INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo LARGACTIL

SCHEDULING STATUS
S5

PROPRIETARY NAME
(and dosage form):

LARGACTIL
Chlorpromazine

LARGACTIL 25 Tablets
LARGACTIL 50 Tablets
LARGACTIL 100 Tablets
LARGACTIL SYRUP
LARGACTIL 2 mL INJECTION

COMPOSITION:
LARGACTIL 25:                        each tablet contains
25 mg Chlorpromazine Hydrochloride.
LARGACTIL 50: each tablet contains
50 mg Chlorpromazine Hydrochloride.
LARGACTIL 100: each tablet contains
100 mg Chlorpromazine Hydrochloride.
LARGACTIL SYRUP: each 5 mL contains
25 mg Chlorpromazine Hydrochloride.
LARGACTIL 2 mL INJECTION each 2 mL contains
50 mg Chlorpromazine Hydrochloride.
Sodium sulphite 0,1% and
Sodium Metabisulphite 0,075% as anti-oxidants.

PHARMACOLOGICAL CLASSIFICATION:
A 2.6.1. Phenothiazines and their derivatives.

PHARMACOLOGICAL ACTION:
LARGACTIL has marked pharmacological activity affecting both the autonomic and central nervous systems.
It has a powerful peripheral anti-adrenaline action and also central effects which include depression of the vomiting and thermoregulating mechanisms, but it has comparatively low antihistamine activity. In addition to these intrinsic actions it enhances the effects of some central depressant drugs, including hypnotics, analgesics and anaesthetics.

INDICATIONS:
Chlorpromazine is used in the management of psychotic conditions. It controls excitement, agitation and other psychomotor disturbances in schizophrenic patients and reduces the manic phase of manic-depressive conditions. It is used to control hyperkinetic states and aggression and is sometimes given in other psychiatric conditions for the control of anxiety and tension. Chlorpromazine is an anti-emetic and is used to control vomiting. Chlorpromazine may be effective in the alleviation of intractable hiccups.

CONTRA-INDICATIONS:
Chlorpromazine is contra-indicated in patients with pre-existing CNS depression or coma, bone-marrow suppression or phaeochromocytoma.
It should be used with caution or not at all in patients with impaired liver, kidney, cardiovascular, cerebrovascular and respiratory function and in those with closed-angle glaucoma, parkinsonism, diabetes mellitus, hyperthyroidism, myasthenia gravis or prostatic hypertrophy.

WARNINGS:
Care is required in epileptic patients receiving anticonvulsant therapy as chlorpromazine may lower the seizure threshold. It should be avoided if possible in untreated epileptics.
The sedative effects of chlorpromazine are most marked during the first few days of administration; affected patients should not drive or operate machinery.
Syrup and Injection only:
Contact with the skin should be avoided to minimise the risk of dermatitis.

DOSAGE AND DIRECTIONS FOR USE:
Dosage varies with both the individual and the purpose for which the drug is being used.
Oral:
In most patients oral treatment may be used from the start. commencing with a dosage of 25 to 50 mg three times daily and increasing as necessary; daily doses of 75 mg may be given as a single dose at night. Lower doses (10 to 25 mg every 4 to 6 hours) may be sufficient in some cases, particularly for control of nausea and vomiting. Maintenance doses, when required, usually range from 25 to 100 mg three times daily, although psychotic patients may require daily doses of up to 1 g or more.
Parenteral:
DO NOT ADMINISTER SUBCUTANEOUSLY.
Deep intramuscular injection is the preferred route of administration. Intravenous injection is usually limited to severe hiccups; the injection must be diluted (normal saline solution) before intravenous administration.
After injection of chlorpromazine, patients should remain in the supine position for at least 30 minutes. The usual dose by injection is 25 to 50 mg repeated as required.
If intractable hiccups do not respond to 25 to 50 mg three or four times daily by mouth for 2 to 3 days then 25 to 50 mg should be administered intramuscularly. If this fails, 25 to 50 mg in 500 to 1 000 mL of sodium chloride injection should be infused slowly, with the patient supine, and with careful monitoring of the blood pressure.
Elderly and debilitated:
Initial doses of chlorpromazine of one-third to one-half the normal adult dose have been recommended for elderly and debilitated patients; doses should be increased more gradually.
Children:
Children may be given chlorpromazine hydrochloride in a dose of 500 micrograms per kg body mass every 4 to 6 hours by mouth or every 6 to 8 hours by intramuscular injection. For psychiatric indications the oral dose for children aged over 5 years is usually one-third to one-half of the adult dose.
Daily doses should not normally exceed 40 mg for children aged 1 to 5 years or 75 mg for children over 5 years of age.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Chlorpromazine has antimuscarinic properties and may cause adverse effects such as dry mouth, constipation, difficulty with micturition, blurred vision and mydriasis. Tachycardia, electrocardiographic changes (particularly Q- and T-wave abnormalities) and rarely, cardiac arrhythmias, may occur after administration of chlorpromazine. Hypotension (usually postural) is common. Other adverse effects include delirium, agitation and rarely, catatonic-like states, insomnia, depression, miosis, EEG changes and convulsions, nasal congestion, minor abnormalities in liver function tests, inhibition of ejaculation, impotence and priapism.
Hypersensitivity reactions include urticaria, exfoliative dermatitis, erythema multiforme and contact sensitivity. A syndrome resembling systemic lupus erythematosus has been reported. Jaundice has occurred, and probably has an immunological origin. Prolonged therapy may lead to deposition of pigment in the skin, or more frequently the eyes; corneal and lens opacities have been observed. Pigment retinopathy has occurred only rarely with chlorpromazine. Photosensitivity reactions also occur.
Various haematological disorders, including haemolytic anaemia, aplastic anaemia, thrombocytopenic purpura and a potentially fatal agranulocytosis have occasionally been reported in patients receiving phenothiazines; they may be manifestations of a hypersensitivity reaction. Most cases of agranulocytosis have occurred within 4 to 10 weeks of starting treatment and symptoms such as sore throat or fever should be watched for and white cell counts instituted should they appear. Mild leucopenia has been stated to occur in up to 30% of patients on prolonged, high dosage chlorpromazine.
Chlorpromazine may produce extrapyramidal dysfunction, probably as a result of its effects on central dopaminergic transmission. Resultant disorders include acute dystonia, a parkinsonism-like syndrome, and akathisia; late effects include tardive dyskinesia and perioral tremor. The neuroleptic malignant syndrome may also occur.
Chlorpromazine alters endocrine and metabolic functions. Patients have experienced amenorrhoea, galactorrhoea, gynaecomastia, mass gain and hyperglycaemia and altered glucose tolerance. Body temperature regulation is impaired and may result in both hypo- or hyperthermia, depending on environment.
There have been isolated reports of sudden death with phenothiazines; possible causes include cardiac arrhythmias or aspiration and asphyxia due to suppression of the cough and gag reflexes.
Pain and irritation at the injection site have been reported.
Mild symptoms resembling the withdrawal symptoms of dependence have been seen following the abrupt withdrawal of chlorpromazine from patients receiving prolonged maintenance therapy.
Special Precautions:
Symptoms of CNS depression may be enhanced by other drugs with CNS-depressant properties including alcohol, general anaesthetics, hypnotics and sedatives and opioid anaesthetics.
Chlorpromazine effects on the vomiting centre may mask the symptoms of overdosage of other agents, or of disorders such as gastro-intestinal obstruction. Administration at extremes of temperature may be hazardous since body temperature regulation is impaired by phenothiazines.
Regular eye examinations are advisable for patients receiving long-term chlorpromazine therapy and avoidance of undue exposure to direct sunlight is recommended. Haematological parameters should also be monitored periodically.
Chlorpromazine may prolong labour and should be withheld until the cervix is dilated 3 to 4 cm.
Patients should remain supine for at least 30 minutes after parenteral administration of chlorpromazine; blood pressure should be monitored.
Abrupt withdrawal of chlorpromazine therapy is best avoided.

INTERACTIONS:
The most common interactions encountered with chlorpromazine are adverse effects resulting from concomitant administration of agents with similar pharmacological actions. When given with other drugs that produce postural hypotension, dosage adjustments may be necessary. However, it should be noted that chlorpromazine has been reported to reduce the antihypertensive action of guanethidine and other adrenergic neurone blockers. As chlorpromazine possesses antimuscarinic actions, it may potentiate the adverse effects of other anti muscarinics, including the antimuscarinic, antiparkinsonian agents which may be given to treat phenothiazine-induced extrapyramidal effects. In theory, neuroleptics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic. Concomitant administration of metoclopramide may increase the risk of neuroleptic-induced extrapyramidal effects and anti-arrhythmics which prolong the QT interval may increase the likelihood of ventricular arrhythmias. CNS depression may be enhanced by drugs with similar activity.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See "Side-effects and Special Precautions" above.
Following recent ingestion of an overdose of chlorpromazine, the stomach must be emptied by gastric lavage and activated charcoal administered. Patients should be managed with intensive symptomatic and supportive therapy. Dialysis is of little or no value in poisoning by chlorpromazine.

IDENTIFICATION:
LARGACTIL 25: Circular, off-white or very pale cream, sugar coated tablets, approximately 4,25 mm thick and approximately 7,6 mm in diameter.
LARGACTIL 50: Circular, off-white or very pale cream, sugar coated tablets, approximately 5,4 mm thick and approximately 9,5 mm in diameter.
LARGACTIL 100: Circular, off-white or very pale cream, sugar coated tablets, approximately 6,0 mm thick and approximately 10,0 mm in diameter.
LARGACTIL SYRUP: A clean, bright or almost bright, dark brownish-orange liquid.
LARGACTIL 2 mL INJECTION: A colourless or almost colourless solution.

PRESENTATION:
Tablets of 25 mg, 50 mg and 100 mg in containers of 50 and 500.
Syrup in bottles of 100 mL.
Injections of 2 mL in packs of 10.

STORAGE INSTRUCTIONS:
Protect from light.
Store below 25°C.
Keep out of reach of children.

APPLICATION NUMBERS:
LARGACTIL 25:         B511 ]
LARGACTIL 50:         B512 ]
LARGACTIL 100:         B513 ] (Act 101/1965)
LARGACTIL Syrup:         B515 ]
LARGACTIL 2 mL Injection:         B1641 ]

NAME AND BUSINESS ADDRESS OF APPLICANT:
Aventis Pharma (Pty) Ltd.
2 Bond Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
July 1969

Aventis Pharma (Pty) Ltd
2 Bond Street
Midrand
1685       

LL2-A0001
Pro-Print

New addition to this site: December 2004
Source: Community Pharmacy

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004