Fenofibrate 200 mg capsules - (emc) - eMC

Fenofibrate 200 mg capsule is a formulation containing 200 mg of micronised fenofibrate: the administration of this product results in effective plasma ... Skiptomaincontent Fenofibrate200mgcapsules Backtotop Accord-UKLtdcontactdetails Activeingredient fenofibrate LegalCategory POM:Prescriptiononlymedicine ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:01Jun2021 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 Fenofibrate200mgcapsules 2.Qualitativeandquantitativecomposition Eachcapsulecontains200mgofmicronisedfenofibrate. Excipientwithknowneffect: Eachcapsulecontains101mglactosemonohydrateand0.12mgponceau4R,cochinealredA(E124). Forthefulllistofexcipients,seesection6.1. 3.Pharmaceuticalform Capsule,hard. Orange,hardgelatinecapsule. 4.Clinicalparticulars 4.1Therapeuticindications Fenofibrate200mgcapsulesareindicatedasanadjuncttodietandothernonpharmacologicaltreatment(e.g.exercise,weightreduction)forthefollowing: -TreatmentofseverehypertriglyceridaemiawithorwithoutlowHDLcholesterol. -Mixedhyperlipidaemiawhenastatiniscontraindicatedornottolerated. -MixedhyperlipidaemiainpatientsathighcardiovascularriskinadditiontoastatinwhentriglyceridesandHDLcholesterolarenotadequatelycontrolled. 4.2Posologyandmethodofadministration Dietarymeasuresinitiatedbeforetherapyshouldbecontinued.Responsetotherapyshouldbemonitoredbydeterminationofserumlipidvalues.Ifanadequateresponsehasnotbeenachievedafterseveralmonths(e.g.3months),complementaryordifferenttherapeuticmeasuresshouldbeconsidered. Posology Adults Therecommendeddoseis200mgdailyadministeredasonecapsuleofFenofibrate200mgcapsules. Thedosecanbetitratedupto267mgdailyadministeredas4capsulesofFenofibrate67mgcapsules,ifrequired.Thismaximumdoseisnotrecommendedinadditiontoastatin. Specialpopulations Elderlypatients(≥65yearsold) Nodoseadjustmentisnecessary.Theusualdoseisrecommended,exceptfordecreasedrenalfunctionwithestimatedglomerularfiltrationrate<60mL/min/1.73(seePatientswithrenalimpairment). Patientswithrenalimpairment Fenofibrateshouldnotbeusedifsevererenalimpairment,definedaseGFR<30mL/minper1.73m2,ispresent. IfeGFRisbetween30and59mL/minper1.73m2,thedoseoffenofibrateshouldnotexceed100mgstandardor67mgmicronizedoncedaily. If,duringfollow-up,theeGFRdecreasespersistentlyto<30mL/minper1.73m2,fenofibrateshouldbediscontinued. Hepaticimpairment Fenofibrate200mgcapsulesareisnotrecommendedforuseinpatientswithhepaticimpairmentduetothelackofdata. Paediatricpopulation Thesafetyandefficacyoffenofibrateinchildrenandadolescentsyoungerthan18yearshasnotbeenestablished.Nodataareavailable. Therefore,theuseoffenofibrateisnotrecommendedinpaediatricsubjectsunder18years Methodofadministration Capsulesshouldbeswallowedwholeduringameal. 4.3Contraindications •Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1. •Hepaticinsufficiency(includingbiliarycirrhosisandunexplainedpersistentliverfunctionabnormality). •Knowngallbladderdisease. •Severerenalinsufficiency(estimatedglomerularfiltrationrate<30mL/min/1.73m2)Chronicoracutepancreatitiswiththeexceptionofacutepancreatitisduetoseverehypertriglyceridemia. •Knownphotoallergyorphototoxicreactionduringtreatmentwithfibratesorketoprofen 4.4Specialwarningsandprecautionsforuse Secondarycausesofhyperlipidaemia: Secondarycausesofhyperlipidaemia,suchasuncontrolledtype2diabetesmellitus,hypothyroidism,nephroticsyndrome,dysproteinemia,obstructiveliverdisease,pharmacologicaltreatment,alcoholism,shouldbeadequatelytreatedbeforefenofibratetherapyisconsidered.Secondarycauseofhypercholesterolemiarelatedtopharmacologicaltreatmentcanbeseenwithdiuretics,β-blockingagents,oestrogens,progestogens,combinedoralcontraceptives,immunosuppressiveagentsandproteaseinhibitors.Inthesecasesitshouldbeascertainedwhetherthehyperlipidaemiaisofprimaryorsecondarynature(possibleelevationoflipidvaluescausedbythesetherapeuticagents). Liverfunction: Aswithotherlipidloweringagents,increaseshavebeenreportedintransaminaselevelsinsomepatients.Inthemajorityofcasestheseelevationsweretransient,minorandasymptomatic.Itisrecommendedthattransaminaselevelsaremonitoredevery3monthsduringthefirst12monthsoftreatmentandthereafterperiodically.AttentionshouldbepaidtopatientswhodevelopincreaseintransaminaselevelsandtherapyshouldbediscontinuedifAST(SGOT)andALT(SGPT)levelsincreasetomorethan3timestheupperlimitofthenormalrange.Whensymptomsindicativeofhepatitisoccur(e.g.jaundice,pruritus),anddiagnosisisconfirmedbylaboratorytesting,fenofibratetherapyshouldbediscontinued. Pancreas: Pancreatitishasbeenreportedinpatientstakingfenofibrate(seesections4.3and4.8).Thisoccurrencemayrepresentafailureofefficacyinpatientswithseverehypertriglyceridaemia,adirectdrugeffect,orasecondaryphenomenonmediatedthroughbiliarytractstoneorsludgeformationwithobstructionofthecommonbileduct. Muscle: Muscletoxicity,includingrarecasesofrhabdomyolysis,withorwithoutrenalfailurehasbeenreportedwithadministrationoffibratesandotherlipid-loweringagents.Theincidenceofthisdisorderincreasesincasesofhypoalbuminaemiaandpreviousrenalinsufficiency.Patientswithpre-disposingfactorsformyopathyand/orrhabdomyolysis,includingageabove70years,personalorfamilialhistoryofhereditarymusculardisorders,renalimpairment,hypothyroidismandhighalcoholintake,maybeatanincreasedriskofdevelopingrhabdomyolysis.Forthesepatients,theputativebenefitsandrisksoffenofibratetherapyshouldbecarefullyweighedup. Muscletoxicityshouldbesuspectedinpatientspresentingdiffusemyalgia,myositis,muscularcrampsandweaknessand/ormarkedincreasesinCPK(levelsexceeding5timesthenormalrange).Insuchcasestreatmentwithfenofibrateshouldbestopped. TheriskofmuscletoxicitymaybeincreasedifthedrugisadministeredwithanotherfibrateoranHMG-CoAreductaseinhibitor,especiallyincasesofpre-existingmusculardisease.Consequently,theco-prescriptionoffenofibratewithaHMG-CoAreductaseinhibitororanotherfibrateshouldbereservedtopatientswithseverecombineddyslipidaemiaandhighcardiovascularriskwithoutanyhistoryofmusculardiseaseandaclosemonitoringofpotentialmuscletoxicity. Renalfunction: Fenofibrate200mgcapsulesarecontraindicatedinsevererenalimpairment(seesection4.3). Fenofibrate200mgcapsulesshouldbeusedwithcautioninpatientswithmildtomoderaterenalinsufficiency.Doseshouldbeadjustedinpatientswhoseestimatedglomerularfiltrationrateis30to59mL/min/1.73m2(seesection4.2). Reversibleelevationsinserumcreatininehavebeenreportedinpatientsreceivingfenofibratemonotherapyorco-administeredwithstatins.Elevationsinserumcreatinineweregenerallystableovertimewithnoevidenceforcontinuedincreasesinserumcreatininewithlongtermtherapyandtendedtoreturntobaselinefollowingdiscontinuationoftreatment. Duringclinicaltrials,10%ofpatientshadacreatinineincreasefrombaselinegreaterthan30μmol/Lwithco-administeredfenofibrateandsimvastatinversus4.4%withstatinmonotherapy.0.3%ofpatientsreceivingco-administrationhadclinicallyrelevantincreasesincreatininetovalues>200μmol/L. Treatmentshouldbeinterruptedwhencreatininelevelis50%abovetheupperlimitofnormal.Itisrecommendedthatcreatinineismeasuredduringthefirst3monthsafterinitiationoftreatmentandperiodicallythereafter. Excipients: Lactose Thismedicinecontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,totallactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine. Sodiumcontent Thismedicinecontainslessthan1mmolsodium(23mg)percapsule,thatistosayessentially'sodium-free'. Ponceau4R,cochinealRedA(E124) Maycauseallergicreactions. 4.5Interactionwithothermedicinalproductsandotherformsofinteraction Oralanti-coagulants Fenofibrateenhancesoralanti-coagulanteffectandmayincreaseriskofbleeding.Inpatientsreceivingoralanti-coagulanttherapy,thedoseofanti-coagulantshouldbereducedbyaboutone-thirdatthecommencementoftreatmentandthengraduallyadjustedifnecessaryaccordingtoINR(InternationalNormalisedRatio)monitoring. Ciclosporin Someseverecasesofreversiblerenalfunctionimpairmenthavebeenreportedduringconcomitantadministrationoffenofibrateandciclosporin.Therenalfunctionofthesepatientsmustthereforebecloselymonitoredandthetreatmentwithfenofibratestoppedinthecaseofseverealterationoflaboratoryparameters. HMG-CoAreductaseinhibitorsorOtherFibrates TheriskofseriousmuscletoxicityisincreasedifafibrateisusedconcomitantlywithHMG-CoAreductaseinhibitorsorotherfibrates.Suchcombinationtherapyshouldbeusedwithcautionandpatientsmonitoredcloselyforsignsofmuscletoxicity(seeSection4.4). Thereiscurrentlynoevidencetosuggestthatfenofibrateaffectsthepharmacokineticsofsimvastatin. Glitazones SomecasesofreversibleparadoxicalreductionofHDL-cholesterolhavebeenreportedduringconcomitantadministrationoffenofibrateandglitazones.ThereforeitisrecommendedtomonitorHDL-cholesterolifoneofthesecomponentsisaddedtotheotherandstoppingofeithertherapyifHDL-cholesterolistoolow. CytochromeP450enzymes Invitrostudiesusinghumanlivermicrosomesindicatethatfenofibrateandfenofibricacidarenotinhibitorsofcytochrome(CYP)P450isoformsCYP3A4,CYP2D6,CYP2E1,orCYP1A2.TheyareweakinhibitorsofCYP2C19andCYP2A6,andmild-to-moderateofCYP2C9attherapeuticconcentrations. Patientsco-administeredfenofibrateandCYP2C19,CYP2A6,andespeciallyCYP2C9metaboliseddrugswithanarrowtherapeuticindexshouldbecarefullymonitoredand,ifnecessary,doseadjustmentofthesedrugsisrecommended. Other Incommonwithotherfibrates,fenofibrateinducesmicrosomalmixed-functionoxidasesinvolvedinfattyacidmetabolisminrodentsandmayinteractwithdrugsmetabolisedbytheseenzymes. 4.6Fertility,pregnancyandlactation Pregnancy Therearenoadequatedatafromtheuseoffenofibrateinpregnantwomen.Animalstudieshavenotdemonstratedanyteratogeniceffects.Embryotoxiceffectshavebeenshownatdosesintherangeofmaternaltoxicity(seesection5.3).Thepotentialriskforhumansisunknown.Therefore,Fenofibrate200mgcapsulesshouldonlybeusedduringpregnancyafteracarefulbenefit/riskassessment. Breast-feeding Itisunknownwhetherfenofibrateand/oritsmetabolitesareexcretedinhumanmilk.Arisktothesucklingchildcannotbeexcluded.Thereforefenofibrateshouldnotbeusedduringbreast-feeding. Fertility Reversibleeffectsonfertilityhavebeenobservedinanimals(seesection5.3).TherearenoclinicaldataonfertilityfromtheuseofFenofibrate200mgcapsules. 4.7Effectsonabilitytodriveandusemachines Fenofibrate200mgcapsuleshasnoornegligibleinfluenceontheabilitytodriveandusemachines. 4.8Undesirableeffects ThemostcommonlyreportedADRsduringfenofibratetherapyaredigestive,gastricorintestinaldisorders. Thefollowingundesirableeffectshavebeenobservedduringplacebo-controlledclinicaltrials(n=2344)withthebelowindicatedfrequencies: Theadversedrugreactionsarestatedinthetablebelowusingthefollowingconvention: Verycommon(>1/10);common(>1/100;<1/10);uncommon(>1/1,000;<1/100);rare(>1/10,000;<1/1,000);veryrare(<1/10,000)includingisolatedreports. MedDRAsystemorganclass Common ≥1/100,<1/10 Uncommon ≥1/1,000,<1/100 Rare ≥1/10,000,<1/1,000 Veryrare <1/10,000incl.isolatedreports Bloodandlymphaticsystemdisorders Haemoglobindecreased Whitebloodcellcountdecreased Immunesystemdisorders Hypersensitivity Nervoussystemdisorders Headache Vasculardisorders Thromboembolism(pulmonaryembolism,deepveinthrombosis)* Gastrointestinaldisorders Gastrointestinalsignsandsymptoms(abdominalpain,nausea,vomiting,diarrhoea,flatulence) Pancreatitis* Hepatobiliarydisorders Transaminasesincreased(seesection4.4) Cholelithiasis(seesection4.4) Hepatitis Skinandsubcutaneoustissuedisorders Cutaneoushypersensitivity(e.g.Rashes,pruritus,urticaria) Alopecia Photosensitivityreactions Musculoskeletal,connectivetissueandbonedisorders Muscledisorder(e.g.myalgia,myositis,muscularspasmsandweakness) Reproductivesystemandbreastdisorders Sexualdysfunction Investigations Bloodhomocysteinelevelincreased** Bloodcreatinineincreased Bloodureaincreased *IntheFIELD-study,arandomizedplacebo-controlledtrialperformedin9795patientswithtype2diabetesmellitus,astatisticallysignificantincreaseinpancreatitiscaseswasobservedinpatientsreceivingfenofibrateversuspatientsreceivingplacebo(0.8%versus0.5%;p=0.031).Inthesamestudy,astatisticallysignificantincreasewasreportedintheincidenceofpulmonaryembolism(0.7%intheplacebogroupversus1.1%inthefenofibrategroup;p=0.022)andastatisticallynon-significantincreaseindeepveinthromboses(placebo:1.0%[48/4900patients]versusfenofibrate1.4%[67/4895patients];p=0.074). **IntheFIELDstudytheaverageincreaseinbloodhomocysteinelevelinpatientstreatedwithfenofibratewas6.5µmol/L,andwasreversibleondiscontinuationoffenofibratetreatment.Theincreasedriskofvenousthromboticeventsmayberelatedtotheincreasedhomocysteinelevel.Theclinicalsignificanceofthisisnotclear. Inadditiontothoseeventsreportedduringclinicaltrials,thefollowingsideeffectshavebeenreportedspontaneouslyduringpostmarketinguseoffenofibrate.Aprecisefrequencycannotbeestimatedfromtheavailabledataandisthereforeclassifiedas“notknown”. -Respiratory,thoracicandmediastinaldisorders:Interstitiallungdisease. -Musculoskeletal,connectivetissueandbonedisorders:Rhabdomyolysis. -Hepatobiliarydisorders:jaundice,complicationsofcholelithiasis(e.g.cholecystitis,cholangitis,biliarycolic) -SkinandSubcutaneousTissueDisorders:severecutaneousreactions(e.gerythemamultiforme,Stevens-Johnsonsyndrome,toxicepidermalnecrolysis) -Generaldisordersandadministrationsiteconditions:Fatigue Reportingofsuspectedadversereactions Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinuedmonitoringofthebenefit/riskbalanceofthemedicinalproduct.HealthcareprofessionalsareaskedtoreportanysuspectedadversereactionsdirectlyviatheYellowCardSchemewebsite:www.mhra.gov.uk/yellowcardorsearchforMHRAYellowCardintheGooglePlayorAppleAppStore. 4.9Overdose Onlyanecdotalcasesoffenofibrateoverdosagehavebeenreceived.Inthemajorityofcasesnooverdosesymptomswerereported. Nospecificantidoteisknown.Ifoverdoseissuspected,treatsymptomaticallyandinstituteappropriatesupportivemeasuresasrequired.Fenofibratecannotbeeliminatedbyhaemodialysis. 5.Pharmacologicalproperties 5.1Pharmacodynamicproperties SerumLipidReducingAgents/CholesterolandTriglycerideReducers/Fibrates.ATCcode:C10AB05. Fenofibrate200mgcapsuleisaformulationcontaining200mgofmicronisedfenofibrate:theadministrationofthisproductresultsineffectiveplasmaconcentrationsidenticaltothoseobtainedwith3capsulesofFenofibrate67mgcapsulescontaining67mgofmicronisedfenofibrate. FenofibrateisafibricacidderivativewhoselipidmodifyingeffectsreportedinhumansaremediatedviaactivationofPeroxisomeProliferatorActivatedReceptortypeα(PPARα).ThroughactivationofPPARα,fenofibrateincreaseslipolysisandeliminationofatherogenictriglyceriderichparticlesfromplasmabyactivatinglipoproteinlipaseandreducingproductionofApoproteinC-III.ActivationofPPARαalsoinducesanincreaseinthesynthesisofApoproteinsA-I,andA-II. Thereisevidencethattreatmentwithfibratesmayreducecoronaryheartdiseaseeventsbuttheyhavenotbeenshowntodecreaseall-causemortalityintheprimaryorsecondarypreventionofcardiovasculardisease. 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. StudieswithfenofibrateonlipoproteinfractionsshowdecreasesinlevelsofLDLandVLDLcholesterol.HDLcholesterollevelsarefrequentlyincreased.LDLandVLDLtriglyceridesarereduced.Theoveralleffectisadecreaseintheratiooflowandverylowdensitylipoproteinstohighdensitylipoproteins,whichepidemiologicalstudieshavecorrelatedwithadecreaseinatherogenicrisk.Apolipoprotein-Aandapolipoprotein-BlevelsarealteredinparallelwithHDLandLDLandVLDLlevelsrespectively. Extravasculardepositsofcholesterol(tendinousandtuberousxanthoma)maybemarkedlyreducedorevenentirelyeliminatedduringfenofibratetherapy. Plasmauricacidlevelsareincreasedinapproximately20%ofhyperlipidaemicpatients,particularlyinthosewithtypeIVdisease. Patientswithraisedlevelsoffibrinogentreatedwithfenofibratehaveshownsignificantreductionsinthisparameter,ashavethosewithraisedlevelsofLp(a).OtherinflammatorymarkerssuchasCReactiveProteinarereducedwithfenofibratetreatment. Theuricosuriceffectoffenofibrateleadingtoreductioninuricacidlevelsofapproximately25%shouldbeofadditionalbenefitinthosedyslipidaemicpatientswithhyperuricaemia. Fenofibratehasbeenshowntopossessananti-aggregatoryeffectonplateletsinanimalsandinaclinicalstudy,whichshowedareductioninplateletaggregationinducedbyADP,arachidonicacidandepinephrine. 5.2Pharmacokineticproperties Absorption: Maximumplasmaconcentrations(Cmax)occurwithin4to5hoursafteroraladministration.Plasmaconcentrationsarestableduringcontinuoustreatmentinanygivenindividual. Theabsorptionoffenofibrateisincreasedwhenadministeredwithfood. Distribution: Fenofibricacidisstronglyboundtoplasmaalbumin(morethan99%). Metabolismandexcretion: Afteroraladministration,fenofibrateisrapidlyhydrolisedbyesterasestotheactivemetabolitefenofibricacid. Nounchangedfenofibratecanbedetectedintheplasma.FenofibrateisnotasubstrateforCYP3A4.Nohepaticmicrosomalmetabolismisinvolved. Thedrugisexcretedmainlyintheurine.Practicallyallthedrugiseliminatedwithin6days.Fenofibrateismainlyexcretedintheformoffenofibricacidanditsglucuronoconjugate. Inelderlypatients,thefenofibricacidapparenttotalplasmaclearanceisnotmodified. Kineticstudiesfollowingtheadministrationofasingledoseandcontinuoustreatmenthavedemonstratedthatthedrugdoesnotaccumulate. Fenofibricacidisnoteliminatedduringhaemodialysis. Theplasmaeliminationhalf-lifeoffenofibricacidisapproximately20hours. 5.3Preclinicalsafetydata Inathree-monthoralnonclinicalstudyintheratspecieswithfenofibricacid,theactivemetaboliteoffenofibrate,toxicityfortheskeletalmuscles(particularlythoserichintypeI-slowoxidative-myofibres)andcardiacdegeneration,anaemiaanddecreasedbodyweightwereseen.Noskeletaltoxicitywasnotedatdosesupto30mg/kg(approximately17-timetheexposureatthehumanmaximumrecommendeddose(MRHD).Nosignsofcardiomyotoxicitywerenotedatanexposureabout3timestheexposureatMRHD.Reversibleulcersanderosionsinthegastro-intestinaltractoccurredindogstreatedfor3months.Nogastro-intestinallesionswerenotedinthatstudyatanexposureapproximately5timestheexposureattheMRHD. Studiesonthemutagenicityoffenofibratehavebeennegative.Inratsandmice,livertumourshavebeenfoundathighdosages,whichareattributabletoperoxisomeproliferation.Thesechangesarespecifictosmallrodentsandhavenotbeenobservedinotheranimalspecies.Thisisofnorelevancetotherapeuticuseinman. Studiesinmice,ratsandrabbitsdidnotrevealanyteratogeniceffect.Embryotoxiceffectswereobservedatdosesintherangeofmaternaltoxicity.Prolongationofthegestationperiodanddifficultiesduringdeliverywereobservedathighdoses. Reversiblehypospermiaandtesticularvacuolationandimmaturityoftheovarieswereobservedinarepeat-dosetoxicitystudywithfenofibricacidinyoungdogs.Howevernoeffectsonfertilityweredetectedinnon-clinicalreproductivetoxicitystudiesconductedwithfenofibrate. 6.Pharmaceuticalparticulars 6.1Listofexcipients Excipients:lactosemonohydrate,pregelatinisedstarch,sodiumlaurylsulfate,povidone,magnesiumstearate. Compositionofthecapsuleshell:gelatin,titaniumdioxide(E171),yellowironoxide(E172)andponceau4R,cochinealredA(E124). 6.2Incompatibilities Notapplicable. 6.3Shelflife 30months. 6.4Specialprecautionsforstorage Donotstoreabove25°C. Storeintheoriginalpackage 6.5Natureandcontentsofcontainer Blister,PVC(250μm)-PVDC(40g/m2)/Alu(20µm)and Blister,PVC(250μm)-PVDC(60g/m2)/Alu(20µm) Packsizes:20,28,30. Notallpacksizesmaybemarketed. 6.6Specialprecautionsfordisposalandotherhandling Nospecialrequirements. AdministrativeData 7.Marketingauthorisationholder Accord-UKLtd (Tradingstyle:Accord) WhiddonValley Barnstaple Devon EX328NS 8.Marketingauthorisationnumber(s) PL00142/0552 9.Dateoffirstauthorisation/renewaloftheauthorisation 29June2004 Renewal–03.08.2009 10.Dateofrevisionofthetext 21/05/2021 ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:01Jun2021 Viewchanges Print Companycontactdetails Accord-UKLtd Address WhiddonValley,Barnstaple,Devon,EX328NS,UK Telephone +44(0)1271385200 MedicalInformationDirectLine +44(0)1271385257 WWW www.accord-healthcare.co.uk Fax +44(0)1271346106 MedicalInformatione-mail [email protected] × Bookmarkthismedicine Tobookmarkamedicineyoumustsignupandlogin. SignUp LogIn Cancel × Emailthismedicine Toemailamedicineyoumustsignupandlogin. 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