This information is intended for use by health professionals
AdultsDosage should be adjusted according to the severity of the patient's illness.The usual dosage is 50-150 mg (1-3 ml), repeated if necessary after 2 or 3 days. Some patients may need an additional injection between 1 and 2 days after the first injection.Clopixol-Acuphase is not intended for long-term use and duration of treatment should not be more than two weeks. The maximum accumulated dosage should not exceed 400 mg and the number of injections should not exceed four.
Older patientsThe dosage may need to be reduced in older patients owing to reduced rates of metabolism and elimination. Maximum dosage per injection should be 100 mg.
Paediatric populationClopixol-Acuphase is not recommended for use in children due to lack of clinical experience.
Patients with renal impairmentClopixol-Acuphase can be given in usual doses to patients with reduced renal function. Where there is renal failure, dosage should be reduced to half the normal dosage.
Patients with hepatic impairmentUse with caution in patients with hepatic disease (see section 4.4). Patients with compromised hepatic function should receive half the recommended dosages. Serum-level monitoring is advised.
Maintenance TherapyClopixol-Acuphase is not intended for long-term use.A single injection of Clopixol-Acuphase has an onset of sedative action shortly after injection and an antipsychotic action persisting for 2 to 3 days. In this period, maintenance treatment with tablets or a longer acting depot neuroleptic can be initiated. The possible side-effects of long-term maintenance treatment with a neuroleptic, including tardive dyskinesia, should be considered.Maintenance treatment where required can be continued with Clopixol tablets, Clopixol Injection or Clopixol Conc. Injection, according to the following guidelines:1. Introduce Clopixol tablets at a dosage of 20-60 mg/day in divided doses, 2 to 3 days after the last injection of Clopixol-Acuphase. If necessary increase the tablet dosage by 10-20 mg each day up to a maximum of 150 mg/day.Or2. Concomitantly with the last injection of Clopixol-Acuphase, administer 200-400 mg of Clopixol injection or Clopixol Conc. Injection by deep intramuscular injection and repeat the Clopixol injection or Clopixol Conc. injection at intervals of 2 to 4 weeks. Higher dosages or a shorter interval may be necessary.
Method of administrationDeep intramuscular injection into the upper outer buttock or lateral thigh. Injection volumes exceeding 2 ml should be distributed between two injection sites.
NoteAs with all oil-based injections it is important to ensure, by aspiration before injection, that inadvertent intravascular entry does not occur.
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 (see section 4.5).As described for other psychotropics, zuclopenthixol acetate may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.
Older peopleOlder people require close supervision because they are especially prone to experience such adverse effects as sedation, hypotension, confusion, and temperature changes.
CerebrovascularAn 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 DementiaData 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.
PregnancyZuclopenthixol 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 (see section 5.3).
Breast-feedingAs 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 therapy if considered of clinical importance, but observation of the infant is recommended, particularly in the first 4 weeks after giving birth.
FertilityIn humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile dysfunction and ejaculation failure have been reported (see section 4.8). 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.
|Blood and lymphatic system disorders||Thrombocytopenia, neutropenia, leukopenia, agranulocytosis.|
|Immune system disorders||Hypersensitivity, anaphylactic reaction.|
|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.|
|Ear and labyrinth disorders||Vertigo.|
|Cardiac disorders||Tachycardia, palpitations.|
|Electrocardiogram QT prolonged.|
|Vascular disorders||Hypotension, hot flush.|
|Respiratory, thoracic and medistianal 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 (see 4.6)|
|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, injection site reaction, hypothermia, pyrexia.|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Mechanism of actionZuclopenthixol is a potent neuroleptic of the thioxanthene series with a piperazine side-chain. The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking effect. The thioxanthenes have a high affinity for both the adenylate cyclase coupled dopamine D1 receptors and for the dopamine D2 receptors; in the phenothiazine group the affinity for D1 receptors is much lower than that for D2 receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity for D2 receptors.In the traditional tests for antipsychotic effect, e.g. antagonism of stereotypic behaviour induced by dopamine agonists, the chemical groups of neuroleptics mentioned reveal equal but dosage dependent activity. However, the antistereotypic effect of phenothiazines, butyrophenones, diphenylbutylpiperidines, and benzamindes is strongly counteracted by the anticholinergic drug, scopolamine, while the antisteriotypic effect of the thioxanthenes, e.g. zuclopenthixol, is not, or only very slightly, influenced by concomitant treatment with anticholinergics.
Reproductive toxicityImpaired mating performance and reduced conception rates were observed in rats treated with zuclopenthixol at doses equal to the maximum recommend human dose of 50 mg on a mg/m2 basis.There was no evidence of embryotoxicity or teratogenic effects in rats treated with zuclopenthixol, however adverse effects on pre-and postnatal development (i.e. increased stillbirths, reduced pup survival and delayed development of pups) was observed. The clinical significance of these findings is unclear and it is possible that the effect on pups was due to neglect from the dams that were exposed to doses of zuclopenthixol producing maternal toxicity.
Mutagenicity and carcinogenicityZuclopenthixol has no mutagenic potential. In a rat oncogenicity study, 30 mg/kg/day resulted in slight non statistical increases in the incidence of mammary adenocarcinomas and pancreatic islet cell adenomas and carcinomas in females of thyroid parafollicular carcinomas. This is a common finding for D2 antagonists which increase prolactin secretion when administered to rats. The physiological differences between rats and humans suggest that these changes are not predictive of an oncogenic risk in patients.
Local toxicityLocal muscle damage is less pronounced with oily solutions of zuclopenthixol (including Clopixol-Acuphase) then with aqueous solutions of zuclopenthixol and other neuroleptics.
Keep ampoules in the outer carton in order to protect from light
This medicinal product does not require any special temperature storage conditions.
|Date of First Authorisation in the UK:||16 March 1990|
|Renewal of the Authorisation:||3 July 2008|
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