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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Elderly
Children
Adolescents
Patients with Renal Impairment
Patients with Hepatic Impairment
Additional Dosage Information

Dosage should be adjusted according to the severity of the patient's illness.

The usual dose is 50-150mg repeated if necessary after 2 or 3 days. Some patients may need an additional injection between 1 and 2 days after the first dose.

Not recommended for long term use, treatment duration should not exceed 2 weeks with maximum accumulated dose in a course less than 400 mg with no more than 4 injections.

Precautions and Warnings

Use with caution in:
Cardiac disease
Arrhythmias
Severe respiratory disease
Hepatic impairment - see Renal impairment
Renal failure - see Hepatic impairment
Epilepsy and conditions predisposing to epilepsy
Parkinson's disease
Angle closure glaucoma
Prostatic hypertrophy
Hypothyroidism
Hyperthyroidism
Myasthenia gravis
Phaeochromocytoma
Organic brain syndrome
Mental retardation
Opiate abuse
Alcohol abuse
Convulsions
Porphyria

Elderly - see Dosage, Elderly
The elderly are more likely to experience adverse effects such as sedation, hypotension, confusion and body temperature changes.

As with others antipsychotics zuclopenthixol should be used with caution in patients with risk factors for cerebrovascular accidents. Cerebrovascular adverse events have been reported in clinical trials with antipsychotics. Use with caution in patients with risk factors for stroke.

Consider possible risk factors for venous thromboembolism (VTE) before and during the treatment, preventive measures should be taken. Cases of VTE have been reported (pulmonary embolism, deep vein thrombosis) with antipsychotic drugs.

There has been found to be a risk of QT interval prolongation in patients receiving an antipsychotic medication. Persistently prolonged QT intervals may increase the risk of malignant arrhythmias. For this reason patients who are susceptible to arrhythmias (e.g. hypokalaemia, hypomagnesaemia or a genetic predisposition) should be treated with caution. Caution should also be exercised in patients with a history of cardiovascular disease, e.g. QT interval prolongation, significant bradycardia (<50 beats per minute), a recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmias.

Data from studies showed a small increased risk of death in elderly people with dementia who are treated with antipsychotics. Not licensed for the treatment of dementia-related behavioural disturbances.

Only recommended for short term use, duration of treatment should not exceed 2 weeks.

Withdrawal should be gradual, as abrupt cessation produce withdrawal symptoms ( see Withdrawal Symptoms ) .

Consider reduction in dose or discontinuation of zuclopenthixol if tardive dyskinesia develops.

Discontinue if the patient develops neuroleptic malignant syndrome and administer symptomatic and supportive treatment.
Symptoms may persist for more than a week after discontinuation of oral neuroleptics.

Perform blood counts if signs of persistent infection develop, as cases of blood dyscrasias have been reported.

Use with caution in diabetic patients as zuclopenthixol like other psychotropics may modify insulin and glucose responses.

Women of child bearing age must use effective contraception throughout treatment and for some time afterwards.

Patients should be warned that their ability to drive and operate machines may be impaired.

Use in Porphyria

The Norwegian Porphyria Centre (napos) lists zuclopenthixol as 'possibly porphyrogenic' in the Drug Database for Acute Porphyria although another source lists it as contraindicated.

Pregnancy and Lactation

Pregnancy

Zuclopenthixol is contraindicated in pregnancy. At the time of writing, there are no published animal or human studies concerning exposed pregnancies and their outcomes.

'There is some indication of an overall increased risk of malformations associated with the use of antipsychotics (2.4%, that is 24 per 1,000), although it is not clear if this may relate to the underlying illness (information on individual drugs is very limited).' (National Institute of Health and Clinical Excellence, CG045, 2007)

Psychosis in pregnancy should be treated, as there is a risk if the psychosis is left untreated. There is also a risk to the mother and foetus from abrupt withdrawal of an antipsychotic. Pharmacological treatment should be with the lowest effective dose for the shortest time.

Deep intramuscular (Depot) injections of antipsychotics should not be used in the mother, as the newborn infant may show extrapyramidal symptoms several months after administration. The extrapyramidal symptoms are usually self limiting.

Regular psychiatric and obstetric care is recommended for the early diagnosis of relapse or pregnancy complications (i.e. intrauterine growth retardation, premature contractions).

The newborn of mothers treated with antipsychotics up to, or during labour, may show signs of intoxication such as lethargy, tremor and hyperexcitability, and have low apgar scores. Neonate exposed to antipsychotics during the third trimester are at risk of extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. Neonates should be monitored carefully.

Schaefer, Peters & Miller (2007) recommend that the newborn infants be observed for adaption disorders, extrapyramidal, and withdrawal symptoms for at least 2 days, if an antipsychotic has been used up to delivery. For the prevention of adaption disorders a reduction in dose, or dose interruption in the days before delivery can be discussed with the patient if the clinical course allows. The dose before delivery should be restored immediately after delivery to prevent a relapse.

The National Institute for Health and Clinical Excellence (NICE) have published guidance for the treatment of mental health patients throughout the antenatal and postnatal period. The guidance can be accessed at https://www.nice.org.uk/nicemedia/pdf/CG45fullguideline.pdf

Women of child bearing age should be informed about the risks of psychotropic medication on any future pregnancy and the risks of untreated illness, together with the appropriate information about contraception.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at https://www.toxbase.org/

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

Known human teratogen? - Unknown.

Lactation

Zuclopenthixol is contraindicated while breastfeeding. Zuclopenthixol is excreted into breast milk. At the time of writing, there are no published studies concerning the use of zuclopenthixol while breastfeeding.

Schaefer, Peters & Miller (2007) and Briggs, Freeman & Yaffe (2008) list some experience from infants whose mothers received zuclopenthixol while breastfeeding. This experience suggests that zuclopenthixol is excreted into breast milk in small quantities. None of the infants experienced and adverse effects.

However, this is only very limited data and caution is still advised when using zuclopenthixol in a nursing mother.

Deep intramuscular (Depot) injections of antipsychotics should not be used in the mother, as the infant may show extrapyramidal symptoms several months after administration. The extrapyramidal symptoms are usually self limiting.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

UK Drugs in Lactation Advisory Service Classification - Minor adverse effects may be anticipated on theoretical grounds. This drug should only be administered where both the mother and infant can be monitored.

Drug substance licensed in infants? - No

Drug known to affect lactation? - Unknown

Presentation

Oily injection containing 50mg/ml zuclopenthixol (5% zuclopenthixol acetate equivalent to 4.526% of zuclopenthixol base)

Drugs List

CLOPIXOL ACUPHASE 50mg/1ml oily injection

zuclopenthixol acetate 50mg/1ml oily injection

Therapeutic Indications

Uses

For the initial treatment of acute psychoses including mania and exacerbation of chronic psychoses, where a rapid onset of action is required with a duration of effect of 2-3 days.

Only recommended for short term use.

Dosage

Adults

Dosage should be adjusted according to the severity of the patient's illness.

The usual dose is 50-150mg repeated if necessary after 2 or 3 days. Some patients may need an additional injection between 1 and 2 days after the first dose.

Not recommended for long term use, treatment duration should not exceed 2 weeks with maximum accumulated dose in a course less than 400 mg with no more than 4 injections.

Elderly

Dosage may need to be reduced in elderly patients owing to reduced rates of metabolism and elimination.

Maximum dosage per injection should be 100mg.

The elderly require close supervision as they are specially susceptible to adverse effects - sedation, hypotension, confusion, temperature changes.

Children

Not recommended

Adolescents

Not recommended

Patients with Renal Impairment

The manufacturer recommends no dose reduction in patients with impaired renal function, but a reduction to half the normal dose in renal failure.

The Renal Drug Handbook suggests:
GFR above 10ml/min - dose as in normal renal function
GFR < 10 ml/min - start with 50% of the dose and titrate slowly

Patients with Hepatic Impairment

Half dose should be used for patients with hepatic impairment.

Serum-level monitoring is recommended.

Additional Dosage Information

A single injection of zuclopenthixol acetate oily injection has an onset of action shortly after administration and a duration of treatment of 2 to 3 days. During this period, maintenance therapy, with a different antipsychotic, may be initiated.

Maintenance treatment can be continued using zuclopenthixol dihydrochloride tablets, or a longer acting depot zuclopenthixol decanoate injection.

Guidelines for transferring patients on to maintenance therapy are as follows:
Introduce zuclopenthixol dihydrochloride tablets at a dosage of 20-60mg/day in divided doses, 2 to 3 days after the last injection. If necessary increase the tablet dosage by 10-20mg each day up to a maximum of 150mg/day.
or
Concurrently with the last injection, administer 200-500mg of a longer acting depot injection of zuclopenthixol decanoate by deep intramuscular injection, and repeat the injection at intervals of 2 to 4 weeks. Higher doses or a shorter interval may be necessary.

Administration

For intramuscular administration.

Zuclopenthixol oily injection should be administered by deep intramuscular injection into the upper outer buttock or lateral thigh.

Contraindications

Circulatory collapse
Coma
Depressed level of consciousness - (e.g. acute alcohol, barbiturate or opioid intoxication)
Children under 18 years
Pregnancy - see Pregnancy
Breastfeeding - see Lactation
Apathetic or withdrawn states