COMPOSITION: CLOPIXOL ACUPHASE® Injection is a sterile solution of zuclopenthixol acetate in an oily vehicle intended for intramuscular injection.
1 mL ampoule
: Zuclopenthixol acetate 50 mg/mL
2 mL ampoule
: Zuclopenthixol acetate 100 mg/2 mL
PHARMACOLOGICAL CLASSIFICATION: A 2.6.5. Thioxanthenes
PHARMACOLOGICAL ACTION: CLOPIXOL ACUPHASE® induces a transient dose-dependent sedation. The unspecific sedation appears rapidly after administration of the injection, is significant within 2 hours and reaches its maximum within approximately 8 hours, whereupon it declines substantially and remains weak in spite of repeated injection. The duration of action is 2 to 3 days.
By esterification of zuclopenthixol with acetic acid, zuclopenthixol has been converted to a more lipophilic substance, zuclopenthixol acetate. When dissolved in oil (CLOPIXOL ACUPHASE®) and injected intramuscularly, this substance diffuses rather slowly into the surrounding body water, where it undergoes enzymatic breakdown to release the active component zuclopenthixol.
Maximum serum concentration of zuclopenthixol is reached on an average of 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 is distributed in the organism with the highest concentration of drug and metabolites occurring in liver, lungs, intestines and kidneys and lower concentrations in heart, spleen, brain and blood. The apparent volume of distribution is about 20 L/kg and the protein binding about 98%.
Zuclopenthixol crosses the placental barrier in small amounts. Zuclopenthixol is excreted in breast milk in small amounts - the milk concentration/serum concentration ratio in women is on an average 0,3.
The metabolism of zuclopenthixol proceeds along three main routes:
Sulphoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are psychopharmacologically inactive. Excretion occurs mainly via the faeces, with some degree of urinary excretion. The systemic clearance is about 0,9 L/minute.
The kinetics seem to be linear, since highly significant correlations exist between the dose and the area under the serum concentration curve.
INDICATIONS: Initial treatment of acute psychoses, including mania, exacerbations of chronic psychoses.
CONTRA-INDICATIONS: Acute alcohol, barbiturate and opiate intoxications, comatose states.
Safety and efficacy have not been established in children.
WARNINGS: CLOPIXOL ACUPHASE® should be used with caution in patients with convulsive disorders or advanced hepatic, renal or cardiovascular disease.
CLOPIXOL ACUPHASE® should preferably not be administered during pregnancy and lactation.
The ability to drive or operate machinery may be affected. Therefore, caution should be exercised initially, until the individuals reaction to treatment is known.
DOSAGE AND DIRECTIONS FOR USE: Adults: Dosage should be individually adjusted according to the patients condition. CLOPIXOL ACUPHASE® is administered by intramuscular injection.
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.
In the maintenance therapy, treatment should be continued with CLOPIXOL® DEPOT i.m. according to the following guidelines:
Change to maintenance treatment with CLOPIXOL® DEPOT:
Concomitantly with the last injection of CLOPIXOL ACUPHASE® 200 - 400 mg (1 - 2 mL) of CLOPIXOL® DEPOT should be given intramuscularly and repeated every 2nd week. Higher doses or shorter intervals may be needed.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects: The following side-effects have been reported: Central nervous system / neuromuscular: Hyperkinesia, somnolence, paraesthesia, sleeping disturbances and the malignant neuroleptic syndrome. Extrapyramidal symptoms (dystonia, rigidity, motor akathisia, hypokinesia and tremor). These side-effects can be satisfactorily controlled by antiparkinsonian drugs. Autonomic nervous system: Orthostatic dizziness, hypotension, reduced salivation, tachycardia and visual accommodation disturbances. Interactions: CLOPIXOL ACUPHASE® enhances the response to alcohol and the effects of barbiturates and other central nervous system depressants. CLOPIXOL ACUPHASE® 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 ACUPHASE® may reduce the effect of levodopa and the effect of adrenergic drugs. Concomitant use of metoclopramide and piperazine increases the risk of extrapyramidal symptoms.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms: Somnolence, coma, extrapyramidal symptoms, convulsions, shock, hyper- or hypothermia. 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.
IDENTIFICATION: Clear, yellowish oil, practically free from particles.
:1 x 1 mL ampoule
5 x 1 mL ampoules
100 mg/2 mL:
1 x 2 mL ampoule
5 x 2 mL ampoules
STORAGE INSTRUCTIONS: Store below 25°C and protect from light.
Do not remove the ampoules from the carton long before use.
Keep out of reach of children.
100 mg/ 2 mL
NAME AND BUSINESS ADDRESS OF THE APPLICANT: H. LUNDBECK (PTY) LTD
P.O. BOX 2357
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 15 March 1991