Clopixol Acuphase

/ Lundbeck

Adults: Dosage should be individually adjusted according to the condition of the patient. The dose range would normally be 50-150 mg (1-3 ml) i.m., repeated if necessary, preferably with a time interval of 2 to 3 days. In a few patients an additional injection may be needed 24 to 48 hours following the first injection. Zuclopenthixol acetate is not intended for long-term use and duration of treatment should not be more than two weeks. The maximum accumulated dosage in a course should not exceed 400 mg and the number of injections should not exceed four. In the maintenance therapy, treatment should be continued with oral zuclopenthixol or zuclopenthixol decanoate i.m., after the following guidelines:
Change to oral zuclopenthixol: 2 to 3 days after the last injection of zuclopenthixol acetate a patient who has been treated with 100 mg zuclopenthixol acetate, should be started at an oral dosage of about 40 mg daily, possibly in divided dosages. If necessary the dose can be further increased by 10-20 mg every 2 to 3 days up to 75 mg daily or more.
Change to zuclopenthixol decanoate: Concomitantly with the (last) injection of zuclopenthixol acetate (100 mg), 200-400 mg (1-2 ml) of zuclopenthixol decanoate 200 mg/ml should be given intramuscularly and repeated every 2nd week. Higher doses or shorter intervals may be needed. Zuclopenthixol acetate and zuclopenthixol decanoate can be mixed in a syringe and given as one injection (co-injection). Subsequent doses of zuclopenthixol decanoate and interval between injections should be adjusted according to the response of the patient.
Older patients: The dosage may need to be reduced in the older . Maximum dosage per injection should be 100 mg.
Children:Clopixol-Acuphase is not recommended for use in children due to lack of clinical experience. Reduced renal function Clopixol-Acuphase can be given in usual doses to patients with reduced renal function.
Reduced liver function: Patients with compromised hepatic function should receive half the recommended dosages and, if possible, a serum level determination is advisable.
For full details see prescribing information.

Initial treatment of acute psychoses.

As for other neuroleptics, intolerance to thioxanthenes. Acute alcohol, barbiturate and opiate intoxications, comatose states.

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.
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 acetate should be used with caution in patients with organic brain syndrome, convulsions or advanced hepatic, renal or cardiovascular 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 acetate may cause QT prolongation. Persistently prolonged QT intervals may increase the risk of malignant arrhythmias. Therefore, zuclopenthixol acetate 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 acetate and preventive measures undertaken.
Concomitant treatment with other antipsychotics should be avoided.
As described for other psychotropics, zuclopenthixol acetate may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.
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 acetate 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 elderly 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-Acuphase is not licensed for the treatment of dementia-related behavioural disturbances

Undesirable effects are for the majority 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 during the first few days after an injection and 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.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs
See prescribing information for full details.

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.
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.
See prescribing information for full details.

Pregnancy: Zuclopenthixol acetate 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 acetate) 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.
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 acetate 4 therapy if considered of clinical importance but observation of the infant is recommended, particularly in the first 4 weeks after giving birth.

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.

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.