Loniten Tablets 5mg - Summary of Product Characteristics ...

Minoxidil lowers the elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance via vasodilation. The smooth musculature of the ... Skiptomaincontent LonitenTablets5mg 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 Loniten5mgTablets 2.Qualitativeandquantitativecomposition EachLonitentabletcontains5mgminoxidil. Excipientswithknowneffect: Eachtabletcontains94.2mgoflactosemonohydrate. Forthefulllistofexcipients,seesection6.1. 3.Pharmaceuticalform Tablet. Round,whitetolighttan,biconvextablet,with“5”imprintedononeside,scoredonthereversewitha'U'oneithersideofthescore. Thescorelineisnotintendedforbreakingthetablet. 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 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/yellowcard. 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,minoxidilinducesseveraltypesofcardiaclesionsincludingnecroticandhemorrhagiclesionsofthemyocardiumandpapillarymuscles,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. Storeinoriginalpackageinordertoprotectfrommoisture. Bottles: Storebelow25°C. Keepthebottletightlyclosedinordertoprotectfrommoisture. 6.5Natureandcontentsofcontainer Highdensitypolyethylene(HDPE)bottleswithLDPEcaps.Eachbottlecontains100tablets. 20-25micronaluminiumfoil/250micronopaquePVCblister.Packcontains60tablets. Notallpacksizesmaybemarketed. 6.6Specialprecautionsfordisposalandotherhandling Nospecialrequirements. 7.Marketingauthorisationholder PfizerLimited,RamsgateRoad,Sandwich,CT139NJ,UK 8.Marketingauthorisationnumber(s) PL00057/1007 9.Dateoffirstauthorisation/renewaloftheauthorisation 24May1995 10.Dateofrevisionofthetext 10/2020 Ref:16_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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