- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
The preparations being discontinued are:
- Haldol 10mg tablets (Janssen-Cilag Ltd)
The pharmaceutical company has decided to discontinue the product and so it may not be available in the future. This document has been left on the eMC for information purposes.
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.
Schizophrenia, psychoses and maniaUse as an antipsychotic agent for schizophrenia, psychoses, mania and hypomania, organic brain damage (depending on symptoms).Acute phase:Doses between 2 and 20 mg/day should be administered either as a single dose or in divided doses.Chronic phase:1-3 mg orally three times a day, may be increased up to 20 mg per day in divided doses, depending on the response.
Psychomotor anti-agitationUse as a psychomotor anti-agitation agent for mental or behavioural problems such as aggression, hyperactivity and self-mutilation in the mentally retarded and in patients with organic brain damage (depending on symptoms), violent or dangerously impulsive behaviour, Gilles de la Tourette syndrome, severe tics, intractable hiccup.Adults:
Acute phase:Moderate symptomatology: 1.5-3 mg twice or three times dailySevere symptomatology/resistant patients: 3-5 mg twice or three times daily
Chronic phase:0.5-1 mg three times a day orally, may be increased to 2-3 mg three times a day, if required, to obtain a response.Once satisfactory control of symptoms has been achieved dosage should be gradually reduced to the lowest effective maintenance dose. Too rapid a dosage reduction should be avoided.
Restlessness or agitation in the elderlyTreatment should start with half the dosage stated for adults and adjusted according to the results if necessary.
Childhood SchizophreniaThe recommended doses below provide a total dose in the approximate range 0.03 to 0.15 mg/kg/day, when administered orally in divided doses (two or three times a day).
Children 3 to 12 years of ageThe recommended- starting dose is a total 0.5 mg/day orally, preferably in divided doses- target dose range is a total 1 to 4 mg/day orally, in divided doses- maximum dose is a total 6 mg/day orally, in divided doses.
Adolescents 13 to 17 years of ageThe recommended - starting dose is a total 0.5 mg/day orally, preferably in divided doses- target dose range is a total 1 to 6 mg/day orally, in divided doses- maximum dose is a total 10 mg/day orally, in divided doses.
Childhood Psychomotor anti-agitationThe recommended doses below provide a total dose in the approximate range 0.02 to 0.075 mg/kg/day when administered orally in divided doses (two to three times a day).
Children 3 to 12 years of ageThe recommended - starting dose is a total 0.25 mg/day orally, preferably in divided doses.- target dose range is a total 0.5 to 3 mg/day orally, in divided doses.- maximum dose is a total 3 mg/day orally, in divided doses.
Adolescents 13 to 17 years of ageThe recommended - starting dose is a total 0.25 mg/day orally, preferably in divided doses.- target dose range is a total 2 to 6 mg/day orally, in divided doses.- maximum dose is a total 6 mg/day orally, in divided doses.
Cardiovascular effectsVery rare reports of QT prolongation and/or ventricular arrhythmias, in addition to rare reports of sudden death, have been reported with haloperidol. They may occur more frequently with high doses and in predisposed patients.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, family history of sudden death and/or QT prolongation; uncorrected electrolyte disturbances, subarachnoid haemorrhage, starvation or alcohol abuse, should be monitored carefully (ECGs and potassium levels), particularly during the initial phase of treatment, to obtain steady plasma levels.The risk of QT prolongation and/or ventricular arrhythmias may be increased with higher doses (see Sections 4.8 and 4.9) or with parenteral use, particularly intravenous administration. ECG monitoring should be performed for QT interval prolongation and for serious cardiac dysrhythmias if Haldol is administered intravenously.Haloperidol should be used with caution in patients known to be slow metabolisers of CYP2D6, and during use of cytochrome P450 inhibitors. Concomitant use of antipsychotics should be avoided. (See Section 4.5)Baseline ECG is recommended prior to treatment in all patients, especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. During therapy, the need for ECG monitoring (e.g. at dose escalation) should be assessed on an individual basis. Whilst on therapy, the dose should be reduced if QT is prolonged, and haloperidol should be discontinued if the QTc exceeds 500 ms.Periodic electrolyte monitoring is recommended, especially for patients taking diuretics, or during intercurrent illness.An approximately 3-fold increase risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Haloperidol should be used with caution in patients with risk factors for stroke.
Neuroleptic malignant syndromeIn common with other antipsychotic drugs, Haldol has been associated with neuroleptic malignant syndrome: a rare idiosyncratic response characterised by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness. Hyperthermia is often an early sign of this syndrome. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.
Tardive dyskinesiaAs 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 rhythmic 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.
Extrapyramidal symptomsIn common with all neuroleptics, extrapyramidal symptoms may occur, e.g. tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia.Antiparkinson drugs of the anticholinergic type may be prescribed as required, but should not be prescribed routinely as a preventive measure. If concomitant antiparkinson medication is required, it may have to be continued after stopping Haldol if its excretion is faster than that of Haldol in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with Haldol.
Seizures/ConvulsionsIt has been reported that seizures can be triggered by Haldol. Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g., alcohol withdrawal and brain damage).
Hepatobiliary concernsAs Haldol is metabolised by the liver, caution is advised in patients with liver disease. Isolated cases of liver function abnormalities or hepatitis, most often cholestatic, have been reported.
Endocrine system concernsThyroxin may facilitate Haldol toxicity. Antipsychotic therapy in patients with hyperthyroidism should be used only with great caution and must always be accompanied by therapy to achieve a euthyroid state.Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo- or amenorrhoea. Very rare cases of hypoglycaemia and of Syndrome of Inappropriate ADH Secretion have been reported.
Venous thromboembolismCases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Haldol and preventive measures undertaken.
Additional considerationsIn schizophrenia, the response to antipsychotic drug treatment may be delayed. Also, if drugs are withdrawn, recurrence of symptoms may not become apparent for several weeks or months. 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.As with all antipsychotic agents, Haldol should not be used alone where depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis coexist.Caution is advised in patients with renal failure and phaeochromocytoma.Available safety data in the paediatric population indicate a risk of extrapyramidal symptoms, including tardive dyskinesia, and sedation. No long-term safety data are available.
Effect of Other Drugs on HaloperidolWhen prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicin is added to Haldol therapy, this results in a significant reduction of haloperidol plasma levels. Therefore, during combination treatment, the Haldol dose should be adjusted, when necessary. After stopping such drugs, it may be necessary to reduce the dosage of Haldol.Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Effect of Haloperidol on Other DrugsIn common with all neuroleptics, Haldol 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 also been reported.Haldol may antagonise the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure-lowering effects of adrenergic-blocking agents such as guanethidine.Haldol may impair the antiparkinson effects of levodopa.Haloperidol is an inhibitor of CYP 2D6. Haldol inhibits the metabolism of tricyclic antidepressants, thereby increasing plasma levels of these drugs.
Other Forms of InteractionIn 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.Antagonism of the effect of the anticoagulant phenindione has been reported.The dosage of anticonvulsants may need to be increased to take account of the lowered seizure threshold.
|System Organ Class||Adverse Drug Reactions|
|Very Common (≥ 1/10)||Common(≥ 1/100 to < 1/10)||Uncommon (≥ 1/1,000 to < 1/100)||Rare(≥ 1/10,000 to <1/1,000)||Not Known|
|Blood and lymphatic System Disorders||Leukopenia||Agranulocytosis; Neutropenia; Pancytopenia; Thrombo-cytopenia|
|Immune System Disorders||Hypersensitivity||Anaphylactic reaction|
|Endocrine Disorders||Hyper-prolactinaemia||Inappropriate antidiuretic hormone secretion|
|Metabolic and Nutritional Disorders||Hypoglycaemia|
|Psychiatric Disorders||Agitation; Insomnia||Depression; Psychotic disorder||Confusional state; Libido Decreased; Loss of libido; Restlessness|
|Nervous System Disorders||Extrapyramidal disorder; Hyperkinesia; Headache||Tardive dyskinesia; Oculogyric Crisis; Dystonia; Dyskinesia; Akathisia; Bradykinesia; Hypokinesia; Hypertonia; Somnolence; Masked Facies, Tremor; Dizziness||Convulsion; Parkinsonism; Akinesia; Cogwheel rigidity; Sedation; Muscle Contractions Involuntary||Motor dysfunction; Neuroleptic malignant syndrome; Nystagmus;|
|Eye Disorders||Visual disturbance;||Vision blurred|
|Cardiac Disorders||Tachycardia||Ventricular Fibrillation; Torsade de pointes; Ventricular Tachycardia; Extrasystoles|
|Vascular Disorders||Orthostatic Hypotension; Hypotension|
|Respiratory, thoracic and mediastinal Disorders||Dyspnoea||Bronchospasm||Laryngeal Oedema; Laryngospasm|
|Gastrointestinal Disorders||Constipation; Dry mouth; Salivary hypersecretion; Nausea; Vomiting|
|Hepatobiliary Disorders||Liver function test abnormal||Hepatitis; Jaundice||Acute Hepatic Failure; Cholestasis|
|Skin and subcutaneous tissue disorders||Rash||Photosensitivity Reaction; Urticaria; Pruritis; Hyperhidrosis||Leukocytoclastic Vasculitis; Dermatitis Exfoliative|
|Musculoskeletal and Connective Tissue Disorders||Torticollis; Muscle rigidity; Muscle Spasms; Musculoskeletal stiffness||Trismus; Muscle Twitching|
|Renal and Urinary Disorders||Urinary retention|
|Pregnancy, Puerperium and Perinatal Conditions||Drug withdrawal syndrome neonatal (see section 4.6)|
|Reproductive System and Breast Disorders||Erectile dysfunction||Amenorrhoea; Dysmenorrhoea; Galactorrhoea; Breast Discomfort; Breast Pain;||Menorrhagia; Menstrual Disorder; Sexual Dysfunction||Gynaecomastia, Priapism|
|General Disorders and Administration Site Conditions||Gait disturbance; Hyperthermia; Oedema||Sudden Death; Face Oedema; Hypothermia|
|Investigations||Weight increased; Weight decreased||Electrocardiogram QT prolonged|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
SymptomsIn 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.
TreatmentThere 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-Parkinsonian medication should be administered.
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