Clopixol

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Zuclopenthixol hydrochloride 25 mg
Available from:
Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
INN (International Name):
Zuclopenthixol hydrochloride 25 mg
Dosage:
25 mg
Pharmaceutical form:
Tablet
Composition:
Active: Zuclopenthixol hydrochloride 25 mg
Units in package:
Bottle, plastic, 100 tablets
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
H Lundbeck A/S
Product summary:
Package - Contents - Shelf Life: Bottle, plastic, - 100 tablets - 60 months from date of manufacture stored at or below 25°C protect from light
Authorization number:
TT50-4535b
Authorization date:
1988-04-22

Clopixol ®

(clo-PIK-sol)

Clopixol ®

Tablets 10 mg

Clopixol ®

Acuphase Injection 50 mg/mL

Clopixol ®

Depot Injection 200 mg/mL

Zuclopenthixol hydrochloride

(zoo-clo-PEN-thic-sol high-dro-CLOR-ride)

Zuclopenthixol acetate

(zoo-clo-PEN-thic-sol AS-se-tate)

Zuclopenthixol decanoate

(zoo-clo-PEN-thic-sol deck-can-OH-ate)

Consumer Medicine Information (CMI)

What is in this leaflet

This leaflet contains answers to

somecommon questions about

Clopixol.

Itdoes notcontain allthe

information thatisknown about

Clopixol. It does nottake the place

of talking toyour doctor or

pharmacist.

Allmedicines have risks and

benefits. Your doctor has weighed

the risk of you using thismedicine

againstthe benefitshe/she expects

it will havefor you.

If you have any concerns about

usingthis medicine, ask your

doctor or pharmacist.

Keep this leaflet with the

medicine.

You may need to read it again.

What Clopixol is used

for

Clopixoltablets are used for the

acuteand long-termtreatmentof

schizophreniaand other mental

illnesses withdisturbances in

thinking, emotionalreactions and

behaviour.

It is also used to treat the manic

phase ofmanic depressiveillness.

excitement, over-activity and

uninhibited behaviour.

ClopixolAcuphase injection isused

for the initial treatmentofacute

episodes of mentaldisorders. Itis

also used to treat mania (a mental

condition characterised by episodes

ofoveractivity, elationorirritability)

and used incase of worsening of

chronic mentalconditions.

ClopixolDepotinjection isusually

used topreventfurther episodes of

yourillness.

Clopixolbelongs toa group of

medicines called thioxanthene

neuroleptics. Ithelps tocorrect

chemical imbalances in the brain,

whichmay cause mental illness.

Your doctor, however, may

prescribe itfor another purpose.

Ask your doctor ifyou have any

questions about why it has been

prescribed for you.

This medicineis only available with

a doctor’s prescription.

Clopixolisnotaddictive.

Before you use it

When you must not use it

Do not use Clopixolifyou are

allergic toit, toanyother similar

medicines (such as thioxanthenes

ingredients listed atthe end ofthis

leaflet.

Symptomsofanallergic reactionmay

include shortness of breath, wheezing

or difficultybreathing, swelling of the

face, lips, tongue or other parts of the

body, or rash, itching or hives on the

skin.

Do not use Clopixolifyou have:

collapse due toverylow blood

pressure

diminished consciousness due to

any cause

brain damage

diseases of the blood with

abnormalor reduced number of

red or whiteblood cellsor platelets

phaeochromocytoma, a rare tumour

of the adrenalgland which sits

near the kidney.

Do not give Clopixolto anyone who

currently has alcohol poisoning, or

poisoningwith medicines used to

produce calmness or to help you

sleep, or medicines used to treat

epilepsy or strong pain.

Do not give Clopixolto anyone who

is unconscious orin acoma.

Do not use it after the expiry date

printed on the pack.

If you use itafter the expirydatehas

passed, itmaynotwork as well.The

expiry date refers tothe last day ofthe

month.

Do not use it if the packaging is torn

or shows signs of tampering.

Before you start to use it

Tellyour doctor if:

1.you have allergies to any

other substances such as

foods, preservatives or dyes.

2.you are pregnant or intend to

become pregnant.

Clopixolmayaffectyour

fertility. If youare intendingto

starta family, ask your doctor

for advice.

Like mostmedicines of this

kind, Clopixolisnot

recommended for use during

pregnancyunless clearly

necessary. The general

condition of your babymightbe

affected by the use of this

medicine.

Thefollowingsymptomsmay

occur innewborn babies of

mothers who have used

Clopixolinthe last three

months of their pregnancy:

shaking, muscle stiffness and/or

weakness, sleepiness, agitation,

breathing problems and

difficultyinfeeding. If your

babydevelops anyof these

symptomsyou should contact

your doctor.

3.you are breast-feeding or

planning to breast-feed.

Itisnotrecommended thatyou

breast-feed whileusing

Clopixol. Its active ingredient

passes intobreast milkand

therefore there is a possibility

thatyour babymightbe

affected.

4.you have, or have had, the

followingmedicalconditions:

arteriosclerosis, a disease

affecting the arteries

convulsions, fitsor seizures

decreased blood supplyto

the brain

diabetes, a disorder of

metabolisminwhichthe

amountof sugar inthe blood

istoo high

feeling lethargic, indifferent,

glaucoma, a condition in

whichthere is usually a

build-up of pressure inthe

eye

heartand blood vessel

problems

kidneyproblems

liver problems

low potassiumand/or low

magnesiumlevels inthe

blood

organic brain syndrome

parkinsonism, a disease of the

brain affecting movement

risk factors for stroke

tardive dyskinesia, a reaction

tosomemedicines with

worm-like movements of the

tongue, or other uncontrolled

movements of the mouth,

tongue, cheeks or jaw which

mayprogress tothe armsand

legs.

treatment for cancer

ifyou or someone else in

your familyhas a historyof

blood clots, as medicines like

these have been associated

withformation of blood clots

Alsotell your doctorif youwill be

ina hot environment or you do a

lot of vigorous exercise.

Clopixolmaymake you sweatless,

causing your bodytooverheat.

Tellyour doctor ifyou are exposed

to pesticides that contain

phosphorus.

The risk of you experiencing a side

effect may be increased.

If you are lactose intolerant,

contact your doctor before taking

Clopixoltablets.

Clopixoltablets contain lactose.

Do not give Clopixolto a childor

adolescent.

There is no experience with its use

inchildren or adolescentsunder

18 years old.

If you have not toldyour doctor

about any of the above, tellthem

before you use Clopixol.

Tellyour doctor ifyou are taking

any other medicines, including any

that you buy without a prescription

from your pharmacy, supermarket

or health food shop.

Somemedicines and Clopixolmay

interfere with each other. These

include:

tricyclic antidepressants and

lithium,medicines usedtotreat

depression or mood swings

medicines used totreatstrong pain

medicines used toproduce

calmness or tohelpyou sleep

medicines used totreathigh blood

pressure (hypertension), such as

guanethidine

levodopa, a medicine used totreat

Parkinson’s disease

medicines which stimulate the

body, getting it ready for action,

such as adrenaline

metoclopramide, a medicine used

torelieve nausea and vomiting

piperazine, a medicine used totreat

worminfections

medicines known toinhibitthe

activity ofcertainliver enzymes

medicines used to treat changes in

the rhythmor rate of the heart beat,

e.g. quinidine, amiodarone, sotalol

anddofetilide

antipsychotics, a class of medicines

used to treat certain mental and

emotionalconditions, e.g.

thioridazine

certain medicines used to treat

infections, such as erythromycin,

gatifloxacin and moxifloxacin

medicines used torelieve the

symptomsof allergy,including

terfenadine and astemizole

cisapride, used to treat stomach

problems

medicines thatdisturb water or salt

balance e.g. thiazide diuretics, also

called fluid or water tablets

medicines known toincrease the

concentration of Clopixolinyour

blood

medicines used torelieve stomach

cramps or spasms, to prevent travel

sickness and totreatParkinson’s

disease, such as atropine or

related medicines.

medicines used to treat cancer

These medicines may be affected

byClopixol, or mayaffecthow well

itworks. You mayneed touse

differentamounts of your

medicines, or take different

medicines. Yourdoctor will advise

you.

Your doctor or pharmacisthas more

information on medicines tobe

carefulwithor avoid whileusing

Clopixol.

How to use it

How much to use

Clopixoltablets

The usualdose is10 to50 mgper

day.

Ask your doctor or pharmacist if

you are unsure of the correct dose

for you.

They will tell youexactly how

muchtotake.

Follow the instructions they give

you.

If you take the wrong dose,

Clopixolmaynotwork as welland

your condition maynotimprove.

ClopixolAcuphase injection

The usualdose is50 to150 mg

(1 to3 mL) every2 to3 daysor as

instructed byyour doctor.

The duration of the treatment

should notbe more than 2 weeks.

The maximumdose should notbe

more than 400 mgand the total

number of injections should notbe

more than 4 per course of treatment.

ClopixolDepotinjection

The usualdose is200 to400 mg

(1 to2 mL) everysecond tofourth

week.

Yourdoctor will decidewhat dose

you will receive. This depends on

your condition and other factors,

response tothe medicine. Generally,

yourdoctor will start youonsmaller

doses whichwill begradually

increased until a dose is reached

where Clopixolworks bestfor you.

Your doctor mayhave prescribed a

differentdose.

Ask your doctor or pharmacist if

you are unsure of the correct dose

for you. Follow the instructions

they give you.

They will tell youexactly howmuch

youwill begiven.

Elderly patients

The dosage of Clopixolmayneed to

be reduced inelderlypatients.

How to use it

Clopixoltablets

Swallow the tablets whole with a

fullglass of water.

To open this child resistant bottle,

please hold,twist andturnthe bottle

as per the diagrambelow.

Clopixolinjections

Clopixolisgiven as an injection into

a large muscle where it is slowly

released over time. The injection

should onlybe given bya doctor,

nurse or other trained person.

When to use it

You maybe given Clopixoltablets

or injections which both have the

sameeffects onyourillness,

although theylastfor different

lengths of time.

Clopixoltablets

Clopixoltablets onlywork for a

short time, sothey needtobetaken

Take Clopixoltablets once a day at

about the same time.

Taking themat the sametime each day

will alsohelpyouremember whento

takethe tablets.

Take Clopixoltablets before or after

food.

Clopixolinjections

ClopixolAcuphase injection has tobe

given every2 - 3 days, whileClopixol

Depot injection lasts several weeks, so

itisgiven once every2 - 4 weeks.

Yourdoctor will advise you.

How long to use it

Continue taking your tablets and/or

having your injections for as long as

your doctor tellsyou to.

Clopixolhelps controlyour condition,

butdoes notcure it. Therefore, you

will needregular treatment.

If you forget to use it

Clopixoltablets

If it is almost time for your next

dose, skip the dose you missed and

take the next dose when you are

meant to.

Do not take a double dose to make

up for the dose you have missed.

If there is still a long time to go

before your next dose, take it as

soon as you remember, and then go

back to taking it as you would

normally.

If you are not sure what to do, ask

your doctor or pharmacist.

If you have trouble remembering

when to take your medicine, ask

your pharmacist for hints.

Clopixol injections

If you forget to keep an

appointment, contact your doctor as

soon as you remember, so that you

can make another one.

Overdose

Immediately telephone your doctor,

or the Poisons Information Centre

(Tel: 13 11 26 for Australiaand Tel:

0800 764 766 for NewZealand), or

go to Accident and Emergency at

your nearest hospital, if

you think you or anyone else

may have taken too many

Clopixol tablets. Do this even

if there are no signs of

discomfort or poisoning.

you experience any side effects

after being given Clopixol

injections.

You mayneed urgentmedical

attention.

As Clopixolinjections are given

to you under the supervision of

your doctor, it is very unlikely

that you will receive too much.

Symptomsof an overdose may

include sleepiness, coma, cramps,

convulsions, low blood pressure

and extremelyhigh or low body

temperature. Uncontrollable

movements maydevelop, and

collapse due toverylow blood

pressure may occur. Changes in the

rhythmor rateof the heartbeat

have been seen inClopixol

overdose when medicines known to

affect the heart have also been

taken.

While you are using it

Things you must do

If you are about to be started on

any new medicine, remind your

doctor and pharmacist that you

are using Clopixol.

Tellany other doctors, dentists

and pharmacists who treat you

that you are using thismedicine.

If you become pregnant while

using Clopixol, tellyour doctor

immediately.

Tell your doctor immediately if

you notice any worm-like

movements of the tongue, or

other uncontrolled movements of

the tongue, mouth, cheeks or jaw

which may progress to the arms

and legs.

These are symptomsof a condition

maydevelop inpeople taking similar

medicines, including Clopixol.

This conditionis more likely to

occur during long-termtreatment

withClopixol, especiallyinelderly

women. In veryrare cases, this may

be permanent. However, if detected

early, these symptomsare usually

reversible.

Also tellyour doctor ifyou notice

any soreness of the mouth, gums,

throat or other flu-like symptoms.

Talkto your doctor or mental

health professionalifyou are

thinking or talking about death,

suicide, self-harm or harm to

others.

These maybe signs of changes or

worseninginyourmental illness.

If you are going to have surgery,

tell the surgeon or anaesthetist

that you are using thismedicine.

Clopixolmayaffectother medicines

used during surgery.

If you are about to have any blood

tests, tellyour doctor that you are

usingthis medicine.

It may interfere withthe results of

sometests.

Protect your skin when you are in

the sun, especiallybetween 10am

and 3pm.

If you are outdoors, wear

protective clothing and use a 30+

sunscreen.

If your skinappears to be

burning, tell your doctor.

Clopixolmaycause your skintobe

muchmore sensitive tosunlightthan

it is normally. This couldcause skin

rash, itching, redness, or severe

sunburn.

Keep allof your doctor’s

appointments so that your

progress can be checked.

Your doctor maydo someblood and

liver tests fromtime totime,

particularlyduring the firstmonths

oftherapy, tomakesure the

medicine isworking and toprevent

unwanted side effects.

Do not give your medicine to anyone

else, even if they have the same

condition as you.

Do not use Clopixolto treat any

other complaints unless your doctor

tells you to.

Do not take any medicines that

cause drowsiness while you are

using Clopixol, unless recommended

by your doctor.

Do not stop using Clopixol, or lower

the dosage, without checking with

your doctor.

Do not miss any injections, even if

you feel better.

Clopixolhelps controlyour condition,

butdoes notcure it. Therefore, you

will needregular injections.

Do not stop using Clopixol suddenly.

If Clopixolisstopped suddenly,you

may experience symptomssuch as

nausea, vomiting,loss ofappetite,

diarrhoea, runnynose, sweating,

aching muscles, pins and needles,

sleeplessness, restlessness, anxiety, or

agitation.

Your doctor maywanttogradually

reduce the amountyou are using

before stopping completely.

Things to be careful of

Be careful driving or operating

machinery until you know how

Clopixolaffects you.

It may cause drowsiness, tiredness,

sleepiness or blurred vision insome

people. If you have anyof these

symptoms, do notdrive, operate

machinery, or do anything else that

could be dangerous.

Be careful when drinking alcohol

while youare usingthis medicine.

If you drink alcohol, drowsiness or

sleepiness may be worse.

If you feel light-headed, dizzyor

faint when getting out of bed or

standing up, get up slowly.

Standingupslowly will helpyour

body get used to the change in position

and blood pressure. If thisproblem

continues or getsworse, talktoyour

doctor.

Side effects

Allmedicines mayhave some

unwanted side effects. Sometimes

theyare serious, butmostof the

time theyare not. Your doctor has

weighed the risks of using this

medicine againstthe benefitshe/she

expects it will havefor you.

Tell your doctor or pharmacist as

soon as possible ifyou do not feel

wellwhileyou are using Clopixol.

Ithelps mostpeople withmental

illness, butit may haveunwanted

side effects in a few people.

If you are over 65 years of age you

may have an increased chance of

getting side effects.

Tellyour doctor ifyou notice any

of the following and they worry

you:

drowsiness, sleepiness

inability tosleep

abnormaldreams

headache

fatigue

depressed mood

anxiousness

nervousness, agitation

headaches

nasalcongestion

drymouth

constipation or diarrhoea

increased salivation or increased

sweating

nausea, vomiting, dyspepsia

weightandappetite changes

change inyour menstrual

periods

impaired sexualfunction

swelling of hands, ankles or feet

skinrash, itching.

abnormalsensations, such as

burning or prickling

changes inattention and

memory

dizziness or spinning sensation

painful orweakmuscles

feeling generallyunwell

Tell your doctor immediately if

you notice any of the following:

sudden onsetof unusual

movements, including trembling

and shaking of the hands and

fingers, twisting movements of

the body, or shuffling walkand

stiffness of the armsand legs

worm-like movements of the

tongue or other uncontrolled

movements of the mouth,

tongue, cheeks or jaws, which

mayprogress tothe armsand

legs

inability tokeepstill

increased, slowed or unusual

musclemovements

feeling dizzywhen standing up

irregular heart beat and changes

inheartrateand blood pressure

fainting

blurred vision or difficulty

focusing

difficultypassing urine

increased urination or other

urinarydisorder

high pressure inthe eye

unusualsecretion of breastmilk

breast enlargement in men

difficultor painfulbreathing

frequentinfections such as fever,

severe chills, sore throat or

mouth ulcers

bleeding or bruising more easily

than normal, nosebleeds

yellowing of the skinand/or

eyes, also called jaundice

severe paininthe stomachwith

bloating, gutcramps and

vomiting.

Blood clots inthe veins

especially inthe legs(symptoms

include swelling, painand

redness inthe leg), whichmay

travelthrough blood vesselsto

the lungs causing chestpainand

difficultyinbreathing. If you

notice any of these symptoms

seek medical advice

immediately.

In elderlypeople withdementia,

deaths has been reported for

patients taking antipsychotics

compared with those not receiving

antipsychotics.

These maybe serious side effects of

Clopixol. You mayneed urgent

medicalattention.

Tell your doctor immediately, or go

to Accident and Emergency at your

nearest hospital, ifyou notice any of

the following:

seriousallergic reaction

(symptoms of an allergicreaction

may include swelling of the face,

lips, mouth or throatwhich may

cause difficulty inswallowingor

breathing, or hives)

sudden increase inbody

temperature, unusualstiffness of

the muscles and changes in

consciousness, especiallyin

conjunction withfastheartrateand

sweating. Thismaybe due toa

veryrare condition called

neurolepticmalignantsyndrome,

which has been reported with

various antipsychoticmedicines.

These are very serious side effects.

You mayneed urgentmedical

attentionorhospitalisation.

These side effects are generally rare.

Tellyour doctor ifyou notice

anything else that ismaking you feel

unwell.

Other side effects notlisted above may

occur insomepeople.

Do not be alarmed by this list of

possible side effects.

You maynotexperience anyof them.

After using it

Storage

Keep Clopixolin the pack until it is

time to use it.

If you take the tablets or the ampoules

outof the pack theymaynotkeep

well.

Keep Clopixolaway from

sunlight.

Keep the medicine in a cool dry

place where the temperature

stays below25 ° C.

Do not store itor any other

medicine in the bathroom, near a

sink, oronawindow-sill.

Donot leaveit in the car.

Heat and dampcan destroy some

medicines.

Keep it where children cannot

reach it.

A locked cupboard atleastone-and-

a-halfmetres above the ground isa

good place to store medicines.

Disposal

If your doctor tellsyou to stop

using this medicine, or the expiry

date has passed, ask your

pharmacist what to do with any

that is left over.

Return any unused medicine to

your pharmacist.

Product description

What it looks like

Clopixolcomes as tablets and in

twotypes ofinjections:

Clopixol10 mgfilm-coated

tablets - lightred brown, round

ClopixolAcuphase 50 mg/mL

solutionfor injection- clear,

yellowishoil

ClopixolDepot200 mg/mL

solutionfor injection- clear,

yellowishoil.

The tablets are available inbottles of

100 tablets and the injections come

inboxes of 5 ampoules.

Ingredients

Active ingredient(s):

Clopixol10 mgtablets - 10 mg

zuclopenthixol(as

hydrochloride) per tablet

ClopixolAcuphase 50 mg/mL

injection - 50 mgzuclopenthixol

acetate per 1 mLor 100 mg

zuclopenthixol acetate per 2 mL

ClopixolDepot200 mg/mL

injection - 200 mg

zuclopenthixoldecanoateper

1 mL.

Inactive ingredients (tablets):

castor oil- hydrogenated

cellulose - microcrystalline

glycerol

hypromellose

iron oxide red CI77491

lactose

macrogol6000

magnesiumstearate

PVP/VA copolymer

starch - potato

talc - purified

Clopixoltablets do notcontain gluten,

sucrose, tartrazine or any other azo

dyes.

Inactive ingredient(injections):

coconutoil- fractionated.

Manufacturer/Sponsor

Clopixolismade byH. Lundbeck A/S,

Denmark.

Distributed in Australia by:

Lundbeck AustraliaPtyLtd

1 Innovation Rd

North Ryde NSW 2113

Ph:+61 2 8669 1000

Distributed in New Zealand by:

Healthcare Logistics

PO Box 62027

MtWellington, Auckland

Ph:+64 9 9185100

This leaflet was prepared on 20 May

2013.

Australian Registration Numbers:

Clopixoltablets

10 mg AUST R45077

ClopixolAcuphase injection

50 mg/mL AUST R45080

100 mg/2mL AUST R46061

ClopixolDepotinjection

200 mg/1mL AUST R45082

“Clopixol” is the registered

trademark of H. Lundbeck A/S.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

1

15

1 NAME OF THE MEDICINE

Clopixol

10 mg Film-coated Tablets

Clopixol

Acuphase 50 mg/mL Injection

Clopixol

Depot 200 mg/mL Injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Clopixol Film-coated Tablets contain 10 mg zuclopenthixol as the dihydrochloride.

Excipients with known effect:

Lactose monohydrate

Hydrogenated castor oil

Clopixol Acuphase solution for injection contains zuclopenthixol acetate 50 mg/mL, equivalent to

zuclopenthixol 45.25 mg/mL.

Clopixol Depot solution for injection contains zuclopenthixol decanoate 200 mg/mL, equivalent to

zuclopenthixol 144.4 mg/mL.

For the full list of excipients, see Section 6.1 List of excipients

3 PHARMACEUTICAL FORM

Clopixol 10 mg tablets are light red brown, round biconvex film-coated tablets.

Clopixol Acuphase injection presents as a clear, yellowish oil.

Clopixol Depot injection presents as a clear, yellowish oil.

4 CLINICAL PARTICULARS

4.1

Therapeutic indications

Clopixol tablets

Acute and chronic schizophrenia and other psychoses, especially those with symptoms such as

hallucinations, delusions, thought disturbances, agitation, restlessness, hostility or aggressiveness.

Manic phase of manic depressive illness.

Mental

retardation

associated

with

psychomotor

hyperactivity,

agitation,

violence

other

behavioural disturbances.

Senile dementia with significant paranoid ideas, confusion, disorientation or behavioural disturbances.

Clopixol Acuphase injection

Initial treatment of acute psychoses, mania and exacerbation of chronic psychoses.

Clopixol Depot injection

Maintenance treatment. May be an advantage in the treatment of noncompliant patients.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

2

15

4.2

Dose and method of administration

Adults

Clopixol tablets

Dosage should be adjusted individually. In general, small doses should be used initially and increased

to the optimal effective level as rapidly as possible, based on the response. The maintenance dose can

usually be given as a single dose at bedtime.

Concomitant intake of food enhances the bioavailability by approximately 20% of Clopixol tablets

without influencing its absorption rate. C

and elimination half-life (t

) are not altered. The

postulated mechanism for this effect is that food reduces the presystemic clearance of zuclopenthixol.

This effect is of doubtful clinical relevance and it does not appear that Clopixol tablets need to be given

with regard to meals.

Acute schizophrenia and other acute psychoses; severe, acute states of agitation; mania

Usually 10 - 50 mg/day orally. In moderate to severe cases, initially 20 mg/day increasing, if necessary,

by 10 - 20 mg every 2 - 3 days to 75 mg or more daily.

Chronic schizophrenia and other chronic psychoses

The usual maintenance dose is 20 - 40 mg/day orally.

Agitation in mentally retarded patients

6 - 20 mg/day orally, if necessary increased to 25 – 40 mg/day.

Agitation and confusion in senile patients

2 - 6 mg/day orally (preferably given late in the day). If necessary, increase to 10 – 20 mg/day.

Clopixol Acuphase injection

Dosage should be individually adjusted according to the patient's condition. Clopixol Acuphase is

administered by intramuscular injection. Local tolerability is good.

The dose range is usually 50 - 150 mg (1 - 3 mL) i.m., repeated if necessary, preferably at intervals of

2 to 3 days. In some cases, an additional injection may be needed 24 to 48 hours following the

first

injection.

Clopixol Acuphase is not intended for long-term use and the duration of treatment should not be more

than 2 weeks. The maximum accumulated dosage in a course should not exceed 400 mg and the total

number of injections should not exceed 4.

In the maintenance therapy, treatment should be continued with oral Clopixol or Clopixol Depot i.m.

according to the following guidelines:

Change to oral Clopixol 2 to 3 days after the last injection of Clopixol Acuphase:

If the patient has been treated with 100 mg Clopixol Acuphase, oral treatment should be started at a

dosage of about 40 mg daily, possibly in divided dosages. If necessary the dose can be further

increased by 10 - 20 mg every 2 to 3 days up to 75 mg or more.

Change to maintenance treatment with Clopixol Depot:

Concomitantly with the last injection of Clopixol Acuphase, 200 - 400 mg (1 – 2 mL) of Clopixol

Depot should be given intramuscularly and repeated every second week. Higher doses or shorter

intervals may be needed.

Clopixol Depot injection

The usual maintenance dose is 200 - 400 mg (1 - 2 mL) every second to fourth week.

A few patients may need higher doses or shorter intervals between doses.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

3

15

When changing medication from oral Clopixol or Clopixol Acuphase to maintenance treatment with

Clopixol Depot, the following guidelines should be used:

Change from oral Clopixol to Clopixol Depot i.m.:

mg Clopixol orally daily x 8 = mg Clopixol Depot i.m. every second week.

Oral Clopixol should be continued during the first week after the first injection but in diminishing

dosage.

2. Change from Clopixol Acuphase i.m. to Clopixol Depot i.m.:

Concomitantly with the last injection of Clopixol Acuphase, 200 - 400 mg (1 – 2 mL) of Clopixol

Depot should be given intramuscularly and repeated every second week. Higher doses or shorter

intervals between injections may be needed.

Elderly patients

The dosage may need to be reduced in elderly patients.

Children

Since the safety and efficacy of Clopixol in children have not been established, its use is not

recommended in this age group.

Reduced hepatic function

Clopixol should be used with caution in patients with mild to moderate liver disease (

see Section 4.4

Special warnings and precautions for use).

Reduced renal function

Since approximately 10% of a zuclopenthixol dose is excreted via the renal system, patients with renal

dysfunction may require dosage adjustment during long-term treatment (

see Section 4.4 Special

warnings and precautions for use).

Clinical particulars

If a rapid and pronounced reduction in psychotic symptoms is required, it is recommended to start

treatment parenterally with Clopixol Acuphase 50 mg/mL (zuclopenthixol acetate). Clopixol Acuphase

has a duration of action of 2 to 3 days and 1 or 2 injections are usually sufficient prior to the introduction

of maintenance treatment with Clopixol tablets or Clopixol Depot injection solution (

see Section 4.2

Dose and method of administration).

In the maintenance treatment of psychotic patients, particularly where compliance with oral medication

problem,

beneficial

continue

treatment

with

Clopixol

Depot

200 mg/mL

(zuclopenthixol decanoate) which is administered at intervals of 2 – 4 weeks.

In addition to its antipsychotic effect, zuclopenthixol also has a non-specific sedative effect on

accompanying symptoms such as agitation, restlessness, hostility or aggression.

Zuclopenthixol induces dose-dependent sedation. Tolerance to the non-specific sedative effect

develops rapidly. Significant sedation occurs within 2 hours of injection of Clopixol Acuphase,

reaching a maximum after 8 hours then declining to a low level, despite repeated injection.

Instructions to patients

Ambulant patients should be warned not to drive or operate machinery during the use of Clopixol.

Patients should be forewarned and reassured concerning the possible occurrence of extrapyramidal

symptoms.

Patients should be instructed to report any soreness of the mouth, gums, throat or other symptoms

which may indicate suppression of the immune system.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

4

15

4.3

Contraindications

Known hypersensitivity to the thioxanthenes. The possibility of cross-sensitivity between the

thioxanthenes and phenothiazine derivatives should be kept in mind.

Known hypersensitivity to any of the excipients of the particular Clopixol presentation (

see Section 6.1

List of excipients).

Acute alcohol, barbiturate or opiate intoxication.

Circulatory collapse, depressed level of consciousness due to any cause, coma, suspected or established

subcortical brain damage.

Blood dyscrasias.

Phaeochromocytoma.

Leucopenia and/or previous agranulocytosis.

4.4

Special warnings and precautions for use

Neuroleptic Malignant Syndrome

- A potentially fatal syndrome called neuroleptic malignant

syndrome (NMS) has been reported on occasion with antipsychotic drugs. The syndrome is

characterised by muscle rigidity, fever, hyperthermia, altered consciousness and autonomic instability

(e.g. tachycardia, labile blood pressure, profuse sweating, dyspnoea). The management of neuroleptic

malignant syndrome should include immediate discontinuation of antipsychotic drugs, intensive

monitoring of symptoms and treatment of any associated medical problems. Symptoms may persist

for more than a week after oral neuroleptics are discontinued and somewhat longer when associated

with the depot forms of the drugs.

Initiation of therapy -

Severe adverse reactions requiring immediate medical attention may occur and

are difficult to predict. Therefore, the evaluation of tolerance and response, and establishment of

adequate maintenance therapy require careful stabilisation of each patient under continuous, close

medical observation and supervision.

Suicide

– The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder, and

close supervision of high risk patients should accompany therapy.

Dyskinesia -

The possibility of the development of irreversible dyskinesia should be borne in mind

when patients are on prolonged therapy with Clopixol.

Photosensitivity reactions -

Photosensitivity reactions have been reported with related drugs.

Ophthalmological -

Pigmentary retinopathy and lenticular and corneal deposits have been reported with

related drugs. Lens opacity has been reported rarely with zuclopenthixol.

Anaphylactoid reactions -

The possibility of anaphylactoid reactions occurring in some patients should

be borne in mind.

Psychoses with apathy or withdrawal -

Clopixol is unsuitable for patients whose psychoses are

accompanied by features of apathy or withdrawal.

Reduced hepatic function -

Clopixol should be used with caution in patients with liver disease. Patients

with compromised hepatic function should be given half the recommended dose and serum levels

monitored (see Section 4.2 Dose and method of administration)

Reduced renal function -

Since only about 0.1% of a zuclopenthixol dose is excreted unchanged via

the renal system, patients with mild to moderate renal dysfunction can receive Clopixol in the usual

dosage. In patients with renal failure the dosage should be reduced to half the usual dose and close

monitoring instituted.

Parkinsonism -

Clopixol should be used with caution in patients with Parkinsonism.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

5

15

Arteriosclerosis -

Clopixol should be used with caution in patients with severe arteriosclerosis.

Organic brain syndrome -

Like other neuroleptics, Clopixol should be used with caution in patients

with organic brain syndrome.

Stroke -

An approximate 3-fold increase in risk of cerebrovascular adverse events has been seen in

randomised

placebo-controlled

clinical

trials

dementia

population

with

some

atypical

antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be

excluded for other antipsychotics or other patient populations. Therefore, zuclopenthixol should be

used with caution in patients with risk factors for stroke.

Cerebrovascular insufficiency -

Patients who have cerebrovascular insufficiency should be closely

monitored during treatment with Clopixol.

Convulsions -

Clopixol should be used with caution in patients with a history of convulsions since it

may lower the convulsive threshold.

Anticholinergic effects -

Although its anticholinergic properties are weak, zuclopenthixol should be

used with caution in patients who are known to have, or suspected of having, glaucoma; those who

might be exposed to extreme heat or organo-phosphorus insecticides, and those who are receiving

atropine or related drugs. Paralytic ileus has occasionally been reported (particularly in the elderly)

when several drugs with anticholinergic effects have been used simultaneously.

White blood cell disorders -

Leucopenia, neutropenia and agranulocytosis have been reported with

antipsychotics, including zuclopenthixol. Long-acting depot antipsychotics should be used with caution

in combination with other medicines known to have a myelosuppressive potential, as these cannot

rapidly be removed from the body in conditions where this may be required.

Laboratory tests required -

Blood dyscrasias and liver damage have been reported with this class of

drugs. Therefore, routine blood counts and hepatic function tests are advisable, particularly during the

first months of therapy. Should either of these disorders occur, supportive treatment should be instituted

and administration of the drug ceased.

Cellular depression -

If any soreness of the mouth, gums or throat, or any symptoms of upper

respiratory infection occur and confirmatory leucocyte count indicates cellular depression, therapy

should be discontinued and other appropriate measures instituted immediately.

Cardiac disorders -

Caution should be observed when using a drug of this category in patients who

have advanced cardiovascular disease or those who may have a propensity for development of cardiac

conduction defects.

As with other drugs belonging to the therapeutic class of antipsychotics, zuclopenthixol may cause QT

prolongation. Persistently prolonged QT intervals may increase the risk of malignant arrhythmias.

Therefore, zuclopenthixol should be used with caution in susceptible individuals (with hypokalaemia,

hypomagnesaemia or genetic predisposition) and in patients with a history of cardiovascular disorders,

e.g. QT prolongation, significant bradycardia (< 50 beats per minute), recent acute myocardial

infarction, uncompensated heart failure, or cardiac arrhythmia. Concomitant treatment with other

antipsychotics should be avoided (

see Section 4.5 Interaction with other medicines and other forms of

interactions).

Venous thromboembolism (VTE)

– cases have been reported with antipsychotic drugs. Since patients

treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors

for VTE should be identified before and during treatment with zuclopenthixol and preventive

measures undertaken.

Increased Mortality in Elderly people with Dementia

- Data from two large observational studies

showed that elderly people with dementia who are treated with antipsychotics are at a small increased

risk of death compared with those who are not treated. There are insufficient data to give a firm

estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

6

15

Zuclopenthixol is not approved for the treatment of dementia-related behavioural disturbances.

Diabetes -

As described for other psychotropics, zuclopenthixol may modify insulin and glucose

responses calling for adjustment of the antidiabetic therapy in diabetic patients.

Surgery -

Patients on large doses of zuclopenthixol who are undergoing surgery should be carefully

observed for possible hypotensive phenomena. Dosages of anaesthetic or central nervous system

depressant drugs may need to be reduced.

Monitoring -

To lessen the likelihood of adverse reactions related to drug accumulation, patients on

long-term therapy or receiving high doses of zuclopenthixol should be monitored carefully and

evaluated periodically in order to determine whether the maintenance dosage can be lowered or drug

therapy discontinued.

Antiemetic effect -

The antiemetic effect observed with zuclopenthixol in animal studies may also occur

in man. Therefore, the drug may mask signs of toxicity due to overdosage of other drugs, or it may

mask symptoms of disease such as brain tumour or intestinal obstruction.

Effect on laboratory tests -

Transient slight alterations in liver function tests have infrequently been

reported.

Paediatric use -

The safety and efficacy of Clopixol in children have not been established, therefore

its use cannot be recommended in this age group.

Other

Chronic administration of zuclopenthixol (30 mg/kg/day for 2 years) in rats resulted in small, but

significant, increases in the incidence of thyroid parafollicular carcinomas and, in females, of mammary

adenocarcinomas and of pancreatic islet cell adenomas and carcinomas. An increase in the incidence

of mammary adenocarcinomas is a common finding for D

antagonists which increase prolactin

secretion when administered to rats. An increase in the incidence of pancreatic islet cell tumours has

been observed for some other D

antagonists. The physiological differences between rats and humans

with regard to prolactin make the clinical significance of these findings unclear.

Excipients

The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp

lactase deficiency or glucose-galactose malabsorption should not receive this medicine. They also

contain hydrogenated castor oil which may cause stomach upset and diarrhoea.

4.5

Interaction with other medicines and other forms of interaction

Tricyclic antidepressants -

Tricyclic antidepressants and classical neuroleptics mutually inhibit the

metabolism of each other.

Lithium -

Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.

Alcohol, other CNS depressant drugs -

Zuclopenthixol enhances the sedative response to alcohol and

the effects of barbiturates and other CNS depressants.

Hypnotics -

As with phenothiazines, Clopixol should not be used concomitantly with large doses of

hypnotics due to the possibility of potentiation.

Antihypertensives -

Zuclopenthixol should not be given concomitantly with guanethidine or similar

acting compounds since neuroleptics such as zuclopenthixol may block their antihypertensive effects.

Levodopa, adrenergic drugs -

Zuclopenthixol may reduce the effects of levodopa and adrenergic drugs.

Metoclopramide, piperazine -

Concomitant use of metoclopramide or piperazine increases the risk of

extrapyramidal disorder.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

7

15

Medicines metabolised by CYP2D6 -

Since zuclopenthixol is partly metabolised by CYP2D6,

concomitant

drugs

known

inhibit

this

enzyme

lead

decreased

clearance

zuclopenthixol.

Drugs known to increase the QT interval -

Increases in the QT interval related to antipsychotic

treatment may be exacerbated by the co-administration of other drugs known to significantly increase

the QT interval. Co-administration of such drugs should be avoided. Relevant classes include:

class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)

some antipsychotics (e.g. thioridazine)

some macrolides (e.g. erythromycin)

some antihistamines (e.g. terfenadine, astemizole)

some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

The above list is not exhaustive and other individual drugs known to significantly increase the QT

interval (e.g. cisapride, lithium) should be avoided.

Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalaemia) and drugs

known to increase the plasma concentration of zuclopenthixol should also be used with caution as they

may increase the risk of QT prolongation and malignant arrhythmias (

see Section 4.4 Special warnings

and precautions for use).

4.6

Fertility, pregnancy and lactation

Pregnancy

Category C

The safety of Clopixol in pregnant women has not been established. Clopixol should not be

administered to women of child-bearing potential unless, in the opinion of the physician, the expected

benefit to the patient outweighs the potential risk to the foetus.

Animal studies have shown reproductive toxicity.

Non teratogenic class effect:

Zuclopenthixol crosses the placental barrier in small amounts.

Neonates exposed to antipsychotic drugs (including zuclopenthixol) during the third trimester of

pregnancy are at risk of experiencing extrapyramidal neurological disturbances and/or withdrawal

symptoms following delivery. There have been post-market reports of agitation, hypertonia, hypotonia,

tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications

have varied in severity; while in some cases symptoms have been self-limited; in other cases neonates

have required additional medical treatment or monitoring.

Zuclopenthixol should be used during pregnancy only if the anticipated benefit outweighs the risk and

administered dose and duration of treatments should be as low and short as possible.

If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual dysfunctions occur, a

dose reduction (if possible) or discontinuation should be considered. The effects are reversible on

discontinuation.

In a three-generation study in rats a delay in mating was noted. Once mated there was no effect on

fertility. In an experiment where zuclopenthixol was administered via the diet, impaired mating

performance and reduced conception rate was noted.

Oral administration of the drug to rats during the peri/postnatal period at dose levels of 5 and 15

mg/kg/day resulted in an increase in the number of stillbirths, reduced pup survival and delayed

development of pups. The clinical significance of these findings is unclear and it is possible that the

effect on pups was due to neglect by the dams who were exposed to doses of zuclopenthixol

producing maternal toxicity.

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

8

15

Breast-feeding

Zuclopenthixol passes into breast milk in small amounts; the milk/serum concentration ratio in women

is on average 0.3.

Safe use of Clopixol by nursing mothers has not been established, therefore it is recommended that

breast-feeding be discontinued in women taking Clopixol.

Fertility

humans,

adverse

events

such

hyperprolactinaemia,

galactorrhoea,

amenorrhoea,

erectile

dysfunction and ejaculation failure have been reported (see Section 4.8 Undesirable effects

). These

events may have a negative impact on female and/or male sexual function and fertility.

4.7

Effects on ability to drive and use machines

Zuclopenthixol is a sedative drug. Patients who are prescribed psychotropic medication may be

expected to have some impairment in general attention and concentration and should be cautioned

about their ability to drive or operate machinery.

4.8

Undesirable effects

Adverse Effects

The most common adverse reaction reported with zuclopenthixol has been extrapyramidal disorder.

Clopixol has been marketed extensively overseas for many years. Adverse events listed below reflect

those which have been observed during clinical trials, published reports and in the overseas post

marketing period. Events described as "rarely" are those which were reported on 1 - 3 occasions

irrespective of the formulation used and without regard to causality, while those described as

"occasionally" were reported on 4 - 10 occasions. Other events were reported more frequently (see also

the adverse events table below).

Because zuclopenthixol shares many of the pharmacological properties of other thioxanthenes and

phenothiazines, the possible occurrence of the known adverse effects of these drug classes exists.

Autonomic Nervous System

Dry mouth, blurred vision, constipation, excessive salivation, excessive perspiration, nausea, difficulty

in micturition and urinary retention have been observed.

Miosis, mydriasis, paralytic ileus, polyuria, nasal congestion and glaucoma have been reported with

related drugs.

Cardiovascular

Orthostatic dizziness may occur. Tachycardia, palpitations and fainting have been observed.

Hypotension, hypertension, fluctuations in blood pressure, non-specific ECG changes and cardiac

arrhythmias have been reported with related drugs.

If hypotension occurs, adrenalin should

not

be used as a pressor agent since a paradoxical further

lowering of blood pressure may result.

As with other drugs belonging to the therapeutic class of antipsychotics, rare cases of QT prolongation,

ventricular arrhythmias - ventricular fibrillation, ventricular tachycardia, Torsade de Pointes and sudden

unexplained death have been reported for zuclopenthixol (

see Section 4.4. Special warnings and

precautions for use).

Central Nervous System

Extrapyramidal symptoms, including hypo- and hyperkinetic states, tremor, pseudoparkinsonism,

dystonia, hypertonia, rigidity, akathisia, oculogyric crises, opisthotonos, hyper-reflexia and tardive

dyskinesia (see below).

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

9

15

These symptoms (if they occur) usually appear within the first few days of treatment and can usually

be controlled or totally curtailed by reduction in dosage and/or standard antiparkinsonian medication.

However,

routine

prophylactic

antiparkinsonian

medication

recommended.

Extrapyramidal reactions may be alarming and patients should be forewarned and reassured (

Section 4.2 Dose and method of administration). Reduction in dosage or, if possible, discontinuation

of zuclopenthixol therapy is recommended. Other CNS effects include drowsiness and somnolence.

Metabolic and Endocrine

Weight change and menstrual disturbance have been reported. Transient galactorrhoea has been

reported occasionally. Gynaecomastia, thyroid disorder and impotence have been observed rarely.

Related drugs have been associated with breast enlargement, menstrual irregularities, false positive

pregnancy tests, peripheral oedema, hypo- and hyperglycaemia and glycosuria.

Persistent Tardive Dyskinesia

As with all antipsychotic agents, tardive dyskinesia may appear in some patients during long-term use

or may occur after drug therapy has been discontinued. Elderly patients on high dose therapy, especially

elderly females, may be at greater risk. The symptoms may be persistent and, in some patients, appear

to be irreversible.

The syndrome is characterised by rhythmical, involuntary movements of the tongue, face, mouth or jaw

(e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes

these may be accompanied by involuntary movements of the extremities.

There is no known effective treatment for tardive dyskinesia; antiparkinsonian agents usually do not

alleviate the symptoms of this syndrome. If these symptoms appear, it is suggested that all antipsychotic

agents be discontinued. Should it be necessary to reinstitute treatment, increase dosage or change the

antipsychotic agent, the syndrome may be masked.

If manifestations are recognised, particularly in patients over the age of fifty, the risk of this syndrome

developing may be reduced by avoiding unnecessary neuroleptic medication, reducing the dose or

discontinuing the drug altogether (if possible).

It has been reported that if the medication is stopped at the first signs of fine vermicular movements of

the tongue, which may be an early manifestation, the syndrome may not develop.

Toxic and Allergic

Alterations in liver function, particularly increased bilirubin levels have been observed. Transient

increases in ALT and ALP values may occur. Transient, benign leucopenia has been reported rarely.

Peripheral oedema has occasionally been reported. Skin reactions such as pruritus, rash and erythema

have been reported rarely.

Eosinophilia, jaundice and increased levels of alkaline phosphatase have been reported with related

drugs.

Other

antipsychotic

drugs

have

been

associated

with

leucopenia,

agranulocytosis,

thrombocytopenic or non-thrombocytopenic purpura, haemolytic anaemia and pancytopenia.

Discontinuation

Abrupt discontinuation of zuclopenthixol may be accompanied by withdrawal symptoms. The most

common symptoms are nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating, myalgias,

paraesthesias, insomnia, restlessness, anxiety, and agitation. Patients may also experience vertigo,

alternate feelings of warmth and coldness, and tremor. Symptoms generally begin within 1 to 4 days of

withdrawal and abate within 7 to 14 days.

Miscellaneous

Lens opacity has been reported rarely.

Other Post-Marketing Events

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

10

15

Post marketing events from literature and spontaneous reporting for which frequencies have been

further defined are provided in the table below. Frequencies are defined as: very common (>1/10),

common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare

(<1/10000), or not known (cannot be estimated from the available data).

Blood and lymphatic

system disorders

Rare

Thrombocytopenia, neutropenia, leucopenia,

agranulocytosis

Cardiac disorders

Common

Tachycardia, palpitations

Rare

Electrocardiogram QT prolonged

Ear and labyrinth

disorders

Common

Vertigo

Uncommon

Hyperacusis, tinnitus

Endocrine disorders

Rare

Hyperprolactinaemia

Eye disorders

Common

Accommodation disorder, vision abnormal

Uncommon

Oculogyration, mydriasis

Gastrointestinal disorders

Very common

Dry mouth

Common

Salivary hypersecretion, constipation, vomiting,

dyspepsia, diarrhoea

Uncommon

Abdominal pain, nausea, flatulence

General disorders and

administration site

conditions

Common

Asthenia, fatigue, malaise, pain

Uncommon

Thirst, injection site reaction, hypothermia,

pyrexia.

Hepato-biliary disorders

Uncommon

Liver function test abnormal

Very rare

Cholestatic hepatitis, jaundice

Immune system disorders

Rare

Hypersensitivity, anaphylactic reaction

Metabolism and nutrition

disorders

Common

Increased appetite, weight increased

Uncommon

Decreased appetite, weight decreased

Rare

Hyperglycaemia, glucose tolerance

impaired, hyperlipidaemia

Musculoskeletal and

connective tissue disorder

Common

Myalgia

Uncommon

Muscle rigidity, trismus, torticollis

Nervous system disorders

Very common

Somnolence, akathisia, hyperkinesia,

hypokinesia

Common

Tremor, dystonia, hypertonia, dizziness,

headache, paraesthesia, disturbance in

attention, amnesia, gait abnormal.

Uncommon

Tardive dyskinesia, hyperreflexia,

dyskinesia, parkinsonism, syncope,

ataxia, speech disorder, hypotonia,

convulsion, migraine

Pregnancy, puerperium

and perinatal conditions

Not known

Drug withdrawal syndrome neonatal

Psychiatric disorders

Common

Insomnia, depression, anxiety,

nervousness, abnormal dreams, agitation,

libido decreased.

Uncommon

Apathy, nightmare, libido increased,

confusional state

Very rare

Neuroleptic malignant syndrome

Renal and urinary

disorders

Common

Micturition disorder, urinary retention,

polyuria

Reproductive system and

breast disorders

Uncommon

Ejaculation failure, erectile dysfunction,

female orgasmic disorder, vulvovaginal

dryness

Rare

Gynaecomastia, galactorrhoea,

amenorrhoea, priapism

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

11

15

Respiratory, thoracic and

medistianal disorders

Common

Nasal congestion, dyspnoea

Skin and subcutaneous

tissue disorders

Common

Hyperhidrosis, pruritus

Uncommon

Rash, photosensitivity reaction,

pigmentation disorder, seborrhoea,

dermatitis, purpura

Vascular disorders

Uncommon

Hypotension, hot flush

Very rare

Venous thromboembolism

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/

4.9

Overdose

In general, the main therapy for all overdoses is supportive and symptomatic care.

Symptoms

Over dosage may cause somnolence, coma, cramps, convulsions, extrapyramidal symptoms, shock,

decreased blood pressure and hyperthermia/hypothermia.

ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular arrhythmias have

been reported when zuclopenthixol has been taken or has been administered in overdose together with

drugs known to affect the heart.

The highest orally administered dose of zuclopenthixol in clinical trials was 450 mg daily.

Treatment

Treatment is symptomatic and supportive. No further doses of zuclopenthixol should be administered.

Measures to support the respiratory and cardiovascular systems should be instituted. If severe

hypotension occurs, an i.v. vasopressor drug should be administered immediately. Epinephrine

(adrenaline) should

not

be used as further lowering of blood pressure may result. Convulsions may be

treated with diazepam and extrapyramidal symptoms with an antiparkinsonian medication.

For further advice on management of overdose please contact the Poisons Information Centre

(Tel: 13 11 26 for Australia and Tel: 0800 764 766 for New Zealand).

5 PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Neuropleptics (antipsychotics), ATC Code: N05AF05

Mechanism of action

Zuclopenthixol is a potent neuroleptic of the thioxanthene series.

The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking activity. The

thioxanthenes have high affinity for both the adenylate cyclase-coupled dopamine D

receptors and for

the dopamine D

receptors; in the phenothiazine group, the affinity for D

receptors is much lower than

for D

receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity

for D

receptors.

In the traditional tests for antipsychotic effect e.g. antagonism of stereotypic behaviour induced by

dopamine agonists, the mentioned chemical groups of neuroleptics exhibit equal but dose-dependent

activity.

However,

antistereotypic

effect

butyrophenones,

diphenylbutylpiperidines

benzamides

strongly

counteracted

anticholinergic

drug,

scopolamine,

that

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

12

15

phenothiazines less so, while the antistereotypic effect of the thioxanthenes, e.g. zuclopenthixol, is not,

or only very slightly, influenced by concomitant treatment with anticholinergics. Like most other

neuroleptics, zuclopenthixol increases the serum prolactin level.

A clear relationship between serum levels and clinical effects of zuclopenthixol has not been

established. However, data from open trials of zuclopenthixol in the treatment of mania and acute

paranoid psychosis indicate that the minimum effective serum levels are 5 nanogram/mL (12.5

nmol/L) in acute mania patients of moderate severity; 3 -4 nanogram/mL (7.5 - 10 nmol/L) in

moderately psychotic patients (BPRS 26 - 30 points); and 6 - 8 nanogram/mL (15 - 20 nmol/L) in

severely psychotic patients (BPRS 31 - 38 points). Clopixol tablets, when given within the dosage

recommendation, provide adequate zuclopenthixol serum levels for effective control of psychoses.

5.2

Pharmacokinetic properties

Absorption

Clopixol tablets

The absolute bioavailability after oral administration of Clopixol 10 mg tablets is 49%. Maximum

serum concentrations are reached after approximately 4 hours (2 - 12 hours). The mean steady state

serum level corresponding to 20 mg/day zuclopenthixol (as the dihydrochloride) p.o. is about 13 ng/mL

(33 nmol/L). The biological half-life is approximately 20 hours.

Concomitant intake of food enhances the bioavailability by approximately 20% of Clopixol tablets

without influencing its absorption rate. C

and elimination half-life (t

) are not altered. The

postulated mechanism for this effect is that food reduces the presystemic clearance of zuclopenthixol.

This effect is of doubtful clinical relevance and it does not appear that Clopixol tablets need to be given

with regard to meals.

Clopixol Acuphase injection

The acetate ester is rather slowly released from the oil and is rapidly hydrolysed to the active substance,

zuclopenthixol, upon reaching the body water.

Maximum serum concentrations of zuclopenthixol are reached, on average, 24 to 36 hours after i.m.

injection, followed by a gradual decline. Average maximum serum concentration of zuclopenthixol

corresponding to a 100 mg i.m. dose of zuclopenthixol acetate is 41 ng/mL (102 nmol/L). 3 days

following injection, serum levels are approximately one-third of the maximum.

Clopixol Depot injection

The decanoate ester is slowly released from the oil depot and is rapidly hydrolysed to the active

substance, zuclopenthixol, upon reaching the body water phase. Whereas zuclopenthixol itself is

relatively short-acting, the decanoate ester in oil provides a predictable, slow-release preparation of the

active constituent.

Maximum serum concentrations of zuclopenthixol are reached 3 to 7 days following i.m. injection. The

serum concentration curve declines exponentially with a half-life of 19 days, reflecting the rate of

release from the depot. The average steady state pre-injection serum level of zuclopenthixol

corresponding to a 200 mg dose of zuclopenthixol decanoate every 2 weeks is approximately 10 ng/mL

(25 nmol/L).

As no first pass metabolism occurs when a drug is administered parenterally, zuclopenthixol decanoate

can be administered in lower doses than oral zuclopenthixol.

A dose of 200 mg/2 weeks or 400 mg/4 weeks zuclopenthixol decanoate is expected to be equivalent

to a daily dose of 25 mg zuclopenthixol (as the dihydrochloride).

Distribution

As for other neuroleptics, zuclopenthixol is distributed with highest concentrations of drug and

metabolites in liver, lungs, intestines and kidneys and lower concentrations in heart, spleen, brain and

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

13

15

blood. The apparent volume of distribution is 20 L/kg and protein binding is approximately 98% at

concentrations above the therapeutic range.

Biotransformation

The metabolism of zuclopenthixol is mainly by means of sulphoxidation, side chain N-dealkylation and

glucuronic acid conjugation. The metabolites are devoid of psychopharmacological activity.

Elimination

Excretion is mainly via the faecal route and to a smaller degree (about 10%) via the urine. Only about

0.1% of the dose is excreted unchanged in the urine, so the drug load on the kidneys is negligible. The

systemic clearance is approximately 0.9 L/min.

Linearity

The kinetics appear to be linear, since highly significant correlations exist between dose and serum

level, and between dose and area under the serum concentration curve, respectively

6 PHARMACEUTICAL PARTICULARS

Clopixol

®

Tablets 10 mg

Clopixol

®

Acuphase

Injection 50 mg/mL

Clopixol

®

Depot Injection

200 mg/mL

Zuclopenthixol hydrochloride

Zuclopenthixol acetate

Zuclopenthixol decanoate

Clopixol

tablets

contain

zuclopenthixol hydrochloride, an

off-white, granular powder. It is

very soluble in water, sparingly

soluble in ethanol (96%), slightly

soluble

chloroform

very

slightly soluble in ether

Clopixol

Acuphase

contains

acetate

ester

zuclopenthixol.

Zuclopenthixol

acetate

yellowish, viscous oil. It is

very slightly soluble in water,

very soluble in ethanol (96%),

ether and dichloromethane

Clopixol

Depot

contains

decanoate ester of zuclopenthixol.

Zuclopenthixol

decanoate

yellow viscous oily liquid. It is very

slightly

soluble

water,

very

soluble in alcohol and methylene

chloride

Chemical name:

(Z)-2-4-[3-(2-chlorothioxanthene-

9-ylidene)propyl]piperazin-1-

ylethanol dihydrochloride

(Z)-2-4-[3-(2-

chlorothioxanthene-9-

ylidene)propyl]piperazin-1-

ylethyl acetate

2-[4-[3-[(Z)-2-chloro-9H-

thioxanthen-9-

ylidene]propyl]piperazin-1-yl]ethyl

decanoate

CAS number:

633-59-0

85721-05-7

64053-00-5

Molecular formula: Molecular weight

OS,2HCl: 473.9

S: 443.0

S: 555.3

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

14

15

Structural formula:

6.1

List of excipients

Clopixol Film-coated Tablets contain the following excipients: Starch - potato, lactose, cellulose -

microcrystalline, PVP/VA copolymer, glycerol, talc - purified, castor oil - hydrogenated and

magnesium stearate, with a coating of hypromellose and macrogol 6000, coloured with titanium

dioxide and iron oxide red CI7749.

Clopixol Acuphase solution for injection and Clopixol Depot solution for injection contain Coconut

oil – fractionated.

6.2

Incompatibilities

Clopixol Acuphase and Clopixol Depot should not be mixed with depot preparations formulated with a

sesame oil vehicle since this will produce changes in pharmacokinetic properties.

Zuclopenthixol acetate should only be mixed with zuclopenthixol decanoate which is also dissolved in

coconut oil, and vice versa.

6.3

Shelf life

Clopixol tablets: 2 years

Clopixol Acuphase injection: 2 years

Clopixol Depot injection: 3 years

6.4

Special precautions for storage

Store below 25°C. Protect from light.

6.5

Nature and contents of container

Clopixol tablets - Bottles of 100 tablets.

Clopixol Acuphase injection -1 and 2 mL glass ampoules in packs of 5 ampoules.

Clopixol Depot injection -1 mL glass ampoules in packs of 5 ampoules.

6.6

Special precautions for disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

7 MEDICINE SCHEDULE

Prescription only medicine

NEW ZEALAND DATA SHEET

Clopixol v 1.0 December 2018

Page

15

15

8 SPONSOR

Australian Sponsor:

Lundbeck Australia Pty Ltd

1 Innovation R

North Ryde NSW 2113

Ph: 1800 025 554

New Zealand Sponsor:

Healthcare Logistics

PO Box 62027

Mt Wellington, Auckland

Ph: 0800 540 555

9 DATE OF FIRST APPROVAL

05 November1992

10 DATE OF REVISION OF THE TEXT

05 December 2018

Summary table of changes

Section Changed

Summary of new information

All

Update to new format

“Clopixol” is the registered trademark of H. Lundbeck A/S.

Similar products

Search alerts related to this product

Share this information