg/ 120mg filmdragerade tabletter

Denna bipacksedel ändrades senast 2021-05-25

Läs hela dokumentet

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Etoricoxib Brown 30 mg film-coated tablets

Etoricoxib Brown 60 mg film-coated tablets

Etoricoxib Brown 90 mg film-coated tablets

Etoricoxib Brown 120 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 30, 60, 90 or 120 mg of etoricoxib.

Excipients with known effect:

30 mg: 1.40 mg lactose monohydrate

60 mg: 2.80 mg lactose monohydrate

90 mg: 4.20 mg lactose monohydrate

120 mg: 5.60 mg lactose monohydrate

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet.

30 mg: Blue-green, apple-shaped, biconvex film coated tablets engraved ‘30’ on one face and other

face plain, approximately 6.4 mm length and 6.2 mm width.

60 mg: Dark-green, apple-shaped, biconvex film coated tablets engraved ‘60’ on one face and other

face plain, approximately 7.4 mm length and 7.1 mm width.

90 mg: White, apple-shaped, biconvex film coated tablets engraved ‘90’ on one face and other face

plain, approximately 8.5 mm length and 8.3 mm width.

120 mg: Pale-green, apple-shaped, biconvex film coated tablets engraved ‘120’ on one face and other

face plain, approximately 9.3 mm length and 9.1 mm width.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Etoricoxib Brown is indicated in adults and adolescents 16 years of age and older for the symptomatic

relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs

of inflammation associated with acute gouty arthritis.

Etoricoxib Brown is indicated in adults and adolescents 16 years of age and older for the short-term

treatment of moderate pain associated with dental surgery.

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the

individual patient's overall risks (see sections 4.3, 4.4).

4.2 Posology and method of administration

Posology

As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the

shortest duration possible and the lowest effective daily dose should be used. The patient's need for

symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients

with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).

Osteoarthritis

The recommended dose is 30 mg once daily. In some patients with insufficient relief from symptoms,

an increased dose of 60 mg once daily may increase efficacy. In the absence of an increase in

therapeutic benefit, other therapeutic options should be considered.

Rheumatoid arthritis

The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms,

an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilised,

down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in

therapeutic benefit, other therapeutic options should be considered.

Ankylosing spondylitis

The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms,

an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilised,

down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in

therapeutic benefit, other therapeutic options should be considered.

Acute pain conditions

For acute pain conditions, etoricoxib should be used only for the acute symptomatic period.

Acute gouty arthritis

The recommended dose is 120 mg once daily. In clinical trials for acute gouty arthritis, etoricoxib was

given for 8 days.

Postoperative dental surgery pain

The recommended dose is 90 mg once daily, limited to a maximum of 3 days. Some patients may

require other postoperative analgesia in addition to etoricoxib during the three day treatment period.

Doses greater than those recommended for each indication have either not demonstrated additional

efficacy or have not been studied. Therefore:

The dose for OA should not exceed 60 mg daily.

The dose for RA and ankylosing spondylitis should not exceed 90 mg daily.

The dose for acute gout should not exceed 120 mg daily, limited to a maximum of 8 days treatment.

The dose for postoperative acute dental surgery pain should not exceed 90 mg daily, limited to a

maximum of 3 days.

Special populations

Elderly patients

No dosage adjustment is necessary for elderly patients. As with other drugs, caution should be

exercised in elderly patients (see section 4.4).

Patients with hepatic impairment

Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose of

60 mg once daily should not be exceeded. In patients with moderate hepatic dysfunction (Child-Pugh

score 7-9), regardless of indication, the dose of 30 mg

once daily

should not be exceeded.

Clinical experience is limited particularly in patients with moderate hepatic dysfunction and caution is

advised. There is no clinical experience in patients with severe hepatic dysfunction (Child-Pugh score

≥10); therefore, its use is contraindicated in these patients (see sections 4.3, 4.4 and 5.2).

Patients with renal impairment

No dosage adjustment is necessary for patients with creatinine clearance ≥30 ml/min (see section 5.2).

The use of etoricoxib in patients with creatinine clearance <30 ml/min is contra-indicated (see

sections 4.3 and 4.4).

Paediatric population

Etoricoxib is contra-indicated in children and adolescents under 16 years of age (see section 4.3).

Method of administration

Etoricoxib Brown is administered orally and may be taken with or without food. The onset of the

effect of the medicinal product may be faster when Etoricoxib Brown is administered without food.

This should be considered when rapid symptomatic relief is needed.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Active peptic ulceration or active gastro-intestinal (GI) bleeding.

Patients who, after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2)

inhibitors, experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema,

urticaria, or allergic-type reactions.

Pregnancy and lactation (see sections 4.6 and 5.3).

Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).

Estimated renal creatinine clearance <30 ml/min.

Children and adolescents under 16 years of age.

Inflammatory bowel disease.

Congestive heart failure (NYHA II-IV).

Patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg

and has not been adequately controlled.

Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

4.4 Special warnings and precautions for use

Gastrointestinal effects

Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them

resulting in fatal outcome, have occurred in patients treated with etoricoxib.

Caution is advised with treatment of patients most at risk of developing a gastrointestinal

complication with NSAIDs; the elderly, patients using any other NSAID or acetylsalicylic acid

concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and GI

bleeding.

There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or

other gastrointestinal complications) when etoricoxib is taken concomitantly with acetylsalicylic acid

(even at low doses). A significant difference in GI safety between selective COX-2 inhibitors +

acetylsalicylic acid

vs

. NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical

trials (see section 5.1).

Cardiovascular effects

Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with a risk

of thrombotic events (especially myocardial infarction (MI) and stroke), relative to placebo and some

NSAIDs. As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure,

the shortest duration possible and the lowest effective daily dose should be used. The patient's need

for symptomatic relief and response to therapy should be re-evaluated periodically, especially in

patients with osteoarthritis (see sections 4.2, 4.3, 4.8 and 5.1).

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia,

diabetes mellitus, smoking) should only be treated with etoricoxib after careful consideration (see

section 5.1).

COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of

cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effect. Therefore

antiplatelet therapies should not be discontinued (see sections above, 4.5 and 5.1.).

Renal effects

Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore,

under conditions of compromised renal perfusion, administration of etoricoxib may cause a reduction

in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function.

Patients at greatest risk of this response are those with pre-existing significantly impaired renal

function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients

should be considered.

Fluid retention, oedema and hypertension

As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention, oedema

and hypertension have been observed in patients taking etoricoxib. All Nonsteroidal Anti

inflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent

congestive heart failure. For information regarding a dose related response for etoricoxib see section

5.1. Caution should be exercised in patients with a history of cardiac failure, left ventricular

dysfunction, or hypertension and in patients with pre-existing oedema from any other reason. If there

is clinical evidence of deterioration in the condition of these patients, appropriate measures including

discontinuation of etoricoxib should be taken.

Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs

and selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be

controlled before treatment with etoricoxib (see section 4.3) and special attention should be paid to

blood pressure monitoring during treatment with etoricoxib. Blood pressure should be monitored

within two weeks after initiation of treatment and periodically thereafter. If blood pressure rises

significantly, alternative treatment should be considered.

Hepatic effects

Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)

(approximately three or more times the upper limit of normal) have been reported in approximately

1% of patients in clinical trials treated for up to one year with etoricoxib 30, 60 and 90 mg daily.

Any patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver

function test has occurred, should be monitored. If signs of hepatic insufficiency occur, or if

persistently abnormal liver function tests (three times the upper limit of normal) are detected,

etoricoxib should be discontinued.

General

If during treatment, patients deteriorate in any of the organ system functions described above,

appropriate measures should be taken and discontinuation of etoricoxib therapy should be considered.

Medically appropriate supervision should be maintained when using etoricoxib in the elderly and in

patients with renal, hepatic, or cardiac dysfunction.

Caution should be used when initiating treatment with etoricoxib in patients with dehydration. It is

advisable to rehydrate patients prior to starting therapy with etoricoxib.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson

syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use

of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see section 4.8).

Patients appear to be at highest risk for these reactions early in the course of therapy with the onset of

the reaction occurring in the majority of cases within the first month of treatment. Serious

hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients

receiving etoricoxib (see section 4.8). Some selective COX-2 inhibitors have been associated with an

increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be

discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of

hypersensitivity.

Etoricoxib may mask fever and other signs of inflammation.

Caution should be exercised when co-administering etoricoxib with warfarin or other oral

anticoagulants (see section 4.5).

The use of etoricoxib, as with any medicinal product known to inhibit cyclooxygenase / prostaglandin

synthesis, is not recommended in women attempting to conceive (see sections 4.6, 5.1, and 5.3).

Etoricoxib Brown contain lactose. Patients with rare hereditary problems of galactose intolerance, the

Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

Oral anticoagulants: In subjects stabilised on chronic warfarin therapy, the administration of

etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time

International Normalised Ratio (INR). Therefore, patients receiving oral anticoagulants should be

closely monitored for their prothrombin time INR, particularly in the first few days when therapy with

etoricoxib is initiated or the dose of etoricoxib is changed (see section 4.4).

Diuretics, ACE inhibitors and Angiotensin II Antagonists:

NSAIDs may reduce the effect of diuretics

and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated

patients or elderly patients with compromised renal function) the co-administration of an ACE

inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further

deterioration of renal function, including possible acute renal failure, which is usually reversible.

These interactions should be considered in patients taking etoricoxib concomitantly with ACE

inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with

caution, especially in the elderly. Patients should be adequately hydrated and consideration should be

given to monitoring of renal function after initiation of concomitant therapy, and periodically

thereafter.

Acetylsalicylic Acid:

In a study in healthy subjects, at steady state, etoricoxib 120 mg once daily had

no effect on the anti-platelet activity of acetylsalicylic acid (81 mg once daily). Etoricoxib can be used

concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose

acetylsalicylic acid). However, concomitant administration of low-dose acetylsalicylic acid with

etoricoxib may result in an increased rate of GI ulceration or other complications compared to use of

etoricoxib. Concomitant administration of etoricoxib with doses of acetylsalicylic acid above those for

cardiovascular prophylaxis or with other NSAIDs is not recommended (see sections 5.1 and 4.4.).

Cyclosporin and tacrolimus:

Although this interaction has not been studied with etoricoxib,

coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of

cyclosporin or tacrolimus. Renal function should be monitored when etoricoxib and either of these

drugs is used in combination.

Pharmacokinetic interactions

The effect of etoricoxib on the pharmacokinetics of other drugs

Lithium:

NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If

necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being

taken and when the NSAID is withdrawn.

Methotrexate:

Two studies investigated the effects of etoricoxib 60, 90 or 120 mg administered once

daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for

rheumatoid arthritis. Etoricoxib at 60 and 90 mg had no effect on methotrexate plasma concentrations

or renal clearance. In one study, etoricoxib 120 mg had no effect, but in the other study, etoricoxib

120 mg increased methotrexate plasma concentrations by 28% and reduced renal clearance of

methotrexate by 13%. Adequate monitoring for methotrexate-related toxicity is recommended when

etoricoxib and methotrexate are administered concomitantly.

Oral contraceptives:

Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35

micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady

state AUC0-24hr of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive

concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%.

This increase in EE concentration should be considered when selecting an oral contraceptive for use

with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated

with oral contraceptives (e.g., venous thrombo-embolic events in women at risk).

Hormone Replacement Therapy (HRT):

Administration of etoricoxib 120 mg with hormone

replacement therapy consisting of conjugated estrogens (0.625 mg PREMARINTM) for 28 days,

increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-

estradiol (22%). The effect of the recommended chronic doses of etoricoxib (30, 60, and 90 mg) has

not been studied. The effects of etoricoxib 120 mg on the exposure (AUC0-24hr) to these estrogenic

components of PREMARIN were less than half of those observed when PREMARIN was

administered alone and the dose was increased from 0.625 to 1.25 mg. The clinical significance of

these increases is unknown, and higher doses of PREMARIN were not studied in combination with

etoricoxib. These increases in estrogenic concentration should be taken into consideration when

selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen

exposure might increase the risk of adverse events associated with HRT.

Prednisone/prednisolone:

In drug-interaction studies, etoricoxib did not have clinically important

effects on the pharmacokinetics of prednisone/prednisolone.

Digoxin:

Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not alter

the steady-state plasma AUC0-24hr or renal elimination of digoxin. There was an increase in digoxin

(approximately 33%). This increase is not generally important for most patients. However,

patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are

administered concomitantly.

Effect of etoricoxib on drugs metabolised by sulfotransferases

Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been

shown to increase the serum concentrations of ethinyl estradiol. While knowledge about effects of

multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still

being examined, it may be prudent to exercise care when administering etoricoxib concurrently with

other drugs primarily metabolised by human sulfotransferases (e.g., oral salbutamol and minoxidil).

Effect of etoricoxib on drugs metabolised by CYP isoenzymes

Based on

in vitro

studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9,

2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of etoricoxib 120 mg did

not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.

Effects of other drugs on the pharmacokinetics of etoricoxib

The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to

contribute to the metabolism of etoricoxib

in vivo

In vitro

studies indicate that CYP2D6, CYP2C9,

CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles

have not been studied

in vivo

Ketoconazole:

Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days

to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics

of 60 mg etoricoxib (43% increase in AUC).

Voriconazole and Miconazole

: Co-administration of either oral voriconazole or topical miconazole

oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to etoricoxib,

but is not considered to be clinically meaningful based on published data.

Rifampicin:

Co-administration of etoricoxib with rifampicin, a potent inducer of CYP enzymes,

produced a 65% decrease in etoricoxib plasma concentrations. This interaction may result in

recurrence of symptoms when etoricoxib is co-administered with rifampicin. While this information

may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have

not been studied in combination with rifampicin and are therefore not recommended (see section 4.2).

Antacids:

Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.

4.6 Fertility, pregnancy and lactation

Pregnancy

No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown

reproductive toxicity (see section 5.3). The potential for human risk in pregnancy is unknown.

Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine

inertia and premature closure of the ductus arteriosus during the last trimester. Etoricoxib is

contraindicated in pregnancy (see section 4.3). If a woman becomes pregnant during treatment,

etoricoxib must be discontinued.

Breastfeeding

It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of

lactating rats. Women who use etoricoxib must not breast feed (see sections 4.3 and 5.3).

Fertility

The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in

women attempting to conceive.

4.7 Effects on ability to drive and use machines

Patients who experience dizziness, vertigo or somnolence while taking etoricoxib should refrain from

driving or operating machinery.

4.8

Undesirable effects

Summary of the safety profile

In clinical trials, etoricoxib was evaluated for safety in 9,295 individuals, including 6,757 patients

with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients with OA

or RA were treated for one year or longer).

In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with

etoricoxib for one year or longer.

In a clinical study for acute gouty arthritis, patients were treated with etoricoxib 120 mg once daily for

eight days. The adverse experience profile in this study was generally similar to that reported in the

combined OA, RA, and chronic low back pain studies.

In a cardiovascular safety outcomes programme of pooled data from three active comparator

controlled trials, 17, 412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for a

mean duration of approximately 18 months. The safety data and details from this programme are

presented in section 5.1.

In clinical studies for acute postoperative dental pain following surgery including 614 patients treated

with etoricoxib (90 mg or 120 mg), the adverse experience profile in these studies was generally

similar to that reported in the combined OA, RA, and chronic low back pain studies.

Tabulated list of adverse reactions

The following undesirable effects were reported at an incidence greater than placebo in clinical trials

in patients with OA, RA, chronic low back pain or ankylosing spondylitis treated with etoricoxib 30

mg, 60 mg or 90 mg up to the recommended dose for up to 12 weeks; in the MEDAL Programme

studies for up to 3½ years; in short term acute pain studies for up to 7 days; or in post-marketing

experience (see Table 1):

Table 1:

System Organ Class

Adverse Reactions

Frequency Category*

Infections and infestations

alveolar osteitis

Common

gastroenteritis, upper respiratory infection,

urinary tract infection

Uncommon

Blood and lymphatic system

disorders

anaemia (primarily associated with

gastrointestinal bleeding), leukopenia,

thrombocytopenia

Uncommon

Immune system disorders

hypersensitivity

‡ ß

Uncommon

angioedema/anaphylactic /anaphylactoid

reactions including shock

Rare

Metabolism and nutrition

disorders

oedema/fluid retention

Common

appetite increase or decrease, weight gain

Uncommon

Psychiatric disorders

anxiety, depression, mental acuity decreased,

hallucinations

Uncommon

confusion

,

restlessness

Rare

Nervous system disorders

dizziness, headache

Common

dysgeusia, insomnia, paresthaesia/hypaesthesia,

somnolence

Uncommon

Eye disorders

blurred vision, conjunctivitis

Uncommon

Ear and labyrinth disorders

tinnitus, vertigo

Uncommon

Cardiac disorders

palpitations, arrhythmia

Common

atrial fibrillation, tachycardia

,

congestive

heart failure, non-specific ECG changes, angina

pectoris

, myocardial infarction

Uncommon

Vascular disorders

Hypertension

Common

flushing, cerebrovascular accident

, transient

ischaemic attack, hypertensive crisis

,

vasculitis

Uncommon

Respiratory, thoracic and

mediastinal

disorders

bronchospasm

Common

cough, dyspnoea, epistaxis

Uncommon

Gastrointestinal disorders

abdominal pain

Very common

Constipation, flatulence, gastritis, heartburn/acid

reflux, diarrhea, dyspepsia/epigastric discomfort,

nausea, vomiting, oesophagitis, oral ulcer

Common

abdominal distention, bowel movement pattern

change, dry mouth, gastroduodenal

ulcer, peptic ulcers including gastrointestinal

perforation and bleeding, irritable bowel

syndrome, pancreatitis

Uncommon

Hepatobiliary disorders

ALT increased, AST increased

Common

hepatitis

Rare

hepatic failure

, jaundice

Rare

Skin and subcutaneous

tissue disorders

ecchymosis

Common

facial oedema, pruritus, rash, erythema

urticaria

Uncommon

Stevens-Johnson syndrome

, toxic epidermal

necrolysis

, fixed drug eruption

Rare

Musculoskeletal and

connective tissue disorders

muscular cramp/spasm, musculoskeletal

pain/stiffness

Uncommon

Renal and urinary disorders

proteinuria, serum creatinine increased, renal

failure/renal insufficiency

(see section 4.4)

Uncommon

General disorders and

administration site

conditions

asthenia/fatigue, flu-like disease

Common

chest pain

Uncommon

Investigations

blood urea nitrogen increased, creatine

phosphokinase increased, hyperkalaemia, uric

acid increased

Uncommon

blood sodium decreased

Rare

Frequency Category: Defined for each Adverse Experience Term by the incidence reported in the clinical

trials data base: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100),

Rare (≥1/10,000 to <1/1000), Very Rare (<1/10,000).

This adverse reaction was identified through post-marketing surveillance. Its reported frequency has

been estimated based upon the highest frequency observed across clinical trial data pooled by indication

and approved dose.

The frequency category of “Rare” was defined per the Summary of Product Characteristics (SmPC)

guidance (rev.2, Sept 2009) on the basis of an estimated upper bound of the 95% confidence interval for 0

events given the number of subjects treated with etoricoxib in the analysis of the Phase III data pooled by

dose and indication (n=15,470).

Hypersensitivity includes the terms "allergy", "drug allergy", "drug hypersensitivity", "hypersensitivity",

"hypersensitivity NOS", "hypersensitivity reaction" and nonspecific allergy".

Based on analyses of long-term placebo and active controlled clinical trials, selective COX-2 inhibitors

have been associated with an increased risk of serious thrombotic arterial events, including myocardial

infarction and stroke. The absolute risk increase for such events is unlikely to exceed 1% per year based

on existing data (uncommon).

The following serious undesirable effects have been reported in association with the use of NSAIDs

and cannot be ruled out for etoricoxib: nephrotoxicity including interstitial nephritis and nephrotic

syndrome.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare

professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard

4.9 Overdose

In clinical studies, administration of single doses of etoricoxib up to 500 mg and multiple doses up to

150 mg/day for 21 days did not result in significant toxicity. There have been reports of acute

overdosage with etoricoxib, although adverse experiences were not reported in the majority of cases.

The most frequently observed adverse experiences were consistent with the safety profile for

etoricoxib (e.g. gastrointestinal events, cardiorenal events).

In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove

unabsorbed material from the GI tract, employ clinical monitoring, and institute supportive therapy, if

required.

Etoricoxib is not dialysable by haemodialysis; it is not known whether etoricoxib is dialysable by

peritoneal dialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids, coxibs,

ATC code: M01AH05

Mechanism of Action

Etoricoxib is an oral, selective cyclo-oxygenase-2 (COX-2) inhibitor within the clinical dose range.

Across clinical pharmacology studies, Etoricoxib produced dose-dependent inhibition of COX-2

without inhibition of COX-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric

prostaglandin synthesis and had no effect on platelet function.

Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2,

have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by pro-

inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of

prostanoid mediators of pain, inflammation, and fever.COX-2 is also involved in ovulation,

implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous

system functions (fever induction, pain perception and cognitive function). It may also play a role in

ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its relevance to

ulcer healing has not been established.

Clinical efficacy and safety

Efficacy

In patients with osteoarthritis (OA), etoricoxib 60 mg once daily provided significant improvements

in pain and patient assessments of disease status. These beneficial effects were observed as early as

the second day of therapy and maintained for up to 52 weeks. Studies with etoricoxib 30 mg once

daily demonstrated efficacy superior to placebo over a 12 week treatment period (using similar

assessments as the above studies). In a dose ranging study, etoricoxib 60 mg demonstrated

significantly greater improvement than 30 mg for all 3 primary endpoints over 6 weeks of treatment.

The 30 mg dose has not been studied in osteoarthritis of hands.

In patients with rheumatoid arthritis (RA), etoricoxib 60 mg and 90 mg once daily both provided

significant improvements in pain, inflammation, and mobility. In studies evaluating the 60 mg and 90

mg dose, these beneficial effects were maintained over the 12-week treatment periods. In a study

evaluating the 60 mg dose compared to the 90 mg dose, etoricoxib 60 mg once daily and 90 mg once

daily were both more effective than placebo. The 90 mg dose was superior to the 60 mg dose for

Patient Global Assessment of Pain (0-100mm visual analogue scale), with an average improvement of

-2.71 mm (95% CI: -4.98 mm, -0.45 mm).

In patients experiencing attacks of acute gouty arthritis, etoricoxib 120 mg once daily over an eight-

day treatment period, relieved moderate to extreme joint pain and inflammation comparable to

indomethacin 50 mg three times daily. Pain relief was observed as early as four hours after initiation

of treatment.

In patients with ankylosing spondylitis, etoricoxib tablets 90 mg once daily provided significant

improvements in spine pain, inflammation, stiffness and function. The clinical benefit of etoricoxib

was observed as early as the second day of therapy after initiation of treatment and was maintained

throughout the 52-week treatment period. In a second study evaluating the 60 mg dose compared to

the 90 mg dose, etoricoxib 60 mg daily and 90 mg daily demonstrated similar efficacy compared to

naproxen 1,000 mg daily. Among inadequate responders to 60 mg daily for 6 weeks, dose escalation

to 90 mg daily improved spinal pain intensity score (0-100 mm visual analogue scale) compared to

continuing on 60 mg daily, with an average improvement of -2.70 mm (95% CI: -4.88 mm, -0.52

mm).

In a clinical study evaluating postoperative dental pain, etoricoxib 90 mg was administered once daily

for up to three days. In the subgroup of patients with moderate pain at baseline, etoricoxib 90 mg

demonstrated a similar analgesic effect to that of ibuprofen 600 mg (16.11 vs. 16.39; P=0.722), and

greater than that of paracetamol/codeine 600 mg/60 mg (11.00; P<0.001) and placebo (6.84; P<0.001)

as measured by total pain relief over the first 6 hours (TOPAR6). The proportion of patients reporting

rescue medication usage within the first 24 hours of dosing was 40.8% for etoricoxib 90 mg, 25.5%

for ibuprofen 600 mg Q6h, and 46.7% for paracetamol/codeine 600 mg/60 mg Q6h compared to

76.2% for placebo. In this study, the median onset of action (perceptible pain relief) of 90 mg

etoricoxib was 28 minutes after dosing.

Safety

Multinational etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Programme

The MEDAL Programme was a prospectively designed Cardiovascular (CV) Safety Outcomes

Programme of pooled data from three randomized, double-blind active comparator controlled trials,

the MEDAL study, EDGE II and EDGE.

The MEDAL Study, was an endpoint driven CV Outcomes study in 17,804 OA and 5,700 RA patients

treated with etoricoxib 60 (OA) or 90 mg (OA and RA) or diclofenac 150 mg daily for a mean period

of 20.3 months (maximum of 42.3 months, median 21.3 months). In this trial, only serious adverse

events and discontinuations due to any adverse events were recorded.

The EDGE and EDGE II studies compared the gastrointestinal tolerability of etoricoxib versus

diclofenac. The EDGE study included 7,111 OA patients treated with a dose of etoricoxib 90 mg daily

(1.5 times the dose recommended for OA) or diclofenac 150 mg daily for a mean period of 9.1

months (maximum 16.6 months, median 11.4 months). The EDGE II study included 4,086 RA

patients treated with etoricoxib 90 mg daily or diclofenac 150 mg daily for a mean period of 19.2

months (maximum 33.1 months, median 24 months).

In the pooled MEDAL Programme, 34,701 patients with OA or RA were treated for a mean duration

of 17.9 months (maximum 42.3 months, median 16.3 months) with approximately 12,800 patients

receiving treatment for more than 24 months. Patients enrolled in the Programme had a wide range of

cardiovascular and gastrointestinal risk factors at baseline. Patients with a recent history of

myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention within 6

months preceding enrollment were excluded. Use of gastroprotective agents and low dose aspirin

were permitted in the studies.

Overall Safety:

There was no significant difference between etoricoxib and diclofenac in the rate of cardiovascular

thrombotic events. Cardiorenal adverse events were observed more frequently with etoricoxib than

with diclofenac, and this effect was dose-dependent (see specific results below). Gastrointestinal and

hepatic adverse events were observed significantly more frequently with diclofenac than etoricoxib.

The incidence of adverse experiences in EDGE and EDGE II and of adverse experiences considered

serious or resulting in discontinuation in the MEDAL study was higher with etoricoxib than

diclofenac.

Cardiovascular safety results

The rate of confirmed thrombotic cardiovascular serious adverse events (consisting of cardiac,

cerebrovascular, and peripheral vascular events) was comparable between etoricoxib and diclofenac,

and data are summarized in the table below. There were no statistically significant differences in

thrombotic event rates between etoricoxib and diclofenac across all subgroups analyzed including

patient categories across a range of baseline cardiovascular risk. When considered separately, the

relative risks for confirmed thrombotic cardiovascular serious adverse events with etoricoxib 60 mg or

90 mg compared with diclofenac 150 mg were similar.

Table 2: Rates of Confirmed Thrombotic CV Events (Pooled MEDAL Programme)

Etoricoxib

(N=16,819)

25,836 Patient-Years

Diclofenac

(N=16,483)

24,766 Patient-Years

Between Treatment

Comparison

Rate

(95% CI)

Rate

(95% CI)

Relative Risk (95%

CI)

Confirmed Thrombotic Cardiovascular Serious Adverse Events

Per-protocol

1.24 (1.11, 1.38)

1.30 (1.17, 1.45)

0.95 (0.81, 1.11)

Intent-to-treat

1.25 (1.14, 1.36)

1.19 (1.08, 1.30)

1.05 (0.93, 1.19)

Confirmed Cardiac Events

Per-protocol

0.71 (0.61, 0.82)

0.78 (0.68, 0.90)

0.90 (0.74, 1.10)

Intent-to-treat

0.69 (0.61, 0.78)

0.70 (0.62, 0.79)

0.99 (0.84, 1.17)

Confirmed Cerebrovascular Events

Per-protocol

0.34 (0.28, 0.42)

0.32 (0.25, 0.40)

1.08 (0.80, 1.46)

Intent-to-treat

0.33 (0.28, 0.39)

0.29 (0.24, 0.35)

1.12 (0.87, 1.44)

Confirmed Peripheral Vascular Events

Per-protocol

0.20 (0.15, 0.27)

0.22 (0.17, 0.29)

0.92 (0.63, 1.35)

Intent-to-treat

0.24 (0.20, 0.30)

0.23 (0.18, 0.28)

1.08 (0.81, 1.44)

Events per 100 Patient-Years; CI=confidence interval

N=total number of patients included in Per-protocol population

Per-protocol: all events on study therapy or within 14 days of discontinuation (excluded: patients who

took < 75% of their study medication or took non-study NSAIDs >10% of the time).

Intent-to-treat: all confirmed events up to the end of the trial (included patients potentially exposed to

non-study interventions following discontinuation of study medication). Total number of patients

randomised, n= 17,412 on etoricoxib and 17,289 on diclofenac.

CV mortality, as well as overall mortality, was similar between the etoricoxib and diclofenac

treatment groups.

Cardiorenal Events:

Approximately 50% of patients enrolled in the MEDAL study had a history of hypertension at

baseline. In the study, the incidence of discontinuations due to hypertension-related adverse events

was statistically significantly higher for etoricoxib than for diclofenac. The incidence of congestive

heart failure adverse events (discontinuations and serious events) occurred at similar rates on

etoricoxib 60 mg compared to diclofenac 150 mg but was higher for etoricoxib 90 mg compared to

diclofenac 150 mg (statistically significant for 90 mg etoricoxib vs. 150 mg diclofenac in MEDAL

OA cohort). The incidence of confirmed congestive heart failure adverse events (events that were

serious and resulted in hospitalisation or a visit to an emergency department) was non-significantly

higher with etoricoxib than diclofenac 150 mg, and this effect was dose-dependent. The incidence of

discontinuations due to oedema-related adverse events was higher for etoricoxib than diclofenac 150

mg, and this effect was dose-dependent (statistically significant for etoricoxib 90 mg, but not for

etoricoxib 60 mg).

The cardiorenal results for EDGE and EDGE II were consistent with those described for the MEDAL

Study.

In the individual MEDAL Programme studies, for etoricoxib (60 mg or 90 mg), the absolute incidence

of discontinuation in any treatment group was up to 2.6% for hypertension, up to 1.9% for oedema,

and up to 1.1% for congestive heart failure, with higher rates of discontinuation observed with

etoricoxib 90 mg than etoricoxib 60 mg.

MEDAL Programme Gastrointestinal Tolerability Results:

A significantly lower rate of discontinuations of treatment for any clinical (e.g., dyspepsia, abdominal

pain, ulcer) GI adverse event was observed with etoricoxib compared with diclofenac within each of

the three component studies of the MEDAL Programme. The rates of discontinuations due to adverse

clinical GI events per hundred patient-years over the entire period of study were as follows: 3.23 for

etoricoxib and 4.96 for diclofenac in the MEDAL Study; 9.12 with etoricoxib and 12.28 with

diclofenac in the EDGE study; and 3.71 with etoricoxib and 4.81 with diclofenac in the EDGE II

study.

MEDAL Programme Gastrointestinal Safety Results:

Overall upper GI events were defined as perforations, ulcers and bleeds. The subset of overall upper

GI events considered complicated included perforations, obstructions, and complicated bleeding; the

subset of upper GI events considered uncomplicated included uncomplicated bleeds and

uncomplicated ulcers. A significantly lower rate of overall upper GI events was observed with

etoricoxib compared to diclofenac. There was no significant difference between etoricoxib and

diclofenac in the rate of complicated events. For the subset of upper GI haemorrhage events

(complicated and uncomplicated combined), there was no significant difference between etoricoxib

and diclofenac. The upper GI benefit for etoricoxib compared with diclofenac was not statistically

significant in patients taking concomitant low-dose aspirin (approximately 33% of patients).

The rates per hundred patient-years of confirmed complicated and uncomplicated upper GI clinical

events (perforations, ulcers and bleeds (PUBs)) were 0.67 (95% CI 0.57, 0.77) with etoricoxib and

0.97 (95% CI 0.85, 1.10) with diclofenac, yielding a relative risk of 0.69 (95% CI 0.57, 0.83).

The rate for confirmed upper GI events in elderly patients was evaluated and the largest reduction was

observed in patients ≥ 75 years of age (1.35 [95% CI 0.94, 1.87] vs. 2.78 [95% CI 2.14, 3.56] events

per hundred patient-years for etoricoxib and diclofenac, respectively.

The rates of confirmed lower GI clinical events (small or large bowel perforation, obstruction, or

haemorrhage, (POBs)) were not significantly different between etoricoxib and diclofenac.

MEDAL Programme Hepatic Safety Results:

Etoricoxib was associated with a statistically significantly lower rate of discontinuations due to

hepatic-related adverse experiences than diclofenac. In the pooled MEDAL Programme, 0.3% of

patients on etoricoxib and 2.7% of patients on diclofenac discontinued due to hepatic-related adverse

experiences. The rate per hundred patient-years was 0.22 on etoricoxib and 1.84 for diclofenac (p-

value was <0.001 for etoricoxib vs. diclofenac). However, most hepatic adverse experiences in the

MEDAL Programme were non-serious.

Additional Thrombotic Cardiovascular Safety Data

In clinical studies excluding the MEDAL Programme Studies, approximately 3,100 patients were

treated with etoricoxib ≥60 mg daily for 12 weeks or longer. There was no discernible difference in

the rate of confirmed serious thrombotic cardiovascular events between patients receiving etoricoxib

≥60 mg, placebo, or non-naproxen NSAIDs. However, the rate of these events was higher in patients

receiving etoricoxib compared with those receiving naproxen 500 mg twice daily. The difference in

antiplatelet activity between some COX-1 inhibiting NSAIDs and selective COX-2 inhibitors may be

of clinical significance in patients at risk of thrombo-embolic events. Selective COX-2 inhibitors

reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting

platelet thromboxane. The clinical relevance of these observations has not been established.

Additional Gastrointestinal Safety Data

In two 12-week double-blind endoscopy studies, the cumulative incidence of gastroduodenal

ulceration was significantly lower in patients treated with etoricoxib 120 mg once daily than in

patients treated with either naproxen 500 mg twice daily or ibuprofen 800 mg three times daily.

Etoricoxib had a higher incidence of ulceration as compared to placebo.

Renal Function Study in the Elderly

A randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of 15 days

of treatment of etoricoxib (90 mg), celecoxib (200 mg bid), naproxen (500 mg bid) and placebo on

urinary sodium excretion, blood pressure, and other renal function parameters in subjects 60 to 85

years of age on a 200-mEq/day sodium diet. etoricoxib, celecoxib, and naproxen had similar effects

on urinary sodium excretion over the 2 weeks of treatment. All active comparators showed an

increase relative to placebo with respect to systolic blood pressures; however, etoricoxib was

associated with a statistically significant increase at Day 14 when compared to celecoxib and

naproxen (mean change from baseline for systolic blood pressure: etoricoxib 7.7 mmHg, celecoxib

2.4 mmHg, naproxen 3.6 mmHg).

5.2 Pharmacokinetic properties

Absorption

Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 100%.

Following 120 mg once-daily dosing to steady state, the peak plasma concentration (geometric mean

Cmax = 3.6 μg/ml) was observed at approximately 1 hour (Tmax) after administration to fasted

adults. The geometric mean area under the curve (AUC0-24hr) was 37.8 μghr/ml. The

pharmacokinetics of etoricoxib are linear across the clinical dose range.

Dosing with food (a high-fat meal) had no effect on the extent of absorption of etoricoxib after

administration of a 120-mg dose. The rate of absorption was affected, resulting in a 36% decrease in

Cmax and an increase in Tmax by 2 hours. These data are not considered clinically significant. In

clinical trials, etoricoxib was administered without regard to food intake.

Distribution

Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of

0.05 to 5 μg/ml. The volume of distribution at steady state (Vdss) was approximately 1,20l in humans.

Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.

Biotransformation

Etoricoxib is extensively metabolised with <1% of a dose recovered in urine as the parent drug. The

major route of metabolism to form the 6'-hydroxymethyl derivative is catalyzed by CYP enzymes.

CYP3A4 appears to contribute to the metabolism of etoricoxib

in vivo

In vitro

studies indicate that

CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their

quantitative roles

in vivo

have not been studied.

Five metabolites have been identified in man. The principal metabolite is the 6'-carboxylic acid

derivative of etoricoxib formed by further oxidation of the 6'-hydroxymethyl derivative. These

principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2

inhibitors. None of these metabolites inhibit COX-1.

Elimination

Following administration of a single 25-mg radiolabeled intravenous dose of etoricoxib to healthy

subjects, 70% of radioactivity was recovered in urine and 20% in faeces, mostly as metabolites. Less

than 2% was recovered as unchanged drug.

Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion.

Steady state concentrations etoricoxib are reached within seven days of once daily administration of

120 mg, with an accumulation ratio of approximately 2, corresponding to a half-life of approximately

22 hours. The plasma clearance after a 25-mg intravenous dose is estimated to be approximately 50

ml/min.

Characteristics in patients

Elderly patients:

Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the

young.

Gender:

The pharmacokinetics of etoricoxib are similar between men and women.

Hepatic impairment:

Patients with mild hepatic dysfunction (Child-Pugh score 5-6) administered

etoricoxib 60 mg once daily had an approximately 16% higher mean AUC as compared to healthy

subjects given the same regimen. Patients with moderate hepatic dysfunction (Child-Pugh score 7-9)

administered etoricoxib 60 mg

every other day

had similar mean AUC to the healthy subjects given

etoricoxib 60 mg once daily; etoricoxib 30 mg once daily has not been studied in this population.

There are no clinical or pharmacokinetic data in patients with severe hepatic dysfunction (Child-Pugh

score ≥10). (See sections 4.2 and 4.3.)

Renal impairment:

The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with

moderate to severe renal insufficiency and patients with end-stage renal disease on haemodialysis

were not significantly different from those in healthy subjects. Haemodialysis contributed negligibly

to elimination (dialysis clearance approximately 50 ml/min). (See sections 4.3 and 4.4.)

Paediatric patients:

The pharmacokinetics of etoricoxib in paediatric patients (<12 years old) have

not been studied.

In a pharmacokinetic study (n=16) conducted in adolescents (aged 12 to 17) the pharmacokinetics in

adolescents weighing 40 to 60 kg given etoricoxib 60 mg once daily and adolescents >60 kg given

etoricoxib 90 mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90 mg

once daily. Safety and effectiveness of etoricoxib in paediatric patients have not been established (see

section 4.2).

5.3 Preclinical safety data

In preclinical studies, etoricoxib has been demonstrated not to be genotoxic. etoricoxib was not

carcinogenic in mice. Rats developed hepatocellular and thyroid follicular cell adenomas at >2-times

the daily human dose [90 mg] based on systemic exposure when dosed daily for approximately two

years. Hepatocellular and thyroid follicular cell adenomas observed in rats are considered to be a

consequence of rat-specific mechanism related to hepatic CYP enzyme induction. etoricoxib has not

been shown to cause hepatic CYP3A enzyme induction in humans.

In the rat, gastrointestinal toxicity of etoricoxib increased with dose and exposure time. In the 14-

week toxicity study etoricoxib caused gastrointestinal ulcers at exposures greater than those seen in

man at the therapeutic dose. In the 53- and 106-week toxicity study, gastrointestinal ulcers were also

seen at exposures comparable to those seen in man at the therapeutic dose. In dogs, renal and

gastrointestinal abnormalities were seen at high exposures.

Etoricoxib was not teratogenic in reproductive toxicity studies conducted in rats at 15 mg/kg/day (this

represents approximately 1.5 times the daily human dose [90 mg] based on systemic exposure). In

rabbits, a treatment related increase in cardiovascular malformations was observed at exposure levels

below the clinical exposure at the daily human dose (90 mg). However no treatment-related external

or skeletal foetal malformations were observed. In rats and rabbits, there was a dose dependent

increase in post implantation loss at exposures greater than or equal to 1.5 times the human exposure

(see sections 4.3 and 4.6).

Etoricoxib is excreted in the milk of lactating rats at concentrations approximately two-fold those in

plasma. There was a decrease in pup body weight following exposure of pups to milk from dams

administered etoricoxib during lactation.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Core:

Microcrystalline cellulose

Calcium hydrogen phosphate anhydrous

Croscarmellose sodium

Lactose monohydrate

Hydroxypropyl cellulose

Magnesium stearate

Tablet coating:

Hypromellose

Lactose monohydrate

Titanium dioxide (E171)

Triacetin

indigo carmine aluminium lake (E132)

Iron oxide yellow (E172).

6.2 Incompatibilities

Not applicable

6.3 Shelf life

36 months

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

6.5 Nature and contents of container

Etoricoxib Brown are available in OPA/Alu/PVC – Alu blister.

Pack sizes:

30 mg, 60 mg, 90 mg and 120 mg:

Pack sizes of 2, 5, 7, 10, 14, 20, 28, 30, 49, 50, 84, 98, 100 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

7. MARKETING AUTHORISATION HOLDER

<To be completed nationally>

8. MARKETING AUTHORISATION NUMBER(S)

To be completed nationally

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: {DD month YYYY}

10. DATE OF REVISION OF THE TEXT

2020-03-04

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