Posted by ed_uk on December 3, 2004, at 7:26:47
In reply to flupenthixol doesn't seem to be available here (nm) » ed_uk, posted by gromit on December 2, 2004, at 0:16:34
Were you asking me about flupenthixol? I think you were so I'll say a bit about it.
Flupenthixol (recently renamed flupentixol) is a typical antipsychotic. High doses have an effect similar to haloperidol (Haldol) and are used for the treatment of psychotic disorders. Side effects are very common when high doses are used. Very low doses are said to have an antidepressant effect. Side effects are much less common with very low doses. In England, low dose tablets are called Fluanxol, high dose tablets are called Depixol.
Low doses of flupenthixol sometimes cause hyperprolactinemia. The chance of your prolactin being raised be Fluanxol is probably fairly high. Even so, it might be worth a try, especially if you have tolerated other typical APs well in the past. Which APs have you taken before and not experienced hyperprolactinemia?
Here is the UK data sheet for Fluanxol...
1. NAME OF THE MEDICINAL PRODUCT
Fluanxol Tablets 0.5 and 1 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
0.5 mg tablets (containing 0.584 mg flupentixol dihydrochloride equivalent to 0.5 mg flupentixol base). 1 mg tablets (containing 1.168 mg flupentixol dihydrochloride equivalent to 1 mg flupentixol base).
3. PHARMACEUTICAL FORM
Round, biconvex, red, sugar-coated tablets.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Symptomatic treatment of depression (with or without anxiety).
4.2 Posology and method of administration
Route of administration: Oral.
Adults: The standard initial dosage is 1 mg as a single morning dose. After one week the dose may be increased to 2 mg if there is inadequate clinical response. Daily dosage of more than 2 mg should be in divided doses up to a maximum of 3 mg daily.
Elderly: The standard initial dosage is 0.5 mg as a single morning dose. After one week, if response is inadequate, dosage may be increased to 1 mg once a day. Caution should be exercised in further increasing the dosage but occasional patients may require up to a maximum of 2 mg a day which should be given in divided doses.
Children: Not recommended for children.
Patients often respond within 2-3 days. If no effect has been observed within one week at maximum dosage the drug should be withdrawn.
Severe depression requiring ECT or hospitalisation, states of excitement or overactivity, including mania.
4.4 Special warnings and special precautions for use
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.
Recurrence of depressive symptoms on abrupt withdrawal is rare. Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of thioxanthenes and similar drugs. The emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal is advisable.
Dependence has not been reported to date.
4.5 Interaction with other medicinal products and other forms of Interaction
In common with other similar drugs, 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 αblockers (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, possibily clonidine 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.
4.6 Pregnancy and lactation
As the safety of Fluanxol in human 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 Fluanxol 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.
4.7 Effects on ability to drive and use machines
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.
4.8 Undesirable effects
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.
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. If they do occur, treatment with Fluanxol should be withdrawn. 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. Precipitation of hypomania has been occasionally reported.
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 Fluanxol. 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.
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 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.
Other reactions that have been reported rarely at low doses include nausea, dizziness or headache, migraine, excitement, agitation, or unpleasant subjective feelings of being mentally dulled or slowed down. Other occasional side effects are restlessness and insomnia.
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.
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.
anticholinergic antiparkinson drugs if extrapyramidal symptoms occur.
sedation (with benzodiazepines) in the unlikely event of agitation or excitement or convulsions
noradrenaline in saline intravenous drip if the patient is in shock. Adrenaline must not be given.
gastric lavage should be considered
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
The precise pharmacological mode of action of flupentixol has not been determined. It has been postulated that at low dosage flupentixol binds to presynaptic dopamine receptors causing increased neurotransmitter release. There is evidence that postsynaptic aminergic receptors become down regulated in response to increased levels of neurotransmitter and this is responsible for the observed improvement in depressive symptoms.
5.2 Pharmacokinetic properties
Mean oral bioavailability is about 55%. Maximum drug serum concentrations occur about 4 hours after dosing and the biological half-life is about 35 hours. Flupentixol is widely distributed in the body. Metabolism is by sulphoxidation, N-dealkylation and glucuronic acid conjugation. Excretion is via the urine and faeces.
5.3 Preclinical safety data
Nil of relevance
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Potato starch, Lactose, Gelatin, Talc, Magnesium Stearate, Sucrose and Ultralake Ponceau 4R (E124)
6.3 Shelf life
Fluanxol tablets are stable for 3 years. The box is labelled with an expiry date.
6.4 Special precautions for storage
Do not store above 30°C.
6.5 Nature and contents of container
PVC/PVdC blister strips of 60 tablets per box.
6.6 Instructions for use and handling (and disposal)
7. MARKETING AUTHORISATION HOLDER
Caldecotte Lake Business Park
8. MARKETING AUTHORISATION NUMBER(S)
Fluanxol Tablets 0.5 mg
Fluanxol Tablets 1 mg
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
23 September 1982
Renewal of Authorisation
17 March 2002
10. DATE OF REVISION OF THE TEXT