Serenace Liquid 2mg/Ml

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Serenace Liquid 2mg/ml

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Haloperidol BP 10mg per 5ml

3. PHARMACEUTICAL FORM

Liquid for oral administration.

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Psychotic disorders - schizophrenia, mania and hypomania, especially paranoid psychoses.

Mental or behavioural problems such as aggression, hyperactivity and selfmutilation in the mentally retarded.

Moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour.

Gilles de la Tourette syndrome and severe tics.

Childhood behaviour disorders, especially when associated with hyperactivity and aggression.

Restlessness and agitation in the elderly.

Intractable hiccup.

Nausea and vomiting.

4.2. Posology and Method of Administration

There is considerable variation from patient to patient in the response to treatment and the dosage required. As with all antipsychotics, dosage should be individualised according to the needs and response of each patient.

To determine the initial dosage, consideration should be given to the patient's age, severity of symptoms and previous response to other antipsychotic therapy. Oral dosage may be given in single or divided doses. Administration twice daily is sufficient in most cases.

Adults

Psychotic behaviour; Mental or behavioural problems; Moderate to severe psychomotor agitation or impulsive behaviour.

Initial treatment

Initial dosage may range from as little as 1.5mg daily to 20mg daily, dependent on the characteristics, severity of symptoms and response of each individual patient. It may be necessary to increase the dosage gradually to obtain maximum control of symptoms. In severely disturbed or resistant patients, the maximum daily dose recommended is 30mg.

Maintenance treatment

Once a satisfactory therapeutic response has been achieved, dosage should be reduced gradually to the lowest effective maintenance level which is often as low as 3 to 10mg daily dependent on the characteristics and response of each individual patient.

Gilles de la Tourette syndrome

Initial dosage is usually 2mg daily. During the acute phase of treatment, dosage can be increased gradually to obtain maximum control of symptoms and may range between 6 and 30mg daily.

Once a satisfactory therapeutic response has been achieved, dosage should be reduced gradually to the lowest effective maintenance level which for most patients is 4mg daily.

Nausea and vomiting 1mg daily orally has proved useful.

Intractable hiccup

3 to 15mg daily in divided doses, orally has proven useful.

Elderly

Half the recommended adult starting dose may be sufficient for therapeutic response in the elderly. The maximum and maintenance dose will generally be lower for debilitated or geriatric patients who may be more sensitive to Serenace.

Children (Oral administration)

25 to 50 micrograms per Kg body weight per day to a maximum of 10mg, although, exceptionally, adolescents may require up to 30mg daily.

Route of administration

Oral.

4.3 Contraindications

Comatose states, CNS depression, Parkinson’s disease, known hypersensitivity to Haloperidol, lesions of basal ganglia, and use during lactation.

In common with other neuroleptics, Haloperidol has the potential to cause rare prolongation of the QT interval. Use of Haloperidol is therefore contraindicated in patients with clinically significant cardiac disorders e.g. recent acute myocardial infarction, uncompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic medicinal products, QTc interval prolongation, history of ventricular arrhythmia or torsades de pointes clinically significant bradycardia, second or third degree heart block and uncorrected hypokalaemia. Haloperidol should not be used concomitantly with other QT prolonging drugs (see section 4.5).

4.4 Special warnings and precautions for use

Cases of sudden death have been reported in psychiatric patients receiving anti-psychotic drugs, including Haloperidol.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g. pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Haloperidol is not licensed for the treatment of dementia-related behavioural disturbances.

Cardiovascular effects

Very 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 Haloperidol 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, particularly if on diuretics or during inter-current illness.

An approximately 3-fold increased risk of cerebrovascular adverse events has 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.

Administer with care to patients with severe cardiovascular disorders, because of the possibility of transient hypotension. Should hypotension occur and a vasopressor be required, adrenaline should not be used since Haloperidol may block its vasopressor activity and further lowering of the blood pressure may occur.

Neuroleptic malignant syndrome

In common with other antipsychotic drugs, Haloperidol 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 dyskinesia

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 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 symptoms

In 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 Haloperidol if its excretion is faster than that of Haloperidol 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 Haloperidol .

Seizures/Convulsions

It has been reported that seizures can be triggered by Haloperidol . Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g., alcohol withdrawal and brain damage).

Hepatobiliary concerns

As Haloperidol 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 concerns

Thyroxin may facilitate Haloperidol 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 thromboembolism

Cases 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 Haloperidol and preventive measures undertaken.

Additional considerations

In 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, sweating, and insomnia have very rarely been described after abrupt cessation of high doses 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. Gradual withdrawal is advisable.

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 coexist. Haloperiol may impair the metabolism of tricyclic antidepressant (clinical significance).

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.

Concomitant use of Haloperidol with other neuroleptics should be avoided.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of Haloperidol with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Therefore concomitant use of these products is not recommended (see section 4.3-Contraindications).

Examples include certain antiarrhythmics, such as those of Class 1A (such as quinidine, disopyramide and procainamide) and class III (such as amiodarone, sotalol and dofetilide), certain antimicrobials (sparfloxacin, moxifloxacin, erythromycin IV), tricyclic antidepressants (such as amitriptyline), certain tetracyclic antidepressants (such as maprotiline), other neuroleptics (e.g.phenothiazines, pimozide and sertindole), certain antihistamines (such as terfenadine), cisapride, bretylium and certain anti-malarials such as quinine and mefloquine. This list is not comprehensive.

Concurrent use of drugs causing electrolyte imbalance may increase the risk of ventricular arrhythmias and is not recommended (see section 4.4-Special Warnings and Precautions for Use). Diuretics, in particular those causing hypokalaemia, should be avoided but, if necessary, potassium-sparing diuretics are preferred.

Haloperidol is metabolised by several routes, including glucuronidation and the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6). Inhibition of these routes of metabolism by another drug or a decrease in CYP 2D6 enzyme activity may result in increased Haloperidol concentrations and an increased risk of adverse events, including QT-prolongation. In pharmacokinetic studies, mild to moderately increased Haloperidol concentrations have been reported when Haloperidol was given concomitantly with drugs characterised as substrates or inhibitors of CYP 3A4 or CYP 2D6 isozymes, such as, itraconazole, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine. A decrease in CYP2D6 enzyme activity may result in increased Haloperidol concentrations. Increases in QTc and extrapyramidal symptoms have been observed when Haloperidol was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the Haloperidol dosage.

Effect of Other Drugs on Haloperidol

When prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicin is added to Haloperidol therapy, this results in a significant reduction of Haloperidol plasma levels. Therefore, during combination treatment, the Haloperidol dose should be adjusted, when necessary. After stopping such drugs, it may be necessary to reduce the dosage of Haloperidol.

Sodium valproate, a drug known to inhibit glucuronidation, does not affect Haloperidol plasma concentrations.

The psychotic symptoms in some patients have been exacerbated in association with these lowered Haloperidol levels but in some instance increased efficacy was seen, possibly as a result of the central action of carbamazepine itself. The mechanism for this interaction is thought to be enzyme induction and increased hepatic metabolism of Haloperidol.

Effect of Haloperidol on Other Drugs

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 (sedation, mental disturbances), when combined with methyldopa, has also been reported.

Haloperidol may antagonise the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure-lowering effects of adrenergic-blocking agents such as guanethidine.

Haloperidol may impair the antiparkinson effects of levodopa.

Haloperidol is an inhibitor of CYP 2D6. Haloperidol inhibits the metabolism of tricyclic antidepressants, thereby increasing plasma levels of these drugs.

Other Forms of Interaction

Severe neuromuscular symptoms with impairment of consciousness and fever have been reported with combined use of lithium and Haloperidol. A causal relationship has not been established. However, patients receiving such combined therapy should be carefully observed for early evidence of neurological toxicity and treatment should be discontinued if such signs appear.

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.

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.

Co-administration of indometacin with Haloperidol could cause severe drowsiness and confusion.

Haloperidol should be used in caution in patients known to be slow metabolisers of CYP2D6, and concomitant use of antipsychotics should be avoided during the use of cytochrome P450 inhibitors.

4.6 Fertility, pregnancy and lactation

Pregnancy:

The safety of Haloperidol in pregnancy has not been established. There is some evidence of harmful effects in some but not all animal studies. Neonates exposed to antipsychotic drugs (including Haloperidol) during the third trimester of pregnancy are at risk of adverse effects including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

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. Haloperidol 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.

Lactation:

Haloperidol has been detected in breast milk. There have been isolated cases of extrapyramidal symptoms in breast-fed children. If use of Haloperidol is considered essential, breast feeding should be discontinued.

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

The data provided below covers all haloperidol formulations including the Haloperidol Decanoate formulations.

The safety of Haloperidol was evaluated in 284 haloperidol-treated subjects who participated in 3 placebo-controlled, and in 1295 haloperidol-treated subjects who participated in sixteen double-blind active comparator-controlled clinical trials. The safety of Haloperidol decanoate was evaluated in 410 subjects who participated in 3 comparator trials (one comparing haloperidol vs. fluphenazine and two comparing the decanoate formulation to the oral formulation), 9 open label trials and 1 dose responsive trial. Based on pooled safety data from these clinical trials, the most commonly reported (% incidence) Adverse Drug Reactions (ADRs) were: Extrapyramidal disorder (34), Insomnia (19), Agitation (15), Hyperkinesia (13), Headache (12), Psychotic disorder (9), Depression (8), Weight increased (8), Orthostatic hypotension (7) and Somnolence (5).

Including the above mentioned ADRs, the following ADRs have been observed from clinical trials and post-marketing experiences reported with the use of Haloperidol and Haloperidol Decanoate. Frequencies displayed use the following convention:

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); very rare (<1/10,000), not known (cannot be estimated from the available data).

System Organ Class

Adverse Drug Reactions

Frequency Category

Very

Common

(> 1/100 to

Uncommon

(> 1/1,000 to

Rare

(> 1/10,000

Not Known

	(> 1/10)	< 1/10)	<1/100)	to <1/1,000)
Blood and lymphatic System Disorders			Leukopenia		Agranulocyt osis; Neutropenia 9 Pancytopeni a; Thrombo cytopenia
Immune System Disorders			Hypersensitiv ^ity		Anaphylacti c reaction
Endocrine Disorders				Hyper- prolactinae mia	Inappropriat e antidiuretic hormone secretion
Metabolic and Nutritional Disorders					Hypoglycae mia
Psychiatric Disorders	Agitation; Insomnia	Depression 9 Psychotic disorder	Confusional state; Libido Decreased; Loss of libido; Restlessness
Nervous System Disorders	Extrapyra midal disorder; Hyperkine sia; Headache	Tardive dyskinesia; Oculogyric Crisis; Dystonia; Dyskinesia 9 Akathisia; Bradykines ia; Hypokinesi a; Hypertonia 9 Somnolenc e; Masked Facies, Tremor; Dizziness	Convulsion; Parkinsonism 9 Akinesia; Cogwheel rigidity; Sedation; Muscle Contractions Involuntary	Motor dysfunction 9 Neuroleptic malignant syndrome; Nystagmus;

Eye Disorders	Visual disturbance 9	Vision blurred
Cardiac Disorders		Tachycardia		Ventricular Fibrillation; Torsade de pointes; Ventricular Tachycardia 9 Extrasystole s
Vascular Disorders	Orthostatic Hypotensio n; Hypotensio n
Respiratory, thoracic and mediastinal Disorders		Dyspnoea	Bronchospa sm	Laryngeal Oedema; Laryngospas m
Gastrointest inal Disorders	Constipatio n; Dry mouth; Salivary hypersecret ion; Nausea; Vomiting
Hepatobiliar y Disorders	Liver function test abnormal	Hepatitis; Jaundice		Acute Hepatic Failure; Cholestasis
Skin and subcutaneou s tissue disorders	Rash	Photosensitiv ^ity Reaction; Urticaria; Pruritis; Hyperhidrosi s		Leukocytocl astic Vasculitis; Dermatitis Exfoliative
Musculoskel etal and Connective Tissue Disorders		Torticollis; Muscle rigidity; Muscle Spasms; Musculoskele tal stiffness	Trismus; Muscle Twitching
Renal and	Urinary

Urinary Disorders	retention
Pregnancy, Puerperium and Perinatal Conditions				Drug withdrawal syndrome neonatal (see section 4.6)
Reproductiv e System and Breast Disorders	Erectile dysfunctio n	Amenorrhoea 9 Dysmenorrho ea; Galactorrhoe a; Breast Discomfort; Breast Pain;	Menorrhagi a; Menstrual Disorder; Sexual Dysfunctio n	Gynaecoma stia, Priapism
General Disorders and Administrati on Site Conditions		Gait disturbance; Hyperthermia 9 Oedema		Sudden Death; Face Oedema; Hypothermi a
Investigatio ns	Weight increased; Weight decreased		Electrocardi ogram QT prolonged

Additional Information

Cardiac effects such as QT-interval prolongation, torsade de pointes, ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia), and cardiac arrest have been reported. These effects may occur more frequently with high doses, and in predisposed patients.

Toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported in patients taking haloperidol. The true incidence of these reports is not known.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs- Frequency unknown.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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.

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.

Extrapyramidal reactions may include muscular weakness or rigidity and a generalised or localised tremor. With accidental overdosage hypothermia, bradycardia, sinus arrhythmia and hypertension have been reported in young children.

Treatment:

No specific antidote has been identified. In the event of overdosage the stomach should be emptied by aspiration and lavage. Emetics should not be used. Establishment of patent airway and artificial ventilation may be needed. Hypotension may be counteracted by placing the patient in the head-down position and by the use of a plasma expander and careful use of a vasopressor agent such as noradrenaline. 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.

Severe extrapyramidal reactions should be treated with parenteral antihistamines or antiparkinsonian drugs. The relatively long plasma elimination half-life of Haloperidol should be considered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Haloperidol is a butyrophenone. 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. Its pharmacological profile of activity includes a pronounced capacity to induce extrapyramidal reactions and a low incidence of autonomic side-effects, such as hypotension.

5.2 Pharmacokinetic properties

Haloperidol is absorbed rapidly with 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 metabolism.

Haloperidol is rapidly distributed to extravascular tissues especially liver and adipose tissue. It is approximately 92% bound to plasma proteins.

Haloperidol is extensively metabolised by oxidative dealkylation and ultimately conjugated with glycine. Half-life is approximately 20 hours.

The pharmacokinetics of haloperidol have been studied in healthy volunteers and patients. In volunteers, following a single intravenous or oral dose, serum elimination half-life ranged from 10-19 hours and 12-38 hours respectively. Similar elimination half-lives were observed in patients after administration of a single oral or intramuscular dose of the drug or after withdrawal of the drug from patients who were in a steady state. Steady state serum levels were usually achieved within 6 days on a fixed oral dosage.

5.3 Preclinical safety data

Only limited data are available, however these show no specific hazards apart from decreased fertility, limited teratogenicity as well as embryo-toxic effects in rodents.

Haloperidol has been shown to block the cardiac hERG channel in several published studies in vitro. In a number of in vivo studies intravenous administration of haloperidol in some animal models has caused significant QTc prolongation, at doses around 0.3 mg/kg i.v., giving Cmax plasma levels 3 to 7 times higher than the effective human plasma concentrations of 4 to 20 ng/ml. These intravenous doses which prolonged QTc did not cause arrhythmias. In some studies higher intravenous doses of 1 to 5 mg/kg haloperidol i.v. caused QTc prolongation and/or ventricular arrhythmias at Cmax plasma levels 19 to 68 times higher than the effective human plasma concentrations.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

Propylene Glycol BP Methyl Hydroxybenzoate BP Propyl Hydroxybenzoate BP Lactic Acid BP Purified Water BP

6.2

Incompatibilities

None.

6.3 Shelf Life

3 years

6.4 Special Precautions for Storage

Store between 15°C and 25°C. Protect from light.

6.5 Nature and Contents of Container

Amber glass bottles with ROPP closures containing 100ml or 500ml.

6.6 Special precautions for disposal

No special instructions

7 MARKETING AUTHORISATION HOLDER

Norton Healthcare Ltd Ridings Point,

Whistler Drive,

Castleford,

West Yorkshire,

WF10 5HX

8. MARKETING AUTHORISATION NUMBER

PL 0530/0374

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

DATE OF REVISION OF THE TEXT

08/09/2014