Fenofibrate 160mg Tablets - (emc) - eMC

Adults: The recommended dose is one tablet containing 160 mg fenofibrate taken once daily. Patients currently taking one fenofibrate 200mg capsule can be ... Skiptomaincontent Fenofibrate160mgTablets Backtotop GenusPharmaceuticalscontactdetails Activeingredient fenofibrate LegalCategory POM:Prescriptiononlymedicine ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:07Oct2020 Viewchanges Print Showtableofcontents Hidetableofcontents 1.Nameofthemedicinalproduct2.Qualitativeandquantitativecomposition3.Pharmaceuticalform4.Clinicalparticulars4.1Therapeuticindications4.2Posologyandmethodofadministration4.3Contraindications4.4Specialwarningsandprecautionsforuse4.5Interactionwithothermedicinalproductsandotherformsofinteraction4.6Fertility,pregnancyandlactation4.7Effectsonabilitytodriveandusemachines4.8Undesirableeffects4.9Overdose5.Pharmacologicalproperties5.1Pharmacodynamicproperties5.2Pharmacokineticproperties5.3Preclinicalsafetydata6.Pharmaceuticalparticulars6.1Listofexcipients6.2Incompatibilities6.3Shelflife6.4Specialprecautionsforstorage6.5Natureandcontentsofcontainer6.6Specialprecautionsfordisposalandotherhandling7.Marketingauthorisationholder8.Marketingauthorisationnumber(s)9.Dateoffirstauthorisation/renewaloftheauthorisation10.Dateofrevisionofthetext Thisinformationisintendedforusebyhealthprofessionals 1.Nameofthemedicinalproduct Fenofibrate160mgTablets. 2.Qualitativeandquantitativecomposition Fenofibrate160mg Excipientswithknowneffect EachFenofibrate160mgtabletcontainslactosemonohydrate238.45mg Forthefulllistofexcipients,seesection6.1. 3.Pharmaceuticalform Tablet. Whitetooff-whiteoblong15mmx7mmtablet. 4.Clinicalparticulars 4.1Therapeuticindications Fenofibrate160mgTabletsareindicatedasanadjuncttodietandothernon-pharmacologicaltreatment(e.g.exercise,weightreduction)forthefollowing: -TreatmentofseverehypertriglyceridaemiawithorwithoutlowHDLcholesterol. -Mixedhyperlipidaemiawhenastatiniscontraindicatedornottolerated. -MixedhyperlipidaemiainpatientsathighcardiovascularriskinadditiontoastatinwhentriglyceridesandHDLcholesterolarenotadequatelycontrolled. 4.2Posologyandmethodofadministration Posology: Adults:Therecommendeddoseisonetabletcontaining160mgfenofibratetakenoncedaily.Patientscurrentlytakingonefenofibrate200mgcapsulecanbechangedtoonefenofibrate160mgtabletwithoutfurtherdoseadjustment. Elderlypatients(≥65yearsold):Nodoseadjustmentisnecessary.Theusualdoseisrecommended,exceptfordecreasedrenalfunctionwithestimatedglomerularfiltrationrate<60mL/min/1.73m2(see Patientswithrenalimpairment). Patientswithrenalimpairment:Fenofibrateshouldnotbeusedifsevererenalimpairment,definedaseGFR<30mL/minper1.73m2,ispresent. IfeGFRisbetween30and59mL/minper1.73m2,thedoseofFenofibrateshouldnotexceed100mgstandardor67mgmicronizedoncedaily. If,duringfollow-up,theeGFRdecreasespersistentlyto<30mL/minper1.73m2,Fenofibrateshouldbediscontinued. Paediatricpopulation:Thesafetyandefficacyoffenofibrateinchildrenandadolescentsyoungerthan18yearshasnotbeenestablished.Nodataareavailable.Thereforetheuseoffenofibrateisnotrecommendedinpaediatricsubjectsunder18years. Hepaticdisease:Patientswithhepaticdiseasehavenotbeenstudied. Dietarymeasuresinitiatedbeforetherapyshouldbecontinued. Ifafterseveralmonthsoffenofibrateadministration(e.g.3months)serumlipidlevelshavenotbeenreducedsatisfactorily,complementaryordifferenttherapeuticmeasuresshouldbeconsidered. Methodofadministration:Tabletsshouldbeswallowedwholeduringameal. 4.3Contraindications -hepaticinsufficiency(includingbiliarycirrhosis), -severerenalinsufficiency(estimatedglomerularfiltrationrate<30mL/min/1.73m2), -children, -hypersensitivitytofenofibrateoranycomponentofthismedication, -knownphotoallergyorphototoxicreactionduringtreatmentwithfibratesorketoprofen, -gallbladderdisease. Chronicoracutepancreatitiswiththeexceptionofacutepancreatitisduetoseverehypertriglyceridemia Useduringpregnancyandlactation:seesection4.6. 4.4Specialwarningsandprecautionsforuse Liverfunction: Aswithotherlipidloweringagents,increaseshavebeenreportedintransaminaselevelsinsomepatients.Inthemajorityofcasestheseelevationsweretransient,minorandasymptomatic.Itisrecommendedthattransaminaselevelsbemonitoredevery3monthsduringthefirst12monthsoftreatment.AttentionshouldbepaidtopatientswhodevelopincreaseintransaminaselevelsandtherapyshouldbediscontinuedifASATandALATlevelsincreasetomorethan3timestheupperlimitofthenormalrangeor100IU. Pancreatitis: Pancreatitishasbeenreportedinpatientstakingfenofibrate(seesections4.3and4.8)Thisoccurrencemayrepresentafailureofefficacyinpatientswithseverehypertriglyceridemia,adirectdrugeffect,orasecondaryphenomenonmediatedthroughbilarytractstoneorsludgeformation,resultingintheobstructionofthecommonbileduct. Muscle: Muscletoxicity,includingveryrarecasesofrhabdomyolysis,hasbeenreportedwithadministrationoffibratesandotherlipid-loweringagents.Theincidenceofthisdisorderincreasesincasesofhypoalbuminaemiaandpreviousrenalinsufficiency.Muscletoxicityshouldbesuspectedinpatientspresentingdiffusemyalgia,myositis,muscularcrampsandweaknessand/ormarkedincreasesinCPK(levelsexceeding5timesthenormalrange).Insuchcasestreatmentwithfenofibrateshouldbestopped. Patientswithpre-disposingfactorsformyopathyand/orrhabdomyolysis,includingageabove70yearsold,personalorfamilialhistoryofhereditarymusculardisorders,renalimpairment,hypothyroidismandhighalcoholintake,maybeatanincreasedriskofdevelopingrhabdomyolysis.Forthesepatients,theputativebenefitsandrisksoffenofibratetherapyshouldbecarefullyweighedup. TheriskofmuscletoxicitymaybeincreasedifthedrugisadministeredwithanotherfibrateoranHMG-CoAreductaseinhibitor,especiallyincasesofpre-existingmusculardisease.Consequently,theco-prescriptionoffenofibratewithastatinshouldbereservedtopatientswithseverecombineddyslipidaemiaandhighcardiovascularriskwithoutanyhistoryofmusculardisease. Thiscombinationtherapyshouldbeusedwithcautionandpatientsshouldbemonitoredcloselyforsignsofmuscletoxicity. Renalfunction: Fenofibrateiscontraindicatedinsevererenalimpairment(seesection4.3). Fenofibrateshouldbeusedwithcautioninpatientswithmildtomoderaterenalinsufficiency.Doseshouldbeadjustedinpatientswhoseestimatedglomerularfiltrationrateis30to59mL/min/1.73m2(seesection4.2). ReversibleelevationsinserumcreatininehavebeenreportedinpatientsreceivingFenofibratemonotherapyorco-administeredwithstatins.Elevationsinserumcreatinineweregenerallystableovertimewithnoevidenceforcontinuedincreasesinserumcreatininewithlongtherapyandtendedtoreturntobaselinefollowingdiscontinuationoftreatment. Duringclinicaltrials,10%ofpatientshadacreatinineincreasefrombaselinegreaterthan30µmol/Lwithco-administeredFenofibrateandsimvastatinversus4.4%withstatinmonotherapy.0.3%ofpatientsreceivingco-administrationhadclinicallyrelevantincreasesincreatininetovalues>200µmol/L. Treatmentshouldbeinterruptedwhencreatininelevelis50%abovetheupperlimitofnormal. Itisrecommendedthatcreatinineismeasuredduringthefirst3monthsafterinitiationoftreatmentandperiodicallythereafter. Otherwarnings Forhyperlipidaemicpatientstakingoestrogensorcontraceptivescontainingoestrogensitshouldbeascertainedwhetherthehyperlipidaemiaisofprimaryorsecondarynature(possibleelevationoflipidvaluescausedbyoraloestrogen). Asfenofibrate160mgtabletscontainslactose,patientswithrarehereditaryproblemsofgalactoseintolerance,totallactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine. Thismedicinecontainslessthan1mmolsodium(23mg)pertablet,thatistosayessentially'sodium-free'. 4.5Interactionwithothermedicinalproductsandotherformsofinteraction Oralanticoagulants:Fenofibrateenhancesoralanticoagulanteffectandmayincreaseriskofbleeding.ItisrecommendedthatthedoseofanticoagulantsisreducedbyaboutonethirdatthestartoftreatmentandthengraduallyadjustedifnecessaryaccordingtoINR(InternationalNormalisedRatio)monitoring.Therefore,thiscombinationisnotrecommended Ciclosporin:Someseverecasesofreversiblerenalfunctionimpairmenthavebeenreportedduringconcomitantadministrationoffenofibrateandciclosporin.Therenalfunctionofthesepatientsmustthereforebecloselymonitoredandthetreatmentwithfenofibratestoppedinthecaseofseverealterationoflaboratoryparameters. HMG-CoAreductaseinhibitorsandotherfibrates: TheriskofseriousmuscletoxicityIincreasediffenofibrateisusedconcomitantlywithHMG-CoAreductaseinhibitorsorotherfibrates.Suchcombinationtherapyshouldbeusedwithcautionandpatientsmonitoredcloselyforsignsofmuscletoxicity(seesection4.4) CytochromeP450enzymes:Invitrostudiesusinghumanlivermicrosomesindicatethatfenofibrateandfenofibricacidarenotinhibitorsofcytochrome(CYP)P450isoformsCYP3A4,CYP2D6,CYP2E1,orCYP1A2.TheyareweakinhibitorsofCYP2C19andCYP2A6,andmild-to-moderateinhibitorsofCYP2C9attherapeuticconcentrations. Patientsco-administeredfenofibrateandCYP2C19,CYP2A6,andespeciallyCYP2C9metaboliseddrugswithanarrowtherapeuticindexshouldbecarefullymonitoredand,ifnecessary,doseadjustmentofthesedrugsisrecommended. 4.6Fertility,pregnancyandlactation Therearenoadequatedatafromtheuseoffenofibrateinpregnantwomen.Animalstudieshavenotdemonstratedanyteratogeniceffects.Embryotoxiceffectshavebeenshownatdosesintherangeofmaternaltoxicity(seesection5.3).Thepotentialriskforhumansisunknown.Therefore,fenofibrate160mgtabletsshouldonlybeusedafteracarefulbenefit/riskassessment. Therearenodataontheexcretionoffenofibrateand/oritsmetabolitesintobreastmilk.Consequently,fenofibrate160mgtabletsshouldnotbeusedinnursingmothers. 4.7Effectsonabilitytodriveandusemachines Noeffectnoted. 4.8Undesirableeffects Thefrequenciesofadverseeventsarerankedaccordingtopthefollowing:Verycommon(>1/10),Common(>1/100,<1/10),Uncommon(>1/1,000,<1/100),Rare(>1/10,000,<1/1,000),veryrare(<1/10,000includingisolatedreports Gastrointestinal: Common:Digestive,gastricorintestinaldisorders(abdominalpain,nausea,vomiting,diarrhoea,andflatulence)moderateinseverity Uncommon:Pancreatitis* Hepato-biliarydisorders: Common:Moderatelyelevatedlevelsofserumtransaminases(seeSpecialPrecautionsforuse). Uncommon:Developmentofgallstones Veryrare:Episodesofhepatitis.Whensymptoms(e.g.jaundice,pruritus)indicativeofhepatitisoccur,laboratorytestsaretobeconductedforverificationandfenofibratediscontinued,ifapplicable(seeSpecialWarnings). Cardiovascularsystem: Uncommon:Thromboembolism(pulmonaryembolism,deepveinthrombosis*) Skinandsubcutaneoustissuedisorder: Uncommon:rashes,pruritus,urticariaorphotosensitivityreactions. Rare:alopecia Veryrare:cutaneousphotosensitivitywitherythema,vesiculationornodulationonpartsoftheskinexposetosunlightorartificiallight(e.g.sunlamp)inindividualcases(evenaftermanymonthsofuncomplicateduse) Musculoskeletal,connectivetissueandbonedisorders: Rare:diffusemyalgia,myositis,muscularcrampsandweakness Notknown:rhabdomyolysis Bloodandlymphaticsystemdisorders: Rare:decreaseinhaemoglobinandleukocytes Nervoussystemdisorder: Rare:sexualasthenia Respiratory,thoracicandmediastinaldisorders. Notknown:interstitialpneumopathies Investigation Uncommon:increasesinserumcreatinineandurea *IntheFIELDstudy,arandomisedplacebocontrolledtrialperformedin9795patientswithtypeIIdiabetesmellitus,astatisticallysignificantincreaseinpancreatitiscaseswasobservedinpatientsreceivingfenofibrateversespatientsreceivingplacebo.(0.8%versus05%p=0.031.Inthesamestudy,astatisticallysignificantincreasewasreportedintheincidenceofpulmonaryembolism(0.7%intheplacebogroupversus1.1%inthefenofibrategroup;p=0.022)andastatisticallynon-significantincreaseindeepveinthromboses(placebo1.0%[48/4900patients]versusfenofibrate1.4%[67/4895patients];p=0.074) Reportingofsuspectedadversereactions Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinuedmonitoringofthebenefit/riskbalanceofthemedicinalproduct.HealthcareprofessionalsareaskedtoreportanysuspectedadversereactionsviatheYellowCardSchemeat:www.mhra.gov.uk/yellowcard 4.9Overdose Nocaseofoverdosagehasbeenreported.Nospecificantidoteisknown.Ifanoverdoseissuspected,treatsymptomaticallyandinstituteappropriatesupportivemeasuresasrequired.Fenofibratecannotbeeliminatedbyhaemodialysis. 5.Pharmacologicalproperties 5.1Pharmacodynamicproperties SerumLipidReducingAgents/CholesterolandTriglyceridesReducers/Fibrates. ATCcode:C10AB05 FenofibrateisafibricacidderivativewhoselipidmodifyingeffectsreportedinhumansaremediatedviaactivationofPeroxisomeProliferatorActivatedReceptortypealpha(PPARα). ThroughactivationofPPARα,fenofibrateincreasesthelipolysisandeliminationofatherogenictriglyceride-richparticlesfromplasmabyactivatinglipoproteinlipaseandreducingproductionofapoproteinCIII.ActivationofPPARαalsoinducesanincreaseinthesynthesisofapoproteinsAIandAII. Theabovestatedeffectsoffenofibrateonlipoproteinsleadtoareductioninverylow-andlowdensityfractions(VLDLandLDL)containingapoproteinBandanincreaseinthehighdensitylipoproteinfraction(HDL)containingapoproteinAIandAII. Inaddition,throughmodulationofthesynthesisandthecatabolismofVLDLfractionsfenofibrateincreasestheLDLclearanceandreducessmalldenseLDL,thelevelsofwhichareelevatedintheatherogeniclipoproteinphenotype,acommondisorderinpatientsatriskforcoronaryheartdisease. Duringclinicaltrialswithfenofibrate,totalcholesterolwasreducedby20to25%,triglyceridesby40to55%andHDLcholesterolwasincreasedby10to30%. Inhypercholesterolaemicpatients,whereLDLcholesterollevelsarereducedby20to35%,theoveralleffectoncholesterolresultsinadecreaseintheratiosoftotalcholesteroltoHDLcholesterol,LDLcholesteroltoHDLcholesterol,orApoBtoApoAI,allofwhicharemarkersofatherogenicrisk. BecauseofitssignificanteffectonLDLcholesterolandtriglycerides,treatmentwithfenofibrateshouldbebeneficialinhypercholesterolaemicpatientswithorwithouthypertriglyceridaemia,includingsecondaryhyperlipoproteinaemiasuchastype2diabetesmellitus. Atthepresenttime,noresultsoflong-termcontrolledclinicaltrialsareavailabletodemonstratetheefficacyoffenofibrateintheprimaryorsecondarypreventionofatheroscleroticcomplications. Extravasculardepositsofcholesterol(tendinousandtuberousxanthoma)maybemarkedlyreducedorevenentirelyeliminatedduringfenofibratetherapy. Patientswithraisedlevelsoffibrinogentreatedwithfenofibratehaveshownsignificantreductionsinthisparameter,ashavethosewithraisedlevelsofLp(a).OtherinflammatorymarkerssuchasCReactiveProteinarereducedwithfenofibratetreatment. Theuricosuriceffectoffenofibrateleadingtoreductioninuricacidlevelsofapproximately25%shouldbeofadditionalbenefitinthosedyslipidaemicpatientswithhyperuricaemia. Fenofibratehasbeenshowntopossessananti-aggregatoryeffectonplateletsinanimalsandinaclinicalstudy,whichshowedareductioninplateletaggregationinducedbyADP,arachidonicacidandepinephrine. Thereisevidencethattreatmentwithfibratesmayreducecoronaryheartdiseaseeventsbuttheyhavenotbeenshowntodecreaseallcausemortalityintheprimaryorsecondarypreventionofcardiovasculardisease. TheActiontoControlCardiovascularRiskinDiabetes(ACCORD)lipidtrialwasarandomizedplacebo-controlledstudyof5518patientswithtype2diabetesmellitustreatedwithfenofibrateinadditiontosimvastatin.Fenofibrateplussimvastatintherapydidnotshowanysignificantdifferencescomparedtosimvastatinmonotherapyinthecompositeprimaryoutcomeofnon-fatalmyocardialinfarction,non-fatalstroke,andcardiovasculardeath(hazardratio[HR]0.92,95%CI0.79-1.08,p=0.32;absoluteriskreduction:0.74%).Inthepre-specifiedsubgroupofdyslipidaemicpatients,definedasthoseinthelowesttertileofHDL-C(≤34mg/dlor0.88mmol/L)andhighesttertileofTG(≥204mg/dlor2.3mmol/L)atbaseline,fenofibrateplussimvastatintherapydemonstrateda31%relativereductioncomparedtosimvastatinmonotherapyforthecompositeprimaryoutcome(hazardratio[HR]0.69,95%CI0.49-0.97,p=0.03;absoluteriskreduction:4.95%).Anotherprespecifiedsubgroupanalysisidentifiedastatisticallysignificanttreatment-by-genderinteraction(p=0.01)indicatingapossibletreatmentbenefitofcombinationtherapyinmen(p=0.037)butapotentiallyhigherriskfortheprimaryoutcomeinwomentreatedwithcombinationtherapycomparedtosimvastatinmonotherapy(p=0.069).Thiswasnotobservedintheaforementionedsubgroupofpatientswithdyslipidaemiabuttherewasalsonoclearevidenceofbenefitindyslipidaemicwomentreatedwithfenofibrateplussimvastatin,andapossibleharmfuleffectinthissubgroupcouldnotbeexcluded. 5.2Pharmacokineticproperties Fenofibrate160mgisatabletcontaining160mgofmicronisedfenofibrateandissuprabioavailable(largerbioavailability)comparedtothepreviousformulations. Absorption:Maximumplasmaconcentrations(Cmax)occurwithin4to5hoursafteroraladministration.Plasmaconcentrationsarestableduringcontinuoustreatmentinanygivenindividual. Theabsorptionoffenofibrateisincreasedwhenadministeredwithfood. Distribution:Fenofibricacidisstronglyboundtoplasmaalbumin(morethan99%). Plasmahalf-life:Theplasmaeliminationhalf-lifeoffenofibricacidisapproximately20hours. Metabolismandexcretion:Nounchangedfenofibratecanbedetectedintheplasmawheretheprincipalmetaboliteisfenofibricacid.Thedrugisexcretedmainlyintheurine.Practicallyallthedrugiseliminatedwithin6days.Fenofibrateismainlyexcretedintheformoffenofibricacidanditsglucuronideconjugate.Inelderlypatients,thefenofibricacidapparenttotalplasmaclearanceisnotmodified. Kineticstudiesfollowingtheadministrationofasingledoseandcontinuoustreatmenthavedemonstratedthatthedrugdoesnotaccumulate.Fenofibricacidisnoteliminatedbyhaemodialysis. 5.3Preclinicalsafetydata Chronictoxicitystudieshaveyieldednorelevantinformationaboutspecifictoxicityoffenofibrate. Studiesonmutagenicityoffenofibratehavebeennegative. Inratsandmice,livertumourshavebeenfoundathighdosages,whichareattributabletoperoxisomeproliferation.Thesechangesarespecifictosmallrodentsandhavenotbeenobservedinotheranimalspecies.Thisisofnorelevancetotherapeuticuseinman. Studiesinmice,ratsandrabbitsdidnotrevealanyteratogeniceffect.Embryotoxiceffectswereobservedatdosesintherangeofmaternaltoxicity. Prolongationofthegestationperiodanddifficultiesduringdeliverywereobservedathighdoses.Nosignofanyeffectonfertilityhasbeendetected. 6.Pharmaceuticalparticulars 6.1Listofexcipients Sodiumlaurilsulfate,lactosemonohydrate,hypromellose,microcrystallinecellulose,croscarmellosesodiumandmagnesiumstearate. 6.2Incompatibilities Notapplicable 6.3Shelflife 36months 6.4Specialprecautionsforstorage Nospecialprecautionsforstorage. 6.5Natureandcontentsofcontainer Blisterstrips(PVC/PVDC–Aluminium). Boxesof10,20,28,30,50,84,90,98and100tablets. Hospitalpacksizes:280and300tablets. Notallpacksizesmaybemarketed. 6.6Specialprecautionsfordisposalandotherhandling Nospecialrequirements. 7.Marketingauthorisationholder GenusPharmaceuticalsLimited T/AGenusPharmaceuticals Linthwaite, Huddersfield, HD75QH,UK 8.Marketingauthorisationnumber(s) PL06831/0204 9.Dateoffirstauthorisation/renewaloftheauthorisation 13/07/2011 10.Dateofrevisionofthetext 06/10/2020 ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:07Oct2020 Viewchanges Print Companycontactdetails GenusPharmaceuticals Address Linthwaite,Huddersfield,WestYorkshire,HD75QH,UK Fax +44(0)1484847301 MedicalInformatione-mail [email protected] MedicalInformationFax Telephone +44(0)1484842217 MedicalInformationDirectLine +44(0)1484848164 CustomerCaredirectline +44(0)1484848200 OutofHoursTelephone +44(0)1484848164 × Bookmarkthismedicine Tobookmarkamedicineyoumustsignupandlogin. SignUp LogIn Cancel × Emailthismedicine Toemailamedicineyoumustsignupandlogin. 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