1. Name Of The Medicinal Product
HALDOL Tablets 5 mg
HALDOL Tablets 10 mg
HALDOL 2 mg/ml
2. Qualitative And Quantitative Composition
Haloperidol 5 mg
Haloperidol 10 mg
Haloperidol 2mg/ml
3. Pharmaceutical Form
Tablets.
Oral solution
4. Clinical Particulars
4.1 Therapeutic Indications
Adults:
• Schizophrenia: treatment of symptoms and prevention of relapse
• Other psychoses: especially paranoid
• Mania and hypomania
• Mental or behavioural problems such as aggression, hyperactivity and self mutilation in the mentally retarded and in patients with organic brain damage
• As an adjunct to short term management of moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour
• Intractable hiccup
• Restlessness and agitation in the elderly
• Gilles de la Tourette syndrome and severe tics.
Children:
• Childhood behavioural disorders, especially when associated with hyperactivity and aggression
• Gilles de la Tourette syndrome
• Childhood schizophrenia.
4.2 Posology And Method Of Administration
For oral administration.
Since the oral solution is not intended for administration in multiples of 5 ml, the quantities given are expressed per ml.
Dosage for all indications should be individually determined and is best initiated and titrated under close clinical supervision. To determine the initial dose, consideration should be given to the patient's age, severity of symptoms and previous response to other neuroleptic drugs.
Patients who are elderly or debilitated or those with previously reported adverse reactions to neuroleptic drugs may require less Haldol. The normal starting dose should be halved, followed by a gradual titration to achieve optimal response.
Adults
Schizophrenia, psychoses, mania and hypomania, mental or behavioural problems, psychomotor agitation, excitement, violent or dangerously impulsive behaviour, organic brain damage
Initial dose:
Moderate symptomatology 1.5-3.0 mg bd or tds
Severe symptomatology/resistant patients 3.0-5.0 mg bd or tds
The same starting doses may be employed in adolescents and resistant schizophrenics who may require up to 30 mg/day.
Maintenance dosage:
Once satisfactory control of symptoms has been achieved, dosage should be gradually reduced to the lowest effective maintenance dose, often as low as 5 or 10 mg/day. Too rapid a dosage reduction should be avoided.
Restlessness or agitation in the elderly
Initial dose 1.5-3.0 mg bd or tds titrated as required, to attain an effective maintenance dose (1.5 –30 mg daily).
Gilles de la Tourette syndrome, severe tics, intractable hiccup
Starting dose 1.5 mg tds adjusted according to response. A daily maintenance dose of 10 mg may be required in Gilles de la Tourette syndrome.
Children
Childhood behavioural disorders and schizophrenia
Total daily maintenance dose of 0.025-0.05 mg/kg/day. Half the dose should be given in the morning and the other half in the evening, up to a maximum of 10 mg daily.
Gilles de la Tourette syndrome
Oral maintenance doses of up to 10 mg/day in most patients.
4.3 Contraindications
Comatose states, CNS depression, Parkinson's disease, known hypersensitivity to haloperidol, lesions of basal ganglia.
4.4 Special Warnings And Precautions For Use
Please also refer to section 4.5. Interactions with other Medicinal Products and other forms of Interaction.
Caution is advised in patients with liver disease, renal failure, phaeochromocytoma, epilepsy and conditions predisposing to epilepsy (eg alcohol withdrawal and brain damage) or convulsions. Haloperidol should only be used with great caution in patients with disturbed thyroid function. Antipsychotic therapy in those patients must always be accompanied by adequate management of the underlying thyroid dysfunction.
Cases of sudden death have been reported in psychiatric patients receiving antipsychotic drugs, including haloperidol.
The risk-benefit of haloperidol treatment should be fully assessed before treatment is commenced and patients with risk factors for ventricular arrhythmias such as cardiac disease, subarachnoid haemorrhage, metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia, starvation, alcohol abuse or those receiving concomitant therapy with other drugs known to prolong the QT interval, should be monitored carefully (ECGs and potassium levels), particularly during the initial phase of treatment, to obtain steady plasma levels.
Acute withdrawal symptoms including nausea, vomiting and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic drugs. Relapse may also occur and gradual withdrawal is advisable.
In schizophrenia, the response to antipsychotic drug treatment may be delayed. If drugs are withdrawn, recurrence of symptoms may not become apparent for several weeks or months.
As with all antipsychotic agents, haloperidol should not be used alone where depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis co-exist. Haloperidol may impair the metabolism of tricyclic antidepressants (clinical significance unknown).
If concomitant anti-Parkinson medication is required, it may have to be continued after haloperidol is discontinued to take account of any differences in excretion rates. The physician should keep in mind the possible anticholinergic effects associated with anti-Parkinson agents.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
In common with all neuroleptics, haloperidol can increase the central nervous system depression produced by other CNS-depressant drugs, including alcohol, hypnotics, sedatives or strong analgesics.
An enhanced CNS effect, when combined with methyldopa, has been reported.
Haloperidol may antagonise the action of adrenaline and other sympathomimetic agents and reverses the blood pressure lowering effects of adrenergic-blocking agents such as guanethidine.
The dosage of anticonvulsants may need to be increased to take account of the lowered seizure threshold.
Co-administration of enzyme-inducing drugs such as carbamazepine, phenobarbitone and rifampicin with haloperidol may result in a significant reduction of haloperidol plasma levels. The haloperidol dose may therefore need to be increased, according to the patient's response. After stopping such drugs, it may be necessary to re-adjust the dosage of haloperidol.
Haloperidol may impair the metabolism of tricyclic antidepressants (clinical significance unknown) and the anti-Parkinson effects of levodopa.
In pharmacokinetic studies, increased haloperidol levels have been reported when haloperidol was given concomitantly with the following drugs: quinidine, buspirone and fluoxetine. Haloperidol plasma levels should therefore be monitored and reduced if necessary.
Antagonism of the effect of phenindione has been reported.
In rare cases, an encephalopathy-like syndrome has been reported in combination with lithium and haloperidol. It remains controversial whether these cases represent a distinct clinical entity or whether they are in fact cases of NMS and/or lithium toxicity. Signs of encephalopathy-like syndrome include confusion, disorientation, headache, disturbances of balance and drowsiness. One report showing symptomless EEG abnormalities on the combination has suggested that EEG monitoring might be advisable. When lithium and haloperidol therapy are used concomitantly, haloperidol should be given in the lowest effective dose and lithium levels should be monitored and kept below 1 mmol/l. If symptoms of encephalopathy-like syndrome occur, therapy should be stopped immediately.
4.6 Pregnancy And Lactation
The safety of haloperidol in pregnancy has not been established. There is some evidence of harmful effects in some but not all animal studies. There have been a number of reports of birth defects following foetal exposure to haloperidol for which a causal role for haloperidol cannot be excluded. Haldol should be used during pregnancy only if the anticipated benefit outweighs the risk and the administered dose and duration of treatment should be as low and as short as possible.
Haloperidol is excreted in breast milk. There have been isolated cases of extrapyramidal symptoms in breast-fed children. If the use of Haldol is essential, the benefits of breast feeding should be balanced against its potential risks.
4.7 Effects On Ability To Drive And Use Machines
Some degree of sedation or impairment of alertness may occur, particularly with higher doses and at the start of treatment, and may be potentiated by alcohol or other CNS depressants. Patients should be advised not to undertake activities requiring alertness such as driving or operating machinery during treatment, until their susceptibility is known.
4.8 Undesirable Effects
Central nervous system
In common with all neuroleptics, extrapyramidal symptoms may occur, eg tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia, oculogyric crisis and laryngeal dystonia. Anti-Parkinson agents should not be prescribed routinely.
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long term therapy or after drug discontinuation. The syndrome is mainly characterised by rhythmical involuntary movements of the tongue, face, mouth or jaw. The manifestations may be permanent in some patients. The syndrome may be masked when treatment is reinstituted, when the dosage is increased or when a switch is made to a different antipsychotic drug. Treatment should be discontinued as soon as possible.
However, since its occurrence may be related to duration of treatment, as well as daily dose, Haldol should be given in the minimum effective dose for the minimum possible time, unless it is established that long term administration for the treatment of schizophrenia is required.
It has been reported that fine vermicular movements of the tongue may be an early warning sign of tardive dyskinesia and that the full syndrome may not develop if the medication is stopped at that time.
The following effects have been reported rarely; confusional states or epileptic fits, depression, sedation, agitation, drowsiness, insomnia, headache, vertigo and apparent exacerbation of psychotic symptoms.
In common with other antipsychotic drugs, haloperidol has been associated with neuroleptic malignant syndrome (NMS), an idiosyncratic response characterised by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness, coma and elevated CPK. Signs of autonomic dysfunction such as tachycardia, labile arterial pressure and sweating may precede onset of hyperthermia, acting as early warning signs. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.
Haloperidol, even in low dosage in susceptible (especially non-psychotic) individuals, may cause unpleasant subjective feelings of being mentally dulled or slowed down, dizziness, headache or paradoxical effects of excitement, agitation or insomnia.
Gastro-intestinal system
Gastro-intestinal symptoms, nausea, loss of appetite, constipation and dyspepsia have been reported.
Endocrinological system
Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo- or amenorrhoea. Hypoglycaemia and the syndrome of inappropriate antidiuretic hormone secretion have been reported rarely. Impairment of sexual function including erection and ejaculation has also been occasionally reported.
Cardiovascular system
Tachycardia and dose related hypotension are uncommon, but can occur, particularly in the elderly, who are more susceptible to the sedative and hypotensive effects. Less commonly, hypertension has also been reported.
Cardiac effects such as QT-interval prolongation, Torsade de Pointes and/or ventricular arrhythmias have been reported rarely. They may occur more frequently with high doses, intravenous administration and in predisposed patients (see 4.4. Special Warnings and Special Precautions for Use).
Autonomic nervous system
Dry mouth as well as excessive salivation, blurred vision, urinary retention and hyperhidrosis have been reported.
Dermatological system
The following effects have been reported rarely: oedema, various skin rashes and reactions including urticaria, exfoliative dermatitis and erythema multiforme. Photosensitive skin reactions have been reported very rarely.
Other adverse reactions
The following effects have been reported rarely: jaundice, cholestatic hepatitis or transient abnormalities of liver function in the absence of jaundice; priapism and weight changes. Temperature disorders may also occur, characteristically hyperthermia associated with NMS, although hypothermia has also been reported.
The following have been reported very rarely: blood dyscrasia, including agranulocytosis, thrombocytopenia and transient leucopenia; hypersensitivity reactions including anaphylaxis.
4.9 Overdose
Symptoms
In general, the manifestations of haloperidol overdosage are an extension of its pharmacological actions, the most prominent of which would be severe extrapyramidal symptoms, hypotension and psychic indifference with a transition to sleep. The risk of ventricular arrhythmias possibly associated with QT-prolongation should be considered. The patient may appear comatose with respiratory depression and hypotension which could be severe enough to produce a shock-like state. Paradoxically hypertension rather than hypotension may occur. Convulsions may also occur.
Treatment
There is no specific antidote to haloperidol. A patent airway should be established and maintained with mechanically assisted ventilation if necessary. In view of isolated reports of arrhythmia ECG monitoring is strongly advised. Hypotension and circulatory collapse should be treated by plasma volume expansion and other appropriate measures. Adrenaline should not be used. The patient should be monitored carefully for 24 hours or longer, body temperature and adequate fluid intake should be maintained.
In cases of severe extrapyramidal symptoms, appropriate anti-Parkinson medication should be administered.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Haloperidol acts as a central dopamine receptor antagonist. It also has some anticholinergic activity and binds to opiate receptors. It also acts at peripheral dopamine receptors.
5.2 Pharmacokinetic Properties
Pharmacotherapeutic group: Butyrophenone Derivatives: ATC code: NP5A DO1
Haloperidol is absorbed rapidly with a bioavailability of 44-74% (mean 60%) after tablets and a bioavailability of 38-86% (mean 58%) after oral solution. Variable bioavailability is likely to be due to interindividual differences in gastro-intestinal absorption and extent of first-pass hepatic metabolism.
Haloperidol is rapidly distributed to extravascular tissues especially liver and adipose tissue. Haloperidol crosses the blood-brain barrier and is excreted in human breast milk. It is approximately 92% bound to plasma proteins.
Metabolism is by oxidative dealkylation. The elimination half-life is approximately 20 hours, with considerable diurnal variation.
5.3 Preclinical Safety Data
No relevant information other than that contained elsewhere in the Summary of Product Characteristics.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Haldol 5 mg
Lactose monohydrate
Maize starch
Talc
Cottonseed oil - hydrogenated
Indigotindisulphonate sodium (E132)
Purified water (not in final product)
Haldol 10 mg
Calcium hydrogen phosphate dihydrate
Maize starch
Calcium stearate
Quinoline yellow (E104)
Purified water (not in final product)
Haldol 2mg/ml
Lactic acid
Methyl parahydroxybenzoate
Purified water
6.2 Incompatibilities
None known.
6.3 Shelf Life
60 months.
6.4 Special Precautions For Storage
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Keep out of reach and sight of children.
6.5 Nature And Contents Of Container
5,10mg tablets: Blister packs of aluminium foil and polyvinylchloride genotherm glass clear. The strips are packed in cardboard cartons containing 100 tablets per pack.
2mg/ml oral solution: Bottle: Amber glass (Type III, Ph.Eur); 100 ml
Closure:
Aluminium screw cap, tamper resistant, coated on the inner side with polyvinylchloride.
OR
Child resistant, polypropylene screw cap with low density polyethylene insert.
Dosing Device:
2.5 ml glass pipette with 0.5 ml graduations fitted on a butyl rubber bulb with a polypropylene screw cap.
OR
2.5 ml glass pipette with 0.5 ml graduations fitted on a black siliconised rubber bulb. The pipette has a white polypropylene child-resistant screw cap and polypropylene sheath.
6.6 Special Precautions For Disposal And Other Handling
None.
7. Marketing Authorisation Holder
Janssen-Cilag Limited
Saunderton
High Wycombe
Buckinghamshire
HP14 4HJ
UK
8. Marketing Authorisation Number(S)
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9. Date Of First Authorisation/Renewal Of The Authorisation
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10. Date Of Revision Of The Text
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Legal status POM
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