Zuclopenthixol Decanoate
A potent sedative neuroleptic for long-
term therapy
Composition
Oily injection fluid: 1 ml contains 200 mg
zuclopenthixol decanoate in thin vegetable
oil (Viscoleo) intended for intramuscular
injection.
Pharmacological Information
Pharmacological effects and mode of
Action :
Clopixol Depot is a thioxanthene derivative
with pronounced antipsychotic and specific
dampening effect. The unspecific sedative
effect wanes after 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 Clopixol
Depot makes it particularly useful in the
treatment of psychotic patients, who are
agitated, restless, hostile, or aggressive.
Clopixol is relatively short-acting whereas
Clopixol Depot has a considerably
prolonged duration of action. Clopixol
Depot permits continuous antipsychotic
treatment especially of those patients who
are unreliable in taking the oral medication
prescribed for them. Clopixol Depot thus
prevents the frequent relapses caused by
failure to take oral medication.
Pharmacokinetics
Pharmacokinetic and clinical studies on
Clopixol Depot have shown that Clopixol
Depot injections can be given with intervals
of 2 to 4 weeks. After injection
zuclopenthixol decanoate undergoes
enzymatic break-down into the active
component, zuclopenthixol and decanoic
acid. 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. The maximal serum concentration of
zuclopenthixol is reached by the end of the
first week after injection. The serum
concentration curve declines exponentially
with a half-life of 19 days, reflecting the
rate of release from the depot.
Pharmacokinetically a dose of 200 rng/2
weeks of Clopixol Depot is equivalent to a
daily oral dose of 25 mg Clopixol.
Clinical Information
Indications
Acute and chronic schizophrenia and other
psychosis, especially with symptoms such
as hallucinations, delusions, thought
disturbance, as well as agitation,
restlessness, hostility, and aggressiveness.
Contraindications
Acute alcohol, barbiturate, and opiate
intoxications; comatose states.
Adverse Effects
Neurological: Extrapyramidal symptoms
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. The
routine prophylactic use of
antiparkinsonian medication is not
recommended. Tardive dyskinesias may
occur very occasionally in 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, disturbances of
accommodation, urinary retention,
constipation, tachycardia, orthostatic
hypotension, and dizziness. Liver: Transient
slight alterations in liver function tests
may occur.
Precautions
Clopixol Depot should be used with caution
in patients with convulsive disorders or
advanced hepatic or cardiovascular disease.
Patients on long-term therapy particularly
on high doses should be monitored
carefully and evaluated periodically to
decide whether the maintenance dosage
can be lowered.
Use during pregnancy and lactation
Clopixol Depot should preferably not be
given during pregnancy and lactation.
Drug interactions
Clopixol Depot may enhance the response
to alcohol and the effects of barbiturates
and other CNS depressants. Clopixol Depot
should not be given concomitantly with
guanethidine or similar acting compounds,
since neuroleptics may block the
antihypertensive effect of these
compounds. Clopixol Depot may lower the
effect of levodopa and adrenergic drugs and
concomitant use of metoclopramide and
piperazine increases the risk of
extrapyramidal symptoms.
Dosage regimen
Adults:
Clopixol Depot is administered by
intramuscular injection into the upper
outer quadrant of the buttock. Local
tolerability is good. Dosage and interval
between injections should be individually
adjusted according to the therapeutic
response.
Clopixol Depot 200 mg/ml: In the
maintenance treatment the dosage range
would normally be 200-400 mg (1-2 ml)
every second to fourth week.A few patients
may need higher doses or shorter intervals
between doses.
When changing the medication from oral
Clopixol or Clopixol-Acuphase to
maintenance treatment with Clopixol Depot
the following guidelines should be used:
1) Change from oral Clopixol to Clopixol
Depot i.m.
mg Clopixol orally daily x 8 = mg Clopixol
Oral Clopixol should be continued during
the first week after the first injection but
in diminishing dosage.
2) Change from Clopixol-Acuphase i.m. to
Clopixol Depot i.m.
Concomitantly with the last injection of
Clopixol-Acuphase, a dose of 200-400 mg
(1-2 ml) of Clopixol Depot 200 rng/ml
should be given intramuscularly and
repeated every 2nd week. Higher doses or
shorter interval may be needed.
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 individual's reaction to treatment is