Clopixol/Clopixol-Acuphase/Clopixol Depot

Zuclopenthixol salts.

Clopixol: Each mL of drops contains zuclopenthixol diHCl corresponding to zuclopenthixol 20 mg, spiritus fortis 120 mg and purified water to make 1 mL (1 drop = 1 mg).
Each mL of injection contains zuclopenthixol diHCl corresponding to zuclopenthixol 10 mg, sodium chloride 7.8 mg and water for injection to make 1 mL.
Clopixol-Acuphase: Clopixol-Acuphase contains zuclopenthixol acetate.
Clopixol Depot: Clopixol Depot contains zuclopenthixol decanoate.

Zuclopenthixol is a thioxanthene derivative with pronounced antipsychotic and specific dampening effect. The unspecific sedative effect wanes after a few weeks of treatment. The antipsychotic effect of neuroleptics is normally related to their dopamine receptor-blocking effect, which seems to release a chain reaction as other transmitter systems are influenced as well.
The specific dampening effect of zuclopenthixol makes it particularly useful in the treatment of psychotic patients, who are agitated, restless, hostile or aggressive.
Clopixol-Acuphase: A single injection of zuclopenthixol acetate ensures a pronounced and rapid reduction in psychotic symptoms. The duration of action is 2-3 days and normally only 1 or 2 injections are sufficient before the patient can be switched to maintenance treatment.
Zuclopenthixol acetate induces a transient dose-dependent sedation. However, such an initial sedation is often advantageous in the acute/subacute phase of the psychosis. The unspecific sedation is present rapidly after the injection, is significant after 2 hrs and reaches its maximum in about 8 hrs, whereupon it declines substantially and remains weak inspite of repeated injection.
Clopixol Depot: Zuclopenthixol decanoate has a considerably prolonged duration of action. It is especially useful in patients, who refuse to take drugs and in outpatients, who are unreliable in taking oral medication on their own as it permits continuous antipsychotic treatment and thus prevents the frequent relapses caused by failure to take oral medication.
Pharmacokinetics: Clopixol: The bioavailability after oral administration is 44% on an average. Maximal serum concentration is reached in about 4 hrs. Zuclopenthixol in small amounts crosses the placental barrier and is excreted in small amounts into the breast milk. The metabolites are devoid of psychopharmacological activity. The excretion proceeds mainly with feces but also to some degree with the urine. The biological half-life is about 20 hrs.
Clopixol-Acuphase: Maximum serum concentration of zuclopenthixol is reached on an average of 36 hrs after injection, then the serum curve declines slowly. Three days after the injection, the serum level is about ¹/₃ of the maximum. Zuclopenthixol in small amounts crosses the placental barrier and is excreted in amounts with the milk. The metabolites are devoid of psychopharmacological activity. The excretion proceeds mainly with feces but also to some degree with the urine.
Clopixol Depot: Clinical studies have shown that zuclopenthixol decanoate injections can be given with intervals of 2-4 weeks. The maximum serum concentration is reached by the end of the 1st week after injection. The serum concentration curve declines exponentially with a half-life of 19 days reflecting the rate of release from the depot.

Clopixol: Acute and chronic schizophrenia and other psychoses, especially with symptoms eg, hallucinations, delusions, thought disturbances, withdrawal as well as agitation, restlessness, hostility and aggressiveness. Manic phase of manic-depressive illness. Mental retardation associated with psychomotor excitation, agitation, violence and other behavioural disturbances. Senile or arteriosclerotic dementia with confusion and/or disorientation.
Clopixol-Acuphase: Initial treatment of acute psychoses, including mania, and exacerbations of chronic psychoses.
Clopixol Depot: Acute and chronic schizophrenia and other psychoses, especially with symptoms eg, hallucinations, delusions, thought disturbances, as well as agitation, restlessness, hostility and aggressiveness.

Dosage should be individually adjusted according to condition.
Clopixol: In general, small doses should be used initially and increased to the optimal effective level as rapidly as possible based on the therapeutic response.
Acute Schizophrenia and Other Acute Psychoses; Severe Acute States of Agitation; Mania: Oral treatment: Usually 10-50 mg/day. In moderate to severe cases initially 20 mg/day increased, if necessary, by 10-20 mg/day every 2-3 days to ≥75 mg daily.
Chronic Schizophrenia and Other Chronic Psychoses: Oral treatment: Maintenance dosage 20-40 mg/day.
Agitation in Oligophrenic Patients: Oral treatment: 6-20 mg/day, if necessary increased to 25-40 mg daily.
Agitation and Confusion in Senile Patients: Oral treatment: 2-6 mg/day, which can be administered late in the day. If necessary increased to 10-20 mg/day.
Clopixol-Acuphase: Clopixol-Acuphase is administered by IM injection.
The dosage range should normally be 50-150 mg (1-3 mL) IM repeated if necessary, preferably with a time interval of 2-3 days. In a few patients, an additional injection may be needed 24-48 hrs following the 1st injection.
In the maintenance therapy, treatment should be continued with oral Clopixol or Clopixol Depot IM after the following guidelines:
Change to Oral Clopixol: 2-3 days after the last injection of Clopixol-Acuphase, a patient who has been treated with 100 mg Clopixol-Acuphase, oral treatment should be started at a dosage of about 40 mg daily, possibly in divided dosages. If necessary, the dose can be further increased by 10-20 mg every 2-3 days up to 75 mg or more.
Change to Clopixol Depot: Concomitantly with the last injection of Clopixol-Acuphase, a dose of 200-400 mg (1-2 mL) of Clopixol Depot should be given IM and repeated every 2nd week. Higher doses or shorter interval may be needed.
Clopixol Depot: Dosage and interval between injections should be adjusted according to therapeutic response.
Clopixol Depot is administered by IM injection into the upper outer buttock in doses of 200-400 mg at 2- to 4-week intervals. A few patients need higher doses or shorter intervals.
When changing the medication from Clopixol tablet to Clopixol Depot, the following guideline may be used:
Click on icon to see table/diagram/image
Oral Clopixol should be continued during the 1st week after the 1st injection but in diminishing dosage.

Treatment is symptomatic and supportive. Measures aimed at supporting the respiratory and cardiovascular systems should be instituted. Epinephrine must not be used in these patients. For oral Clopixol, gastric lavage should be carried out immediately and activated charcoal may be administered.

Acute alcohol, barbiturate and opiate intoxications, comatose states. Like other psychotropics, Clopixol/Clopixol-Acuphase/Clopixol Depot should preferably not be given during pregnancy and lactation.

Patients on long-term therapy should be watched carefully. Clopixol/Clopixol-Acuphase/Clopixol Depot should be used with caution in patients with convulsive disorders or advanced hepatic, renal or cardiovascular disease.
Effects on the Ability to Drive or Operate Machinery: The ability to drive a car or operate machinery may be affected. Therefore, caution should be exercised initially, until individual's reaction to treatment is known.

Like other psychotropics, Clopixol/Clopixol-Acuphase/Clopixol Depot should preferably not be given during pregnancy and lactation.

Clopixol/Clopixol Depot: Extrapyramidal syndromes may occur, especially during the early phase of treatment. In most cases, these side effects can be satisfactorily controlled by reduction of dosage and/or antiparkinsonian drugs. Tardive dyskinesias, which can be more or less persistent, may appear in some patients on long-term therapy. Antiparkinsonian drugs do not alleviate these symptoms. Reduction in dosage or, if possible, discontinuation of therapy is recommended.
Psychic: Drowsiness initially.
Autonomic and Cardiovascular: Dry mouth, urinary retention, disturbance of accommodation, constipation, tachycardia, postural hypotension and dizziness.
Liver: Transient mild alterations in liver function tests may occur.
Clopixol-Acuphase: The frequency of unwanted effects is in general low and the severity of the symptoms is most often mild. They are most pronounced the day after the 1st injection and then decrease rapidly.
Extrapyramidal symptoms can be satisfactorily controlled by antiparkinsonian drugs. Occasionally, orthostatic dizziness may occur and reduced salivation of a mild degree has been observed.

Clopixol/Clopixol-Acuphase/Clopixol Depot may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. It should not be given concomitantly with guanethidine or similar acting compounds, since neuroleptics may block the antihypertensive effect of these compounds. Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of each other. Clopixol/Clopixol-Acuphase/Clopixol Depot may lower the effect of levodopa and adrenergic drugs. Concomitant use of metoclopramide and piperazine increases the risk of extrapyramidal symptoms.

Antipsychotics

N05AF05 - zuclopenthixol ; Belongs to the class of thioxanthene derivatives antipsychotics.

B