Chemical formula: C₂₂H₂₅ClN₂OS Molecular mass: 400.965 g/mol PubChem compound: 5311507
Zuclopenthixol interacts in the following cases:
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:
The above list is not exhaustive and other individual drugs known to significantly increase QT interval (e.g. cisapride, lithium) should be avoided.
In common with other antipsychotics, zuclopenthixol enhances the response to alcohol, the effects of barbiturates and other CNS depressants.
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), a recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia.
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.
Caution should be exercised in patients having liver disease.
Caution should be exercised in patients having renal failure.
The metabolism of tricyclic antidepressants may be inhibited.
The hypotensive effect of vasodilator antihypertensive agents such as hydralazine and α-blockers (e.g. doxazosin), or methyl-dopa may be enhanced.
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.
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.
Antipsychotics may impair the effect of anticonvulsants.
Concomitant use of antiparkinson drugs may increase the risk of extrapyramidal effects such as tardive dyskinesia.
Concomitant treatment with other antipsychotics should be avoided.
In humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile dysfunction and ejaculation failure have been reported. These events may have a negative impact on female and/or male sexual function and fertility.
If clinically 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 was 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.
Antipsychotics may impair the effect of levodopa and adrenergic drugs.
Combined use of antipsychotics and lithium has been associated with an increased risk of neurotoxicity.
Concomitant use of drugs such as metoclopramide or piperazine may increase the risk of extrapyramidal effects such as tardive dyskinesia.
Combined use of antipsychotics and sibutramine has been associated with an increased risk of neurotoxicity.
Caution should be exercised in patients having prostatic hypertrophy.
Caution should be exercised in patients having phaeochromocytoma.
Caution should be exercised in patients having blood disorders.
Caution should be exercised in patients having narrow angle glaucoma.
Caution should be exercised in patients having hypothyroidism or hyperthyroidism.
Caution should be exercised in patients having severe respiratory disease.
Caution should be exercised in patients having Parkinson’s disease.
As described for other psychotropics, zuclopenthixol may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.
Caution should be exercised in patients having epilepsy (and conditions predisposing to epilepsy, e.g. alcohol withdrawal or brain damage).
Caution should be exercised in patients having myasthenia gravis.
Zuclopenthixol 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) 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.
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 therapy if considered of clinical importance, but observation of the infant is recommended, particularly in the first 4 weeks after giving birth.
In humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile dysfunction and ejaculation failure have been reported. These events may have a negative impact on female and/or male sexual function and fertility.
If clinically 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 was 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 dyskinesia 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.
Blood and lymphatic system disorders: Thrombocytopenia, neutropenia, leukopenia, agranulocytosis.
Immune system disorders: Hypersensitivity, anaphylactic reaction.
Endocrine disorders: Hyperprolactinaemia.
Metabolism and nutrition disorders: Increased appetite, weight increased. Decreased appetite, weight decreased. Hyperglycaemia, glucose tolerance impaired, hyperlipidaemia.
Psychiatric disorders: Insomnia, depression, anxiety, nervousness, abnormal dreams, agitation, libido decreased.
Apathy, nightmare, libido increased, confusional state.
Nervous system disorders: Somnolence, akathisia, hyperkinesia, hypokinesia. Tremor, dystonia, hypertonia, dizziness, headache, paraesthesia, disturbance in attention, amnesia, gait abnormal. Tardive dyskinesia, hyperreflexia, dyskinesia, parkinsonism, syncope, ataxia, speech disorder, hypotonia, convulsion, migraine. Neuroleptic malignant syndrome.
Eye disorders: Accommodation disorder, vision abnormal. Oculogyration, mydriasis.
Ear and labyrinth disorders: Vertigo. Hyperacusis, tinnitus.
Cardiac disorders: Tachycardia, palpitations. Electrocardiogram QT prolonged.
Vascular disorders: Hypotension, hot flush. Venous thromboembolism
Respiratory, thoracic and mediastinal disorders: Nasal congestion, dyspnoea.
Gastrointestinal disorders: Dry mouth. Salivary hypersecretion, constipation, vomiting, dyspepsia, diarrhoea. Abdominal pain, nausea, flatulence.
Hepato-biliary disorders: Liver function test abnormal. Cholestatic hepatitis, jaundice.
Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritus. Rash, photosensitivity reaction, pigmentation disorder, seborrhoea, dermatitis, purpura.
Musculoskeletal and connective tissue disorder: Myalgia. Muscle rigidity, trismus, torticollis.
Renal and urinary disorders: Micturition disorder, urinary retention, polyuria.
Pregnancy, puerperium and perinatal conditions: Drug withdrawal syndrome neonatal.
Reproductive system and breast disorders: Ejaculation failure, erectile dysfunction, female orgasmic disorder, vulvovaginal dryness. Gynaecomastia, galactorrhoea, amenorrhoea, priapism.
General disorders and administration site conditions: Asthenia, fatigue, malaise, pain. Thirst, hypothermia, pyrexia.
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.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown.
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.
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