Loniten Tablets 2.5 mg - Summary of Product Characteristics ...

This information is intended for use by health professionals · Loniten 2.5 mg Tablets · Each Loniten tablet contains 2.5 mg minoxidil. · Tablet. · 4.1 Therapeutic ... Skiptomaincontent LonitenTablets2.5mg Backtotop PfizerLimitedcontactdetails Activeingredient minoxidil LegalCategory POM:Prescriptiononlymedicine ATCcode C02DC01 Findsimilarproducts ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:24Nov2020 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 Loniten2.5mgTablets 2.Qualitativeandquantitativecomposition EachLonitentabletcontains2.5mgminoxidil. Excipientswithknowneffect: Eachtabletcontains95.8mgoflactosemonohydrate. Forthefulllistofexcipients,seesection6.1. 3.Pharmaceuticalform Tablet. Roundwhitetolighttanbiconvextablets,with'2½'imprintedononeside,scoredonthereversewitha'U'ononesideofthescoreand'121'ontheotherside. Thetabletcanbedividedintoequalhalves. 4.Clinicalparticulars 4.1Therapeuticindications Minoxidilisindicatedforthetreatmentofseverehypertension. Itshouldnotbeusedasthesoleagenttoinitiatetherapy.Itisaperipheralvasodilatorandshouldbegiveninconjunctionwithadiuretic,tocontrolsaltandwaterretention,andabeta-adrenergicblockingagent,orappropriatesubstitute,tocontrolreflextachycardia. 4.2Posologyandmethodofadministration Posology Patientsover12yearsandadults Therecommendedstartingdoseis5mgperday.Ifrequired,thisdosagecanlaterbeincreasedupto20mg,andthento40mgdaily(givenasasingledoseorintwodivideddoses).Doseincreasesshouldbemadeatincrementsof5mgto10mgminoxidilperdayatintervalsofthreeormoredays.Ifadoseof50mgofminoxidilhasbeenreached,thedosemaybeincreasedby25mgminoxidilperdaytoamaximumdoseof100mgperday. Ifthedesireddecreaseofdiastolicbloodpressureexceeds30mmHg,dosageshouldbedividedtotwodailydosestokeepdailybloodpressurefluctuationsaslowaspossible. Patientsyoungerthan12yearsofage Theuseofminoxidilinchildrenisrestrictedtochildrenwithseverehypertensionassociatedwithtargetorgandamagewhereothertreatmenthasfailed.Thedataregardingtheuseofminoxidilinchildrenisverylimited,especiallyininfants.Thedosagerecommendationscanonlybeconsideredasaroughguidetotreatmentatpresentasthisisbasedonthepublicationofafewcasereportsandstudiesinvolvingasmallnumberofchildren.Thestartingdoseusedbasedonthesereportsis0.2mg/kgofminoxidilasasingleordivideddose.Carefultitrationincreasinginstepsof0.1to0.2mg/kg/dayatintervalsofatleast3daysisessential.Theeffectivedoserangeis0.25to1.0mg/kg/day.Themaximumdoseis50mg/day. Treatmentofchildrenwithminoxidilshouldonlybeinitiatedundertheclosesupervisionofaspecialistinhospital. Elderlypatients Atpresenttherearenoextensiveclinicalstudieswithminoxidilinpatientsoverage65.Thereisdataindicatingthatelevatedsystolicanddiastolicpressuresareimportantriskfactorsforcardiovasculardiseaseinindividualsoverage65.However,elderlypatientsmaybesensitivetothebloodpressureloweringeffectofminoxidilandthuscautionisurgedininitiatingtherapyasorthostatichypotensionmayoccur.Itissuggestedthat2.5mgperdaybeusedastheinitialstartingdoseinpatientsover65yearsofage. Renalfailureordialysispatients Dosagerequirementsmaybelowerindialysispatients.Minoxidilisremovedfromthebloodbydialysis,butitspharmacologicalaction,onceestablishedisnotreversed.Thereforehaemodialysispatientsshouldtakeminoxidileitherafteroratleasttwohoursbeforedialysis. Rapidreductionofbloodpressure Underhospitalmonitoringconditions,rapidreductionofbloodpressurecanbeachievedusingcontinuousbloodpressuremonitoringandincrementaldosesof5mgeverysixhours. Concomitantantihypertensivetherapy Itisrecommendedthat,wherepossible,antihypertensivetherapy,otherthanabeta-adrenergicblockingagentandadiureticbediscontinuedbeforeminoxidiltreatmentisstarted.Itisrecognisedthatsomeantihypertensiveagentsshouldnotbeabruptlydiscontinued.Thesedrugsshouldbegraduallydiscontinuedduringthefirstweekofminoxidiltreatment. Minoxidilcausessodiumretentionandifusedalonecanresultinseveralhundredmilli-equivalentsofsaltbeingretainedtogetherwithacorrespondingvolumeofwater. Therefore,inallpatientswhoarenotondialysis,minoxidilmustbegiveninconjunctionwithadiureticinsufficientdosagetomaintainsaltandwaterbalance.Examplesofthedailydosagesofdiureticscommonlyusedwhenstartingtherapywithminoxidilinclude: 1.Hydrochlorothiazide(100mg)-orotherthiazidesatequi-effectivedosage. 2.Chlortalidone(100mg). 3.Furosemide(80mg). Ifexcessivewaterretentionresultsinaweightgainofmorethan3poundswhenathiazideorchlortalidoneisbeingused,diuretictherapyshouldbechangedtofurosemide,thedoseofwhichmaybeincreasedinaccordancewiththepatient'srequirements.Diureticdosageinchildrenshouldbeproportionallylessinrelationtoweight. Patientswillrequireasympatheticnervoussystemsuppressanttolimitaminoxidil-inducedriseinheartrate.Thepreferredagentisabeta-blockerequivalenttoanadultpropranololdosageof80-160mg/day.Higherdosesmayberequiredwhenpre-treatedpatientshaveanincreaseinheartrateexceeding20beatsperminuteorwhensimultaneousintroductioncausesanincreaseexceeding10beatsperminute.Whenbeta-blockersarecontra-indicated,alternativessuchasmethyldopamaybeusedinsteadandshouldbestarted24hourspriortominoxidil. MethodofAdministration Oraladministration 4.3Contraindications Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1 Minoxidiliscontra-indicatedinpatientswithaphaeochromocytomabecauseitmaystimulatesecretionofcatecholaminesfromthetumourthroughitsantihypertensiveaction. 4.4Specialwarningsandprecautionsforuse Saltandwaterretention Ifusedalone,minoxidilcancauseasignificantretentionofsaltandwaterleadingtophysicalsignssuchasoedema,andtoclinicaldeteriorationofsomepatientswithheartfailure.Diuretictreatmentalone,orincombinationwithrestrictedsaltintakeis,therefore,necessaryforallpatientstakingminoxidil.Haemodilutionmayoccurleadingtotemporarydecreaseinhaematocrit,haemoglobin,anderythrocytecount(byapproximately7%initiallywhichthenrecoverstopre-treatmentlevels).Thepatient'sbodyweight,fluidandelectrolytebalanceshouldbemonitoredforevidenceoffluidretention. Saltandwaterretentioninexcessof1to1.5kgmaydiminishtheeffectivenessofminoxidil.Patientsshould,therefore,becarefullyinstructedaboutcompliancewithdiuretictherapyandadetailedrecordofbodyweightshouldbemaintained. Theproductshouldbeusedwithparticularattentiontomaintenanceofsaltandwaterbalanceinpatientswithrenalimpairment,butwhoarenotondialysis. Renalfailureordialysispatients Thosepatientswithrenalfailureoronhaemodialysismayrequiresmallerdosesofminoxidil(seesection4.2). Myocardialinfarction Patientswhohavehadmyocardialinfarctionshouldonlybetreatedwithminoxidilafterastablepost-infarctionstatehasbeenestablished. Tachycardia Becauseminoxidilisavasodilator,reflextachycardiamayoccurandpossiblyanginapectorismayoccurinpatientsatrisk;itisrecommendedthatminoxidilbeusedincombinationwithbeta-adrenergicblockingagentorothersympatheticnervoussystemsuppressantstobluntorpreventsucharesponse. Hypertrichosis Hypertrichosisoccursinmostpatientstreatedwithminoxidilandallpatientsshouldbewarnedofthispossibilitybeforestartingtherapy.Mostpatientswillexperienceanelongation,thickeningandenhancedpigmentationoffinebodyhair.Usuallythesesignswillemerge3to6weeksafterstartingtreatment.Theyinitiallyemergeintheface,andtheymayslightlysubsidewithcontinuedtreatment.However,hypertrichosiswashardlyornotatalltolerableinlessthan10%ofpatients.Spontaneousreversaltothepre-treatmentstatecanbeexpectedonetosixmonthsaftercessationoftherapy. ECGalterations Soonafterstartingminoxidiltherapyapproximately60%ofpatientsexhibitECGalterationsinthedirectionandmagnitudeoftheirTwaves.LargechangesmayencroachontheSTsegment,unaccompaniedbyevidenceofischaemia.Theseasymptomaticchangesusuallydisappearwithcontinuingminoxidiltreatment.TheECGrevertstothepre-treatmentstatewhenminoxidilisdiscontinued. Thrombocytopeniaandleucopoenia Thrombocytopeniaandleucopoeniahavebeenrarelyreported. Pericarditis,PericardialEffusionandTamponade Althoughthereisnoevidenceofacausalrelationship,therehavebeenmultiplereportsofpericarditisoccurringinassociationwithminoxidil. Pericardialeffusionandoccasionallytamponade,hasbeenobservedinabout3%-5%oftreatedpatientsnotondialysis.Whileinmanycases,thepericardialeffusionisassociatedwithotherpotentialaetiologies,therehavebeencasesinwhichthesepotentialcausesofeffusionwerenotpresent.Patientsshouldbeobservedcloselyforanysuggestionofapericardialeffusionandpericardiocentesis,orsurgerymayberequired.Iftheeffusionpersists,withdrawalofminoxidilshouldbeconsideredinlightofothermeansofcontrollingthehypertensionandthepatient'sclinicalstatus. Paediatricpopulation Childrenstrictlyrequireappropriateandindividualiseddosingofminoxidil,beta-blockersanddiuretics.Theyshouldbeunderclosespecialistsupervisioninhospital.Cautionisrequiredwhenthereissignificantrenalimpairment.Thedevelopmentofperipheraloedemaoranysignssuggestiveofcongestiveheartfailureorofpericardialorpleuraleffusionshouldbecarefullywatchedfor.Renalfunctionshouldbemonitored.Bodyweightandurineoutputshouldbemonitored. Regularfollowupmustbeensuredduringtreatmentwithminoxidil. Beforestartingtreatmentparentsandcarersshouldbewarnedofthelikelyoccurrenceofhypertrichosis. Thismedicinecontainslactose Patientswithrarehereditaryproblemsofgalactoseintolerance,totallactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine. 4.5Interactionwithothermedicinalproductsandotherformsofinteraction Theeffectofminoxidilmaybeadditivetoconcurrentantihypertensiveagentsandotheragentswithbloodpressureloweringeffects.Theinteractionofminoxidilwithsympathetic-blockingagentssuchasguanethidineorbetanidinemayproduceexcessivebloodpressurereductionand/ororthostatichypotension. Ifpossibleguanethidineshouldbediscontinuedwellbeforeminoxidilisbegun.Ifthisisnotfeasible,minoxidiltherapyshouldbeinstitutedinthehospitalandthepatientmonitoredcarefullyfororthostaticevents. 4.6Fertility,pregnancyandlactation Pregnancy Thereislimiteddatafromtheuseofminoxidilinpregnantwomen.Studiesinanimalshaveshownreproductivetoxicity(seesection5.3). Minoxidilisnotrecommendedduringpregnancyandinwomenofchildbearingpotentialnotusingcontraception.Neonatalhirsutismhasbeenreportedfollowingexposureofminoxidilduringpregnancy. Breast-feeding Minoxidilhasbeenreportedtobeexcretedinhumanmilk.Arisktothesucklingchildcannotbeexcluded.Adecisionmustbemadewhethertodiscontinuebreast-feedingortodiscontinue/abstainfromminoxidiltherapytakingintoaccountthebenefitofbreast-feedingforthechildandthebenefitoftherapyforthewoman. Fertility Therearenofertilitydatafromtheuseofminoxidilinhumans.Inafertilitystudywithmaleandfemalerats,adose-dependentreductionoftheconceptionratewasfound.Thedosecorrespondedtoonetofivetimesthemaximumdoseusedinhumanstotreathypertension. 4.7Effectsonabilitytodriveandusemachines Nostudiesontheeffectofminoxidilontheabilitytodriveorusemachineshavebeenperformed. Theabilitytodriveoroperatemachinerymaybeinfluencedbytheindividualresponsetotreatment,particularlyatthestartoftherapy. 4.8Undesirableeffects Mostpatientsreceivingminoxidilexperienceadiminutionofpre-existingside-effectsattributabletotheirdiseaseorprevioustherapy.Neweventsorside-effectslikelytoincreaseareincludedinthefollowingtable: Frequenciesaredefinedas: Verycommon (≥1/10) Common (≥1/100to<1/10) Uncommon (≥1/1,000to<1/100) Rare (≥1/10,000to<1/1,000) Veryrare (<1/10,000) Notknown (cannotbeestimatedfromtheavailabledata). MedDRA SystemOrganClass Frequency UndesirableEffects BloodandLymphaticSystemDisorders Rare Leucopoenia,thrombocytopenia MetabolismandNutritionDisorders Common Fluidretention,oedema CardiacDisorders VeryCommon Tachycardia,pericarditis Common Pericardialeffusion,cardiactamponade NotKnown Anginapectoris Respiratory,ThoracicandMediastinalDisorders NotKnown Pleuraleffusion GastrointestinalDisorders Notknown Gastrointestinaldisorder SkinandSubcutaneousTissueDisorders VeryCommon Hypertrichosis,haircolourchanges Rare Stevens-Johnsonsyndrome,dermatitisbullous,rash, ReproductiveSystemandBreastDisorders Notknown Breasttenderness GeneralDisordersandAdministrationSiteConditions Notknown Peripheraloedemaassociatedwithorindependentofweightgain Investigations VeryCommon ECGabnormal NotKnown Bloodcreatinineincreased Bloodureaincreased SaltandWaterRetention–seesection4.4. Tachycardia–seesection4.4. Pericarditis,PericardialEffusionandTamponade–seesection4.4. Postauthorisationexperiencehasshownthat,inaparticularstudy,outof50patientsonoralminoxidil,onecaseinvolvedatwoyearoldfemalewithahistoryofchronicrenalfailureandperitonealdialysiswhodevelopedpericardialeffusionfromwhichsherecoveredaftertreatment. Inaddition,theestimatedtotalexposure(basedononlyninemonthsofdata)wasabout17,000patient-yearswithhowevernoappreciableuseinchildren. Reportingofsuspectedadversereactions Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinuedmonitoringofthebenefit/riskbalanceofthemedicinalproduct.HealthcareprofessionalsareaskedtoreportanysuspectedadversereactionsviatheYellowCardSchemeat:www.mhra.gov.uk/yellowcardorsearchforMHRAYellowCardintheGooglePlayorAppleAppStore. 4.9Overdose Ifexaggeratedhypotensionisencountered,itismostlikelytooccurinassociationwithresidualsympatheticnervoussystemblockade(guanethidine-likeeffectsoralpha-adrenergicblockade).Recommendedtreatmentisintravenousadministrationofnormalsaline.Sympathomimeticdrugs,suchasnoradrenaline(norepinephrine)oradrenaline(epinephrine),shouldbeavoidedbecauseoftheirexcessivecardiac-stimulatingaction.Phenylephrine,angiotensinIIandvasopressin,whichreversetheeffectofminoxidil,shouldbeusedonlyifinadequateperfusionofavitalorganisevident. 5.Pharmacologicalproperties 5.1Pharmacodynamicproperties Pharmacotherapeuticgroup:Pyrimidinederivatives ATCCode:C02DC01 Mechanismofaction Minoxidillowerstheelevatedsystolicanddiastolicbloodpressurebydecreasingperipheralvascularresistanceviavasodilation.Thesmoothmusculatureoftheresistancevesselsmustberegardedasthesiteofactionfortherelaxanteffectofminoxidil.TheactivemetaboliteofminoxidilactivatestheATP-modulatedpotassium(K+ATP)channelcausingK+efflux,hyperpolarization,andsmoothmusclerelaxation. Pharmacodynamiceffects Sympatheticreflexesmediatedbybaroreceptorssecondarilyincreaseheartrateandmyocardialcontractility,therebyincreasingcardiacoutput.Inaddition,theplasmareninactivityisincreasedviasympatheticnervoussystemstimulation,whichresultsinanincreasedangiotensinIIconcentrationwithsubsequentincreasedaldosteronesecretion.Inthisway,therenalsodiumexcretionisreducedandextracellularvolumeincreased.Thepulmonaryarterypressuremayoccasionallyincreaseaftertheadministrationofminoxidilalone,butitdecreaseswiththerecommendedconcomitanttherapy(beta-blockerplusdiuretic). Paediatricpopulation Asseverehypertensionrequiringmulti-drugtherapyisuncommoninchildren,paediatricuseofminoxidilwaslimitedinthedevelopmentprogrammeandhasremainedsoinpublishedliterature.Dataavailableinchildrenyoungerthan10yearsofageisverylimited;itinvolvesapproximately40patients,eightofwhomwereunderoneyearofage. 5.2Pharmacokineticproperties Absorptionanddistribution Afteroraladministrationinhumans,atleast90%ofminoxidilisabsorbedinthegastrointestinaltract.Minoxidilisdetectedwithin30minutesintheplasma.Maximumplasmalevelsarereached60minutesafteradministration. Basedonresultsfromarelativebioavailabilitystudy,tabletandoralsolutionformulationshavesimilarvaluesinareaundertheserumconcentration-timecurve(AUC),maximumserumconcentration,timetoreachmaximumserumconcentration(approximately40minutes),andthetypeofeffect(antihypertensive).Thereisnoaccumulationfollowingchronicadministrationoforaltabletscomparedwithsingledose. Minoxidilisnotboundtoplasmaproteins. Minoxidildoesnotcrosstheblood-brainbarrier. Metabolism Atleast90%oftheadministeredminoxidilismetabolizedintheliver.TheprimarymetaboliteinhumansistheminoxidilO-glucuronide.Somepolarmetabolitesarealsoproduced.Theknownmetaboliteshaveaweakerantihypertensiveeffectthantheactiveingredientitself. Elimination Inhumans,minoxidilplasmaconcentrationsdecreasewithanaveragehalf-lifeofapproximately4hours.However,thedurationofactionisoverseveraldays. Minoxidilanditsmetabolitesaredialyzable. Therenalclearanceofminoxidilcorrespondstotheglomerularfiltrationrate.Nosubstantialchangesintheglomerularfiltrationrateandtherenalplasmaflowcouldbedetectedunderminoxidil. Paediatricpopulation Nopharmacokineticdataregardingminoxidilinthepaediatricpopulationiscurrentlyavailable. Hepaticimpairment Nodataareavailable. 5.3Preclinicalsafetydata Cardiaclesionsinanimals Innon-clinicalstudiesinavarietyofspecies,minoxidilinducesseveraltypesofcardiaclesionsincludingnecroticandhaemorrhagiclesionsofthemyocardiumandpapillarymuscles,andcardiachypertrophyanddilation.Thesechangesoccuronlyinthecontextofprofoundhypotensionandtachycardiaandreflecthaemodynamicand/orhypoxicstressratherthandirectcytotoxicity.Asgreaterexperiencewiththedrughasaccumulated,ithasbecomeapparentthatthesecardiaclesionsdonotoccurinhumanstreatedwithminoxidil. Carcinogenicity Incarcinogenicitystudiesinratsandmicedosedviaoralordermalroutesofadministrationnofindingsconsideredrelevanttohumanswerefound. Reproductivetoxicity Inafertilitystudywithmaleandfemalerats,adose-dependentreductionoftheconceptionratewasfound.Thenoobservedadverseeffectlevel(NOAEL)forthisfindingwas1mg/kgperdayintreatedrats. Teratogenicityhasbeendemonstratedintheratatdosesabove80mg/kg/day.Oraladministrationofminoxidilhasbeenassociatedwithevidenceofincreasedfoetalresorptioninrabbitsatdosesassociatedwithmaternaltoxicity.Teratogenicitywasnotdemonstratedintherabbit. Nodataregardingjuvenileanimaltoxicitystudiesiscurrentlyavailable. 6.Pharmaceuticalparticulars 6.1Listofexcipients Lactosemonohydrate Microcrystallinecellulose Starch Colloidalsilicondioxide Magnesiumstearate. 6.2Incompatibilities Notapplicable. 6.3Shelflife 3years. 6.4Specialprecautionsforstorage Blisters: Storebelow25°C. Storeintheoriginalpackageinordertoprotectfrommoisture. Bottles: Storebelow25°C. Keepthebottletightlyclosedinordertoprotectfrommoisture. 6.5Natureandcontentsofcontainer Highdensitypolyethylene(HDPE)bottleswithlowdensitypolyethylene(LDPE)caps.Eachbottlecontains100tablets. 20-25micronaluminiumfoil/250micronopaquepolyvinylchloride(PVC)blister.Packcontains60tablets. Notallpacksizesmaybemarketed. 6.6Specialprecautionsfordisposalandotherhandling Nospecialrequirements. 7.Marketingauthorisationholder PfizerLimited,RamsgateRoad,Sandwich,CT139NJ,UK 8.Marketingauthorisationnumber(s) PL00057/1006 9.Dateoffirstauthorisation/renewaloftheauthorisation 24May1995 10.Dateofrevisionofthetext 10/2020 Ref:17_0 ReportSideEffect RelatedMedicines Sameactiveingredients Samecompany Bookmark Email Lastupdatedonemc:24Nov2020 Viewchanges Print Companycontactdetails PfizerLimited Address RamsgateRoad,Sandwich,Kent,CT139NJ MedicalInformationDirectLine +44(0)1304616161 Telephone +44(0)1304616161 MedicalInformationWebsite www.pfizermedicalinformation.co.uk × Bookmarkthismedicine Tobookmarkamedicineyoumustsignupandlogin. SignUp LogIn Cancel × Emailthismedicine Toemailamedicineyoumustsignupandlogin. SignUp LogIn Cancel × Viewmedicinechanges Toviewthechangestoamedicineyoumustsignupandlogin. SignUp LogIn Cancel × Findsimilarproducts Tofindsimilarproductsyoumustsignupandlogin. 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