Chloractil 10mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
CHLORACTIL/Chlorpromazine HC1
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Chlorpromazine HC1 BP 10.00 mg
3 PHARMACEUTICAL FORM
Film-Coated Tablet
White, film-coated, biconvex, odourless tablets, plain on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Schizophrenia and other psychoses (especially paranoid), mania and hypomania. In anxiety psychomotor agitation excitement, violent or dangerously impulsive behaviour. Is used as an adjunct in the short term management of these conditions.
Intractable hiccup.
Nausea and vomiting of terminal illness (where other drugs have failed or are not available).
Induction of hypothermia is facilitated by chloractil which prevents shivering causes vasodilatation.
Childhood schizophrenia and autism.
4.2 Posology and method of administration
Dosages should be low to begin with and gradually increased under close supervision until the optimum dosage for the individual is reached.
Individuals vary considerably and the optimum dose may be affected by the formulation used.
Dosage of chlorpromazine in schizophrenia, other psychoses, anxiety and agitation etc.
Adult:
Initially 25 mg t.d.s. or 75 mg at bedtime increasing by daily amounts of 25 mg to an effective maintenance dose. This is usually in the range 75 to 300mg daily but some patients may require up to 1 g daily.
Children under 1 year:
Do not use unless need is life saving.
Children 1-5 years:
0.5 mg/kg body weight every 4-6 hours to a maximum recommended dose of 40mg daily.
Children 6-12 years:
V3 - 1/2 adult dose to a maximum recommended dose of 75 mg dally.
Elderly or debiltated patients:
Start with V3 - V2 usual adult dose with a more gradual increase in dosage.
Hiccups
Adult:
25-50 mg t.d.s. or q.d.s.
Children under 1 year:
No information available.
Children 1-5 years:
No information available.
Children 6-12 years:
No information available.
Elderly or debilitated patients:
As for adults.
Nausea and vomiting of terminal illness: Adults:
10-25 mg every 4-6 hours.
Children under 1 year:
Do not use, unless need is life saving.
Children 1-5 years:
0.5 mg/kg every 4-6 hours. Maxhnum daily dosage should not exceed 40 mg. Children 6-12 years:
0.5 mg/kg every 4-6 hours. Maximum.daily dosage should not exceed 75 mg. Elderly or debilitated patients:
Initially V3 - V2 adult dose. The physician should then use his clinical judgment to obtain control.
Method of administration: Oral.
4.3 Contraindications
Chloractil should be avoided in patients with liver or renal dysfunction, epilepsy, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostate hypertrophy. It should be avoided in patients known to be hyper-sensitive to phenothiazines or with a history of narrow angle glaucoma. It should be used with caution in the elderly, particularly during very hot or very cold weather, (risk of hyper/hypothermia).
4.4 Special warnings and precautions for use
Blood Dyscrasias: Agranulocytosis has been reported rarely, most commonly in the first three months of treatment, but occasionally later. Blood counts should be performed if the patient develops signs of a persistent infection. Transient leucopenia can also occur. Other blood dyscrasias including thrombocytopenia and haemolytic anaemia have occurred very rarely.
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
Chlorpromazine commonly causes increased susceptibility to sunburn and patients should be warned to avoid excessive exposure. Phototoxic or photoallergic reactions may occur. Various skin rashes and reactions, including exfoliative dermatitis and erythema multiforme have been reported. Contact skin sensitivity may be produced by contact with chlorpromazine.
The occurrence of antinuclear antibodies has been reported. SLE has very rarely occurred. Chlorpromazine impairs body temperature regulation and cases of severe hypothermia or hyperpyrexia have been reported, usually in association with moderate or high dosage. The elderly or hypothyroid patient may be particularly susceptible to hypothermia. The hazard of hyperthermia may be increased by especially hot or humid weather or by drugs, such as anti-Parkinson agents, which impair sweating. It has also been reported after intramuscular injections of chlorpromazine.
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.
Chlorpromazine can rarely cause obstructive jaundice associated with stasis in billiary canaliculi. It has been thought to be a hypersensitivity reaction and some cases have shown premonitory fever and associated eosinophilia. It has normally been reversible on stopping the drug, but extremely rare cases of progressive liver disease have been reported. In most cases the jaundice has appeared between one to four weeks after the start of the treatment. Chlorpromazine treatment should be withdrawn and not given again.
Transient abnormalities of liver function tests may occur in the absence of jaundice.
Faecal impaction, severe paralytic ileus or megacolon have been reported.
The signs of intestinal obstruction may be obscured by the anti-emetic action of chlorpromazine.
With long term usage, chlorpromazine can cause increased melanin pigmentation of the skin, which eventually may develop a bluish-grey colouration. Pigment deposits also occur in the eye and other tissues. Permanent deposits, leading to impairment of vision, may develop in the lens. Epithelial keratopathy has been reported. Toxic pigmentary retinopathy, which may cause progressive loss of vision has occurred very rarely, with excessively high doses. Acute withdrawal symptoms including nausea, vomiting and insomnia have rarely been described after abrupt cessation of high doses of chlorpromazine. Gradual withdrawal is advisable.
Anti-Parkinson agents should not be prescribed routinely, because of the possible risks of aggravating anticholinergic side effects of chlorpromazine, of precipitating toxic-confusional states or of impairing its, therapeutic efficacy. They should only be given as required.
The elderly are especially susceptible to the sedative and hypotensive effects of Chloractil.
4.5 Interaction with other medicinal products and other forms of interaction
The CNS depressant actions of Chloractil and other neuroleptic agents may be intensified (additively) by alcohol, cimetidine, opioid analgesics, barbiturates and other sedatives. Respiratory depression may occur. The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by Chloractil. The mild anticholinergic effect of Chloractil may be enhanced by other anticholinergic drugs possibly leading to constipation, heat stroke etc.
Phenothiazines enchance the hypotensive effect of anaesthetics and calcium channel blockers. Severe postural hypotension may occur with concomitant administration of chlorpromazine and ACE inhibitors.
The action of some drugs may be opposed by Chloractil; these include antiepileptics, amphetamine, levodopa, clonidine, guanethidine, adrenaline.
Anticholinergic agents may reduce the antipsychotic effect of Chloractil.
Some drugs interfere with absorption of neuroleptic agents; antacids, anti-Parkinson, lithium. Increases or decreases in the plasma concentrations of a number of drugs, e.g. propanolol, phenobarbitone have been observed but were not of clinical significance. Phenothiazines increase the risk of ventricular arrhythmias with drugs that prolong the QT interval such as sotalol.
The serum concentration of chlorpromazine may be incresed by some antimalarial agents.
High doses of Chloractil reduce the response to hypoglycaemic agents the dosage, of which might have to be raised.
Documented adverse clinically significant interactions occur with alcohol, guanethidine and hypoglycaemic agents. Adrenaline must not be used in patients overdosed with Chloractil. Other interactions are of a theoretical nature and not serious.
4.6 Fertility, Pregnancy and lactation
There is inadequate evidence of the safety of Chloractil in human pregnancy but it has been widely used for many years without apparent ill consequence. There is evidence of harmful effects in animals. Like other drugs it should be avoided in pregnancy unless the physician considers it essential.
Neonates exposed to antipsychotics (including 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, somnolence, respiratory distress or feeding disorder. Consequently, newborns should be monitored carefully.
It may occasionally prolong labour and at such a time should be withheld until the cervix is dilated 3-4 cm. Other possible adverse effects on the foetus include lethargy or paradoxical hyperexcitability, tremor and low Apgar score. Chloractil being excreted in milk, breast-feeding should be suspended during treatment.
4.7 Effects on ability to drive and use machines
Patients should be warned about drowsiness during which the early days of treatment, and advised not to drive or operate machinery.
4.8 Undesirable effects
Common side effects, particularly with higher dosage and at the start of treatment include drowsiness, sedation, dry mouth, nasal stuffiness.
Dose related postural hypotension may occur, particularly in the elderly and after intramuscular injections.
Other dose-related antichlorinergic-type side effects include blurring of the vision, tachycardia, constipation, and urinary hesitancy or retention.
Chlorpromazine may impair alertness, especially at the start of the treatment. These effects may be potentiated by alcohol.
Extrapyramidal reactions in the form of acute dystonias, parknsonian rigidity, tremor or akinesia, akathisia and oculogyric crises may occur, and are common on moderate to high dosage.
Tardive dyskinesia may occur during administration or withdrawal of Chlorpromazine and other neuroleptic drugs. This syndrome is common among patients treated with moderate to high doses of antipsychotic drugs for prolonged periods of time and may prove irreversible, particularly in patients over the age of 50. It is unlikely to occur in the short-term when low or moderate doses of chlorpromazine are used as recommonded, but since its occurrence may be related to duration of treatment as well as daily dose, chlorpromazine should given in the minimal effective dose for the minimum possible time, unless it is established that long-term administration for the treatment of schizophrenia is required. The potential seriousness and unpredictability of tardive dyskinesia and the fact that it has occasionally been reported to occur when neuroleptic antipsychotic drugs have been prescribed for relatively short periods in low dosage means that the prescribing of such agents requires especially careful assessment of risks versus benefit. Tardive dyskinesia can be precipitated or aggravated by anti-Parkinson drugs. Shortlived dyskinesias may occur after abrupt drug withdrawal. 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.
Neuroleptic malignant syndrome is rare but may occur with any neuroleptic. Chlorpromazine, even in low dosage in susceptible (especially non-psychotic) individuals, may cause unpleasant subjective feelings of being mentally dulled or slowed down, nausea, dizziness, headache, or paradoxical effects of excitement, agitation, or insomnia. Confusional states or epileptic fits can occur. The effects of chlorpromazine on the heart are dose related. ECG changes, with prolongation of the QT interval and T-wave changes have been commonly reported in patients treated with moderate to high dosage; they are reversible on reducing the dose. In a small number of cases, they have been reported to precede serious arrhythmias, including ventricular tachycardia and fibrillation, which have occurred after overdosage.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs- Frequency unknown.
Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia which may cause galactorrhoea, gynaecomastia and oligo- or amenorrhoea.
Sexual function, including erection and ejaculation is sometimes impaired by chlorpromazine. Weight gain is common.
Pregnancy, puerperium and perinatal conditions: drug withdrawal syndrome neonatal (see 4.6), Frequency: not known.
Oedema has been reported. These effects may be prevented by reduction in dosage. Raised serum cholesterol and, rarely, hyperglycaemia have been reported in association with phenothiazines.
4.9 Overdose
Symptoms of chlorpromazine overdosage include drowsiness or loss of consciousness, hypotension, tachycardia, E.C.G. changes, ventricular arrhythmias and hypothermia. Severe extra-pyramidal dyskinesias may occur.
If the patient is seen up to 6 hours after ingestion of a toxic dose, gastric lavage may be attempted. Induction of emesis is unlikely to be of any use. Activated charcoal should be given. There is no specific antidote. Treatment is supportive.
Generalised vasodilatation may result in circulatory collapse; raising the patient's legs may suffice, in severe cases, volume expansion by intravenous fluids may be needed; infusion fluids should be warmed before administration in order not to aggravate hypothermia.
Positive inotropic agents such as dopamine may be tried if fluid replacement is insufficient to correct the circulatory collapse. Avoid use of adrenaline. Cardiac monitoring should be immediately instituted and continued for at least 48 hours. Ventricular or supraventricular tacy-arrythmias usually respond to restoration of normal body temperature and correction of circulatory or metabolic disturbances. If persistent or life threatening, appropriate antiarrhythmic therapy may be considered. Avoid lignocaine and, as far as possible, long acting antiarrhythmic drugs.
Central nervous system depression requires airway maintenance or, in extreme circumstances, assisted respiration. Severe dystonic reactions usually respond to procyclidine (5-10 mg) or orphenedrine (20-40 mg) administered intramuscularly or intravenously. Convulsions should be treated with intravenous diazepam. Neuroleptic malignant syndrome should be treated with cooling. Dantrolene sodium may be tried.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Chlorpromazine has depressant actions on the Central Nervous System, with alpha-adrenergic blocking and anticholinergic activities. It inhibits Dopamine and Prolactin release-inhibitory factor, thus stimulating the release of Prolactin. It increases the turnover of Dapamine in the brain.
It has anti-emetic, anti-puritic, serotonin-blocking and weak anti-histamine properties and slight ganglion blocking activity. It inhibits the heat regulating centre in the brain, and is analgesic and can relax skeletal muscle.
Due to its action on the autonomic system it produces vasodilation, hypotension and tachycardia.
Salivary and gastric secretions are reduced.
5.2 Pharmacokinetic properties
Chlorpromazine is readily absorbed in the gastro-intestinal tract. It is subject to first pass metabolism in the gut wall. It is extensively metabolised in the liver and excreted in the urine and faeces. The plasma half-life is only a few hours but it has a prolonged terminal elimination phase of up to about 3 weeks. Chlorpromazine is extensively bound to plasma proteins.
Preclinical safety data
5.3
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core:
Lactose Maize Starch Povidone
Sodium starch glycollate Colloidal anhydrous silica Magnesium stearate
Coating:
Hydroxypropylmethyl cellulose 5/6 cps 2910 Ethylcellulose 10 cps Diethylphthalate Titanium dioxide
6.2 Incompatibilities
Chlorpromazine can increase the central nervous system depression produced by other CNS-depressant drugs including alcohol, hypnotics, sedatives or strong analgesics.
It antagonises the action of adrenaline and other sympathomimetic agents and reverses the blood pressure lowering effects of adrenergic blocking agents such guanethidine and clonidine. It may impair the metabolism of tricyclic antidepressants, the anti-Parkinson effects of levodopa and the effects of anticonvulsants; it may possibly affect the control of diabetes, or the action of anticoagulants. Antacids can impair absorption. Tea and coffee may prevent absorption by causing insoluble precipitates.
Undesirable anticholinergic effects can be enhanced by anti-Parkinson or other anticholinergic drugs. It may enhace the cardiac-depressant effects of quinidine, the absorption of corticosteroids and digoxin, the effect of diazoxide and of neuromuscular blocking agents. Interactions with propanolol have been reported. The possibility of interaction with lithium should be bone in mind.
Further information: Chlorpromazine is a phenothiazide with an alphatic side-chain. Its pharmacological profile of activity includes pronounced sedative and hypotensive properties, with fairly marked anticholinergic and anti-emetic activity and a moderate tendency to cause extrapyramidal reactions.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store below 25 °C in a dry place, protect from light, keep containers closed.
6.5 Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers with polypropylene or polythene lids and polyurethane/polythene wads. PVC/aluminium foil blister packs.
Pack sizes: 28, 30, 50 56, 60, 84,100, 250, 500, 1000, 5000
250 micron PVC glass-clear/green rigid PVC (pharmaceutical grade). 20 micron hard-tempered aluminium foil coated on the dull side with 6-7 gsm heat seal lacquer and printed on the bright side.
Pack sizes: 28, 30, 50 56, 60, 84,100, 250, 500, 1000, 5000
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited 11 Boumpoulinas,
Nicosia 1060,
Cyprus
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0129
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17 May 1988 / 16 November 1998
DATE OF REVISION OF THE TEXT
05/01/2016