Clonidine BNM

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Clonidine hydrochloride 25 µg
Available from:
Boucher & Muir (New Zealand) Limited t/a BNM Group
INN (International Name):
Clonidine hydrochloride 25 µg
Dosage:
25 mcg
Pharmaceutical form:
Tablet
Composition:
Active: Clonidine hydrochloride 25 µg Excipient: Lactose monohydrate Magnesium stearate Maize starch Microcrystalline cellulose Pregelatinised maize starch Purified talc Sodium starch glycolate
Units in package:
Blister pack, PVC/Al, 112 tablets
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
PCAS Finland Oy
Therapeutic indications:
The prophylactic management of migraine or recurrent vascular headaches in adult patients. The management of vasomotor conditions commonly associated with the menopause and characterised by flushing.
Product summary:
Package - Contents - Shelf Life: Blister pack, PVC/Al - 112 tablets - 36 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-9082
Authorization date:
2012-07-12

1

Clonidine BNM

NewZealandConsumer MedicineInformation

Clonidine BNM

Clonidinehydrochloride

Tablets,25microgram

Whatis in this leaflet?

Please readthisleafletcarefullybeforeyoustarttakingClonidineBNM.

ThisleafletanswerssomecommonquestionsaboutClonidineBNM.Itdoesnotcontainallthe

availableinformation.Themostup-to-dateConsumerMedicineInformationcanbe

downloadedfromwww.medsafe.govt.nz.

Readingthisleafletdoesnottaketheplaceoftalkingto yourdoctororpharmacist.

Allmedicineshaverisksandbenefits.Yourdoctorhasweighedtherisksofyoutaking

ClonidineBNMagainstthebenefitsthismedicineisexpectedto haveforyou.

Ifyouhaveanyconcernsabouttakingthismedicine,askyourdoctororpharmacist.

Keep thisleafletwiththemedicine.

Youmaywanttoreaditagain.

WhatClonidineBNMis usedfor

ClonidineBNMcontainsamedicinecalledclonidine.Thisbelongstoagroupofmedicines

calledvasodilators.Vasodilatorswiden thebloodvesselsand thishelpsthe bloodtoflowmore

easily.

ClonidineBNMtabletsare usedto preventmigraineattacksand similartypesofheadache.It

isalso usedtopreventhotflushesthatmayoccurin womenduringthemenopause(changeof

life).

Yourdoctormayhaveprescribedthismedicineforanotherreason.

Askyourdoctorifyouhave anyquestions aboutwhyithas beenprescribedforyou.

ClonidineBNMisavailable onlywith adoctor'sprescription.

ClonidineBNMisnotaddictive.

2

Clonidine BNM

BeforeyoutakeClonidineBNM

ClonidineBNMisnotsuitableforeveryone.

When you must nottake it

Do nottakeClonidineBNMifyou:

youareallergictoanymedicinecontainingclonidineoranyoftheingredientslistedatthe

end ofthisleaflet

youhave certain heartproblems,such asirregular/slowheartbeat

youare alreadytaking othermedicinesthatcontain clonidine.

Do nottakeitaftertheexpirydate (‘Exp.’aspercartonandblisterprintedonthepack.

Ifyoutakeitaftertheexpirydate haspassed,itmaynotworkaswell.

Do nottakeitifthepackagingistornorshows signsoftampering.

Ifyouarenotsurewhetheryoushouldstarttakingthismedicine,talktoyourdoctoror

pharmacist.

Beforeyou start totake it

Tellyourdoctororpharmacistifyouhaveallergiestoanyothermedicines,foods,

preservativesordyes.

Tellyourdoctorifyouhaveorhavehadanymedicalconditions,especiallythe

following:

heartfailureoranyheartorcirculation problem

stroke,ortransientischaemic attack(TIA)

mentaldepression

sugardiabetes

constipation

nerve damage,which maylead to weaknessinthearmsandlegs

anyproblemswith yourkidneys

Pregnancy andbreast feeding

Tellthedoctorifyouarepregnant,thinkyoumightbepregnantoraretryingtobecome

pregnant.

ClonidineBNM canreach yourbabyandmayloweryourbaby’sheartrate.

ClonidineBNMtabletsarenotrecommendedforusewhilebreastfeeding;tellyourdoctorif

youarebreastfeeding.

Do notgiveClonidineBNMtoa childorteenageragedupto18yearsofage.

Ifyouhavenottoldyourdoctororpharmacistaboutanyoftheabove,tellthembefore

youstarttakingClonidineBNM.

3

Clonidine BNM

Taking othermedicines

Tellyourdoctororpharmacistifyouaretakinganyothermedicines,includinganythat

yougetwithoutaprescriptionfromyourpharmacy,supermarketorhealthfoodshop.

Tellanyhealthprofessionalwhoisprescribinganewmedicineforyouthatyouare

takingClonidineBNM.

SomemedicinesandClonidineBNMmayinterfere with each other.Theseinclude:

othermedicinesthatmakeyoudrowsy

medicinesfordepressionsuchasimipramine ormirtazapine

medicinesforseverementalillnesssuchasschizophrenia.Thesearealsoknownas

‘antipsychotics’or‘neuroleptics’and include chlorpromazine

beta blockerssuch asatenolol

watertablets(‘diuretics’)suchasfrusemide

alphablockerssuchasprazosinordoxazosin.Thesecanalsobeusedforprostate

problemsinmen

vasodilatorssuchasdiazoxideorsodiumnitroprusside

cardiacglycosidessuchas digoxin

medicinestolowerblood pressure

alcohol

TheabovemedicinesmaybeaffectedbyClonidineBNM,ormayaffecthowwellitworks.You

mayneeddifferentamountsofClonidineBNM,ortakeitatdifferenttimes,oryoumayneedto

take differentmedicines.

Yourdoctorandpharmacisthavemoreinformationonmedicinestobecarefulwithoravoid

while takingClonidineBNM.

HowtotakeClonidine BNM

Readthelabelcarefullyandfollowalldirectionsgiventoyoubyyourdoctorand

pharmacist.

Theymaydifferfromtheinformationcontained inthisleaflet.

Ifyoudonotunderstandtheinstructionsonthepack,askyourdoctororpharmacist

forhelp.

How much to take

Formigraineandmenopausalflushing,theusualstartingdoseisonetablettwiceaday.If

necessaryyourdoctormayincrease thisuptothreetabletstwicea day.

Askyourdoctororpharmacistifyouareunsureofthecorrectdoseforyou.

Theywilltellyouexactlyhowmuchtotake.Thisdependsonyourconditionandwhetheror

notyouaretaking anyothermedicines.

4

Clonidine BNM

Ifyoutakethewrongdose,ClonidineBNMmaynotworkaswellandyourproblemmaynot

improve.

SwallowClonidineBNMwith afullglass ofwater.Takewithorwithoutfood.

When to take it

Take itataboutthesametimeseachday.

Takingitatthesametimes each daywillhave thebesteffect.Itwillalso help you to remember

when to takeit.

How longto take it

Thedurationoftreatmentwilldependonyourcondition.Itmaytake2-4weeksuntilClonidine

BNMisfullyeffective.

Continuetakingthemedicineforaslongasyourdoctortells youto.

IfyouareunsurewhetheryoushouldstoptakingClonidineBNM,talktoyourdoctoror

pharmacist.

If you forget to takeit

Ifitisalmosttimeforyournextdose,skipthedoseyoumissedandtakethenextdose

whenyouaremeantto.

Do nottryto makeupformisseddoses bytakingmorethan onedose atatime.

Thismayincreasethechance ofgettinganunwantedsideeffect.

Ifthereisstilla longtimeto go before yournextdose,take itassoon asyouremember,

and thengobacktotakingitasyouwould normally.

Ifyouarenotsurewhattodo,askyourdoctororpharmacist.

Ifyouhave troublerememberingtotakeyourmedicine,ask yourpharmacistforhints.

Whileyou are takingClonidineBNM

Things you must do

Ifyouareabouttobestartedonanynewmedicine,tellyourdoctorandpharmacistthat

youaretakingClonidineBNM.Likewise,tellanyotherdoctors,dentistsand

pharmacistswhoaretreatingyouthatyouaretakingthismedicine.

Keepallofyourdoctor’sappointmentssothatyourprogresscanbechecked.Have

yourbloodpressurecheckedasinstructedbyyourdoctor,tomakesureClonidineBNMis

working.

Seeyourdoctorifyoufeelthatyourconditionisnotimprovingorisgettingworse.

5

Clonidine BNM

Ifyoubecomepregnantwhiletakingthismedicine,tellyourdoctorimmediately.

Things you must not do

Do notgiveyourmedicineto anyone else,eveniftheyhave thesameconditionasyou.

Thismedicineisonlyintendedfortheuseofthepatientithasbeenprescribedfor.

DonottakeClonidineBNMtotreatanyothercomplaintsunlessyourdoctortellsyou

to.

Things tobe careful of

BecarefuldrivingoroperatingmachineryuntilyouknowhowClonidineBNMaffects

you.

Itmaycausedizzinessorlight-headednessinsomepeople,especiallyafterthefirstdose.

Makesureyouknowhowyoureacttoitbeforeyoudriveacar,operatemachinery,ordo

anythingelse thatcould bedangerousifyoufeeldizzy.Ifyoudrinkalcohol,ortake strongpain

killersorbarbiturates,the effectsmaybeworse.

Ifyoufeellight-headed,dizzyorfaint,getupslowlywhen gettingoutofbed orstanding

up.

Youmayfeellight-headedwhenyoubegintotakethesetabletsorifthedoseisincreased.

Thisisbecauseyourbloodpressureisfallingsuddenly.Standingupslowly,especiallywhen

yougetupfrombed orchairs,willhelpyourbodygetused to thechange inpositionand blood

pressure,theproblemusuallygoesawayafterafewdays.

Ifyoucontinue tofeelunwell,tellyourdoctor.

In caseofoverdose

If you take toomuch

Immediatelytelephoneyourdoctor,orthePoisonsInformationCentre(0800POISONor

0800764766),ifyouthinkthatyouoranyoneelsemayhavetakentoomuchClonidine

BNM.

Symptomsofanoverdosemayincludedrynessofmouth,slowheartbeat,drowsiness,

temporarilystoppingbreathingandcoma.Othersignsincludedizziness,weakness,lethargy,

feelingcold,vomiting,lookingpale,orhavinganirregularheartbeat.

Side effects

Tellyourdoctororpharmacistassoonaspossibleifyoudonotfeelwellwhileyouare

takingClonidineBNM.

6

Clonidine BNM

Likeallmedicines,ClonidineBNMmayoccasionallycausesideeffectsinsomepeople.

Sometimestheyareserious,mostofthetimetheyarenot.Youmayneedmedicalattentionif

yougetsome ofthesideeffects.

Askyourdoctororpharmacistto answeranyquestionsyoumayhave.

Frequentlyreportedsideeffectsinclude:

drowsiness

drynessofthemouth

lightheadedness(when youstand upsuddenly)

Thesesideeffectsareusuallymild.

Lessfrequentlyreportedsideeffectsinclude:

blurredvision

dizziness

confusion

nausea and vomiting

sleep disturbances

mentaldepression

irrationalorabnormalthoughts

irritability

decreasedsexualdrive /impotence

generallyfeelingunwell

thinningofhair

rash/hives /itching

constipation

drynessofthenose andeyes (cautioncontactlensusers)

pain inthesalivaryglands

tinglingornumbnessofthehandsorfeet

largerbreaststhan normal,inmen

sloworirregularheartbeat

blood glucoseincreased

Tellyourdoctorassoonaspossibleifyouexperienceanysideeffectsduringorafter

takingClonidineBNM,sothatthesesymptoms maybeproperlytreated.

Tellyourdoctorimmediately,orgotoAccidentandEmergencyatyournearesthospital

ifyounoticeanyofthefollowing:

serious allergicreaction(swellingoftheface,lips,mouthorthroatwhich maycause

difficultyin swallowingorbreathing)

severelight-headednessordizziness

numbnessin thehandsorfeet.

Theseareveryserious sideeffects;youmayneedurgentmedicalattention orhospitalisation.

Tellyourdoctororpharmacistifyounoticeanythingelsethatismakingyoufeel

unwell.

Othersideeffectsnotlistedabove mayalso occurin some patients.

Do notbealarmedbythislistofpossiblesideeffects.

Youmaynotexperienceanyofthem.

7

Clonidine BNM

AftertakingClonidine BNM

Storage

Keepyourtabletsinthe packuntilitistimetotakethem.

Ifyoutakethetabletsoutofthepacktheymaynotkeepwell.

KeepClonidineBNMina cooldryplacewherethetemperaturestaysbelow25ºC

Do notstoreitoranyothermedicineinthebathroom,nearasink,oronawindowsill.

Do notleave itinthecar.

Heatand dampcandestroysomemedicines.

Keep itand anyothermedicinewherechildren cannotreachit.

Alockedcupboardatleastone-and-a-halfmetresabovethegroundisagoodplacetostore

medicines.

Do notkeepClonidineBNMpastits expirydate.

Disposal

Returnanyunusedmedicine,andanymedicinepastitsexpirydate(asshownonthe

dispensinglabeloronthepackaging)toyourpharmacy.

Product description

What it looks like

ClonidineBNMisavailableincartonsof112tablets(4blisterstripsof28tabletseach).The

tabletsareround,white to off-whitein colourwith ‘CD25’markingononeside.

Ingredients

Active ingredient:

clonidinehydrochloride

Inactive ingredients:

cellulose-microcrystalline

starch-maize

starch-pregelatinisedmaize

lactosemonohydrate

talc-purified

sodiumstarchglycollateTypeA

magnesiumstearate(E470b)

ClonidineBNMcontainslactose.

8

Clonidine BNM

ClonidineBNMdoes notcontain sucrose,tartrazineoranyotherazo dyes.

Sponsor details

Boucher&Muir(NZ)Ltdt/aBNMGroup

39Anzac Road

Browns Bay

Auckland 0753

Ph:0800565 633

Dateofpreparation

Thisleafletwas prepared on20December2012.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

New Zealand Data Sheet

1

CLONIDINE BNM

CLONIDINE BNM 25 microgram tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains clonidine hydrochloride 25 micrograms

Excipient(s) with known effect: lactose monohydrate

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

White to off-white circular tablet, engraved with ‘CD 25’ on one side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

The prophylactic management of migraine or recurrent vascular headaches in adult

patients.

The management of vasomotor conditions commonly associated with menopause and

characterised by flushing.

4.2

Dose and method of administration

Dose

Adults (including elderly patients)

Therapy should be started with one tablet twice daily (morning and evening).

If there is no relief after two weeks the dosage can be gradually increased to 3 tablets twice

daily.

Duration of treatment will depend on the frequency and severity of attacks. It may take 2

- 4 weeks until Clonidine BNM is fully effective.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

Note: Clonidine BNM is not suitable for clearing acute migraine headaches.

Special populations

Renal impairment

Clonidine BNM should be used with caution in patients with renal insufficiency. Careful

monitoring of blood pressure is required.

Paediatric population

The safety and efficacy of clonidine in children and adolescents have not been established.

4.3

Contraindications

Clonidine BNM should not be used in patients with known hypersensitivity to the active

ingredient

other

components

product,

patients

with

severe

bradyarrhythmia resulting from either sick sinus syndrome or AV blocks of 2nd or 3rd

degree.

In case of rare hereditary conditions that may be incompatible with an excipient of the

product (see section 4.4 Special warnings and precautions for use) the use of the product

is contraindicated.

4.4

Special warnings and precautions for use

At doses higher than those recommended above, clonidine is an effective antihypertensive

agent. Caution should be observed where antihypertensive agents are being used, as

potentiation of the hypotensive effect may occur. Provided the recommended dosage

regimen is followed, no difficulty with hypotension should arise during the routine

management of patients with either migraine or menopausal flushing.

Clonidine

should

used

with

caution

patients

with

mild

moderate

bradyarrhythmia, such as low sinus rhythm, with disorders of cerebral or peripheral

perfusion (e.g. Raynaud’s disease), depression, polyneuropathy and constipation.

Clonidine and its metabolites are extensively excreted with the urine. Clonidine BNM

should therefore be used with caution in patients with renal insufficiency (see section 4.2

Dose and method of administration).

As with other antihypertensive drugs, treatment with Clonidine BNM should be monitored

particularly carefully in patients with heart failure or severe coronary disease.

In patients who have developed localised skin reaction to patches containing clonidine,

substitution of oral clonidine therapy may be associated with the development of a

generalised rash.

If long-term treatment with a beta-receptor blocker has to be interrupted, then the beta-

receptor blocker should first be phased out gradually and then clonidine.

Patients should be instructed not to discontinue therapy without consulting their physician.

Following sudden discontinuation of Clonidine BNM after prolonged treatment with high

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

doses,

restlessness,

palpitations,

rapid

rise

blood

pressure,

nervousness,

tremor,

headaches or nausea have been reported. When discontinuing therapy with Clonidine

BNM, the physician should reduce the dose gradually over 2 - 4 days. An excessive rise

in blood pressure following discontinuation of clonidine therapy can be reversed by

intravenous phentolamine or tolazoline (see section 4.5 Interaction with other medicines

and other forms of interaction

Patients who wear contact lenses should be warned that treatment with clonidine may

cause decreased lacrimation.

This product contains 48 mg lactose monohydrate per tablet. Patients with the rare

hereditary conditions of galactose intolerance (e.g. galactosaemia), the Lapp lactase

deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

The use and the safety of clonidine in children and adolescents under 18 years have little

supporting evidence in randomised controlled trials and therefore cannot be recommended

for use in this population (see section 5.1 Pharmacodynamic properties).

In particular, when clonidine is used off-label concomitantly with methylphenidate in

children with ADHS, serious adverse reactions, including death, have been observed.

Therefore, clonidine in this combination is not recommended.

4.5

Interaction with other medicines and other forms of interaction

Clonidine

administered

concomitantly

with

agents

such

diuretics,

vasodilators,

beta-receptor

blockers,

calcium

antagonists

ACE-inhibitors,

their

hypotensive effect can be potentiated.

Substances with alpha

-receptor blocking properties such as mirtazapine, phentolamine or

tolazoline may abolish the alpha

-receptor mediated effects of clonidine in a dose-

dependent manner.

Concomitant administration of substances with a negative chronotropic or dromotropic

effect such as beta-receptor blockers or digitalis glycosides can cause or potentiate

bradycardic rhythm disturbances.

It cannot be ruled out that concomitant administration of a beta-receptor blocker will cause

or potentiate peripheral vascular disorders. Studies with combined administration of

clonidine and beta-receptor blockers have shown that if treatment is to be discontinued,

the dose of the beta-receptor blocker must always be slowly diminished first, followed by

the clonidine.

Orthostatic regulation disturbances may be provoked or aggravated by concomitant

administration of tricyclic anti-depressants or neuroleptics with alpha-receptor blocking

properties. It may be necessary to adjust the dosage of Clonidine BNM if these agents are

administered concurrently.

The effect of centrally depressant substances or alcohol can be potentiated by clonidine.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

4.6

Fertility, pregnancy and lactation

Pregnancy

Category B3

There are limited data from the use of clonidine in pregnant women. During pregnancy,

Clonidine BNM, as any drug, should only be administered if the benefit justifies any

possible risks to the foetus. Careful monitoring of mother and child is recommended.

Clonidine passes the placenta barrier and may lower the heart rate of the foetus. There is

no adequate experience regarding long-term effects of prenatal exposure.

During pregnancy the oral forms of clonidine should be preferred. Intravenous injection

of clonidine should be avoided.

Non-clinical studies do not indicate direct or indirect harmful effects with respect to

reproductive toxicity (see section 5.3 Preclinical safety data - Toxicology). Post partum,

a transient rise in blood pressure in the newborn cannot be excluded.

Breastfeeding

Clonidine is excreted in human milk. However, there is insufficient information on the

effect on newborns. The use of Clonidine BNM is therefore not recommended during

breast feeding.

Fertility

No clinical studies on the effect on human fertility have been conducted with clonidine.

Non-clinical studies with clonidine indicate no direct or indirect harmful effects with

respect to the fertility index (see section 5.3 Preclinical safety data - Toxicology).

4.7

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

However, patients should be advised that they may experience undesirable effects such as

dizziness, sedation and accommodation disorder during treatment with Clonidine BNM.

Therefore, caution should be recommended when driving a car or operating machinery. If

patients experience the above mentioned side effects they should avoid potentially

hazardous tasks such as driving or operating machinery.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

4.8

Undesirable effects

Most adverse effects are mild and tend to diminish with continued therapy. Frequent side

effects are dryness of mouth, sedation and reduction of blood pressure.

Endocrine disorders:

gynaecomastia

Psychiatric disorders:

confusional state, delusional perception, depression, hallucination, libido decreased,

nightmare, sleep disorder

Nervous system disorders:

dizziness, headache, paraesthesia, sedation Eye disorder:

accommodation disorder, lacrimation decreased

Cardiac disorders:

atrioventricular block, bradyarrhythmia, sinus bradycardia

Vascular disorders:

orthostatic hypotension, Raynaud's phenomenon

Respiratory, thoracic and mediastinal disorders:

nasal dryness

Gastrointestinal disorders:

colonic

pseudo-obstruction,

constipation,

mouth,

nausea,

salivary

gland

pain,

vomiting. Very rarely pain in the parotid gland.

Skin and subcutaneous tissue disorders:

alopecia, pruritus, rash, urticaria

Reproductive system and breast disorders:

erectile dysfunction

General disorders and administration site conditions:

fatigue, malaise

Investigations:

blood glucose increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It

allows continued monitoring of the benefit/risk balance of the medicine. Healthcare

professionals are asked to report any suspected adverse reactions

https://nzphvc.otago.ac.nz/reporting/

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

4.9

Overdose

Symptoms

Clonidine has a wide therapeutic range. The symptoms of overdosage are due to

generalised

sympathetic

depression

include

pupillary

constriction,

lethargy,

bradycardia, hypotension, somnolence including coma, respiratory depression including

apnoea. Paradoxic hypertension caused by stimulation of peripheral alpha

-receptors may

occur.

Treatment

Careful monitoring and symptomatic measures.

Gastric lavage and/or administration of activated charcoal should be performed where

appropriate.

For advice on the management of overdose please contact the National Poisons Centre

on 0800 POISON (0800 764766).

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Other antimigraine preparations

ATC code: N02CX02

Mechanism of action

Clonidine is a centrally acting α

-agonist. The central inhibiting effect on noradrenergic

neurotransmission generally dominates the peripheral excitatory α

-effect.

In the prophylaxis of migraine, based on observations that vascular responsiveness is

reduced after long-term administration of low doses of clonidine, a hypothesis of a

peripheral mode of action has been put forward. The reduced responsiveness of the vessels

to adrenergic stimuli due to clonidine possibly also plays a significant role in the reduction

of menopausal hot flushes. Central as well as peripheral mode of action are discussed as

affecting climateric complaints, e.g. reduced noradrenergic activity in the hypothalamus

and changes in central hormone secretion.

Paediatric population

There were two small paediatric studies in migraine, neither of which demonstrated

efficacy. In paediatric studies the most frequent adverse events were drowsiness, dry

mouth, headache, dizziness and insomnia. These adverse events might have serious

impact on daily functioning in paediatric patients.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

5.2

Pharmacokinetic properties

Absorption

The pharmacokinetics of clonidine is dose-proportional in the range of 75 - 300 mcg.

Clonidine is well absorbed and undergoes a minor first pass effect. Peak plasma

concentrations are reached within 1 - 3 h after oral administration. The plasma protein

binding is 30 - 40%.

Distribution

Clonidine is rapidly and extensively distributed into tissues and crosses the blood brain

barrier, as well as the placental barrier. Clonidine is excreted in human milk. However,

there is insufficient information on the effect on newborns

Biotransformation

The terminal elimination half-life of clonidine has been found to range from 5 to 25.5

hours. It can be prolonged in patients with severely impaired renal function up to 41 hours.

About 70% of the dose administered is excreted with the urine mainly in form of the

unchanged parent drug (40-60% of the dose). The main metabolite p-hydroxy-clonidine

is pharmacologically inactive.

Elimination

Approximately 20% of the total amount is excreted with the faeces. The pharmacokinetics

of clonidine is not influenced by food or by the race of the patient.

The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0

ng/ml in patients with normal renal function. The hypotensive effect is attenuated or

decreases with plasma concentrations above 2.0 ng/mL.

5.3

Preclinical safety data

Toxicology

Single dose toxicity studies with clonidine were performed in different animal species by

oral and parenteral routes of administration. The approximate oral LD

values were

70 mg/kg (mouse), 190 mg/kg (rat), > 15 mg/kg (dog), and 150 mg/kg in monkeys.

Following subcutaneous injection, the LD

values were > 3 mg/kg in dogs and 153 mg/kg

in rats. After intravenous administration the lethal dose ranges were between 6 mg/kg

(dog) and < 21 mg/kg (rat).

Toxic trans-species signs of toxicity following exposure to clonidine were exophthalmus,

ataxia and tremor, independently from the route of administration. At lethal doses,

tonic-clonic convulsions occurred. In addition, excitement and aggressiveness alternating

with sedation (mouse, rat, dog), salivation and tachypnea (dog) as well as hypothermia

and apathy (monkey) were observed.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

In repeated oral dose toxicity studies up to 18 months clonidine was well tolerated at 0.1

mg/kg (rat), 0.03 mg/kg (dog) and 1.5 mg/kg (monkey). In a 13 week study in rats, the no

adverse effect level (NOAEL) was 0.05 mg/kg following subcutaneous administration.

After intravenous administration rabbits and dogs tolerated 0.01 mg/kg/day for 5 and 4

weeks, respectively. Higher dosages caused hyperactivity, aggression, reduced food

consumption and body weight gain (rat), sedation (rabbit) or an increase in heart and liver

weight accompanied by elevated serum GPT, alkaline phosphatase and alpha-globulin

levels and focal liver necroses (dog).

There were no signs of any teratogenic potential after oral administration in mouse and

rat at 2.0 mg/kg and rabbit at 0.09 mg/kg, or after s.c. (0.015 mg/kg, rat) and i.v. treatment

(0.15 mg/kg, rabbit). In rats, increases in resorption rate were observed at oral dosage of

> 0.015 mg/kg/day; however dependent on duration of dosing. Fertility in rats was not

impaired up to 0.15 mg/kg. Doses up to 0.075 mg/kg did not affect the peri- and postnatal

development of the progeny.

There was no mutagenic potential in the Ames test and micronucleus assay in mice.

Clonidine was not tumorigenic in a carcinogenicity assay in rats.

No local irritating or sensitizing potential was found in guinea pigs and rabbits following

i.v. and i.a. administrations.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Cellulose - microcrystalline

Starch - maize

Starch - pregelatinised maize

Lactose monohydrate

Talc - purified

Sodium starch glycollate Type A

Magnesium stearate (E470b)

The tablet formulation is colour-free, preservative-free, sugar-free, and does not contain

gluten.

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

3 years

6.4

Special precautions for storage

Store below 25°C. Keep out of reach of children.

Clonidine BNM

Clonidine hydrochloride tablets 25 microgram

6.5

Nature and contents of container

PVC/aluminium blister.

Each carton contains 112 tablets (4 blister strips of 28 tablets each).

6.6

Special precautions for disposal and other handling

No special requirements for disposal.

7

MEDICINE SCHEDULE

Prescription Medicine

8

SPONSOR

BNM Group

39 Anzac Road

Browns Bay

Auckland 0753

Phone 0800 565 633

9

DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine:

20 December 2012

10

DATE OF REVISION OF TEXT

04 March 2019

Summary table of changes

Section changed

Summary of new information

Datasheet re-formatted in line with the

SPC style template

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