Loniten (Minoxidil Tablets, USP): Uses, Dosage, Side ... - RxList

Loniten is a prescription medicine used to treat the symptoms of Severe or Refractory Hypertension (HTN). Loniten Topper may be used alone or with other ... Loniten GenericName:minoxidiltablets,uspBrandName:Loniten DrugClass:Vasodilators MedicalEditor: JohnP.Cunha,DO,FACOEP LastupdatedonRxList:3/10/2022 home drugsa-zlist sideeffectsdrugcenterloniten(minoxidiltablets,usp)drug RelatedDrugs Apresazide Atacand AtacandHCT Capozide Cardura CarduraXL Edecrin Hyzaar IrbesartanGeneric Lotensin LotensinHct Methyldopa Midamor Monopril MonoprilHCT Prinivil Zestril HealthResources HighBloodPressure(Hypertension) PROFESSIONAL CONSUMER SIDEEFFECTS DrugDescription Indications Dosage SideEffects&DrugInteractions Warnings Precautions Overdosage&Contraindications ClinicalPharmacology MedicationGuide DrugDescription WhatisLonitenandhowisitused? LonitenisaprescriptionmedicineusedtotreatthesymptomsofSevereorRefractoryHypertension(HTN).LonitenToppermaybeusedaloneorwithothermedications. LonitenbelongstoaclassofdrugscalledVasodilators. ItisnotknownifLonitenissafeandeffectiveinchildrenyoungerthan12yearsofage. WhatarethepossiblesideeffectsofLoniten? Lonitenmaycauseserioussideeffectsincluding: hives, difficultybreathing, swellingofyourface,lips,tongue,orthroat, neworworseningchestpain, chestpainspreadingtoyourjaworshoulder, fastorpoundingheartbeats, swellinginyourlegs,ankles,orfeet, rapidweightgain(especiallyinyourfaceandmidsection), shortnessofbreath, lightheadedness, painwhenyoubreathe, wheezing, gaspingforbreath, coughwithfoamymucus, fever, sorethroat, swellinginyourfaceortongue, burninginyoureyes, skinpain,and redorpurpleskinrashthatspreads(especiallyinthefaceorupperbody)andcausesblisteringandpeeling Getmedicalhelprightaway,ifyouhaveanyofthesymptomslistedabove. ThemostcommonsideeffectsofLoniteninclude: changesincolor,length,orthicknessofbodyorfacialhair, nausea, vomiting, rash,and breastpainortenderness Tellthedoctorifyouhaveanysideeffectthatbothersyouorthatdoesnotgoaway. ThesearenotallthepossiblesideeffectsofLoniten.Formoreinformation,askyourdoctororpharmacist. Callyourdoctorformedicaladviceaboutsideeffects.YoumayreportsideeffectstoFDAat1-800-FDA-1088. WARNING LONITENTabletscontainthepowerfulantihypertensiveagent,minoxidil,whichmayproduceseriousadverseeffects.Itcancausepericardialeffusion,occasionallyprogressingtotamponade,andanginapectorismaybeexacerbated.LONITENshouldbereservedforhypertensivepatientswhodonotrespondadequatelytomaximumtherapeuticdosesofadiureticandtwootherantihypertensiveagents. Inexperimentalanimals,minoxidilcausedseveralkindsofmyocardiallesionsaswellasotheradversecardiaceffects(seeCardiacLesionsinAnimals). LONITENmustbeadministeredunderclosesupervision,usuallyconcomitantlywiththerapeuticdosesofabeta-adrenergicblockingagenttopreventtachycardiaandincreasedmyocardialworkload.Itmustalsousuallybegivenwithadiuretic,frequentlyoneactingintheascendinglimboftheloopofHenle,topreventseriousfluidaccumulation.Patientswithmalignanthypertensionandthosealreadyreceivingguanethidine(seeWARNINGS)shouldbehospitalizedwhenLONITENisfirstadministeredsothattheycanbemonitoredtoavoidtoorapid,orlargeorthostatic,decreasesinbloodpressure. DESCRIPTION LONITENTabletscontainminoxidil,anantihypertensiveperipheralvasodilator.Minoxidiloccursasawhiteoroff-white,odorless,crystallinesolidthatissolubleinwatertotheextentofapproximately2mg/mL,isreadilysolubleinpropyleneglycolorethanol,andisalmostinsolubleinacetone,chloroformorethylacetate.Thechemicalnameforminoxidilis2,4-pyrimidinediamine,6-(1-piperidinyl)-,3-oxide(mw=209.25).Thestructuralformulaisrepresentedatright:  LONITENTabletsfororaladministrationcontaineither2.5mgor10mgofminoxidil.Inactiveingredients:cellulose,cornstarch,lactose,magnesiumstearate,silicondioxide. Indications INDICATIONS Becauseofthepotentialforseriousadverseeffects, LONITENTabletsareindicatedonlyinthetreatmentofhypertensionthatis symptomaticorassociatedwithtargetorgandamageandisnotmanageablewith maximumtherapeuticdosesofadiureticplustwootherantihypertensivedrugs. Atthepresenttimeuseinmilderdegreesofhypertensionisnotrecommended becausethebenefit-riskrelationshipinsuchpatientshasnotbeendefined. LONITENreducedsupinediastolicbloodpressureby20mm Hgorto90mmHgorlessinapproximately75%ofpatients,mostofwhohad hypertensionthatcouldnotbecontrolledbyotherdrugs. QUESTION Saltandsodiumarethesame. SeeAnswer Dosage DOSAGEANDADMINISTRATION PatientsOver12YearsofAge TherecommendedinitialdosageofLONITENTabletsis5mg ofminoxidilgivenasasingledailydose.Dailydosagecanbeincreasedto10, 20andthento40mginsingleordivideddosesifrequiredforoptimumblood pressurecontrol.Theeffectivedosagerangeisusually10to40mgperday. Themaximumrecommendeddosageis100mgperday. PatientsUnder12YearsofAge Theinitialdosageis0.2mg/kgminoxidilasasingle dailydose.Thedosagemaybeincreasedin50to100%incrementsuntiloptimum bloodpressurecontrolisachieved.Theeffectivedosagerangeisusually0.25 to1.0mg/kg/day.Themaximumrecommendeddosageis50mgdaily(see Pediatric UseunderPRECAUTIONS). DoseFrequency Themagnitudeofwithin-dayfluctuationofarterial pressureduringtherapywithLONITENisdirectlyproportionaltotheextentof pressurereduction.Ifsupinediastolicpressurehasbeenreducedlessthan30 mmHg,thedrugneedbeadministeredonlyonceaday;ifsupinediastolic pressurehasbeenreducedmorethan30mmHg,thedailydosageshouldbe dividedintotwoequalparts. FrequencyofDosageAdjustment Dosagemustbetitratedcarefullyaccordingtoindividual response.Intervalsbetweendosageadjustmentsnormallyshouldbeatleast3 dayssincethefullresponsetoagivendoseisnotobtainedforatleastthat amountoftime.Whereamorerapidmanagementofhypertensionisrequired, doseadjustmentscanbemadeevery6hoursifthepatientiscarefully monitored. ConcomitantTherapy Diureticandbeta-blockerorothersympatheticnervous systemsuppressant. Diuretics LONITENmustbeusedinconjunctionwithadiureticin patientsrelyingonrenalfunctionformaintainingsaltandwaterbalance. Diureticshavebeenusedatthefollowingdosageswhenstartingtherapywith LONITEN:hydrochlorothiazide(50mg,b.i.d.)orotherthiazidesat equieffectivedosage;chlorthalidone(50to100mg,oncedaily);furosemide(40 mg,b.i.d.).Ifexcessivesaltandwaterretentionresultsinaweightgainof morethan5pounds,diuretictherapyshouldbechangedtofurosemide;ifthe patientisalreadytakingfurosemide,dosageshouldbeincreasedinaccordance withthepatient'srequirements. Beta-blockerOrOtherSympatheticNervousSystemSuppressants WhentherapywithLONITENisbegun,thedosageofa beta-adrenergicreceptorblockingdrugshouldbetheequivalentof80to160mg ofpropranololperdayindivideddoses. Ifbeta-blockersarecontraindicated,methyldopa(250to 750mg,b.i.d.)maybeusedinstead.Methyldopamustbegivenforatleast24 hoursbeforestartingtherapywithLONITENbecauseofthedelayintheonsetof methyldopa'saction.Limitedclinicalexperienceindicatesthatclonidinemay alsobeusedtopreventtachycardiainducedbyLONITEN;theusualdosageis0.1 to0.2mgtwicedaily. Sympatheticnervoussystemsuppressantsmaynot completelypreventanincreaseinheartrateduetoLONITENbutusuallydo preventtachycardia.Typically,patientsreceivingabeta-blockerpriorto initiationoftherapywithLONITENhaveabradycardiaandcanbeexpectedto haveanincreaseinheartratetowardnormalwhenLONITENisadded.When treatmentwithLONITENandbeta-blockerorothersympatheticnervoussystem suppressantarebegunsimultaneously,theiropposingcardiaceffectsusually nullifyeachother,leadingtolittlechangeinheartrate. HOWSUPPLIED LONITENTabletsareavailableasfollows: 2.5mg(white,round,scored,imprintedU/121and 2½) Bottlesof100NDC0009-0121-01 10mg(white,round,scored,imprintedLONITEN10) Bottlesof100NDC0009-0137-01 Storeatcontrolledroomtemperature20°to25°C(68°to 77°F)[seeUSP]. Distributedby:Pharmacia&UpjohnCompany,Division ofPfizerInc.,NY,NY10017.RevisedJanuary2015 SideEffects&DrugInteractions SIDEEFFECTS SaltandWaterRetention (seeWARNINGS:ConcomitantUseofAdequateDiureticis Required)—Temporaryedemadevelopedin7%ofpatientswhowerenot edematousatthestartoftherapy. Pericarditis,PericardialEffusionAndTamponade (seeWARNINGS). Dermatologic Hypertrichosis—Elongation,thickening,andenhancedpigmentation offinebodyhairareseeninabout80%ofpatientstakingLONITENTablets. Thisdevelopswithin3to6weeksafterstartingtherapy.Itisusuallyfirst noticedonthetemples,betweentheeyebrows,betweenthehairlineandthe eyebrows,orintheside-burnareaoftheupperlateralcheek,laterextending totheback,arms,legs,andscalp.UpondiscontinuationofLONITEN,newhair growthstops,but1to6monthsmayberequiredforrestorationtopretreatment appearance.Noendocrineabnormalitieshavebeenfoundtoexplaintheabnormal hairgrowth;thus,itishypertrichosiswithoutvirilism.Hairgrowthis especiallydisturbingtochildrenandwomenandsuchpatientsshouldbe thoroughlyinformedaboutthiseffectbeforetherapywithLONITENisbegun. Allergic—Rasheshavebeenreported,includingrare reportsofbullouseruptions,toxicepidermalnecrolysis,andStevens-Johnson Syndrome. Hematologic Thrombocytopeniaandleukopenia(WBC<3000/mm³) haverarelybeenreported. Gastrointestinal Nauseaand/orvomitinghasbeenreported.Inclinical trialstheincidenceofnauseaandvomitingassociatedwiththeunderlying diseasehasshownadecreasefrompretriallevels. Miscellaneous Breasttenderness—Thisdevelopedinlessthan1%of patients. AlteredLaboratoryFindings (a)ECGchanges—Changesindirectionandmagnitudeofthe ECGT-wavesoccurinapproximately60%ofpatientstreatedwithLONITEN.In rareinstancesalargenegativeamplitudeoftheT-wavemayencroachuponthe S-Tsegment,buttheS-Tsegmentisnotindependentlyaltered.Thesechanges usuallydisappearwithcontinuanceoftreatmentandreverttothepretreatment stateifLONITENisdiscontinued.Nosymptomshavebeenassociatedwiththese changes,norhavetherebeenalterationsinbloodcellcountsorinplasma enzymeconcentrationsthatwouldsuggestmyocardialdamage.Long-termtreatment ofpatientsmanifestingsuchchangeshasprovidednoevidenceofdeteriorating cardiacfunction.Atpresentthechangesappeartobenonspecificandwithout identifiableclinicalsignificance.(b)Effectsofhemodilution—hematocrit, hemoglobinanderythrocytecountusuallyfallabout7%initiallyandthen recovertopretreatmentlevels.(c)Other—Alkalinephosphataseincreased varyinglywithoutotherevidenceofliverorboneabnormality.Serumcreatinine increasedanaverageof6%andBUNslightlymore,butlaterdeclinedto pretreatmentlevels. DRUGINTERACTIONS See“InteractionwithGuanethidine” underWARNINGS. SLIDESHOW HowtoLowerBloodPressure:ExerciseTips SeeSlideshow Warnings WARNINGS SaltAndWaterRetention CongestiveHeartFailure concomitantuseofanadequatediureticisrequired— LONITENTabletsmustusuallybeadministeredconcomitantlywithadiuretic adequatetopreventfluidretentionandpossiblecongestiveheartfailure;a highceiling(loop)diureticisalmostalwaysrequired.Body weightshouldbemonitoredclosely.IfLONITENisusedwithoutadiuretic, retentionofseveralhundredmilli-equivalentsofsaltandcorresponding volumesofwatercanoccurwithinafewdays,leadingtoincreasedplasmaand interstitialfluidvolumeandlocalorgeneralizededema.Diuretictreatment alone,orincombinationwithrestrictedsaltintake,willusuallyminimize fluidretention,althoughreversibleedemadiddevelopinapproximately10%of nondialysispatientssotreated.Asciteshasalsobeenreported.Diuretic effectivenesswaslimitedmostlybydisease-relatedimpairedrenalfunction. Theconditionofpatientswithpreexistingcongestiveheartfailure occasionallydeterioratedinassociationwithfluidretentionalthoughbecause ofthefallinbloodpressure(reductionofafterload),morethantwiceasmany improvedthanworsened.Rarely,refractoryfluidretentionmayrequire discontinuationofLONITEN.Providedthatthepatientisunderclosemedical supervision,itmaybepossibletoresolverefractorysaltretentionby discontinuingLONITENfor1or2daysandthenresumingtreatmentin conjunctionwithvigorousdiuretictherapy. ConcomitantTreatmentToPreventTachycardiaIsUsually Required LONITENincreasestheheartrate.Anginamayworsenor appearforthefirsttimeduringLONITENtreatment,probablybecauseofthe increasedoxygendemandsassociatedwithincreasedheartrateandcardiac output.Theincreaseinrateandtheoccurrenceofanginagenerallycanbe preventedbytheconcomitantadministrationofabeta-adrenergicblockingdrug orothersympatheticnervoussystemsuppressant.Theabilityofbetaadrenergic blockingagentstominimizepapillarymusclelesionsinanimalsisfurther reasontoutilizesuchanagentconcomitantly.Round-the-clockeffectivenessof thesympatheticsuppressantshouldbeensured. Pericarditis,PericardialEffusionAndTamponade Therehavebeenreportsofpericarditisoccurringin associationwiththeuseofLONITEN.Therelationshipofthisassociationto renalstatusisuncertain.Pericardialeffusion,occasionallywithtamponade, hasbeenobservedinabout3%oftreatedpatientsnotondialysis,especially thosewithinadequateorcompromisedrenalfunction.Althoughinmanycases, thepericardialeffusionwasassociatedwithaconnectivetissuedisease,the uremicsyndrome,congestiveheartfailure,ormarkedfluidretention,therehave beeninstancesinwhichthesepotentialcausesofeffusionwerenotpresent. Patientsshouldbeobservedcloselyforanysuggestionofapericardial disorder,andechocardiographicstudiesshouldbecarriedoutifsuspicion arises.Morevigorousdiuretictherapy,dialysis,pericardiocentesis,or surgerymayberequired.Iftheeffusionpersists,withdrawalofLONITENshould beconsideredinlightofothermeansofcontrollingthehypertensionandthe patient'sclinicalstatus. InteractionWithGuanethidine Althoughminoxidildoesnotitselfcauseorthostatic hypotension,itsadministrationtopatientsalreadyreceivingguanethidinecan resultinprofoundorthostaticeffects.Ifatallpossible,guanethidineshould bediscontinuedwellbeforeminoxidilisbegun.Wherethisisnotpossible, minoxidiltherapyshouldbestartedinthehospitalandthepatientshould remaininstitutionalizeduntilsevereorthostaticeffectsarenolongerpresent orthepatienthaslearnedtoavoidactivitiesthatprovokethem. HazardOfRapidControlOfBloodPressure Inpatientswithveryseverebloodpressureelevation, toorapidcontrolofbloodpressure,especiallywithintravenousagents,can precipitatesyncope,cerebrovascularaccidents,myocardialinfarctionand ischemiaofspecialsenseorganswithresultingdecreaseorlossofvisionor hearing.Patientswithcompromisedcirculationorcryoglobulinemiamayalso sufferischemicepisodesoftheaffectedorgans.Althoughsucheventshavenot beenunequivocallyassociatedwithminoxidiluse,totalexperienceislimited atpresent. Anypatientwithmalignanthypertensionshouldhave initialtreatmentwithminoxidilcarriedoutinahospitalsetting,bothto assurethatbloodpressureisfallingandtoassurethatitisnotfallingmore rapidlythanintended. Precautions PRECAUTIONS GeneralPrecautions Monitorfluidandelectrolytebalanceandbodyweight (seeWARNINGS:SaltandWaterRetention). Observepatientsforsignsandsymptomsofpericardial effusion(seeWARNINGS:Pericarditis,PericardialEffusion, andTamponade). Useaftermyocardialinfarction—LONITEN Tabletshavenotbeenusedinpatientswhohavehadamyocardialinfarction withintheprecedingmonth.Itispossiblethatareductionofarterial pressurewithLONITENmightfurtherlimitbloodflowtothemyocardium, althoughthismightbecompensatedbydecreasedoxygendemandbecauseoflower bloodpressure. Hypersensitivity—Possiblehypersensitivity toLONITEN,manifestedasaskinrash,hasbeenseeninlessthan1%of patients;whetherthedrugshouldbediscontinuedwhenthisoccursdependson treatmentalternatives. Renalfailureordialysis—Patientsmay requiresmallerdosesofLONITENandshouldhaveclosemedicalsupervisionto preventexacerbationofrenalfailureorprecipitationofcardiacfailure. InformationForPatient Thepatientshouldbefullyawareoftheimportanceof continuingallofhisantihypertensivemedicationsandofthenatureof symptomsthatwouldsuggestfluidoverload.Apatientbrochurehasbeen preparedandisincludedwitheachLONITENpackage.Thetextofthisbrochure isreprintedattheendoftheinsert. LaboratoryTests Thoselaboratorytestswhichareabnormalatthetimeof initiationofminoxidiltherapy,suchasurinalysis,renalfunctiontests,EKG, chestx-ray,echocardiogram,etc.,shouldberepeatedatintervalstoascertain whetherimprovementordeteriorationisoccurringunderminoxidiltherapy. Initiallysuchtestsshouldbeperformedfrequently,eg,1–3monthintervals; laterasstabilizationoccurs,atintervalsof6–12months. Carcinogenesis,MutagenesisAndImpairmentOfFertility Two-yearcarcinogenicitystudiesofminoxidilhavebeen conductedbythedermalandoral(dietary)routesofadministrationinmiceand rats.Therewerenopositivefindingswiththeoral(dietary)routeof administrationinrats. Inthetwo-yeardermalstudyinmice,anincreased incidenceofmammaryadenomasandadenocarcinomasinthefemalesatalldose levels(8,25and80mg/kg/day)wasattributedtoincreasedprolactinactivity. Hyperprolactinemiaisawell-knownmechanismintheenhancementofmouse mammarytumors,buthasnotbeenassociatedwithmammarytumorigenesisin women.Additionally,topicalminoxidilhasnotbeenshowntocause hyperprolactinemiainwomenonclinicaltrials.Absorptionofminoxidilthrough rodentskinisgreaterthanwouldbeexperiencedbypatientstreatedtopically withminoxidilforhairloss.Dietaryadministrationofminoxidiltomicefor upto2yearswasassociatedwithanincreasedincidenceofmalignantlymphomas infemalesatalldoselevels(10,25and63mg/kg/day)andanincreased incidenceofhepaticnodulesinmales(63mg/kg/day).Therewasnoeffectof dietaryminoxidilontheincidenceofmalignantlivertumors. Inthetwo-yeardermalstudyinratstherewere significantincreasesinincidenceofpheochromocytomasinmalesandfemales andpreputialglandadenomasinmales.Changesinincidenceofneoplasmsfound tobeincreasedinthedermalororalcarcinogenicitystudiesweretypicalof thoseexpectedinrodentstreatedwithotherhypotensiveagents(adrenal pheochromocytomasinrats),treatment-relatedhormonalalterations(mammary carcinomasinfemalemice;preputialglandadenomasinmalerats)or representativeofnormalvariationswithintherangeofhistoricalincidence forrodentneoplasms(malignantlymphomas,livernodules/adenomasinmice). Basedondifferencesinabsorptionofminoxidilandmechanismsoftumorigenesis intheserodentspecies,noneofthesechangeswereconsideredtoberelevant tothesafetyofpatientstreatedtopicallywithminoxidilforhairloss. Therewasnoevidenceofepithelialhyperplasiaor tumorigenesisatthesitesoftopicalapplicationofminoxidilineither speciesinthe2-yeardermalcarcinogenesisstudies.Noevidenceof carcinogenicitywasdetectedinratsorrabbitstreatedtopicallywith minoxidilforoneyear.Topicalminoxidil(2%and5%)didnotsignificantly (p<0.05)reducethelatencyperiodofUVlight-initiatedskintumorsin hairlessmice,ascomparedtocontrols,ina12-monthphotocarcinogenicity study. MinoxidilwasnotmutagenicintheSalmonella(Ames) test,theDNAdamagealkalineelutionassay,theinvitrorathepatocyte unscheduledDNAsynthesis(UDS)assay,theratbonemarrowmicronucleusassay, orthemousebonemarrowmicronucleusassay.Anequivocalresultwasrecorded inaninvitrocytogeneticassayusingChinesehamstercellsatlongexposure times,butasimilarassayusinghumanlymphocyteswasnegative. Inastudyinwhichmaleandfemaleratsreceivedoneor fivetimesthemaximumrecommendedhumanoralantihypertensivedoseof minoxidil(multiplesbasedona50kgpatient)therewasadose-dependent reductioninconceptionrate. Pregnancy TeratogenicEffects PregnancyCategoryC.Oraladministration ofminoxidilhasbeenassociatedwithevidenceofincreasedfetalresorptionin rabbits,butnotrats,whenadministeredatfivetimesthemaximumrecommended oralantihypertensivehumandose.Therewasnoevidenceofteratogeniceffects inratsandrabbits.Subcutaneousadministrationofminoxidiltopregnantrats at80mg/kg/daywasmaternallytoxicbutnotteratogenic.Highersubcutaneous dosesproducedevidenceofdevelopmentaltoxicity.Therearenoadequateand wellcontrolledstudiesinpregnantwomen.LONITENshouldbeusedduring pregnancyonlyifthepotentialbenefitjustifiesthepotentialrisktothe fetus. Neonatalhypertrichosishasbeenreportedfollowing exposuretominoxidilduringpregnancy. LaborAndDelivery Theeffectsonlaboranddeliveryareunknown. NursingMothers Therehasbeenonereportofminoxidilexcretioninthe breastmilkofawomantreatedwith5mgoralminoxidiltwicedailyfor hypertension.Becauseofthepotentialforadverseeffectsinnursinginfants fromminoxidilabsorption,LONITENshouldnotbeadministeredtoanursing woman. PediatricUse Useinpediatricpatientshasbeenlimitedtodate, particularlyininfants.TherecommendationsunderDOSAGEANDADMINISTRATION canbeconsideredonlyaroughguideatpresentandacarefultitrationis essential. GeriatricUse ClinicalstudiesofLONITENTabletsdidnotinclude sufficientnumbersofsubjectsaged65andovertodeterminewhetherthey responddifferentlyfromyoungersubjects.Otherreportedclinicalexperience hasnotidentifieddifferencesinresponsesbetweentheelderlyandyounger patients.Ingeneral,doseselectionforanelderlypatientshouldbecautious, usuallystartingatthelowendofthedosingrange,reflectingthegreater frequencyofdecreasedhepatic,renal,orcardiacfunction,andofconcomitant diseaseorotherdrugtherapy. UnapprovedUse UseofLONITENTablets,inanyformulation,topromote hairgrowthisnotanapprovedindication.WhileclinicaltrialswithROGAINE®TopicalSolution2%demonstratedthatformulationanddosageweresafe andeffective,theeffectsofextemporaneousformulationsanddosageshavenot beenshowntobesafeoreffective.Becausesystemicabsorptionoftopically applieddrugmayoccurandisdependentonvehicleand/ormethodofuse, extemporaneoustopicalformulationsmadefromLONITENshouldbeconsideredtoshare inthefullrangeofCONTRAINDICATIONS,WARNINGS,PRECAUTIONS,andADVERSE REACTIONSlistedinthisinsert.Inaddition,skinintolerancetodrugand/or vehiclemayoccur. Overdosage&Contraindications OVERDOSE Therehavebeenonlyafewinstancesofdeliberateor accidentaloverdosagewithLONITENTablets.Onepatientrecoveredaftertaking 50mgofminoxidiltogetherwith500mgofabarbiturate.Whenexaggerated hypotensionisencountered,itismostlikelytooccurinassociationwithresidual sympatheticnervoussystemblockadefromprevioustherapy(guanethidine-like effectsoralpha-adrenergicblockage),whichpreventstheusualcompensatory maintenanceofbloodpressure.Intravenousadministrationofnormalsalinewill helptomaintainbloodpressureandfacilitateurineformationinthese patients.Sympathomimeticdrugssuchasnorepinephrineorepinephrineshouldbe avoidedbecauseoftheirexcessivecardiacstimulatingaction.Phenylephrine, angiotensinII,vasopressin,anddopamineallreversehypotensiondueto LONITEN,butshouldonlybeusedifunderperfusionofavitalorganisevident. Radioimmunoassaycanbeperformedtodeterminethe concentrationofminoxidilintheblood.Atthemaximumadultdoseof100 mg/day,peakbloodlevelsof1641ng/mLand2441ng/mLwereobservedintwo patients,respectively.Duetopatient-to-patientvariationinbloodlevels,it isdifficulttoestablishanoverdosagewarninglevel.Ingeneral,a substantialincreaseabove2000ng/mLshouldberegardedasoverdosage,unless thephysicianisawarethatthepatienthastakennomorethanthemaximum dose. OralLD50inratshasrangedfrom1321–3492mg/kg;in mice,2456–2648mg/kg. CONTRAINDICATIONS LONITENTabletsarecontraindicatedinpheochromocytoma, becauseitmaystimulatesecretionofcatecholaminesfromthetumorthroughits antihypertensiveaction.LONITENiscontraindicatedinthosepatientswitha historyofhypersensitivitytoanyofthecomponentsofthepreparation. ClinicalPharmacology CLINICALPHARMACOLOGY GeneralPharmacologicProperties Minoxidilisanorallyeffectivedirectactingperipheral vasodilatorthatreduceselevatedsystolicanddiastolicbloodpressureby decreasingperipheralvascularresistance.Microcirculatorybloodflowin animalsisenhancedormaintainedinallsystemicvascularbeds.Inman, forearmandrenalvascularresistancedecline;forearmbloodflowincreases whilerenalbloodflowandglomerularfiltrationratearepreserved. Becauseitcausesperipheralvasodilation,minoxidil elicitsanumberofpredictablereactions.Reductionofperipheralarteriolar resistanceandtheassociatedfallinbloodpressuretriggersympathetic,vagal inhibitory,andrenalhomeostaticmechanisms,includinganincreaseinrenin secretion,thatleadtoincreasedcardiacrateandoutputandsaltandwater retention.Theseadverseeffectscanusuallybeminimizedbyconcomitant administrationofadiureticandabeta-adrenergicblockingagentorother sympatheticnervoussystemsuppressant. Minoxidildoesnotinterferewithvasomotorreflexesand thereforedoesnotproduceorthostatichypotension.Thedrugdoesnotenterthe centralnervoussysteminexperimentalanimalsinsignificantamounts,andit doesnotaffectCNSfunctioninman. EffectsOnBloodPressureAndTargetOrgans Theextentandtime-courseofbloodpressurereductionby minoxidildonotcorrespondcloselytoitsconcentrationinplasma.Afteran effectivesingleoraldose,bloodpressureusuallystartstodeclinewithin one-halfhour,reachesaminimumbetween2and3hoursandrecoversatan arithmeticallylinearrateofabout30%/day.Thetotaldurationofeffectis approximately75hours.Whenminoxidilisadministeredchronically,onceor twiceaday,thetimerequiredtoachievemaximumeffectonbloodpressurewith agivendailydoseisinverselyrelatedtothesizeofthedose.Thus,maximum effectisachievedon10mg/daywithin7days,on20mg/daywithin5days,and on40mg/daywithin3days. Thebloodpressureresponsetominoxidilislinearly relatedtothelogarithmofthedoseadministered.Theslopeofthislog-linear dose-responserelationshipisproportionaltotheextentofhypertensionand approacheszeroatasupinediastolicbloodpressureofapproximately85mmHg. Whenusedinseverelyhypertensivepatientsresistantto othertherapy,frequentlywithanaccompanyingdiureticandbeta-blocker, LONITENTabletsusuallydecreasedthebloodpressureandreversed encephalopathyandretinopathy. AbsorptionAndMetabolism Minoxidilisatleast90%absorbedfromtheGItractin experimentalanimalsandman.Plasmalevelsoftheparentdrugreachmaximum withinthefirsthouranddeclinerapidlythereafter.Theaverageplasma half-lifeinmanis4.2hours.Approximately90%oftheadministereddrugis metabolized,predominantlybyconjugationwithglucuronicacidattheN-oxide positioninthepyrimidinering,butalsobyconversiontomorepolarproducts. Knownmetabolitesexertmuchlesspharmacologiceffectthanminoxidilitself;all areexcretedprincipallyintheurine.Minoxidildoesnotbindtoplasma proteinsanddoesnotcrossthebloodbrainbarrier.Itsrenalclearance correspondstotheglomerularfiltrationrate.Intheabsenceoffunctional renaltissue,minoxidilanditsmetabolitescanberemovedbyhemodialysis. CardiacLesionsInAnimals Minoxidilproducesseveralcardiaclesionsinanimals. Somearecharacteristicofagentsthatcausetachycardiaanddiastolic hypotension(beta-agonistslikeisoproterenol,arterialdilatorslike hydralazine)whileothersareproducedbyanarrowerrangeofagentswith arterialdilatingproperties.Thesignificanceoftheselesionsforhumansis notclear,astheyhavenotbeenrecognizedinpatientstreatedwithoral minoxidilatsystemicallyactivedoses,despiteformalreviewofover150 autopsiesoftreatedpatients. Papillarymuscle/subendocardialnecrosis Themostcharacteristiclesionofminoxidil,seeninrat,dog,andminipig(but notmonkeys)isfocalnecrosisofthepapillarymuscleandsubendocardialareas oftheleftventricle.Theselesionsappearrapidly,withinafewdaysof treatmentwithdosesof0.5to10mg/kg/dayinthedogandminipig,andarenot progressive,althoughtheyleaveresidualscars.Theyaresimilartolesions producedbyotherperipheralarterialdilators,bytheobromine,andby beta-adrenergicreceptoragonistssuchasisoproterenol,epinephrine,and albuterol.Thelesionsarethoughttoreflectischemiaprovokedbyincreased oxygendemand(tachycardia,increasedcardiacoutput)andrelativedecreasein coronaryflow(decreaseddiastolicpressureanddecreasedtimeindiastole) causedbythevasodilatoryeffectsoftheseagentscoupledwithreflexor directlyinducedtachycardia. Hemorrhagiclesions Afteracuteoralminoxidiltreatment(0.5to10mg/kg/day)indogsand minipigs,hemorrhagiclesionsareseeninmanypartsoftheheart,mainlyin theepicardium,endocardium,andwallsofsmallcoronaryarteriesand arterioles.Inminipigsthelesionsoccurprimarilyintheleftatriumwhilein dogstheyaremostprominentintherightatrium,frequentlyappearingas grosslyvisiblehemorrhagiclesions.Withexposureof1–20mg/kg/dayinthedog for30daysorlonger,thereisreplacementofmyocardialcellsby proliferatingfibroblastsandangioblasts,hemorrhageandhemosiderin accumulation.Theselesionscanbeproducedbytopicalminoxidiladministration thatgivessystemicabsorptionof0.5to1mg/kg/day.Otherperipheral dilators,includinganexperimentalagent,nicorandil,andtheobromine,have producedsimilarlesions. Epicarditis Alessfullystudiedlesionisfocalepicarditis,seenindogsafter2daysof oralminoxidil.Morerecently,chronicproliferativeepicarditiswasobserved indogstreatedtopicallytwiceadayfor90days.Inaoneyearoraldog study,serosanguinouspericardialfluidwasseen. HypertrophyandDilation Oralandtopicalstudiesinrats,dogs,monkeys(oralonly),andrabbits (dermalonly)showcardiachypertrophyanddilation.Thisispresumedto representtheconsequencesofprolongedfluidoverload;thereispreliminary evidenceinmonkeysthatdiureticspartlyreversetheseeffects. Autopsiesofover150patientswhodiedofvariouscauses afterreceivingminoxidilforhypertensionhavenotrevealedthecharacteristic hemorrhagic(especiallyatrial)lesionsseenindogsandminipigs.Whileareas ofpapillarymuscleandsubendocardialnecrosiswereoccasionallyseen,they occurredinthepresenceofknownpreexistingcoronaryarterydiseaseandwere alsoseeninpatientsneverexposedtominoxidilinanotherseriesusing similar,butnotidentical,autopsymethods. MedicationGuide PATIENTINFORMATION Loniten® (minoxidil)Tablets,USP LONITENTabletscontain minoxidil,amedicineforthetreatmentofhighbloodpressureinthepatient whohasnotbeencontrolledorisexperiencingunacceptablesideeffectswith othermedications.Itmustusuallybetakenwithothermedicines. Beabsolutelysuretotakeall ofyourmedicinesforhighbloodpressureaccordingtoyourdoctor's instructions.DonotstoptakingLONITENunlessyourdoctortellsyouto.Do notgiveanyofyourmedicinetootherpeople. Itisimportantthatyoulook forthewarningsignalsofcertainundesiredeffectsofLONITEN.Callyour doctoriftheyoccur.Yourdoctorwillneedtoseeyouregularlywhileyouare takingLONITEN.Besuretokeepallyourappointmentsortoarrangefornew onesifyoumustmissone. Donothesitatetocallyour doctorifanydiscomfortsorproblemsoccur. Theinformationhereis intendedtohelpyoutakeLONITENproperly.Itdoesnottellyouallthereis toknowaboutLONITEN.Thereisamoretechnicalleafletthatyoumayrequest fromthepharmacist;youmayneedyourdoctor'shelpinunderstandingpartsof thatleaflet. WhatisLONITEN? LONITENTabletscontain minoxidilwhichisadrugforloweringthebloodpressure.Itworksbyrelaxing andenlargingcertainsmallbloodvesselssothatbloodflowsthroughthemmore easily. Whylowerbloodpressure? Yourdoctorhasprescribed LONITENtoloweryourbloodpressureandprotectvitalpartsofyourbody. Uncontrolledbloodpressurecancausestroke,heartfailure,blindness,kidney failure,andheartattacks. Mostpeoplewithhighblood pressureneedtotakemedicinestotreatitfortheirwholelives. WhoshouldtakeLONITEN? Therearemanypeoplewithhigh bloodpressure,butmostofthemdonotneedLONITEN.LONITENisusedONLYwhen yourdoctordecidesthat: yourhighbloodpressureis severe; yourhighbloodpressureis causingsymptomsordamagetovitalorgans;and othermedicinesdidnotwork wellenoughorhadverydisturbingsideeffects. LONITENshouldbetakenonly whenadoctorprescribesit.NevergiveanyofyourLONITENTablets,orany otherhighbloodpressuremedicine,toafriendorrelative. Pregnancy:Insomecasesdoctorsmay prescribeLONITENforwomenwhoarepregnantorwhoareplanningtohave children.However,itssafeuseinpregnancyhasnotbeenestablished. Laboratoryanimalshadareducedabilitytobecomepregnantandareduced survivalofoffspringwhiletakingLONITEN.Ifyouarepregnantorareplanning tobecomepregnant,besuretotellyourdoctor. HowtotakeLONITEN. Usually,yourdoctorwill prescribetwoothermedicinesalongwithLONITEN.Thesewillhelplowerblood pressureandwillhelppreventundesiredeffectsofLONITEN. Often,whenamedicinelike LONITENlowersbloodpressure,yourbodytriestoreturnthebloodpressureto theoriginalhigherlevel.Itdoesthisbyholdingontowaterandsalt(so therewillbemorefluidtopump)andbymakingyourheartbeatfaster.To preventthis,yourdoctorwillusuallyprescribeawatertablettoremovethe extrasaltandwaterfromyourbody(adiuretic:dye-u-RET-tic)andanother medicinetoslowyourheartbeat. Youmustfollowyour doctor'sinstructionsexactly,takingalltheprescribedmedicines,inthe rightamounts,eachday.Thesemedicineswillhelpkeepyourbloodpressuredown. Thewatertabletandheartbeatmedicinewillhelppreventtheundesired effectsofLONITEN. LONITENTabletscomeintwo strengths(2½milligramsand10milligrams)thataremarkedoneachtablet.Pay closeattentiontothetabletmarkingstobesureyouaretakingthecorrect strength.Yourdoctormayprescribehalfatablet;thetabletsarescored (partlycutononeside)sothatyoucaneasilybreakthem. Whenyoufirststarttaking LONITEN,yourdoctormayneedtoseeyouofteninordertoadjustyourdosage. Takeallyourmedicineaccordingtothescheduleprescribedbyyourdoctor.Do notskipanydoses.IfyoushouldforgetadoseofLONITEN,waituntilitis timeforyournextdose,thencontinuewithyourregularschedule.Remember:do notstoptakingLONITEN,oranyofyourotherhighbloodpressuremedicines, withoutcheckingwithyourdoctor.Makesurethatanydoctortreatingor examiningyouknowsthatyouaretakinghighbloodpressuremedicines, includingLONITEN. WARNINGSIGNALS Evenifyoutakeallyour medicinescorrectly,LONITENTabletsmaycauseundesiredeffects.Someofthese areseriousandyoushouldbeonthelookoutforthem.Ifanyofthe followingwarningsignalsoccur,youmustcallyourdoctorimmediately: Increaseinheartrate—Youshouldmeasure yourheartratebycountingyourpulseratewhileyouareresting.If youhaveanincreaseof20beatsormoreaminuteoveryournormalpulse, contactyourdoctorimmediately.Ifyoudonotknowhowtotakeyourpulse rate,askyourdoctor.Alsoaskyourdoctorhowoftentocheckyourpulse. 2.Rapidweightgainofmore than5pounds—Youshouldweighyourselfdaily.Ifyouquicklygainfive ormorepounds,orifthereisanyswellingorpuffinessintheface,hands, ankles,orstomacharea,thiscouldbeasignthatyouareretainingbody fluids.Yourdoctormayhavetochangeyourdrugsorchangethedoseofyour drugs.Youmayalsoneedtoreducetheamountofsaltyoueat.Asmallerweight gain(2to3pounds)oftenoccurswhentreatmentisstarted.Youmay losethisextraweightwithcontinuedtreatment. 3.Increaseddifficultyin breathing,especiallywhenlyingdown. Thistoomaybeduetoanincreaseofbodyfluids.Itcanalsohappenbecause yourhighbloodpressureisgettingworse.Ineithercase,youmightrequire treatmentwithothermedicines. 4.Neworworseningofpain inthechest,arm,orshoulderorsignsofsevereindigestion—Thesecouldbesigns ofseriousheartproblems. 5.Dizziness, lightheadednessorfainting—Thesecanbesignsofhighbloodpressureortheymaybe sideeffectsfromoneofthemedicines.Yourdoctormayneedtochangeor adjustthedosageofthemedicinesyouaretaking. OTHERUNDESIREDEFFECTS LONITENTabletscancauseother undesiredeffectssuchasnauseaand/orvomitingthatareannoyingbutnot dangerous.Donotstoptakingthedrugbecauseoftheseotherundesiredeffects withouttalkingtoyourdoctor. Hairgrowth:About8outofevery10 patientswhohavetakenLONITENnoticedthatfinebodyhairgrewdarkeror longeroncertainpartsofthebody.Thishappenedabout3to6weeksafter beginningtreatment.Thehairmayfirstbenoticedontheforeheadandtemples, betweentheeyebrows,orontheupperpartofthecheeks.Later,hairmaygrow ontheback,arms,legs,orscalp.Althoughhairgrowthmaynotbenoticeable tosomepatients,itoftenisbothersomeinwomenandchildren.Unwanted haircanbecontrolledwithahairremoverorbyshaving.Theextrahairis notpermanent,itdisappearswithin1to6monthsofstoppingLONITEN.Nevertheless, youshouldnotstoptakingLONITENwithoutfirsttalkingtoyourdoctor. Afewpatientshavedevelopeda rashorbreasttendernesswhiletakingLONITENTablets,butthisisunusual. From HeartHealthResources FeaturedCenters GoodandBadFoodsforPsoriasisVideo:GettingPersonalonLifeWithMS HealthSolutionsFromOurSponsors Shot-FreeMSTreatment YourChildandCOVID-19 ReportProblemstotheFoodandDrugAdministration YouareencouragedtoreportnegativesideeffectsofprescriptiondrugstotheFDA.VisittheFDAMedWatchwebsiteorcall1-800-FDA-1088. HealthSolutionsFromOurSponsors PenisCurvedWhenErect CouldIhaveCAD? TreatBentFingers TreatHR+,HER2-MBC TiredofDandruff? 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