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ClonidineInjection
GenericName:clonidinehydrochloride
DosageForm:injection,solution

ClonidineHydrochlorideInjection
Rxonly

The500mcg/mLstrengthproductshouldbedilutedpriortouseinanappropriatesolution.

NOTE:ClonidineHydrochlorideInjection(epiduralclonidine)isnotrecommendedfor
obstetrical,postpartum,orperioperativepainmanagement.Theriskofhemodynamic
instability,especiallyhypotensionandbradycardia,fromepiduralclonidinemaybe
unacceptableinthesepatients.However,inarareobstetrical,postpartumorperioperative
patient,potentialbenefitsmayoutweighthepossiblerisks.

ClonidineInjectionDescription
ClonidineHydrochlorideInjectionisacentrallyactinganalgesicsolutionforuseincontinuousepidural
infusiondevices.
ClonidineHydrochloride,USP,isanimidazolinederivativeandexistsasamesomericcompound.The
chemicalnamesareBenzenamine,2,6dichloroN2imidazolidinylidenemonohydrochlorideand2[(2,6
dichlorophenyl)imino]imidazolidinemonohydrochloride.Thefollowingisthestructuralformula:

C9H9Cl2N3HClM.W.266.56
ClonidineHydrochlorideInjectionissuppliedasaclear,colorless,preservativefree,pyrogenfree,
aqueoussterilesolution(pH5to7)insingledose,10mLvials.
EachmLofthe100mcg/mL(0.1mg/mL)concentrationcontains100mcgofClonidineHydrochloride,
USP,and9mgsodiumchlorideinwaterforinjection.Hydrochloricacidand/orsodiumhydroxidemay
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havebeenaddedforpHadjustment.Each10mLvialcontains1mg(1000mcg)ofclonidine
hydrochloride.
EachmLofthe500mcg/mL(0.5mg/mL)concentrationcontains500mcgofClonidineHydrochloride,
USP,and9mgsodiumchlorideinwaterforinjection.Hydrochloricacidand/orsodiumhydroxidemay
havebeenaddedforpHadjustment.Each10mLvialcontains5mg(5000mcg)ofclonidine
hydrochloride.

ClonidineInjectionClinicalPharmacology
MechanismofAction
Epidurallyadministeredclonidineproducesdosedependentanalgesianotantagonizedbyopiate
antagonists.Theanalgesiaislimitedtothebodyregionsinnervatedbythespinalsegmentswhere
analgesicconcentrationsofclonidinearepresent.Clonidineisthoughttoproduceanalgesiaat
presynapticandpostjunctionalalpha2adrenoceptorsinthespinalcordbypreventingpainsignal
transmissiontothebrain.

Pharmacokinetics
Followinga10minuteintravenousinfusionof300mcgclonidineHCltofivemalevolunteers,plasma
clonidinelevelsshowedaninitialrapiddistributionphase(meanSDt12=119minutes)followedbya
slowereliminationphase(t12=92hours)over24hours.Clonidinestotalbodyclearance(CL)was219
92mL/min.
Followinga700mcgclonidineHClepiduraldosegivenoverfiveminutestofourmaleandfivefemale
volunteers,peakclonidineplasmalevels(4.41.4ng/mL)wereobtainedin1927minutes.Theplasma
eliminationhalflifewasdeterminedtobe2215hoursfollowingsamplecollectionfor24hours.CLwas
19070mL/min.Incerebralspinalfluid(CSF),peakclonidinelevels(418255ng/mL)wereachievedin
2611minutes.TheclonidineCSFeliminationhalflifewas1.30.5hourswhensampleswerecollected
for6hours.Comparedtomen,womenhadalowermeanplasmaclearance,longermeanplasmahalf
life,andhighermeanpeaklevelofclonidineinbothplasmaandCSF.
Incancerpatientswhoreceived14daysofclonidineHClepiduralinfusion(rate=30mcg/hr)plus
morphinebypatientcontrolledanalgesia(PCA),steadystateclonidineplasmaconcentrationsof2.21.1
and2.41.4ng/mLwereobtainedondosingdays7and14,respectively.CLwas279184and272
163mL/minonthesedays.CSFconcentrationswerenotdeterminedinthesepatients.

Distribution
Clonidineishighlylipidsolubleandreadilydistributesintoextravascularsitesincludingthecentralnervous
system.Clonidinesvolumeofdistributionis2.10.4L/kg.Thebindingofclonidinetoplasmaproteinis
primarilytoalbuminandvariesbetween20and40%invitro.Epidurallyadministeredclonidinereadily
partitionsintoplasmaviatheepiduralveinsandattainssystemicconcentrations(0.5to2ng/mL)thatare
associatedwithahypotensiveeffectmediatedbythecentralnervoussystem.

Excretion
Followinganintravenousdoseof14Cclonidine,72%oftheadministereddosewasexcretedinurinein96
hoursofwhich40to50%wasunchangedclonidine.Renalclearanceforclonidinewasdeterminedtobe
13366mL/min.Inastudywhere14Cclonidinewasgiventosubjectswithvaryingdegreesofkidney
function,eliminationhalflivesvaried(17.5to41hours)asafunctionofcreatinineclearance.Insubjects
undergoinghemodialysisonly5%ofbodyclonidinestoreswereremoved.
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Metabolism
Inhumans,clonidinemetabolismfollowsminorpathwayswiththemajormetabolite,phydroxyclonidine,
beingpresentatlessthan10%oftheconcentrationofunchangeddruginurine.

SpecialPopulations
Thepharmacokineticsofepidurallyadministeredclonidinehasnotbeenstudiedinthepediatricpopulation
orinpatientswithrenalorhepaticdisease.

ClinicalTrials
Inadoubleblind,randomizedstudyofcancerpatientswithsevereintractablepainbelowtheC4
dermatomenotcontrolledbymorphine,38patientswererandomizedtoanepiduralinfusionofclonidine
plusepiduralmorphine,whereas47subjectsreceivedepiduralplaceboplusepiduralmorphine.Both
groupswereallowedrescuedosesofepiduralmorphine.Successfulanalgesia,definedasadecreasein
eithermorphineuseorVisualAnalogScore(VAS)pain,wassignificantlymorecommonwithepidural
clonidinethanplacebo(45%vs21%,p=0.016).Onlythesubgroupof36patientswithneuropathicpain,
characterizedbytheinvestigatoraswelllocalized,burning,shooting,orelectriclikepaininadermatomal
orperipheralnervedistributionhadsignificantanalgesiceffectsrelativetoplacebointhisstudy.
Themostfrequentadverseeventswithclonidinewerehypotension(45%vs11%forplacebo,p<0.001),
posturalhypotension(32%vs0%,p<0.001),dizziness(13%vs4%,p=0.234),anxiety(11%vs2%,
p=0.168)anddrymouth(13%vs9%,p=0.505).Bothmeanbloodpressureandheartratewerereduced
intheclonidinegroup.Attheconclusionofthetwoweekstudyperiodintheclinicaltrial,allpatientswere
abruptlywithdrawnfromstudydrugorplacebo.Fourpatientsoftheclonidinegroupsufferedrebound
hypertensionuponwithdrawalofclonidineoneofthesepatientssufferedacerebrovascularaccident.
Asymptomaticbradycardiawasnotedinoneclonidinepatient.

IndicationsandUsageforClonidineInjection
ClonidineHydrochlorideInjectionisindicatedincombinationwithopiatesforthetreatmentofseverepain
incancerpatientsthatisnotadequatelyrelievedbyopioidanalgesicsalone.Epiduralclonidineismore
likelytobeeffectiveinpatientswithneuropathicpainthansomaticorvisceralpain(seeClinicalTrials).
Thesafetyofthisdrugproducthasonlybeenestablishedinahighlyselectedgroupofcancerpatients,
andonlyafteranadequatetrialofopioidanalgesia.Otheruseisofunprovensafetyandisnot
recommended.Inararepatient,thepotentialbenefitsmayoutweightheknownrisks(seeWARNINGS).

Contraindications
Clonidineiscontraindicatedinpatientswithahistoryofsensitizationorallergicreactionstoclonidine.
Epiduraladministrationiscontraindicatedinthepresenceofaninjectionsiteinfection,inpatientson
anticoagulanttherapy,andinthosewithableedingdiathesis.AdministrationofclonidineabovetheC4
dermatomeiscontraindicatedsincetherearenoadequatesafetydatatosupportsuchuse(see
WARNINGS).

Warnings
UseinPostoperativeorObstetricalAnalgesia
Clonidine(epiduralclonidine)isnotrecommendedforobstetrical,postpartum,orperioperativepain
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management.Theriskofhemodynamicinstability,especiallyhypotensionandbradycardia,fromepidural
clonidinemaybeunacceptableinthesepatients.

Hypotension
Becauseseverehypotensionmayfollowtheadministrationofclonidine,itshouldbeusedwithcautionin
allpatients.Itisnotrecommendedinmostpatientswithseverecardiovasculardiseaseorinthosewho
areotherwisehemodynamicallyunstable.Thebenefitofitsadministrationinthesepatientsshouldbe
carefullybalancedagainstthepotentialrisksresultingfromhypotension.
Vitalsignsshouldbemonitoredfrequently,especiallyduringthefirstfewdaysofepiduralclonidine
therapy.Whenclonidineisinfusedintotheupperthoracicspinalsegments,morepronounceddecreases
inthebloodpressuremaybeseen.
Clonidinedecreasessympatheticoutflowfromthecentralnervoussystemresultingindecreasesin
peripheralresistance,renalvascularresistance,heartrate,andbloodpressure.However,intheabsence
ofprofoundhypotension,renalbloodflowandglomerularfiltrationrateremainessentiallyunchanged.
Inthepivotaldoubleblind,randomizedstudyofcancerpatients,where38subjectswereadministered
epiduralclonidineat30mcg/hrinadditiontoepiduralmorphine,hypotensionoccurredin45%ofsubjects.
Mostepisodesofhypotensionoccurredwithinthefirstfourdaysafterbeginningepiduralclonidine.
However,hypotensiveepisodesoccurredthroughoutthedurationofthetrial.Therewasatendencyfor
theseepisodestooccurmorecommonlyinwomen,andinthosewithhigherserumclonidinelevels.
Patientsexperiencinghypotensionalsotendedtoweighlessthanthosewhodidnotexperience
hypotension.Thehypotensionusuallyrespondedtointravenousfluidsand,ifnecessary,appropriate
parenterallyadministeredpressoragents.
Publishedreportsontheuseofepiduralclonidineforintraoperativeorpostoperativeanalgesiaalsoshow
aconsistentandmarkedhypotensiveresponsetoclonidine.Severehypotensionmayoccurevenif
intravenousfluidpretreatmentisgiven.

Withdrawal
Suddencessationofclonidinetreatment,regardlessoftherouteofadministration,has,insomecases,
resultedinsymptomssuchasnervousness,agitation,headache,andtremor,accompaniedorfollowedby
arapidriseinbloodpressure.Thelikelihoodofsuchreactionsappearstobegreaterafteradministration
ofhigherdosesorwithconcomitantbetablockertreatment.Specialcautionisthereforeadvisedinthese
situations.Rareinstancesofhypertensiveencephalopathy,cerebrovascularaccidentsanddeathhave
beenreportedafterabruptclonidinewithdrawal.Patientswithahistoryofhypertensionand/orother
underlyingcardiovascularconditionsmaybeatparticularriskoftheconsequencesofabrupt
discontinuationofclonidine.Inthepivotaldoubleblind,randomizedcancerpainstudy,fourof38subjects
receiving720mcgofclonidineperdayexperiencedreboundhypertensionfollowingabruptwithdrawal.
Oneofthesepatientswithreboundhypertensionsubsequentlyexperiencedacerebrovascularaccident.
Carefulmonitoringofinfusionpumpfunctionandinspectionofcathetertubingforobstructionor
dislodgementcanhelpreducetheriskofinadvertentabruptwithdrawalofepiduralclonidine.Patients
shouldnotifytheirphysicianimmediatelyifclonidineadministrationisinadvertentlyinterruptedforany
reason.Patientsshouldalsobeinstructednottodiscontinuetherapywithoutconsultingtheirphysician.
Whendiscontinuingtherapywithepiduralclonidine,thephysicianshouldreducethedosegraduallyover2
to4daystoavoidwithdrawalsymptoms.
Anexcessiveriseinbloodpressurefollowingdiscontinuationofepiduralclonidinecanbetreatedby
administrationofclonidineorbyintravenousphentolamine.Iftherapyistobediscontinuedinpatients
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receivingabetablockerandclonidineconcurrently,thebetablockershouldbewithdrawnseveraldays
beforethegradualdiscontinuationofepiduralclonidine.

Infections
Infectionsrelatedtoimplantableepiduralcathetersposeaseriousrisk.Evaluationoffeverinapatient
receivingepiduralclonidineshouldincludethepossibilityofacatheterrelatedinfectionsuchasmeningitis
orepiduralabscess.

Precautions
General
CardiacEffects:Epiduralclonidinefrequentlycausesdecreasesinheartrate.Symptomaticbradycardia
canbetreatedwithatropine.Rarely,atrioventricularblockgreaterthanfirstdegreehasbeenreported.
Clonidinedoesnotalterthehemodynamicresponsetoexercise,butmaymasktheincreaseinheartrate
associatedwithhypovolemia.
RespiratoryDepressionandSedation:Clonidineadministrationmayresultinsedationthroughthe
activationofalphaadrenoceptorsinthebrainstem.Highdosesofclonidinecausesedationand
ventilatoryabnormalitiesthatareusuallymild.Tolerancetotheseeffectscandevelopwithchronic
administration.Theseeffectshavebeenreportedwithbolusdosesthataresignificantlylargerthanthe
infusionraterecommendedfortreatingcancerpain.
Depression:Depressionhasbeenseeninasmallpercentageofpatientstreatedwithoralortransdermal
clonidine.Depressioncommonlyoccursincancerpatientsandmaybeexacerbatedbytreatmentwith
clonidine.Patients,especiallythosewithaknownhistoryofaffectivedisorders,shouldbemonitoredfor
thesignsandsymptomsofdepression.
PainofVisceralorSomaticOrigin:Intheclinicalinvestigations,atdosestested,clonidinewasmost
effectiveinwelllocalized,neuropathicpainthatwascharacterizedaselectrical,burning,orshootingin
nature,andwhichwaslocalizedtoadermatomalorperipheralnervedistribution.Clonidinemaybeless
effective,orpossiblyineffectiveinthetreatmentofpainthatisdiffuse,poorlylocalized,orvisceralinorigin.

InformationforPatients
Patientsshouldbeinstructedabouttherisksofreboundhypertensionandwarnednottodiscontinue
clonidineexceptunderthesupervisionofaphysician.Patientsshouldnotifytheirphysicianimmediatelyif
clonidineadministrationisinadvertentlyinterruptedforanyreason.Patientswhoengageinpotentially
hazardousactivities,suchasoperatingmachineryordriving,shouldbeadvisedofthepotentialsedative
andhypotensiveeffectsofepiduralclonidine.Theyshouldalsobeinformedthatsedativeeffectsmaybe
increasedbyCNSdepressingdrugssuchasalcoholandbarbiturates,andthathypotensiveeffectsmay
beincreasedbyopiates.

DrugInteractions
ClonidinemaypotentiatetheCNSdepressiveeffectofalcohol,barbituratesorothersedatingdrugs.
Narcoticanalgesicsmaypotentiatethehypotensiveeffectsofclonidine.Tricyclicantidepressantsmay
antagonizethehypotensiveeffectsofclonidine.Theeffectsoftricyclicantidepressantsonclonidines
analgesicactionsarenotknown.
Betablockersmayexacerbatethehypertensiveresponseseenwithclonidinewithdrawal.Also,duetothe
potentialforadditiveeffectssuchasbradycardiaandAVblock,cautioniswarrantedinpatientsreceiving
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clonidinewithagentsknowntoaffectsinusnodefunctionorAVnodalconduction,e.g.,digitalis,calcium
channelblockers,andbetablockers.
Thereisonereportedcaseofapatientwithacutedeliriumassociatedwiththesimultaneoususeof
fluphenazineandoralclonidine.Symptomsresolvedwhenclonidinewaswithdrawnandrecurredwhen
thepatientwasrechallengedwithclonidine.
Epiduralclonidinemayprolongthedurationofpharmacologiceffectsofepidurallocalanesthetics,
includingbothsensoryandmotorblockade.

Carcinogenesis,Mutagenesis,ImpairmentofFertility
Ina132weekstudyinrats,clonidinehydrochlorideadministeredasadietaryadmixtureat5to8times
(basedonbodysurfacearea)the50mcg/kgmaximumrecommendeddailyhumandose(MRDHD)for
hypertensiondidnotshowanycarcinogenicpotential.ClonidinewasinactiveintheAmestestof
mutagenicity.Fertilityofmaleorfemaleratswasunaffectedbyoralclonidinehydrochloridedosesashigh
as150mcg/kg,orabout0.5timestheMRDHD.Fertilityoffemaleratsdid,however,appeartobe
affectedinanotherexperimentatoraldoselevelsof500to2000mcg/kg,or2to7timestheMRDHD.

UsageinPregnancy/TeratogenicEffects
PREGNANCYCATEGORYC:Reproductionstudiesinrabbitsatclonidinehydrochloridedosesupto
approximatelytheMRDHDrevealednoevidenceofteratogenicorembryotoxicpotential.Inrats,
however,dosesaslowasonethirdtheMRDHDwereassociatedwithincreasedresorptionsinastudyin
whichdamsweretreatedcontinuouslyfrom2monthspriortomating.Increasedresorptionswerenot
associatedwithtreatmentwiththesameorhigherdosesupto0.5timestheMRDHDwhendamswere
treatedondays6to15ofgestation.Increasedresorptionswereobservedathigherlevels(7timesthe
MRDHD)inratsandmicetreatedondays1to14ofgestation.
Clonidinereadilycrossestheplacentaanditsconcentrationsareequalinmaternalandumbilicalcord
plasmaamnioticfluidconcentrationscanbe4timesthosefoundinserum.Therearenoadequateand
wellcontrolledstudiesinpregnantwomenduringearlygestationwhenorganformationtakesplace.
Studiesusingepiduralclonidineduringlaborhavedemonstratednoapparentadverseeffectsonthe
infantatthetimeofdelivery.However,thesestudiesdidnotmonitortheinfantsforhemodynamiceffects
inthedaysfollowingdelivery.Clonidineshouldbeusedduringpregnancyonlyifthepotentialbenefits
justifythepotentialrisktothefetus.

LaborandDelivery
Therearenoadequatecontrolledclinicaltrialsevaluatingthesafety,efficacy,anddosingofclonidinein
obstetricalsettings.Becausematernalperfusionoftheplacentaiscriticallydependentonbloodpressure,
useofclonidineasananalgesicduringlaboranddeliveryisnotindicated(seeWARNINGS).

NursingMothers
Concentrationsofclonidineinhumanbreastmilkareapproximatelytwicethosefoundinmaternalplasma.
Cautionshouldbeexercisedwhenclonidineisadministeredtoanursingwoman.Becauseofthepotential
forsevereadversereactionsinnursinginfants,adecisionshouldbemadetoeitherdiscontinuenursingor
todiscontinueclonidine.

PediatricUse
Thesafetyandeffectivenessofclonidineinthislimitedindicationandclinicalpopulationhavebeen
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establishedinpatientsoldenoughtotolerateplacementandmanagementofanepiduralcatheter,based
onevidencefromadequateandwellcontrolledstudiesinadultsandexperiencewiththeuseofclonidine
inthepediatricagegroupforotherindications.Theuseofclonidineshouldberestrictedtopediatric
patientswithsevereintractablepainfrommalignancythatisunresponsivetoepiduralorspinalopiatesor
othermoreconventionalanalgesictechniques.Thestartingdoseofclonidineshouldbeselectedonper
kilogrambasis(0.5mcgperkgperhour)andcautiouslyadjustedbasedontheclinicalresponse.

AdverseReactions
Adversereactionsseenduringcontinuousepiduralclonidineinfusionaredosedependentandtypicalfora
compoundofthispharmacologicclass.Theadverseeventsmostfrequentlyreportedinthepivotal
controlledclinicaltrialofcontinuousepiduralclonidineadministrationconsistedofhypotension,postural
hypotension,decreasedheartrate,reboundhypertension,drymouth,nausea,confusion,dizziness,
somnolence,andfever.Hypotensionistheadverseeventthatmostfrequentlyrequirestreatment.The
hypotensionisusuallyresponsivetointravenousfluidsand,ifnecessary,appropriateparenterally
administeredpressoragents.Hypotensionwasobservedmorefrequentlyinwomenandinlowerweight
patients,butnodoserelatedresponsewasestablished.
Implantableepiduralcathetersareassociatedwithariskofcatheterrelatedinfections,includingmeningitis
and/orepiduralabscess.Theriskdependsontheclinicalsituationandthetypeofcatheterused,but
catheterrelatedinfectionsoccurin5%to20%ofpatients,dependingonthekindofcatheterused,
catheterplacementtechnique,qualityofcathetercare,andlengthofcatheterplacement.
Theinadvertentintrathecaladministrationofclonidinehasnotbeenassociatedwithasignificantly
increasedriskofadverseevents,butthereareinadequatesafetyandefficacydatatosupporttheuseof
intrathecalclonidine.
Epiduralclonidinewascomparedtoplaceboinatwoweekdoubleblindstudyof85terminalcancer
patientswithintractablepainreceivingepiduralmorphine.Thefollowingadverseeventswerereportedin
twoormorepatientsandmayberelatedtoadministrationofeitherclonidineormorphine.

IncidenceofAdverseEventsintheTwoWeekTrial

Clonidine Placebo

AdverseEvents

N=38

N=47

n(%)

n(%)

TotalNumberofPatientsWhoExperiencedatLeastOneAdverseEvent 37(97.4) 38(80.5)

Hypotension

17(44.8) 5(10.6)

PosturalHypotension

12(31.6)

0(0)

DryMouth

5(13.2)

4(8.5)

Nausea

5(13.2) 10(21.3)

Somnolence

5(13.2) 10(21.3)

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Dizziness

5(13.2)

2(4.3)

Confusion

5(13.2) 5(10.6)

Vomiting

4(10.5) 7(14.9)

Nausea/Vomiting

3(7.9)

1(2.1)

Sweating

2(5.3)

0(0)

ChestPain

2(5.3)

0(0)

Hallucination

2(5.3)

1(2.1)

Tinnitus

2(5.3)

0(0)

Constipation

1(2.6)

2(4.3)

Tachycardia

1(2.6)

2(4.3)

Hypoventilation

1(2.6)

2(4.3)

Anopenlabellongtermextensionoftheabovetrialwasperformed.Thirtytwosubjectsreceivedepidural
clonidineandmorphineforupto94weekswithamediandosingperiodof10weeks.Thefollowing
adverseevents(andpercentincidence)werereported:hypotension/posturalhypotension(47%)nausea
(13%)anxiety/confusion(38%)somnolence(25%)urinarytractinfection(22%)constipation,dyspnea,
fever,infection(6%each)asthenia,hyperaesthesia,pain,skinulcer,andvomiting(5%each).Eighteen
percentofsubjectsdiscontinuedthisstudyasaresultofcatheterrelatedproblems(infections,accidental
dislodging,etc.),andonesubjectdevelopedmeningitis,possiblyasaresultofacatheterrelatedinfection.
Inthisstudy,reboundhypertensionwasnotassessed,andECGandlaboratorydatawerenot
systematicallysought.
Thefollowingadversereactionshavealsobeenreportedwiththeuseofanydosageformofclonidine.In
manycasespatientswerereceivingconcomitantmedicationandacausalrelationshiphasnotbeen
established:
BodyasaWhole:Weakness,10%fatigue,4%headacheandwithdrawalsyndrome,each1%.Also
reportedwerepallor,aweaklypositiveCoombstest,andincreasedsensitivitytoalcohol.
Cardiovascular:Palpitationsandtachycardia,andbradycardia,each0.5%.Syncope,Raynauds
phenomenon,congestiveheartfailure,andelectrocardiographicabnormalities(i.e.,sinusnodearrest,
functionalbradycardia,highdegreeAVblock)havebeenreportedrarely.Rarecasesofsinusbradycardia
andatrioventricularblockhavebeenreported,bothwithandwithouttheuseofconcomitantdigitalis.
CentralNervousSystem:Nervousnessandagitation,3%mentaldepression,1%insomnia,0.5%.
Cerebrovascularaccidents,otherbehavioralchanges,vividdreamsornightmares,restlessness,and
deliriumhavebeenreportedrarely.
Dermatological:Rash,1%pruritus,0.7%hives,angioneuroticedemaandurticaria,0.5%alopecia,
0.2%.
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Gastrointestinal:Anorexiaandmalaise,each1%mildtransientabnormalitiesinliverfunctiontests,1%
hepatitis,parotitis,ileusandpseudoobstruction,andabdominalpain,rarely.
Genitourinary:Decreasedsexualactivity,impotence,andlibido,3%nocturia,about1%difficultyin
micturition,about0.2%urinaryretention,about0.1%.
Hematologic:Thrombocytopenia,rarely.
Metabolic:Weightgain,0.1%gynecomastia,1%transientelevationofglucoseorserumphosphatase,
rarely.
Musculoskeletal:Muscleorjointpain,about0.6%legcramps,0.3%.
Orootolaryngeal:Drynessofthenasalmucosawasrarelyreported.
Ophthalmological:Drynessoftheeyes,burningoftheeyesandblurredvisionwererarelyreported.

Overdosage
Hypertensionmaydevelopearlyandmaybefollowedbyhypotension,bradycardia,respiratory
depression,hypothermia,drowsiness,decreasedorabsentreflexes,irritability,andmiosis.Withlargeoral
overdoses,reversiblecardiacconductiondefectsorarrhythmias,apnea,coma,andseizureshavebeen
reported.Aslittleas100mcgoforalclonidinehasproducedsignsoftoxicityinpediatricpatients.
Thereisnospecificantidoteforclonidineoverdosage.Supportivecaremayincludeatropinesulfatefor
bradycardia,intravenousfluidsand/orvasopressoragentsforhypotension.Hypertensionassociatedwith
overdosagehasbeentreatedwithintravenousfurosemide,diazoxideoralphablockingagentssuchas
phentolamine.Naloxonemaybeausefuladjunctinthetreatmentofclonidineinducedrespiratory
depression,hypotension,and/orcomabloodpressureshouldbemonitoredsincetheadministrationof
naloxonehasoccasionallyresultedinparadoxicalhypertension.Tolazolineadministrationhasyielded
inconsistentresultsandisnotrecommendedasfirstlinetherapy.Dialysisisnotlikelytosignificantly
enhancetheeliminationofclonidine.
Thelargestoverdosereportedtodateinvolveda28yearoldwhitemalewhoingested100mgofclonidine
hydrochloridepowder.Thispatientdevelopedhypertensionfollowedbyhypotension,bradycardia,apnea,
hallucinations,semicoma,andprematureventricularcontractions.Thepatientfullyrecoveredafter
intensivetreatment.Plasmaclonidinelevelswere60ng/mLafter1hour,190ng/mLafter1.5hours,370
ng/mLafter2hours,and120ng/mLafter5.5and6.5hours.Inmiceandrats,theoralLD50ofclonidineis
206and465mg/kg,respectively.

ClonidineInjectionDosageandAdministration
TherecommendedstartingdoseofClonidineHydrochlorideInjectionforcontinuousepiduralinfusionis30
mcg/hr.Althoughdosagemaybetitratedupordowndependingonpainreliefandoccurrenceofadverse
events,experiencewithdosageratesabove40mcg/hrislimited.
Familiarizationwiththecontinuousepiduralinfusiondeviceisessential.Patientsreceivingepidural
clonidinefromacontinuousinfusiondeviceshouldbecloselymonitoredforthefirstfewdaystoassess
theirresponse.
The500mcg/mL(0.5mg/mL)strengthproductmustbedilutedpriortousein0.9%SodiumChloridefor
Injection,USP,toafinalconcentrationof100mcg/mL:

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VolumeofClonidine
HydrochlorideInjection500
mcg/mL

Volumeof0.9%Sodium
ChlorideforInjection,USP

ResultingFinalClonidine
HydrochlorideInjection
Concentration
(100mcg/mL)

1mL

4mL

500mcg/5mL

2mL

8mL

1000mcg/10mL

3mL

12mL

1500mcg/15mL

4mL

16mL

2000mcg/20mL

5mL

20mL

2500mcg/25mL

6mL

24mL

3000mcg/30mL

7mL

28mL

3500mcg/35mL

8mL

32mL

4000mcg/40mL

9mL

36mL

4500mcg/45mL

10mL

40mL

5000mcg/50mL

RenalImpairment:Dosageshouldbeadjustedaccordingtothedegreeofrenalimpairment,andpatients
shouldbecarefullymonitored.Sinceonlyaminimalamountofclonidineisremovedduringroutine
hemodialysis,thereisnoneedtogivesupplementalclonidinefollowingdialysis.
ClonidineHydrochlorideInjectionmustnotbeusedwithapreservative.
Parenteraldrugproductsshouldbeinspectedvisuallyforparticulatematteranddiscolorationpriorto
administration,wheneversolutionandcontainerpermit.

HowisClonidineInjectionSupplied
Product NDC
No.

No.

Strength
402510 6332340510100mcg/mL10mLSingledosevial,packagedindividually.
402710 6332342710500mcg/mL10mLSingledosevial,packagedindividually.
Storeat20to25C(68to77F)[seeUSPControlledRoomTemperature].
PreservativeFree.Discardunusedportion.
Vialstoppersdonotcontainnaturalrubberlatex.
http://www.drugs.com/pro/clonidineinjection.html

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