Monograph: |
Zuclopenthixol Acetate
A potent sedative neuroleptic
Composition
Oily injection fluid: 1 ml contains 50 mg
zuclopenthixol acetate in thin vegetable oil
(Viscoleo') intended for intramuscular
injection.
Pharmacological Information
Pharmacological effects and mode of action
Clopixol-Acuphase is a thioxanthene
derivative with pronounced antipsychotic
and specific dampening effect. 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.
Clopixol-Acuphase is intended for the initial
treatment of acute psychosis, including
mania, and exacerbations of chronic
psychosis. A single injection of Clopixol-
Acuphase ensures a pronounced and rapid
reduction in psychotic symptoms. The
duration of action is 2 to 3 days and normally
only one or two injections are sufficient
before the patient can be switched to oral
or depot treatment.
Clopixol-Acuphase induces a transient dose-
dependent sedation. However, such an initial
sedation is often advantageous in the acute
phase of the psychosis as it calms the patient
in the period before the antipsychotic effect
sets in. The unspecific sedation is present
rapidly after the injection, is significant after
2 hours and reaches its maximum in about
8 hours, whereupon it declines substantially
and remains weak in spite of repeated
injection.
Clopixol-Acuphase is particularly useful in
the treatment of psychotic patients, who are
agitated, restless, hostile or aggressive.
Pharmacokinetics
After injection zuclopenthixol acetate
undergoes enzymatic breakdown into the
active component, zuclopenthixol and acetic
acid. Maximum serum concentration of
zuclopenthixol is reached over a period of
24 to 48 hours, on an average at about 36
hours after an injection, then the serum
curve declines rather slowly. Three days after
the injection the serum level is about one
third of the maximum. Zuclopenthixol in
small amounts crosses the placental barrier;
zuclopenthixol is excreted in small amounts
with the milk. The metabolites are devoid of
neuroleptic activity. The excretion proceeds
mainly with feces but also to some degree
with the urine.
Clinical Information
Indications
Initial treatment of acute psychosis,
including mania, and exacerbations of
chronic psychosis.
Contraindications
Acute alcohol, barbiturate, and opiate
intoxications; comatose states.
Adverse effects
Neurological: Extrapyramidal symptoms
may occur. In most cases these side effects
can be satisfactorily controlled by
antiparkinsonian drugs. The routine
prophylactic use of antiparkinsonian
medications is not recommended.
Autonomic: Dry mouth and disturbances of
accommodation may occur. Micturition
disturbances are rare. Cardiovascular:
Orthostatic dizziness and tachycardia may
occur. Orthostatic hypotension is rare. Liver:
Transient slight alterations in liver function
tests have rarely been reported.
Precautions
Clopixol-Acuphase should be used with
caution in patients with convulsive disorders
or advanced hepatic or cardiovascular
disease
Use during pregnancy and lactation
Clopixol-Acuphase should preferably not be
given during pregnancy and lactation.
Drug interactions
Clopixol-Acuphase may enhance the
sedative effect of alcohol and the effects of
barbiturates and other CNS depressants.
Clopixol-Acuphase should not be given
concomitantly with guanethidine or similar
acting compounds, since neuroleptics may
block the antihypertensive effect of these
compounds. Clopixol-Acuphase may lower
the effect of levodopa and adrenergic drugs.
Concomitant use of metoclopramide and
piperazine increases the risk of
extrapyramidal symptoms.
Dosage regimen
Adults:
Clopixol-Acuphase is administered by
intramuscular injection into the upper outer
quadrant of the gluteal region. Local
tolerability is good. Dosage should be
individually adjusted according to the
patient's condition.
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 few patients an additional injection may
be needed 24 to 48 hours following the first
injection.
In the maintenance therapy, treatment
should be continued with oral Clopixol or
Clopixol Depot i.m. after the following
guidelines:
1 ) Change to oral Clopixol:
2 to 3 days after the last injection of
Clopixol-Acuphase a patient who has been
treated with 100 mg Clopixol-Acuphase,
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.
2) Change to Clopixol Depot:
Concomitantly with the last injection of
Clopixol-Acuphase (100 mg), 200-400 mg
(1-2 ml) of Clopixol Depot 200 mg/ml
should be given intramuscularly and
repeated every 2nd week. Higher doses or
shorter intervals may be needed.
Clopixol-Acuphase and Clopixol Depot can
be mixed in the same syringe and given as
one injection (co-injection). Subsequent
doses of Clopixol Depot and interval
between injections should be adjusted
according to the patients response.
Overdose
Symptoms: Somnolence, coma,
extrapyramidal symptoms, convulsions,
hypotension, shock, hyper- or hypothermia.
Treatment: Symptomatic and supportive.
Measures aimed at supporting the
respiratory and cardiovascular systems
should be instituted. Epinephrine
(adrenaline) should not be used, as further
lowering of blood pressure may result.
Convulsions may be treated with diazepam
and extrapyramidal symptoms with
biperiden.
Special warnings
The neuroleptic malignant syndrome (NMS)
is a rare but potentially fatal complication
of the use of neuroleptic drugs. Core features
of NMS are hyperthermia, muscular rigidity
and fluctuating consciousness along with
autonomic dysfunction (labile blood
pressure, tachycardia, diaphoresis). Aside
from immediate cessation of the neuroleptic
medication the use of general supportive
measures and symptomatic treatment are
vital.
Effects on 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 the
individuals reaction to treatment is known.
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