The maintenance treatment of schizophrenia and paranoid psxychoses.

Posology
Adults
Dosage and dosage interval should be adjusted according to the patient's symptoms and response to
treatment.
The usual dosage range of zuclopenthixol decanoate is 200 - 500 mg every one to four weeks, depending
on response, but some patients may require up to 600 mg per week. The maximum single dose at any one
time is 600 mg. For example, 1200 mg every 2 weeks should not be given. In patients who have not
previously received depot antipsychotics, treatment is usually started with a small dose (e.g. 100 mg) to
assess tolerance. An interval, of at least one week should be allowed before the second injection is given
at a dose consistent with the patient's condition.
Adequate control of severe psychotic symptoms may take up to 4 to 6 months at high enough dosage.
Once stabilised lower maintenance doses may be considered, but must be sufficient to prevent relapse.
Injection volumes of greater than 2 ml should be distributed between two injection sites.

In accordance with standard medical practice initial dosage may need to be reduced to a quarter or half
the normal starting dose in the frail or older patients.
Paediatric population
Clopixol is not recommended for use in children due to lack of clinical experience.
Patients with renal impairment
Clopixol can be given in usual doses to patients with reduced renal function. Where there is renal failure
dosage should be reduced to half the normal dosage.
Patients with hepatic impairment
Use with caution in patients with liver disease (see section 4.4). Patients with compromised hepatic
function should receive half the recommended dosages. Serum-level monitoring is advised.
Method of administration
By deep intramuscular injection into the upper outer buttock or lateral thigh.
Note
As with all oil-based injections it is important to ensure, by aspiration before injection, that inadvertent
intravascular entry does not occur.

respiratory disease; renal failure; epilepsy (and conditions predisposing to epilepsy, e.g. alcohol
withdrawal or brain damage); Parkinson's disease; narrow angle glaucoma; prostatic hypertrophy;
hypothyroidism; hyperthyroidism; myasthenia gravis; phaeochromocytoma and patients who have shown
hypersensitivity to thioxanthenes or other antipsychotics.
Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described
after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the
emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been
reported. The plasma concentrations of zuclopenthixol decanoate gradually decrease over several weeks
which make gradual dosage tapering unnecessary.
When transferring patients from oral to depot antipsychotic treatment, the oral medication should not be
discontinued immediately, but gradually withdrawn over a period of several days after administering the
first injection.
The possibility of development of neuroleptic malignant syndrome (hyperthermia, muscle rigidity,
fluctuating consciousness, instability of the autonomous nervous system) exists with any neuroleptic. The
risk is possibly greater with the more potent agents. Patients with pre-existing organic brain syndrome,
mental retardation and opiate and alcohol abuse are over-represented among fatal cases.
Treatment:
Discontinuation of the neuroleptic. Symptomatic treatment and use of general supportive measures.
Dantrolene and bromocriptine may be helpful. 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.

Like other neuroleptics, zuclopenthixol decanoate should be used with caution in patients with organic
brain syndrome, convulsions or advanced hepatic disease.
Blood dyscrasias have been reported rarely. Blood counts should be carried out if a patient develops signs
of persistent infection.
As with other drugs belonging to the therapeutic class of antipsychotics, zuclopenthixol decanoate may
cause QT prolongation. Persistently prolonged QT intervals may increase the risk of malignant
arrhythmias. Therefore, zuclopenthixol decanoate 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), a recent
acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia.
Cases of venous thromboembolism (VTE) 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 decanoate and preventive
measures undertaken.
Concomitant treatment with other antipsychotics should be avoided (see section 4.5).
As described for other psychotropics, zuclopenthixol decanoate may modify insulin and glucose
responses calling for adjustment of the antidiabetic therapy in diabetic patients.
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including
zuclopenthixol decanoate.
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.
Older people
Older people require close supervision because they are especially prone to experience such adverse
effects as sedation, hypotension, confusion and temperature changes.
Cerebrovascular
An approximately 3-fold increased risk of cerebrovascular adverse events has been seen in randomised
placebo controlled clinical trials in the 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.
Zuclopenthixol should be used with caution in patients with risk factors for stroke.
Increased Mortality in Older People with Dementia
Data from two large observational studies showed that older 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.
Clopixol Conc. Injection and Clopixol Conc. Injection are not licensed for the treatment of dementiarelated
behavioural disturbances.

In common with other antipsychotics, zuclopenthixol enhances the response to alcohol, the effects of
barbiturates and other CNS depressants.
Zuclopenthixol may potentiate the effects of general anaesthetics and anticoagulants and prolong the
action of neuromuscular blocking agents.
The anticholinergic effects of atropine or other drugs with anticholinergic properties may be increased.
Concomitant use of drugs such as metoclopramide, piperazine or antiparkinson drugs may increase the
risk of extrapyramidal effects such as tardive dyskinesia.
Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of
neurotoxicity.
Antipsychotics may enhance the cardiac depressant effects of quinidine; the absorption of corticosteroids
and digoxin.
The hypotensive effect of vasodilator antihypertensive agents such as hydralazine and α blockers (e.g.
doxazosin), or methyl-dopa may be enhanced.
Concomitant use of zuclopenthixol and drugs known to cause QT prolongation or cardiac arrhythmias,
such as tricyclic antidepressants or other antipsychotics should be avoided.
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
• some quinolone antibiotics (e.g. moxifloxacin)
The above list is not exhaustive and other individual drugs known to significantly increase QT interval
(e.g. cisapride, lithium) should be avoided. Drugs known to cause electrolyte disturbances such as
thiazide diuretics (hypokalemia) 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).
Antipsychotics may antagonise the effects of adrenaline and other sympathomimetic agents, and reverse
the antihypertensive effects of guanethidine and similar adrenergic-blocking agents.
Antipsychotics may also impair the effect of levodopa, adrenergic drugs and anticonvulsants.
The metabolism of tricyclic antidepressants may be inhibited and the control of diabetes may be impaired.
Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to inhibit this
enzyme may lead to higher than expected plasma concentrations of zuclopenthixol, increasing the risk of
adverse effects and cardiotoxicity.

Pregnancy
Zuclopenthixol decanoate should not be administered during pregnancy unless the expected benefit to the
patient outweighs the theoretical risk to the foetus.
Neonates exposed to antipsychotics (including zuclopenthixol decanoate) during the third trimester of
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia,
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should
be monitored carefully.
Animal studies have shown reproductive toxicity (see section 5.3).
Breast-feeding
As zuclopenthixol is found in breast milk in low concentrations it is not likely to affect the infant when
therapeutic doses are used. The dose ingested by the infant is less than 1% of the weight related maternal
dose (in mg/kg). Breast-feeding can be continued during zuclopenthixol decanoate therapy if considered
of clinical importance but observation of the infant is recommended, particularly in the first 4 weeks after
giving birth.
Fertility
In humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile dysfunction
and ejaculation failure have been reported (see section 4.8). These events may have a negative impact on
female and/or male sexual function and fertility.
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.
Administration of zuclopenthixol to male and female rats were associated with a slight delay in mating. In
an experiment where zuclopenthixol was administered via the diet, impaired mating performance and
reduced conception rate was noted.

Zuclopenthixol is a sedative drug.
Alertness may be impaired, especially at the start of treatment, or following the consumption of alcohol;
patients should be warned of this risk and advised not to drive or operate machinery until their
susceptibility is known.
Patients should not drive if they have blurred vision.

The majority of undesirable effects are dose dependent. The frequency and severity are most pronounced
in the early phase of treatment and decline during continued treatment.
Extrapyramidal reactions may occur, especially in the early phase of treatment. In most cases these side
effects can be satisfactorily controlled by reduction of dosage and/or use of antiparkinsonian drugs. The
routine prophylactic use of antiparkinsonian drugs is not recommended.
Antiparkinsonian drugs do not alleviate tardive dyskinsea and may aggravate them. Reduction in dosage
or, if possible, discontinuation of zuclopenthixol therapy is recommended. In persistent akathisia a
benzodiazepine or propranolol may be useful.

Symptoms: somnolence, coma, extrapyramidal symptoms, convulsions, hypotension, shock, hyper or
hypothermia. ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular
arrhythmias have been reported when administered in overdose together with drugs known to affect the
heart.
Treatment: treatment is symptomatic and supportive. Measures aimed at supporting the respiratory and
cardiovascular systems should be instituted.
Adrenaline (epinephrine) must not be used in these patients. There is no specific antidote.

Pharmacotherapeutic group: Neuropleptics (antipsychotics), ATC Code: N05AF05
Mechanism of action
The action of zuclopenthixol, as with other antipsychotics is mediated through dopamine receptor
blockade. Zuclopenthixol has a high affinity for D1 and D2 receptors and activity has been demonstrated
in standard animal models used to assess antipsychotic action. Serotonergic blocking properties, a high
affinity for alpha-adrenoreceptors and slight antihistamine properties have been observed.

After deep intramuscular injection of Clopixol, serum levels of zuclopenthixol increase during the first
week and decline slowly thereafter. A linear relationship has been observed between Clopixol dosage and
serum level. Metabolism proceeds by sulphoxidation, dealkylation and glucuronic acid conjugation.
Sulphoxide metabolites are mainly excreted in the urine while unchanged drug and the dealkylated form
tend to be excreted in the faeces.

Reproductive toxicity
Impaired mating performance and reduced conception rates were observed in rats treated with
zuclopenthixol at doses equal to the maximum recommend human dose of 50 mg on a mg/m2 basis.
There was no evidence of embryotoxicity or teratogenic effects in rats treated with zuclopenthixol,
however adverse effects on pre-and postnatal development (i.e. increased stillbirths, reduced pup survival
and delayed development of pups) was observed. The clinical significance of these findings is unclear and
it is possible that the effect on pups was due to neglect from the dams that were exposed to doses of
zuclopenthixol producing maternal toxicity.

Triglycerides, medium-chain.

This product may be mixed in the same syringe with other products in the Clopixol Injection range,
including Clopixol-Acuphase Injection (zuclopenthixol acetate 50 mg/ml).
It should not be mixed with any other injection fluids.

This medicinal product does not require any special storage condition.
Keep the ampoules in the outer carton in order to protect form light.

200 mg/ml
Colourless ampoules (Type I glass) of 0.5 ml and 1 ml.
Boxes of 10×0.5 ml, 1×1 ml, 10×1 ml.
500 mg/ml
Colourless ampoules (Type I glass) of 1 ml.
Boxes of 1×1 ml and 5×1 ml.
Not all pack sizes may be marketed.

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