Zuclopenthixol

Uses

Bipolar mania, Psychosis, Schizophrenia

Zuclopenthixol is also used to associated treatment for these conditions: Acute Exacerbation of Psychosis, Acute Schizophrenia, Chronic Schizophrenia, Organic Mental Disorder, Schizophrenia, Acute Manic episode

How Zuclopenthixol works

Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for alpha1-adrenergic and 5-HT2 receptors. It has weaker histamine H1 receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors.

Dosage

Zuclopenthixol dosage

Intramuscular-

Chronic psychosis:

• Adult: As decanoate ester: Initially, a test dose of 100 mg by deep IM into the upper outer buttock or lateral thigh to access tolerance, followed after at least 1 wk by 200-500 mg or more, repeated at 1-4 wkly intervals according to response. Max dose: 600 mg wkly. Inj >2 ml to be distributed between 2 inj sites.
• Elderly: Reduce dose to ¼ or ½ of usual initial dose.

Psychoses:

• Adult: As acetate: 50-150 mg via deep IM inj. May repeat, if needed, after 2-3 days. An additional dose 1-2 days after the 1st dose may be required in some patients. Not >4 inj should be given in a max course of 2 wk and total dose should not exceed 400 mg. Maintenance: May start oral zuclopenthixol HCl 2-3 days after the last acetate inj or begin IM inj of decanoate with the last inj of the acetate.
• Elderly: As acetate ester: Dose reduction may be needed. Max: 100 mg/dose.

Oral-

Psychoses:

• Adult: Initially, 20-30 mg daily in divided doses. Usual maintenance dose: 20-50 mg daily. Up to 150 mg daily for severe or resistant cases.

May be taken with or without food.

Side Effects

Drowsiness, blurred vision, tachycardia, nausea, dizziness, headache, excitement, postural hypotension, hyperprolactinaemia, sexual dysfunction, ECG changes (prolongation of QT interval and T wave changes), hyperthermia. Extrapyramidal symptoms may occur, especially during the early phase of treatment; urinary frequency or incontinence; tardive dyskinesia.

Toxicity

Although there have not been any cases of overdosage reported, the symptoms are likely to be somnolence, coma, extrapyramidal symptoms, convulsions, hypotension, shock, or hyper- or hypothermia.

Neuroleptic malignant syndrome may occur. Zuclopenthixol may potentiate anticholinergic effects of concurrent medications. Zuclopenthixol has a demonstrated antiemetic effect in animals, and may mask signs of toxicity due to other drug overdoses, or may mask symptoms of disease.

Precaution

Hepatic and renal impairment, heart disease, recent acute MI, arrhythmias, significant bradycardia (<50 beats/min), severe respiratory disease, epilepsy (and conditions at risk of epilepsy, e.g. alcohol withdrawal or brain damage), Parkinson's disease, acute angle glaucoma, prostatic hypertrophy, hypothyroidism, hyperthyroidism, myasthenia gravis, phaeochromocytoma. Patients at risk of stroke and QT interval prolongation. Avoid abrupt withdrawal. Ability to drive a car or operate machinery may be impaired.

Interaction

Zuclopenthixol may enhance the sedative effects of alcohol and the effects of barbiturates and other CNS depressants. Zuclopenthixol reduces the antihypertensive effect of guanethidine. Concomitant use of metoclopramide and piperazine with zuclopenthixol increases the risk of extrapyramidal symptoms. Increased risk of severe neurotoxicity with lithium and sibutramine. Increased anticholinergic side effects with drugs with anticholinergic properties.

Food Interaction

• Avoid alcohol. Acute alcohol intoxication is a contraindication for zuclopenthixol therapy.
• Take with or without food.

Volume of Distribution

20 L/kg.

Elimination Route

Upon reaching the body water phase, the decanoate ester is slowly released from the oil depot, which is resultantly hydrolyzed to the active substance, zuclopenthixol. The decanoate ester provides a means of slow release since zuclopenthixol itself is a short-acting drug.

Half Life

20 hours (range 12-28 hours) for the tablet form, 19 days for the depot form.

Clearance

approximately 0.9 L/min.

Elimination Route

Primarily in the feces with approximately 10% in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity. Comatose states e.g. alcohol, barbiturate and opiate intoxications; porphyria. children.

Special Warning

Renal Impairment: Intramuscular:

• Chronic psychosis: Dose reduction may be needed.
• Psychoses: Renal failure: Half of the normal dose.

Oral: Dose reduction may be needed.Hepatic Impairment: Intramuscular:

• Chronic psychosis: Dose reduction may be needed.
• Psychoses: Half of the normal recommended dose.

Oral: Dose reduction may be needed.

Acute Overdose

Symptoms: Somnolence, extrapyramidal symptoms, convulsions, hypotension, shock, hyper or hypothermia, ECG changes e.g. QT prolongation, torsade de pointes, cardiac arrest, ventricular arrhythmias and coma. Management: Treatment is symptomatic and supportive with close monitoring of the respiratory and CV systems. Do not use adrenaline (epinephrine) in these patients.

Storage Condition

Store below 25° C. Protect from light.

Innovators Monograph

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