INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
SPARINE* INJECTION
SPARINE* SYRUP

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

SPARINE* INJECTION
SPARINE* SYRUP

COMPOSITION:
SPARINE INJECTION: Each mL of parenteral SPARINE contains 50 mg promazine hydrochloride in water for injection with 3,6 mg sodium citrate, 0,75 mg citric acid and 1,0 mg sodium formaldehyde sulphoxylate (0,1 % ) as preservative.

SPARINE SYRUP: Each 5 mL contains 10 mg promazine hydrochloride in a flavoured syrup base with 0,25 % sodium benzoate and 0,25 % sodium propionate as preservatives.
Contains TARTRAZINE.

PHARMACOLOGICAL CLASSIFICATION:
Category A, 2.6.1. Phenothiazines and derivatives.

PHARMACOLOGICAL ACTION:
SPARINE (promazine) has actions at all levels of the central nervous system as well as on multiple organ systems. Its main actions are central sedation, potentiation of analgesics, anaesthetics, hypnotics and sedatives. It is also a potent antipsychotic and anti-emetic agent. The mechanism whereby its therapeutic action takes place is not known.

INDICATIONS:

1.	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.
2.	SPARINE (promazine) is anti-emetic and is used to control the nausea and vomiting of a variety of diseases and that caused by various drugs.
3.	For sedation in labour and as premedication for surgical or diagnostic procedures.
4.	Alcoholic hallucinosis.
5.	Alleviation of intractable hiccup.

CONTRA-INDICATIONS:
Promazine should not be used in comatose states due to central nervous system depressants (alcohol, barbiturates, opiates, etc.). In patients with cerebral arteriosclerosis, coronary heart disease, severe hypotension or other conditions where a drop in blood pressure may be undesirable, promazine should be used with caution.
Intra-arterial injection of promazine is contra-indicated.
Promazine is contra-indicated in patients known to be sensitive to promazine. Bone-marrow depression is also a contra-indication.

WARNINGS:
The use of alcohol should be avoided since there may be additive effects and hypotension.
The sedative effect of promazine is a desirable action under most circumstances; however, in certain cases the drug may cause undesirable drowsiness. Drowsiness will usually disappear on continued therapy or can be controlled by decreasing the dose.
Promazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery, especially during the first few days of therapy.
Care should be exercised during intravenous administration not to allow perivascular extravasation since under such circumstances chemical irritation may be severe.
Promazine when used intravenously, should be used in a concentration no greater than 25 mg per mL. The injection should be given slowly.
Usage in pregnancy:
Safe usage of promazine in the first trimester of pregnancy has not been established; therefore it should be given to these patients or women of child-bearing potential only when the expected benefits outweigh the possible hazards to mother and child.
Although allergic manifestations have been extremely rare with promazine, it is advisable to administer the drug with caution to patients who have shown an idiosyncrasy to other phenothiazine derivatives.
Promazine is not recommended for use in children under 12 years of age.
SPARINE SYRUP contains F. D. and C Yellow No 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of tartrazine-sensitivity in the general population is currently thought to be low, it is frequently seen in patients who also have aspirin-sensitivity.

DOSAGE AND DIRECTIONS FOR USE:
The amount, route of administration and frequency of dose should be governed by the severity of the condition treated and the response of the patient. For maximal therapeutic benefit dosage must be individualised for the patient. The oral route of administration should be used whenever possible, but when it is thought that the effect obtained by oral dosage would not produce a sufficient response, it may be given parenterally, as for instance when nausea, vomiting or lack of co-operation is evident.
The preferred parenteral route of administration is by intramuscular injection. In general, parenteral administration should be reserved for non-ambulatory patients, although acute states in ambulatory patients may also be treated by intramuscular injection provided proper precautions are taken to eliminate the possibility of postural hypotension. It is important to make sure that intramuscular injections are given deeply into large muscle masses, i.e., gluteal region.
The intravenous route of medication is not without hazards. Routine use of the intravenous route of administration is not recommended. When intravenous administration is deemed preferable, it should be reserved only for those patients who are hospitalized. Under no circumstances should intra-arterial injection be given.
The intravenous injection, when indicated, should be given slowly in diluted solutions (25 mg per mL or less). The whole contents of the syringe should be injected into the lumen of the vein and injections made only into vessels previously undamaged by multiple injections or trauma.
Mental and emotional disturbances:
The dosage of SPARINE (promazine) for acute and chronic mental disease will vary with the severity of the condition. In the management of severely agitated patients it is recommended that SPARINE (promazine) be given intramuscularly in initial doses of 50 mg to 150 mg, depending on the degree of excitation. In general these doses are sufficient, but if the desired calming effect is not apparent within 30 minutes, additional doses up to a total of 300 mg may be given. Once the desired control is obtained, SPARINE (promazine) SYRUP may be given orally. The oral or intramuscular dose is 10 mg to 200 mg at 4 to 6 hour intervals, depending on the response of the patient.
In less severe disturbances the dosage should be adjusted downward. Maintenance dosage may range from 10 mg to 200 mg given at 4 to 6 hourly intervals.
The degree of central nervous depression induced by SPARINE (promazine) has not been great; however, in the acutely inebriated patient, the initial dose should not exceed 50 mg to be sure that the depressant effect of alcohol is not enhanced.

NOTE:

THE PERCENTAGE OF EFFECTIVE RESULTS DOES NOT APPEAR TO BE MATERIALLY AFFECTED BY THE ADMINISTRATION OF DOSES IN EXCESS OF 800 MG TO 1 000 MG PER DAY. IT IS THEREFORE RECOMMENDED THAT THE TOTAL DAILY DOSE OF SPARINE (promazine) NOT EXCEED ONE (1) GRAM (1 000 MG).

Obstetrics:
SPARINE (promazine) may be given orally or intramuscularly at a dose of 25 mg to 100 mg early in labour to produce calmness in tense, agitated patients. If administered intravenously, an initial dose of 25 mg diluted with an equal volume of normal saline should be utilised.
Pethidine 50 to 100 mg intramuscularly may be administered together with SPARINE (promazine) to provide analgesia in labour.
Nausea vomiting and hiccup:
An initial dose of 50 to 100 mg should be given orally or intramuscularly, depending on the severity of the condition, and may be followed by a maintenance dose of 25 to 100 mg three times daily, if necessary.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Drowsiness:
The sedative effect of promazine is a desirable action under most circumstances. However, in certain cases the drug may cause undesirable drowsiness. Drowsiness will usually disappear on continued therapy or can be controlled by decreasing the dose.
Jaundice:
Overall incidence is low. This is generally regarded as a sensitivity reaction and usually occurs during the early weeks of therapy. The clinical picture resembles infectious hepatitis, but the liver function test results mimic those of hepatic obstruction. There is no conclusive evidence that pre-existing liver disease makes patients more susceptible to jaundice. It is usually reversible on withdrawal of the phenothiazine, though chronic jaundice has been reported.
Haematologic disorders:
Include agranulocytosis, eosinophilia, leucopenia, haemolytic anaemia, thrombocytopenic purpura, and pancytopenia, though rare, have been reported.
Agranulocytosis:
Most cases have occurred between the 4th and 10th week of therapy. Patients should be watched closely during that period for the sudden appearance of signs of infection, such as sore throat. If white-blood-cell count and differential smears give an indication of significant cellular depression, discontinue the drug and start appropriate therapy. However, a slightly lowered white count in itself is not necessarily an indication for immediate discontinuance of the drug.
Cardiovascular:
TRANSITORY POSTURAL HYPOTENSION HAS BEEN NOTED IN A FEW PATIENTS, USUALLY FOLLOWING THE FIRST PARENTERAL DOSE, PARTICULARLY WHEN GIVEN INTRAVENOUSLY AND RELATED TO THE RATE OF ADMINISTRATION. WHEN THIS HAPPENED, RECOVERY WAS SPONTANEOUS AND THE SYMPTOMS OF WEAKNESS AND DIZZINESS DISAPPEARED. RARELY, PARTICULARLY IN ALCOHOLICS, THE DOSAGE HAD TO BE DECREASED OR THE DRUG DISCONTINUED. IT IS DESIRABLE TO KEEP PATIENTS UNDER OBSERVATION (PREFERABLY IN BED) FOR A SHORT TIME AFTER THE INITIAL DOSE.
Should hypotension occur it can usually be controlled by placing the patient in recumbent position with head lowered and the legs elevated. Administration of oxygen may also be advisable. Occasionally, the effects are severe and prolonged, producing a shock-like condition.
IF IT IS DESIRABLE TO ADMINISTER A VASOPRESSOR DRUG, NORADRENALINE APPEARS TO BE THE MOST SUITABLE. ADRENALINE SHOULD NOT BE USED BECAUSE PROMAZINE HYDROCHLORIDE MAY REVERSE ITS ACTION, CAUSING A FURTHER LOWERING OF BLOOD PRESSURE INSTEAD OF ITS USUAL ELEVATING EFFECT.
ECG changes, nonspecific and usually reversible, have been observed in some patients receiving phenothiazines. The relationship to myocardial damage has not been confirmed. When the patient's blood pressure has returned to normal, promazine therapy may be resumed at a lower dosage level.
CNS effects:
Extrapyramidal symptoms, including pseudoparkinsonism, dysarthria, and dyskinetic disturbances, have been reported following the use of large doses of promazine, as in hospitalized mental patients. These symptoms are reversible and may be managed by reducing the dose or the addition of antiparkinsonism drug - if severe, promazine therapy should be discontinued.
In rare instances, persistent dyskinesia, usually involving the face, tongue and jaw, has been reported to be irreversible, particularly in elderly patients with previous brain damage. Hyperreflexia has been reported in the newborn when a phenothiazine was used during pregnancy.
Adverse behavioural effects:
Paradoxical exacerbation of psychotic symptoms.
Other CNS effects:
Cerebral oedema, abnormality of CSF protein, convulsive seizures, particularly in patients with EEG abnormalities or a history of seizures.
Allergic reaction:
Allergic skin reactions, including dermatitis, dry skin, and oedema, have been reported in rare instances during the use of promazine. The incidence is considerably lower than that reported for chlorpromazine.
Mild urticaria and photosensitivity are seen. To minimize, avoid undue exposure to sunlight. Nursing personnel sensitive to phenothiazines should exercise caution when handling these compounds and thus avoid contact dermatitis.
Evidence has become available to indicate a relationship between phenothiazine therapy and the occurrence of systemic lupus erythematosus-like syndrome.
Endocrine disorders:
Lactation, moderate breast engorgement and amenorrhoea in females and gynaecomastia in males may necessitate a lower dosage or withdrawal of the drug. False-positive pregnancy tests have been reported, but are less likely to occur when a serum test is used. Hyperglycaemia, hypoglycaemia, and glycosuria have been reported.
Autonomic reactions:
Autonomic reactions such as dryness of the mouth may occur, particularly when large oral doses are administered over prolonged periods of time.
Nasal congestion, constipation, adynamic ileus, miosis, and mydriasis, have been reported with other phenothiazines.
Persistent tardive dyskinesia:
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may occur after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear irreversible. The syndrome is characterised by rhythmical involuntary movements of the tongue, face, mouth, or jaw, (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities.
There is no known effective treatment for tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment or increase the dosage of the agent, or switch to a different antipsychotic agent this syndrome may be masked.
It has been reported that fine, vermicular movements of the tongue may be an early sign of the syndrome, and if the medication is stopped at that time the syndrome may not develop.
Other adverse reactions:
Mild fever may occur after large intramuscular doses. Increase in appetite and mass sometimes occurs.
Reactions occurring with other phenothiazines have included ocular changes and changes related to skin pigmentation; such reactions should be kept in mind during the administration of promazine even though they have not been noted with this agent to date. The aetiology of these reactions is not clear but exposure to light along with dosage/duration of therapy appears to be the most significant factor. If any of these reactions are observed, the physician should weigh the benefits of continued therapy against the possible risks and on the merits of the individual case, determine whether or not to continue present therapy, lower the dosage, or withdraw the drug.
Patients with a history of epilepsy should be treated with phenothiazine compounds only when such therapy is absolutely necessary. In such cases, adequate anticonvulsant therapy should be given concomitantly.
Promazine may potentiate the effect of organic phosphates found in certain insecticides.
Promazine must be used with caution in persons exposed to extreme heat and administered cautiously to persons with cardiovascular or liver disease. It should be kept in mind that the anti-emetic effect may mask toxicity of other drugs or obscure other diagnosis such as gastrointestinal obstruction.
Promazine should be given with caution to patients who are suffering from respiratory impairment due to acute pulmonary infections or chronic respiratory disorders such as severe asthma or emphysema.
Additive effect:
Promazine prolongs and intensifies the central nervous system depressant action of anaesthetic barbiturates and narcotics; a quarter to half the usual dose of these drugs is required when promazine is administered concomitantly. When the additive effect is not desired, such depressants should be discontinued before starting promazine therapy.
Promazine should also be used with caution in persons receiving atropine or related drugs, since phenothiazines have occasionally been shown to potentiate anticholinergic drugs.
Abrupt withdrawal:
In general, phenothiazines (including promazine), do not produce psychic dependence. However gastritis nausea and vomiting dizziness and tremulousness have been reported following abrupt cessation of high-dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinson agents are continued for several weeks after the phenothiazine is withdrawn.
There is sufficient experimental evidence to conclude that chronic administration of antipsychotic drugs, which increase prolactin secretion has the potential to induce mammary neoplasms in rodents under the appropriate conditions. There are recognized differences in the physiological role of prolactin between rodents and humans. Since there are, at present, no adequate epidemiological studies, the relevance of mammary cancer risk from prolonged exposure to promazine and other antipsychotic drugs is not known.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
One of three clinical pictures may be seen in overdosage:

1.	Extreme somnolence: patients can usually be roused with prodding, but if permitted, will fall asleep. General condition is usually satisfactory. The skin, though pale, is warm and dry. Slight blood pressure, respiratory, and pulse changes may occur but are not problems.
2.	Mild-to-moderate drop in blood pressure (whether patient is conscious or unconscious). Skin is markedly gray but warm and dry. Nail beds are pink. Respiration is slow and regular. Pulse is strong but the rate slightly increased.
3.	Severe hypotension, possibly accompanied by weakness, cyanosis, sweating, rapid thready pulse, and respiratory depression.

Treatment is essentially symptomatic and supportive. Early gastric lavage and intestinal purges may help. Centrally acting emetics will not help because of the antiemetic effect of promazine.
Severe hypotension usually responds to measures described under cardiovascular effects.
Additional measures include pressure bandages to lower limbs, oxygen and I.V. fluids.
Avoid stimulants that may cause convulsion.
Limited experience with dialysis indicates that it is not helpful.

IDENTIFICATION:
SPARINE INJECTION is a clear colourless solution in a 1 mL glass ampoule.
SPARINE SYRUP is a clear, pale yellow viscous liquid having a characteristic odour which is predominantly that of lime.

PRESENTATION:
SPARINE INJECTION: Boxes of 10 x 1 mL ampoules, each ampoule containing SPARINE (promazine) 50 mg/mL
SPARINE SYRUP: Bottles of 100 mL containing SPARINE (promazine) 10 mg/5 mL.

STORAGE DIRECTIONS:
Store in a cool (below 25 °C), dry place. Protect from light.
Keep out of reach of children.

REFERENCE NUMBERS:
SPARINE INJECTION: B1347 (Act 101/1985)
SPARINE SYRUP: B1348 (Act 101/1985)

NAME AND BUSINESS ADDRESS OF APPLICANT:
AKROMED PRODUCTS
Electron Avenue, ISANDO 1600
Trademark and product, under licence from
WYETH-AYERST LABORATORIES, U.S.A.

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
20 August 1986

24905 GM401
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