Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Caution should be exercised in patients having: liver disease; cardiac disease, or arrhythmias; severe 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 Clopixol Depot 200 and Clopixol Depot 500 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from oral to depot antipsychotic treatment, the oral medication should not be discontinued immediately, but gradually withdrawn over a period of several days after administering the first injection.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 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 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 hypokalemia, hypomagnesia 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 Clopixol and preventive measures undertaken.
Concomitant treatment with other antipsychotics should be avoided (see section 4.5).
As described for other psychotropics zuclopenthixol 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 Depot 200 and Clopixol Depot 500 are not licensed for the treatment of dementia-related behavioural disturbances.

Effects on Driving

4.7   Effects on ability to drive and use machines
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.