| 1. NAME OF THE MEDICINAL PRODUCT |
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| 2. QUALITATIVE AND QUANTITATIVE COMPOSITION |
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3.504 mg flupentixol dihydrochloride corresponding to 3 mg flupentixol base. |
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Round, biconvex, yellow, sugar-coated tablets. |
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4.1 Therapeutic indications
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The treatment of schizophrenia and other psychoses. |
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4.2 Posology and method of administration
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Route of administration: Oral.Adults:1 - 3 tablets twice daily to a maximum of 18 mg (6 tablets) per day. It is recommended that commencement of treatment and increase in dosage should be carried out under close supervision. As with all antipsychotic drugs, the dose of Depixol should be titrated to the needs of each patient.When transferring patients from oral to depot antipsychotic treatment, the oral medication should not be discontinued immediately, but gradually withdrawn over a period of several days after administering the first injection.Elderly:In accordance with standard medical practice, initial dosage may need to be reduced to a quarter or half the normal starting dose in the frail or elderly.Children: Not indicated for children. |
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Comatose states, including alcohol, barbiturate, or opiate poisoning. Not recommended for excitable or agitated patients. |
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4.4 Special warnings and precautions for use
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Caution should be exercised in patients having: liver disease; cardiac disease or arrhythmias; severe respiratory disease; renal failure; epilepsy (and conditions predisposing to epilepsy e.g. alcohol withdrawal or brain damage); Parkinson's disease; narrow angle glaucoma; prostatic hypertrophy; hypothyroidism; hyperthyroidism; myasthenia gravis; phaeochromocytoma and patients who have shown hypersensitivity to thioxanthenes or other antipsychotics.The elderly require close supervision because they are specially prone to experience such adverse effects as sedation, hypotension, confusion and temperature changes.Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal is advisable. |
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4.5 Interaction with other medicinal products and other forms of interaction
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In common with other antipsychotics, flupentixol enhances the response to alcohol, the effects of barbiturates and other CNS depressants. Flupentixol may potentiate the effects of general anaesthetics and anticoagulants and prolong the action of neuromuscular blocking agents.The anticholinergic effects of atropine or other drugs with anticholinergic properties may be increased. Concomitant use of drugs such as metoclopramide, piperazine or antiparkinson drugs may increase the risk of extrapyramidal effects such as tardive dyskinesia. Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of neurotoxicity.Antipsychotics may enhance the cardiac depressant effects of quinidine; the absorption of corticosteroids and digoxin. The hypotensive effect of vasodilator antihypertensive agents such as hydralazine and α blockers (e.g. doxazosin), or methyl-dopa may be enhanced. Concomitant use of flupentixol and drugs known to cause QT prolongation or cardiac arrhythmias, such as tricyclic antidepressants, other antipsychotics or terfenadine should be avoided.Antipsychotics may antagonise the effects of adrenaline and other sympathomimetic agents, and reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents. Antipsychotics may also impair the effect of levodopa, adrenergic drugs and anticonvulsants.The metabolism of tricyclic antidepressants may be inhibited and the control of diabetes may be impaired.Antacids may impair absorption, as may tea or coffee. |
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4.6 Pregnancy and lactation
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As the safety of this drug during pregnancy has not been established, use during pregnancy, especially the first and last trimesters, should be avoided, unless the expected benefit to the patient outweighs the potential risk to the foetus.Flupentixol is excreted into the breast milk. If the use of Depixol is considered essential, nursing mothers should be advised to stop breast feeding.The newborn of mothers treated with antipsychotics in late pregnancy, or labour, may show signs of intoxication such as lethargy, tremor and hyperexcitability, and have a low apgar score. |
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4.7 Effects on ability to drive and use machines
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Alertness may be impaired, especially at the start of treatment, or following the consumption of alcohol; patients should be warned of this risk and advised not to drive or operate machinery until their susceptibility is known. Patients should not drive if they have blurred vision. |
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Drowsiness and sedation are unusual. Sedation, if it occurs, is more often seen with high dosage and at the start of treatment, particularly in the elderly. Other adverse effects include blurring of vision, tachycardia and urinary incontinence and frequency. Dose-related postural hypotension may occur, particularly in the elderly.Because Depixol may impair alertness, especially at the start of treatment or following the consumption of alcohol, patients should be warned of the risk and advised not to drive or operate machinery, until their susceptibility is known.Extrapyramidal reactions in the form of acute dystonias (including oculogyric crisis), parkinsonian rigidity, tremor, akinesia and akathisia have been reported and may occur even at lower dosage in susceptible patients. Such effects would usually be encountered early in treatment, but delayed reactions may also occur. Antiparkinson agents should not be prescribed routinely because of the possible risk of precipitating toxic-confusional states, impairing therapeutic efficacy or causing anticholinergic side-effects. They should only be given if required and their requirement reassessed at regular intervals.Tardive dyskinesia can occur with antipsychotic treatment. It is more common at high doses for prolonged periods but has been reported at lower dosage for short periods. The risk seems to be greater in the elderly, especially females. It has been reported that fine vermicular movements of the tongue are an early sign. It has been observed occasionally in patients receiving Depixol. The concurrent use of anticholinergic antiparkinson drugs may exacerbate this effect. The potential irreversibility and seriousness, as well as the unpredictability of the syndrome, requires especially careful assessment of the risk versus benefit, and the lowest possible dosage and duration of treatment consistent with therapeutic efficacy. Short-lived dyskinesia may occur after abrupt withdrawal of the drug (see section 4.4).The neuroleptic malignant syndrome has rarely been reported in patients receiving antipsychotics, including flupentixol. This potentially fatal syndrome is characterised by hyperthermia, a fluctuating level of consciousness, muscular rigidity and autonomic dysfunction with pallor, tachycardia, labile blood pressure, sweating and urinary incontinence. Antipsychotic therapy should be discontinued immediately and vigorous symptomatic treatment implemented.Epileptic fits have occasionally been reported. Confusional states can occur.The hormonal effects of antipsychotic drugs include hyperprolactinaemia, which may be associated with galactorrhoea, gynaecomastia, oligomenorrhoea or amenorrhoea. Sexual function, including erection and ejaculation may be impaired; but increased libido has also been reported.ECG changes with prolongation of the QT interval and T-wave changes may occur with moderate to high doses; they are reversible on reducing the dose.Flupentixol may impair body temperature control, and cases of hyperthermia have occurred rarely. The possible development of hypothermia, particularly in the elderly and hypothyroid, should be borne in mind.Blood dyscrasias, including thrombocytopenia, have occasionally been reported. Blood counts should be carried out if a patient develops signs of persistent infection. Jaundice and other liver abnormalities have been reported rarely.Weight gain and less commonly weight loss have been reported; oedema has occasionally been reported and has been considered to be allergic in origin. Rashes have occurred rarely. Although less likely than with phenothiazines, flupentixol can rarely cause increased susceptibility to sunburn.Flupentixol, even in low doses, in susceptible (especially non-psychotic) individuals may unusually cause nausea, dizziness or headache, excitement, agitation, insomnia, or unpleasant subjective feelings of being mentally dulled or slowed down. |
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Overdosage may cause somnolence, or even coma, extrapyramidal symptoms, convulsions, hypotension, shock, hyper-or hypothermia. Treatment is symptomatic and supportive, with measures aimed at supporting the respiratory and cardiovascular systems. The following specific measures may be employed if required.
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anticholinergic antiparkinson drugs if extrapyramidal symptoms occur.
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sedation (with benzodiazepines) in the unlikely event of agitation or excitement or convulsions.
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noradrenaline in saline intravenous drip if the patient is in shock. Adrenaline must not be given.
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gastric lavage should be considered.
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| 5. PHARMACOLOGICAL PROPERTIES |
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5.1 Pharmacodynamic properties
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Flupentixol is a antipsychotic of the thioxanthene series.The antipsychotic effect of antipsychotic is believed to be related to their dopamine receptor blocking effect. The thioxanthenes have high affinity for D1 and D2 receptors. |
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5.2 Pharmacokinetic properties
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Oral administration to volunteers (8 mg single dose and 1.5 mg/day) and patients (5-60 mg/d) resulted in serum drug concentration curves with a maximum around four hours after administration. Mean biological half-life was about 35 hours in patients. No difference was seen in patients between half-lives estimated after single-dose administration and those estimated after repeated administration. Mean oral bioavailability of flupentixol varied between 40% and 55%. |
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5.3 Preclinical safety data
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| 6. PHARMACEUTICAL PARTICULARS |
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Potato starch, lactose, gelatin, talc, magnesium stearate, sucrose and yellow iron oxide (E172). |
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Depixol tablets are stable for 3 years. |
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6.4 Special precautions for storage
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Store in original container, protected from light and moisture. Do not store above 30°C. |
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6.5 Nature and contents of container
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Grey polypropylene container with screw cap or glass bottles with white plastic stoppers. Contents 100 tablets. |
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6.6 Instructions for use, handling and disposal
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| 7. MARKETING AUTHORISATION HOLDER |
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Lundbeck Limited
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Lundbeck House
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Caldecotte Lake Business Park
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Caldecotte
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Milton Keynes
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MK7 8LF
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| 8. MARKETING AUTHORISATION NUMBER(S) |
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| 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION |
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First Authorisation
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29 January 1987
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Renewal of Authorisation
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17 March 2002
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| 10. DATE OF REVISION OF THE TEXT |
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17 September 2004® Registered trademark
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