SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Chlorpromazine 25 mg/5 ml Solution.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Chlorpromazine solution contains 0.5% w/v Chlorpromazine Hydrochloride (25 mg Chlorpromazine Hydrochloride in 5 ml).

For excipients, see 6.1

3. PHARMACEUTICAL FORM

Oral Solution

Chlorpromazine solution is a clear orange colour.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Chlorpromazine is a phenothiazine neuroleptic. It is indicated in the treatment of schizophrenia, other psychoses (in particular paranoid) mania and hypomania. It is also indicated in the treatment of anxiety, psychomotor agitation, excitement, violent or dangerously impulsive behaviour. Chlorpromazine is used as an adjunct in the short term treatment of the following conditions, intractable hiccup, nausea and vomiting of terminal illness (only administered when other drugs have failed or are not available), childhood schizophrenia and autism.

4.2 Posology and method of administration

For oral administration. Initial dosage should be low and gradually increased until the optimal dosage for the patient is achieved. Patients should be under close supervision at the start of treatment until their optimal dosage has been reached. Individual patient dosage varies considerably and the optimum dosage may vary according to the formulation.

Dosage of Chlorpromazine in:

Schizophrenia, other psychoses, anxiety, childhood schizophrenia and autism

Adult	Children under 1 year	Children 1-under 6 years	Children 6-12 years	Elderly or debilitated patients
Initially 25mg three times a day or 75mg at bedtime increasing the daily amounts of 25mg to an effective maintenance dose. This is usually between 75mg and 300mg daily, but some patients may require up to 1g per day.	Do not use unless need is life saving.	0.5mg/kg bodyweight every 4-6 hours to a maximum recommended dose of 40mg daily.	1/3 to / of adult dose /to a maximum recommended daily dose of 75mg.	Start with 1/3 to / of the usual adult dose with a more gradual increase in dosage.
Hiccup
Adult	Children under 1 year	Children 1-under 6 years	Children 6-12 years	Elderly or debilitated patients
25 -50mg three times a day or four times a day	No information available	No information available	No information available	No information available
NAUSEA AND VOMITING OF TERMINAL ILLNESS
Adults	Children under 1 year	Children 1 -under 6 years	Children 6-12 years	Elderly or debilitated patients
10-25mg every 4-6 hours	Do not use unless need is life saving	0.5mg/kg of bodyweight every 4-6 hours. Maximum daily dosage should not	0.5mg/kg of bodyweight every 4-6 hours. Maximum daily dose should not exceed 75mg.	Initially V3 to / the adult dose. The physician should then use his clinical judgement to obtain control.

4.3 Contraindications

None stated.

4.4    Special warnings and precautions for use

Chlorpromazine should not be used in patients with a known sensitivity to phenothiazines or with a history of narrow angle glaucoma. Chlorpromazine should be avoided in patients with hepatic or renal dysfunction, epilepsy, Parkinson’s disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis and prostate hypertrophy. Chlorpromazine should be used with caution in the elderly, particularly in extreme hot or cold weather, as there is a risk of hyperthermia and hypothermia. Also elderly patients are particularly susceptible to postural hypotension.

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.

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 Chlorpromazine and preventive measures undertaken.

Increased Mortality in Elderly people with Dementia Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

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

4.5    Interaction with other medicinal products and other forms of interaction

Alcohol, barbiturates and other sedatives may additively increase the CNS depressant effects of chlorpromazine and other neuroleptic agents. Respiratory depression may occur. Chlorpromazine may exaggerate the hypotensive effects of most antihypertensive drugs especially alpha adrenoceptor blocking agents. Chlorpromazine has mild anticholinergic effects, which may enhance

other anticholinergic drugs, which may lead to constipation, heat stroke etc. The action of some drugs may be opposed by chlorpromazine, these include; amphetamine, levodopa, clonidine, guanethidine and adrenaline. The antipsychotic effect of chlorpromazine may be reduced by anticholinergic agents. Some drugs interfere with neuroleptic agent absorption, these include; antacids, anti-Parkinson’s, lithium. Increases or decreases in the plasma concentrations of a number of drugs e.g. propranolol, phenobarbitone have been observed but are of no clinical significance. High doses of chlorpromazine reduce the response to hypoglycaemic agents, in which case the dosage of the hypoglycaemic agent may need to be increased. There have been documented adverse clinically significant interactions with alcohol, guanethidine and hypoglycaemic agents. Adrenaline must not be used in the event of an overdosage of chlorpromazine. Other interactions are theoretical in nature and not serious. Concurrent administration of desferrioxamine and prochlorperazine has been observed to induce a transient metabolic encephalopathy, which is characterised by a loss of consciousness for about 48-72 hours. It is possible that chlorpromazine may induce this effect as it has a lot of similar pharmacological properties of prochlorperazine.

4.6    Fertility, pregnancy and lactation

There is inadequate evidence of the safety of chlorpromazine use during pregnancy but it has been widely used for several years without any apparent ill effects. There is evidence of harmful effects in animal studies. Chlorpromazine should not be administered during pregnancy unless considered essential by a physician. Chlorpromazine may prolong labour and therefore use should be avoided until the cervix is 3-4cm dilated. The possible adverse effects of chlorpromazine on the foetus are lethargy or paradoxical hyperexcitability, tremor or low apgar score. Chlorpromazine is excreted in breast milk and therefore breastfeeding is not recommended while being treated with chlorpromazine.

Neonates exposed to antipsychotics includeing Chlorpromazine during the third trimester of pregnancy are at risk of adverse reactions 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

4.7    Effects on ability to drive and use machines

Drowsiness may occur during the initial days of treatment, therefore patients should be warned not to drive or operate machinery until these effects have ceased.

4.8 Undesirable effects

Chlorpromazine may cause some minor side effects, which are nasal stuffiness, dry mouth, insomnia and agitation.

System Organ Class:    Pregnancy, puerperium and perinatal

conditions.

Adverse Drug Reaction/Frequency: Drug withdrawal syndrome neonatal (see 4.6) / not known.

Allergic phenomena such as angioedema, bronchospasm and urticaria have occurred with phenothiazines but anaphylactic reactions have been exceedingly rare.

Liver Effects: Jaundice, which is usually transient, occurs in a very small percentage of patients. A warning sign of this may be a sudden onset of fever one to three weeks into the treatment. This is followed by the development of jaundice. Chlorpromazine jaundice has the biochemical and other properties of obstructive jaundice which is associated with the obstruction of the canaliculi by bile thrombi; the frequent presence of eosinophilia indicates the allergic nature of this phenomenon. Treatment should cease on the development of jaundice.

Skin and Eyes: There have been rare occurrences of skin sensitisation in those who have frequently handled chlorpromazine. Great care should be taken to avoid contact of chlorpromazine with the skin. Skin rashes of various kinds have been reported in patients on chlorpromazine. There have been cases of patients who are on high dosages developing photosensitivity in sunny weather and they should avoid exposure to direct sunlight. Ocular changes and the appearance of a greyish metallic mauve coloration of exposed skin have been reported in some patients, mainly females who have been receiving chlorpromazine continuously for long periods of time (4-8 years).

Cardiorespiratory: Hypotension, usually postural commonly occurs. The elderly or volume depleted patients are particularly susceptible, it is most likely to occur after intramuscular administration. Cardiac arrhythmia’s including atrial arrhythmia, A-V block, ventricular tachycardia and fibrillation have been observed during neuroleptic therapy, possibly related to the dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressent may predispose. There have been reports of ECG changes, which are usually benign; these include widening of the QT interval, ST depression, U-waves and T-wave changes. Respiratory depression should not be ruled out in susceptible patients.

Blood picture: 30% of patient’s on prolonged high doses showed mild leucopenia. Rarely agranulocytosis may occur but this is not dose related. In the event of unexplained infections or fever, an immediate haematological investigation should be carried out.

Extrapyramidal effects: In children and young adults acute dystonias or dyskinesias, which is usually transitory, have been reported. These usually occur within the first 4 days of starting treatment or after a dosage increase. Akathisia characteristically occurs after a large initial dose. In adults and the elderly Parkinsonism has been reported. It usually develops after weeks or months of treatment. The following are a list of warning signs, tremor, ridgity, akinesia or other features of Parkinsonism. Most common sign is just tremor.

Tardive dyskinesia: can occur after prolonged high dosage. It can even occur after termination of treatment with Chlorpromazine. Therefore dosage should be kept low wherever possible.

Endocrine: Hyperprolactinaemia, which may result in galactorrhoea, gynaecomastia, amenorrhoea and impotence.

Neuroleptic Malignant Syndrome: Hyperthermia, rigidity, autonomic dysfunction and altered consciousness, which may occur with any neuroleptic.

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 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 Website :www.mhra. gov.uk/yellowcard

4.9 Overdose

The symptoms of Chlorpromazine overdose are drowsiness or loss of consciousness, hypotension, Tachycardia, ECG changes, ventricular arrhythmia’s and hypothermia. Severe extrapyramidal dyskinesias can occur. For up to 6 hours after ingestion of a toxic dose of Chlorpromazine, gastric lavage may be attempted. Pharmacological induction of emesis is unlikely to be of any benefit. Activated charcoal should be given. There is no specific antidote for Chlorpromazine. Supportive therapy should be applied. Raising the patients legs may be helpful in the prevention of circulatory collapse due to generalised vasodilation. In severe cases of overdose, volume expansion by intravenous fluids may be needed (Note infusion fluids should be warmed before administration so as not to aggravate hypothermia). If circulatory collapse occurs positive inotropic agents such as dopamine may be tried if fluid replacement is unsuccessful. Peripheral vasoconstriction agents are not generally administered, the use of adrenaline should be avoided. Ventricular or supraventricular tachyarrhythmia usually respond to the restoration of body temperature and the correction of circulatory or metabolic disturbances. If the arrhythmia is life threatening or persistent, appropriate anti-arrhythmic therapy may be considered. Avoid the use of Lignocaine and, as far as possible any long acting anti-arrhythmic drugs. Pronounced central nervous system depression requires airway maintenance or in extreme cases assisted respiration. Severe dystonic reactions usually respond to treatment with procyclidine (5-10mg) or orphenadrine (20-40mg) administered intravenously or intramuscularly. Convulsions should be treated with intravenous diazepam. Neuroleptic, malignant syndrome should be treated by cooling. Dantrolene sodium may be tried.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Chlorpromazine is a phenothiazine neuroleptic. N05A A01

5.2 Pharmacokinetic properties

Chlorpromazine is rapidly absorbed and widely distributed in the body. It is metabolised in the liver and excreted in the urine and in the bile. Although the plasma concentrations of Chlorpromazine decline rapidly the excretion of Chlorpromazine metabolites from the body is very slow. Chlorpromazine is highly bound to plasma proteins. It readily diffuses across the placental barrier and small quantities have been detected in breastmilk. Children require smaller dosages than adults.

5.3 Preclinical safety data

There is no additional preclinical safety data of relevance to the prescriber other than that already mentioned in the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Hydroxyethylcellulose Glycerol (E422)

Sorbitol 70% Hydrochloric Acid Aspartame

Citric Acid Monohydrate Sunset Yellow (E110) Polysorbate 20 Ethanol 96%

Star Anise Oil Sodium Benzoate Purified Water

6.2 Incompatibilities

None Stated

6.3 Shelf-Life

Shelf life of medicinal product as packaged for sale:

4 years unopened.

Shelf life after opening the container:

Once opened the solution must be used within 1 month.

6.4 Special Precautions for Storage

Do not store above 25° C. Keep container in the outer carton.

6.5 Nature and Content of Container

Packs sizes of 100ml, 150ml and 200ml.

Type III amber glass bottles or High Density Polyethylene bottles with aluminium screw cap, polypropylene tamper evident screw cap or child resistant closure.

6.6 Instructions for Use, Handling and Disposal

This solution should be handled with care as there is a risk of contact sensitization.

Pinewood Laboratories Limited, Trading as Pinewood Healthcare.

Ballymacarbry

Clonmel

Co. Tipperary

8.    MARKETING AUTHORISATION NUMBER

PL 04917/0036

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/03/2009

10    DATE OF REVISION OF THE TEXT

30/04/2015