Mannitol
medicaldialogues.in/generics/mannitol-2721823
Indications,Uses,Dosage,DrugsInteractions,Sideeffects
Mannitol
MedicineType: Allopathy
PrescriptionType: PrescriptionRequired
Approval: DCGI(DrugsControllerGeneralofIndia)
Schedule ScheduleH
PharmacologicalClass:
OsmoticDiuretics, TherapyClass:
Antihypertensive, Innovatorname: BaxterHealthcareCorporation
Mannitolisanantihypertensiveagentbelonging toOsmosisDiuretics.
MannitolisanOsmoticdiureticusedtoremove excesswaterandtoxinsfromthebodyinpatientswithkidneydisease.Itis alsousedin thetreatmentofcerebraledemaandintraocularpressure.
Approximately7%ofingestedmannitolis absorbedduringgastrointestinalperfusioninuremicpatients. Mannitoladministered intravenouslyhasavolumeofdistributionof34.3 L.Mannitolismetabolizedonlyslightly,ifatall,to glycogenintheliver.
Mannitol isprimarilyexcretedunchangedintheurine.Intravenousadministrationof mannitolyieldsatotalclearanceof5.1L/hrand renalclearanceof4.4L/hr.
MannitolshowscommonsideeffectsHeadache, nausea,diarrhea,vomiting,drymouth,thirst,dehydration,blurredvision, runnynose, armpain,chills,dizziness,lowbloodpressure(hypotension), hives,irregularheartbeat,andelectrolyteimbalance,etc.
Mannitolis availableintheformofanInjectablesolution
Mannitolis availableinIndia,US,Japan,England,China,Austria,Canada,Europeand Italy.
Mannitolbelongingtothe OsmoticDiureticsactsasanantihypertensiveagent.
Producesosmoticdiuresisbyincreasingtheosmoticpressureofglomerularfiltrate, whichinhibitstubularreabsorptionofwaterand electrolytesandincreases urinaryoutput.ThemechanismofactioninthereductionofIntracranial pressure(ICP)islessclear.However, itisthoughtthatmannitolreducesICP byreducingbloodviscositywhichtransientlyincreasescerebralbloodflowand oxygentransport andconstrictspialarterioles.Thisinturnreducescerebral bloodvolumeandICP.Furthermore,mannitolreducesICPbywithdrawing waterfromthebrainparenchymaandexcretingwaterintheurine.
TheonsetofactionofMannitolis forDiuresis:1to3hours;Reductioninintracranial pressure:~15to30minutes.
TheDurationofActionforMannitolinthebodyforReductioninintracranial pressure:1.5to6hours.
TheTmax wasnotclinicallyestablished.
Mannitolis availableintheformofanInjectablesolution.
MannitolInjectablesolutionsbyIntravenousas singleorseveraldoses.
Mannitolisadiureticused toforceurineproductioninpeoplewithacute(sudden)kidneyfailure. Mannitolinjectionisalsousedto reduceswellingandpressureinsidetheeye oraroundthebrain.
Mannitolisanantihypertensiveagentbelonging toOsmosisDiuretics.Mannitolisanosmoticdiureticusedtoremoveexcess waterand toxinsfromthebodyinpatientswithkidneydisease.Itisalsoused inthetreatmentofcerebraledemaandintraocularpressure.Frequent monitoringofelectrolyteslevelsisnecessaryduringtreatmentwiththis medicine.
Mannitolis approvedforuseinthefollowingclinicalindications
Thereductionofintracranial pressureandtreatmentofcerebraledemabyreducingbrainmass. Thereductionofelevated intraocularpressurewhenthepressurecannotbeloweredbyothermeans. Promotingtheurinaryexcretionof toxicsubstances.
Intracranialpressure,cerebraledema, reduction(off-labeldosing):
IV:0.25to1g/kg/dose; mayrepeatevery6to8hoursasneeded.Somesuggestmaintainingserum osmolality<320mOsm/kg. However, thisvalueisroutinelyexceededwithoutilleffect.Abettermarkerfor mannitoltoxicitymaybetheserumosmolgap(orosmolal gap)andthetargetis <18to20.
Intraocularpressure,reduction:
Presurgicaldosing: IV: 1.5to2g/kgadministeredover30to60minutes1 to1.5hourspriortosurgery.
Traumatichyphema: IV:1.5g/kgadministeredover45minutestwicedaily forIntraocularpressure>35mmHg;mayadministerevery8 hoursinpatients withextremelyhighpressure.
Kidneytransplant,intraoperativevolumeoptimization(offlabel):Note: Concentratedmannitol(ie,20%)is preferredto optimizeintravascularvolumestatus.
IV:12.5to25gatkidneyrevascularization dosesupto50ghavebeenstudied.Someexpertsutilize1g/kg(maximumdose: 75g); however,manycentersutilizefixeddosing.
Mannitolisavailableinvariousstrengthas5%, 10%,15%,20%and25%.
Mannitolis availableintheformofanInjectablesolution.
Mannitolis contraindicatedinpatientswith:
Well-establishedanuriaduetosevererenaldisease. Severepulmonary congestionorfrankpulmonaryedema. Activeintracranial bleedingexceptduringcraniotomy.
Severedehydration.
Progressiveheart failureorpulmonarycongestionafterinstitutionofmannitoltherapy. Donotadministerto patientswithaknownhypersensitivitytomannitol.
●Extravasation: Vesicant(atconcentrations>5%);ensure propercatheterorneedlepositionpriortoandduringIVinfusion.Avoid extravasationofIVinfusions;maycausecompartmentsyndrome.Administration intoalargecentralveinisrecommended.
●Fluid/electrolyteimbalance: Maycausehypervolemiaandelectrolyte disturbances;monitorfornewonsetorworseningcardiacor pulmonary congestion.Alsomaycauseprofounddiuresiswithfluidandelectrolyteloss; closemedicalsupervisionanddoseevaluationare required.Correctelectrolyte disturbances;adjustthedosetoavoiddehydration.
●Hypersensitivity: Serioushypersensitivityreactions(eg, anaphylaxis),includingfatalities,havebeenreported.Discontinuemannitol immediatelyifahypersensitivityreactiondevelopsandtreataccordingly.
●Nephrotoxicity: Maycauserenaldysfunction,especiallywith highdoses;usecautioninpatientstakingothernephrotoxicagents,with sepsisorpreexistingrenaldisease.Tominimizeadverserenaleffects,adjust tokeepserumosmolality<320mOsm/L.Discontinueif evidenceofacute tubularnecrosis.
●Cerebraledema: Inpatientsbeingtreatedforcerebraledema, mannitolmayaccumulateinthebrain(causingreboundincreasesin intracranial pressure)ifcirculatingforlongperiodsoftimeaswithcontinuousinfusion; intermittentbolusesarepreferred. Cardiovascularstatusshouldalsobe evaluated;donotadministerelectrolyte-freemannitolsolutionswithblood.If hypotensionoccurs, monitorcerebralperfusionpressure;reassessdoseanduse ofmannitolifcerebralperfusionpressuredecreased.
●CNSeffects: CNStoxicity(eg,coma,confusion,lethargy)mayoccur;the riskmaybeincreasedinpatientswithimpairedrenal functionorwith concomitantuseofneurotoxicdrugs.DiscontinuemannitolifCNStoxicity develops.
●Renalimpairment: Usewithcaution.Inpatientswithsevere impairment,donotuseuntiladequacyofrenalfunctionandurineflow isestablished;use1to2testdosestoassessrenalresponse.
BreastFeedingWarning
Itisnotknownwhetherthisdrugis excretedinhumanmilk.Becausemanydrugsareexcretedinhumanmilk,caution shouldbe exercisedwhenmannitolisadministeredtoanursingwoman
PregnancyWarning
PregnancycategoryC
Animalreproductionstudieshavenot beenconductedwithmannitolinjection.Itisalsonotknownwhethermannitol injectioncancause fetalharmwhengiventoapregnantwomanorcanaffect reproduction.Mannitolinjectionshouldbegiventoapregnantwomanonlyif clearlyneeded.
CommonAdverseeffects
Cardiacfailure,chestpain,edema,hypertension, localizedphlebitis,palpitations,peripheraledema,tachycardia, thrombophlebitis, Chills,coma,confusion,dizziness,headache,increased intracranialpressure(rebound),lethargy,malaise,pain,seizure, Diaphoresis, localizederythema,localizedrash,pruritus,skinnecrosis,skinrash, urticaria,Dehydration,fluidandelectrolyte disturbance,hyperkalemia, hypernatremia,hypervolemia,hypokalemia,hyponatremia,hypovolemia,increased thirst,metabolic acidosis,metabolicalkalosis,Nausea,vomiting,xerostomia, Anuria,azotemia,diuresis,hematuria,oliguria,osmoticnephrosis, urinary retention,Hemoconcentration, Localinflammation,localpain,localpruritus,Armand/orwristpain, asthenia,muscle rigidity,myalgia,Blurredvision,Polyuria,Cough,pulmonary congestion,pulmonaryedema,rhinitis,Fever.
RareAdverseeffects
Acuterenalfailure,anaphylaxis,centralnervoussystem toxicity,dyspnea,hypersensitivityreaction,hypotension.
AmikacinLiposome
MayenhancethenephrotoxiceffectofMannitol (Systemic).
●Aminoglycosides
Mannitolmayenhancethenephrotoxiceffectof Aminoglycosides.
●ArsenicTrioxide
OsmoticDiureticsmayenhancethe QTc-prolongingeffectofArsenicTrioxide.Management:Whenpossible,avoid concurrentuseof arsenictrioxidewithdrugsthatcancauseelectrolyte abnormalities,suchasosmoticdiuretics.
●Desmopressin
Hyponatremia-AssociatedAgentsmayenhancethe hyponatremiceffectofDesmopressin.
●Diacerein
Mayenhancethetherapeuticeffectof Diuretics.Specifically,theriskfordehydrationorhypokalemiamaybe increased.
●OpioidAgonists
Mayenhancetheadverse/toxiceffectof Diuretics.OpioidAgonistsmaydiminishthetherapeuticeffectofDiuretics.
●SodiumPhosphates
Diureticsmayenhancethenephrotoxiceffect ofSodiumPhosphates.Specifically,theriskofacutephosphatenephropathymay be enhanced.Management:Consideravoidingthiscombinationbytemporarily suspendingtreatmentwithdiuretics,orseekingalternatives tooralsodium phosphatebowelpreparation.Ifthecombinationcannotbeavoided,hydrate adequatelyandmonitorfluidandrenal status.
●Tobramycin
Mannitolmayenhancethenephrotoxiceffectof Tobramycin(OralInhalation).
ThecommonsideeffectsofMannitolincludethefollowing
Common
Headache,nausea, diarrhea,vomiting,drymouth,thirst,dehydration,blurredvision,runnynose, armpain,chills,dizziness,low bloodpressure(hypotension),hives, irregularheartbeat,andelectrolyteimbalance.
Fever,infectionatthe injectionsite,blotclotinadeepvein,thrombosis,leakageofintravenously infusedmedication,andfluid overloadintheblood(hypervolemia).
Pregnancy
PregnancyCategoryC
Animalreproductionstudieshavenotbeenconductedwith MannitolInjection.Itisalsonotknownwhethermannitolcancausefetal harmwhengiventoapregnantwomanorcanaffectreproduction.MannitolInjection shouldbegiventoapregnantwomanonlyifclearly needed.
Nursingmothers
ItisnotknownwhetherMannitolisexcretedinhumanmilk. Becausemanydrugsareexcretedinhumanmilk,cautionshouldbe exercisedwhen mannitolisadministeredtoanursingwoman.
Pediatricuse
Safetyandeffectivenessinchildrenbelowthe ageof12havenotbeenestablished. Dosagerequirementsforpatients12yearsofage andunderhavenotbeenestablished.
Geriatricuse
ClinicalstudiesofMannitolInjectiondidnot includesufficientnumbersofsubjectsaged65andovertodeterminewhether theyrespond differentlyfromyoungersubjects.Otherreportedclinical experiencehasnotidentifieddifferencesinresponsesbetweentheelderlyand youngerpatients.Ingeneral,doseselectionforanelderlypatientshouldbe cautious,usuallystartingatthelowendofthedosingrange, reflectingthe greaterfrequencyofdecreasedhepatic,renal,orcardiacfunction,andofconcomitant diseaseorotherdrugtherapy.This drugisknowntobesubstantiallyexcreted bythekidney,andtheriskoftoxicreactionstothisdrugmaybegreaterin patientswith impairedrenalfunction.Becauseelderlypatientsaremorelikely tohavedecreasedrenalfunction,careshouldbetakenindoseselection, anditmaybeusefultomonitorrenalfunction.
Toorapidinfusionof largeamountsofmannitolwillcauseashiftofintracellularwaterintothe extracellularcompartmentresulting incellulardehydrationandoverexpansion oftheintravascularspacewithhyponatremia,congestiveheartfailure,andpulmonary edema.
Repeateddosesshould notbegiventopatientswithpersistentoliguriaasthiscanproducea hyperosmolarstateandprecipitate congestiveheartfailureandpulmonaryedema duetovolumeoverload.Dosagemustbecarefullymonitoredandadjustedin accordancewiththeclinicalsituationtoavoidtheconsequencesofoverdosage.
Pharmacodynamic
Chemically,mannitolisanalcoholandasugar,orapolyol;it issimilartoxylitolorsorbitol.However,mannitolhasatendencytolosea hydrogenioninaqueoussolutions,whichcausesthesolutiontobecomeacidic. Forthisreason,itisnotuncommontoaddasubstanceto adjustitspH,such assodiumbicarbonate.Mannitoliscommonlyusedtoincreaseurineproduction (diuretic).Itisalsousedtotreator preventmedicalconditionsthatare causedbyanincreaseinbodyfluids/water(e.g.,cerebraledema,glaucoma, kidneyfailure).Mannitol isfrequentlygivenalongwithotherdiuretics(e.g., furosemide,chlorothiazide)and/orIVfluidreplacement.Inhaledmannitolhas the possibilitytocausebronchospasmandhemoptysis;theoccurrenceofeithershould leadtodiscontinuationofinhaledmannitol.
Pharmacokinetics
Absorption
Approximately7%ofingestedmannitolis absorbedduringgastrointestinalperfusioninuremicpatients.Inhalationof635mg ofmannitol powderyieldsaplasmaC of13.71μg/mLin1.5 hours(T )andameansystemicAUCof73.15μg*h/mL.
Distribution
Mannitol administeredintravenouslyhasavolumeofdistributionof34.3L.
MetabolismandExcretion
Mannitol ismetabolizedonlyslightly,ifatall,toglycogenintheliver.
Mannitol isprimarilyexcretedunchangedintheurine.Followingoralinhalationof635 mgofmannitolinhealthyvolunteers,55%ofthe totaldosewasrecovered unchangedintheurine;followingoralorintravenousadministrationof500mg, thecorrespondingvalueswere 54and87%,respectively.Mannitolhasan eliminationhalf-lifeof4.7hoursfollowingoraladministration;themean terminalelimination half-lifeissimilarregardlessofadministrationroute (oral,inhalation,andintravenous.Intravenousadministrationofmannitol yieldsa totalclearanceof5.1L/hrandrenalclearanceof4.4L/hr.
TherearesomeclinicalstudiesofthedrugMannitolmentionedbelow:
1 ShawkatH,WestwoodMM,MortimerA. Mannitol:areviewofitsclinicaluses.Continuingeducationinanaesthesia, criticalcare andpain.2012Apr1;12(2):82-5.
2.YangB,XuJ,XuF,ZouZ,YeC,MeiC, MaoZ.Intravascularadministrationofmannitolforacutekidneyinjury prevention:a systematicreviewandmeta-analysis.PloSone.2014Jan 14;9(1):e85029.
3 WEISSDI,SHAFFERRN,WISEBL.Mannitol infusiontoreduceintraocularpressure.ArchivesofOphthalmology.1962Sep 1;68(3):341-7.
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JyotiSuthar
JyotiisaPostgraduate inPharmaceutics(MPharm)Shedidhergraduation(BPharm) FromSSRCOLLEGEOF PHARMACY AndthereafterdidherMPharmspecializedinPharmaceuticsfromSSRCOLLEGEOFPHARMACY
DrJUHISINGLA
DrJUHISINGLA hascompletedherMBBSfromEra’sLucknowMedicalcollegeanddone MDpharmacologyfromSGT UNIVERSITYGurgaon.Shecanbecontactedateditorial@medicaldialogues.in.Contactno.011-43720751
