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

DOVAL TABLETS 2 mg. DOVAL TABLETS 5 mg. SCHEDULING STATUS: S5
PROPRIETARY NAME (and dosage form):
DOVAL TABLETS 2 mg. DOVAL TABLETS 5 mg.
COMPOSITION: Each Doval Tablet 2 mg contains 2 mg diazepam. Each Doval Tablet 5 mg contains 5 mg diazepam.
PHARMACOLOGICAL CLASSIFICATION: Category A:2.6 Tranquillizers.
PHARMACOLOGICAL ACTION: It has been found that the major locus of CNS depressant action of Doval on spinal reflexes is the brain stem reticular system. After oral administration peak plasma concentrations are reached in 1 to 4 hours. Drug elimination follows a biphasic pattern with a rapid phase (halflife = 2 to 3 hours) followed by a slow decay with a halflife of 2 to 8 days. Doval is metabolized to active products including oxazepam. One third is excreted as oxazepam and 70% of the metabolites appears in the urine. Metabolites have been found in the urine and in the plasma 14 days after a 10 mg dose.
INDICATIONS: Doval is used in the treatment of anxiety in neurotic patients, agitated depression and for pre-operative medication. It may be effective in relieving the acute symptoms of the alcohol withdrawal syndrome, but has no specific usefulness in the treatment of psychotic patients.
CONTRA-INDICATIONS: Doval is contra-indicated in infants and in patients with known hypersensitivity to diazepam. Caution should be observed when giving Doval to patients with impaired hepatic or renal function.
In elderly or debilitated patients and patients with obstructive airways disease large doses may produce syncope. The effects of Doval may be enhanced by alcohol, barbiturates, narcotics, MAO inhibitors and other depressants of the central nervous system. The response to treatment with oral anti-coagulants may be variable in patients taking diazepam.
WARNINGS: Elderly or debilitated patients and patients with obstructive airways disease should be given one-half the usual adult dose. Acute narrow angle glaucoma requires caution.
DOSAGE AND DIRECTIONS FOR USE: The usual dosage for mild anxiety states in ambulant patients is 2 mg thrice daily and in severe anxiety and other psychiatric disorders 15 mg to 30 mg daily in divided doses.
For sleep disturbances 5 mg to 30 mg should be given in the evening.
Elderly or debilitated patients and patients with obstructive airways disease should be given one-half the usual adult dose.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: The toxic effects most frequently encountered with Doval are drowsiness, dizziness, fatigue, apathy, constipation, irritability and ataxia; less frequently, depression, diarrhoea, indigestion, impairment of sexual, function may occur. Large doses may produce Syncope. Other side-effects occasionally reported are skin rashes, headaches, nausea, frequency of urination and menstrual irregularities. Blood dyscrasias and hepatic dysfunction have occasionally been reported. Care should be taken when administered in obstetrics during labour because of the possible effect of central respiratory depression, hypothermia and hypotonia and an increase in foetal heart rate in the infant.
In severely disturbed patients treatment with Doval may result in paradoxical reactions provoking excitement instead of sedation. There is a risk of dependence of the barbiturate-alcohol type and withdrawal reactions including convulsions have been observed in patients receiving large doses for prolonged periods when the drug was stopped abruptly.
KNOWN SYMPTOMS OF OVERDOSE AND PARTICULARS OF ITS TREATMENT: Sedation is the most prominent symptom of overdosage. This usually follows symptoms of dizziness, fatigue, apathy or irritability. Large doses may produce syncope.
Treatment: In severe overdosage the stomach should be emptied by aspiration or lavage. There is no specific treatment and recovery usually follows symptomatic treatment.
CONDITIONS OF REGISTRATION: Advertising to the medical professions only.
IDENTIFICATION: 2 mg –White tablets with scoremark on the one side. 5 mg –Yellow tablets with scoremark on the one side.
PRESENTATION: Containers with 10, 30 or 100 tablets.
STORAGE INSTRUCTIONS: Store below 25°C and protect from light and moisture. KEEP OUT OF THE REACH OF CHILDREN.
REGISTRATION NO.: K/2.6/116.
NAME AND BUSINESS ADDRESS: Ormed Limited, Howard Studios, Howard Drive, Pinelands 7405.
DATE OF PUBLICATION OF THIS PACKAGE INSERT: March 1988         RSA Litho

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

MICRO DIAZEPAM INJECTION 10 mg/2 mL SCHEDULING STATUS: S5
PROPRIETARY NAME (and dosage form):
MICRO DIAZEPAM INJECTION 10 mg/2 mL
COMPOSITION: Each 2 mL ampoule contains 10 mg of diazepam with 5% m/v benzoate buffer, 1,5% v/v benzyl alcohol and 19,2% v/v ethanol.
PHARMACOLOGICAL CLASSIFICATION: A 2.6 Tranquillizers.
PHARMACOLOGICAL ACTION: The effect of diazepam, a benzodiazepine, results from its action on the central nervous system i.e. sedation, hypnosis, decreased anxiety, muscle relaxation, anterograde amnesia and anticonvulsant activity. Elimination follows a biphasic pattern, with a rapid distribution phase, followed by a prolonged terminal elimination phase of 1 to 2 days. The half life of its principal metabolite, desmethyldiazepam, is 2 to 5 days. It is excreted in the urine. In addition to crossing the blood-brain barrier, diazepam and its metabolites also cross the placental barrier and is excreted in breast milk.
INDICATIONS: Diazepam is used in the treatment of anxiety and tension states as a sedative and pre-medication, in the control of muscle spasm as in tetanus, as well as in the management of alcohol withdrawal syndrome. It can also be used for the control of status epilepiticus. Diazepam is only indicated when the disorder is severe, disabling or subjecting the individual to extreme stress.
CONTRA-INDICATIONS: Diazepam is contra-indicated in patients with known hypersensitivity to benzodiazepines. Caution should be taken when giving diazepam to patients with impaired liver, kidney or respiratory function. Elderly and debilitated patients are especially sensitive to its side-effects. Infants may be unable to metabolise diazepam. The effects of diazepam may be enhanced by alcohol, barbiturates, narcotics and other depressants of the central nervous system. Benzodiazepines should be avoided in psychotic patients unless there is a marked component of anxiety in their illness. The use of diazepam should be avoided in patients with pre-existing central nervous system depression or coma, acute pulmonary insufficiency, or sleep apnoea, and with care in those with chronic pulmonary insufficiency. Use of diazepam in the first trimester of pregnancy has been associated with various congenital malformations in infants, but no clear relationship has been established. Diazepam should also be avoided in lactating mothers.
WARNINGS: When given intravenously in the undiluted form, the injection should be administered at a rate not exceeding 5 mg/minute. Because of drowsiness and impaired concentration, affected patients should not drive or operate machinery, where loss of concentration could lead to accidents. There is potential for abuse and dependence, especially with prolonged used and high doses. Withdrawal symptoms may occur after long periods of ordinary therapeutic doses.
DOSAGE AND DIRECTIONS FOR USE: Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. Diazepam is given by deep intramuscular or slow intravenous injection. Absorption following intramuscular injection is erratic and provides lower blood concentrations than those following oral administration. Intravenous injection should be carried out slowly into a large vein of the antecubital fossa at a recommended rate of not more than 1 mL of a 0.5% solution (5 mg) per minute. It is advisable to keep the patient in the supine position for at least an hour after administration. Facilities for respiratory assistance must be available. In severe anxiety or acute muscle spasm, diazepam 10 mg may be given intramuscularly or intravenously and repeated after 4 hours. Higher doses may be required for treatment of delirium tremens. Patients with tetanus may be given 100 to 300 micrograms per kg body-mass intravenously and repeated every 1 to 4 hours; similar doses may be given by nasoduodenal tube. Treatment should be as short as possible. The patient should be re-assessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free. The overall duration of treatment generally should not be more than 8 to 12 weeks, including a tapering off process. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient’s status. In status epilepticus 150 to 250 micrograms per kg is given by intramuscular or intravenous injection for adults and repeated if required after 30 to 60 minutes. Dose in minor surgical procedures and dentistry is 100 to 200 micrograms per kg by injection adjusted to the patient’s requirements. Sedative dose for children is up to 200 micrograms per kg body-mass. A suggested parenteral regimen for children with status epilepticus or severe recurrent seizures of febrile convulsions is 200 to 300 micrograms per kg body-mass or 1 mg per year of age; if necessary these doses may be repeated 30 minutes or 1 hour later. Maintenance therapy may then follow. Elderly and debilitated patients should be given not more than one half the usual adult dose. Dosage reduction may also be required in patients with liver or kidney dysfunction.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: Dizziness, vertigo, light-headedness, headache, confusion, mental depression, slurred speech or dysarthria, changes in libido, ataxia, tremor, blurred vision, urinary retention or incontinence, gastro-intestinal disturbances, changes in salivation, jaundice and occasional blood disorders have been reported. The benzodiazepines can cause amnesia and paradoxical excitation. Respiratory depression and hypotension may occur with high dosage and parenteral administration. Overdosage can produce central nervous system depression and coma. Other agents with central nervous system depressant properties may enhance the sedation or respiratory and cardio-vascular depression e.g. alcohol, antidepressants, anthistamines, general anaesthetics, other hypnotics or sedatives, neuroleptics and opioid analgesics. Care should be taken in patients with personality disorders as diazepam-induced disinhibition may precipitate suicide or aggressive behaviour. Caution is required in patients with organic brain changes, particularly arteriosclerosis. In cases of bereavement, psychological adjustment may be inhibited by diazepam. Pain and thrombophlebitis may occur with some intravenous formulations of diazepam. Diazepam is not recommended for the primary treatment of psychotic illness. Diazepam should not be used alone to treat depression or anxiety with depression (suicide may be precipitated in such patients). Diazepam should be used with extreme caution in patients with history of alcohol or drug abuse. Dependence There is potential for abuse and the development of physical and psychic dependence, especially with prolonged use and high doses. The risk of dependence is also greater in patients with a history of alcohol or drug abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyper-acousis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures. Rebound effects A transient syndrome whereby the symptoms that led to treatment with diazepam recur in an enhanced form may occur on withdrawal of treatment. It may be accompanied by other reactions, including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually. Duration of treatment The duration of treatment should be as short as possible (see Dosage), but should not exceed 8-12 weeks in case of anxiety, including tapering of process. Extension beyond these periods should not take place without re-evaluation of the situation. It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, hereby minimising anxiety over such symptoms, should they occur while the product is being discontinued.
KNOWN SYMPTOMS OF OVERDOSAGE AND ITS TREATMENT: For symptoms see “SIDE-EFFECTS AND SPECIAL PRECAUTIONS”. Treatment is intensive and symptomatic and supportive measures should be employed, such as administration of intravenous infusions to maintain electrolyte balance. Cardiovascular, respiratory and renal functions must be maintained.
IDENTIFICATION: A clear, colourless to pale yellow solution in amber ampoules.
PRESENTATION: Amber glass ampoules of 10 mg diazepam per 2 mL packed in boxes of 10 or 100.
STORAGE INSTRUCTIONS: Protect from light. Keep below 25°C. This product may be refrigerated, but do not freeze. STORE ALL MEDICINE OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER: 32/2.6/0197
NAME AND BUSINESS ADDRESS OF THE APPLICANT: MICRO HEALTHCARE (Pty) Ltd 10 Lindley Street BETHLEHEM 9701 South Africa
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 

PAX®-2 TABLET PAX®-5 TABLET PAX®-10 TABLET
SCHEDULING STATUS: S5
PROPRIETARY NAME (and dosage form):
PAX^®-2 TABLET PAX^®-5 TABLET PAX^®-10 TABLET
COMPOSITION: Each tablet contains 2 mg (5 mg, 10 mg) Diazepam.
PHARMACOLOGICAL CLASSIFICATION: A 2.6 Tranquillisers.
PHARMACOLOGICAL ACTION: It has been found that the major locus of CNS depressant action of diazepam on spinal reflexes is the brain stem reticular system. After oral administration peak plasma concentrations are reached in 1 to four hours. Drug elimination follows a biphasic pattern, with a rapid phase (half-life = 2 to 3 hours) followed by a slow decay with a half-life of 2 to 8 days. Diazepam is metabolized to active products including oxazepam. One third is excreted as oxazepam and 70% of the metabolites appear in the urine. Metabolites have been found in the urine and in the plasma 14 days after a 10 mg dose. Diazepam is extensively bound to plasma proteins (99%).
INDICATIONS: Diazepam is used in the treatment of anxiety in neurotic patients and for pre-operative medication. It may be effective in relieving the acute symptoms of the alcohol withdrawal syndrome, but has no specific usefulness in the treatment of psychotic patients. Diazepam is only indicated when the disorder is severe, disabling or subjecting the individual to extreme stress.
CONTRA-INDICATIONS: Diazepam is contra-indicated in infants and in patients with known hypersensitivity to diazepam. Pre-existing CNS depression or coma is normally a contra-indication. Caution should be observed when giving diazepam to patients with impaired hepatic or renal function. In elderly and debilitated patients and patients with impaired obstructive airways disease large doses may produce syncope. The effects of diazepam may be enhanced by alcohol, barbiturates, narcotics, MAO inhibitors and other depressants of the central nervous system. The response to treatment with oral anticoagulants may be variable in patients taking diazepam. Avoid in porphyria as diazepam is considered unsafe although there is conflicting evidence of porphyrogenicity. Use of diazepam in the first trimester of pregnancy has been associated with various congenital malformations in the infant and in the last trimester it has been associated with drowsiness, respiratory depression and intoxication in the new born infant. For these reasons diazepam is contra-indicated in pregnancy. Diazepam is excreted in breast milk and is contra-indicated in nursing mothers because of the side-effects it can cause in the breastfed infant such as drowsiness, slow heartbeat and breathing problems.
WARNING: This medicine may lead to drowsiness or impaired concentration, which may be aggravated by simultaneous intake of alcohol or other central nervous system depressant agents. Patients should not drive or operate machinery where loss of attention might be hazardous. KEEP OUT OF REACH OF CHILDREN
DOSAGE AND DIRECTIONS FOR USE: The usual dose for mild anxiety states in ambulant patients is 2 mg thrice daily and in severe anxiety and other psychiatric disorders 15 mg to 30 mg daily in divided doses. For sleep disturbances 5 mg to 30 mg should be given in the evening. Elderly and debilitated patients with obstructive airways disease should be given one-half the usual adult dose. Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free. The overall duration of treatment generally should not be more than 8 –12 weeks, including a tapering off process. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patients status.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: The side-effects most frequently encountered with diazepam are drowsiness, oversedation, dizziness, light-headedness; mental depression, fatigue, apathy, constipation, irritability. Less frequently gastro-intestinal disturbances such as diarrhoea, indigestion, changes in libido, tremor, visual disturbances such as blurred vision, urinary retention or incontinence, slurred speech or dysarthria, changes in salivation, depression of mood and affect, disorientation or confusion, lethargy and ataxia, jaundice and occasional blood disorders have been reported. The benzodiazepines can also cause amnesia. Paradoxical reactions such as acute hyperexcitable states with rage and hostility may occur. If these occur, the medicine should be discontinued. Respiratory depression and hypotension are rare or absent at usual doses but may occasionally occur with high dosage. Large doses may produce syncope. Other side-effects occasionally reported are skin rashes, headaches, nausea and menstrual irregularities. Hepatic dysfunction has occasionally been reported. When diazepam is administered in obstetrics during labour, special care should be taken, since it may cause central respiratory depression and both hypothermia and hypotonia in the infant. It may also increase the foetal heart-rate. Drowsiness is more common in elderly and debilitated patients and in patients receiving high doses. In severely disturbed patients treatment with diazepam may result in paradoxical reactions provoking excitement instead of sedation. If these occur, the medicine should be discontinued. There is a risk of dependence of the barbiturate – alcohol type and withdrawal reactions including convulsions have been observed in patients receiving large doses for prolonged periods when the drug was stopped abruptly.
Special Precautions: Particular caution should be exercised with:

Given during labour it crosses the placenta and may cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia and poor sucking. Diazepam is not recommended for the primary treatment of psychotic illness. Diazepam should not be used alone to treat depression or anxiety with depression (suicide may be precipitated in such patients). Diazepam should be used with extreme caution in patients with history of alcohol or drug abuse.
Dependence There is a potential for abuse and the development of physical and psychic dependence, especially with prolonged use and high doses. The risk of dependence is also greater in patients with a history of alcohol or drug abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound effects A transient syndrome whereby the symptoms that led to treatment with diazepam recur in an enhanced form may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment it is recommended that the dosage is decreased gradually.
Duration of treatment The duration of treatment should be as short as possible (see Dosage), but should not exceed eight to twelve weeks in case of anxiety, including tapering off process. Extension beyond this period should not take place without re-evaluation of the situation. It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms, should they occur while the product is being discontinued.
INTERACTIONS WITH OTHER MEDICINES: Refer to contra-indications.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: The most prominent symptom of overdosage is sedation which usually follows symptoms of dizziness, fatigue, apathy or irritability. Large doses may produce syncope. Manifestations of overdosage include somnolence, confusion, coma, respiratory and cardiovascular depression and hypotension. The stomach should be emptied by aspiration and lavage, There is no specific treatment and recovery usually follows symptomatic and supportive therapy, with particular attention being paid to the maintenance of cardiovascular, respiratory and renal functions, and to the maintenance of electrolyte balance.
IDENTIFICATION:

PRESENTATION:

STORAGE INSTRUCTIONS: Store below 25°C, in well-closed containers. Protect from light. KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBERS:

NAME AND BUSINESS ADDRESS OF THE APPLICANT: Pharmacare Limited 7 Fairclough Road PORT ELIZABETH 6001
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 20 April 1977
D190         A & S PRINTERS
Updated on this site: May 2000 Current: September 2004 Source: Community Pharmacy

PAX INJECTION 10 mg/2 mL
SCHEDULING STATUS: S5
PROPRIETARY NAME (and dosage form):
PAX INJECTION 10 mg/2 mL
COMPOSITION: Each 2 mL ampoule contains 10 mg of Diazepam, stabilized with 0,12% m/v benzoic acid, 4,88% m/v sodium benzoate and 1,5% v/v benzyl alcohol.
PHARMACOLOGICAL CLASSIFICATION: A.2.6 Tranquilizers.
PHARMACOLOGICAL ACTION: It has been found that the major locus of central nervous system depressant action of diazepam on spinal reflexes is the brain stem reticular system. Drug elimination follows a biphasic pattern, with a rapid phase (plus-minus ½ within 2 to 3 hours) followed by a slow decay with a half-time of 2 to 8 days. Diazepam is metabolized to active products including oxazepam. One third is excreted as oxazepam and 70% of the metabolites appear in the urine. Metabolites have been found in the urine and in the plasma 14 days after a 10 mg dose.
INDICATIONS: Diazepam is used in the treatment of anxiety in neurotic patients, and for preoperative medication. It may be effective in relieving the acute symptoms of the alcohol withdrawal syndrome, but has no specific usefulness in the treatment of psychotic patients. Diazepam injection can also be used to facilitate labour. It can also be used in status epilepticus.
CONTRA INDICATIONS: Diazepam is contra-indicated in infants and in patients with known hypersensitivity to diazepam. Caution should be observed when giving diazepam to patients with impaired hepatic or renal function and to patients with closed-angle glaucoma. Elderly and debilitated patients are specially sensitive to side-effects and in patients with obstructive airway disease, respiratory depression may be produced. The effects of diazepam may be enhanced by alcohol, barbiturates, narcotics. MAO inhibitors and other depressants of the central nervous system.
WARNINGS: When given intravenously in the undiluted form, the injection should be administered at a rate not exceeding 5 mg/minute.
DOSAGE AND DIRECTIONS FOR USE : Intravenous injections should be given into a large lumen vessel, and the solution should be administered slowly (plus-minus 1 mL per minute) if the risk of thrombophlebitis is to be minimised. Intramuscular injection can lead to rise in serum creatine phosphokinase activity, with a maximum between 12 and 24 hours after the injection. Diazepam should not be combined with other aqueous solutions of medicaments except with intravenous solutions of 5 – 10% dextrose or 0,9% sodium chloride.
In this case the contents of the ampoule must quickly be mixed with the total volume of the infusion. In cases of psychiatric disorders and anxiety states the injection can be administered intramuscularly or intravenously in doses of 10 to 20 mg three times daily until acute symptoms subside. In epilepsy an initial dose of 10 to 20 mg intravenously, followed by 20 mg intramuscularly or by intravenous infusion, as required. In severe spasm of central, peripheral and tetanic origin 10 mg once or twice intravenously relieves the spastic state for about 8 hours. For facilitation of labour 20 mg intramuscularly at 2 – 3 fingers dilation. For anaesthesia: 10 to 20 mg intravenously.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: The toxic effects most frequently encountered with intravenous diazepam are cardiovascular and respiratory depression. Amnesia may persist for a variable period after intravenous administration and care is necessary with ambulant patients. Large doses may produce syncope. Blood dyscrasias and hepatic dysfunction have occasionally been reported. Care should be taken when administered in obstetrics during labour because of the possible effects of central respiratory depression, hypothermia and hypotonia and an increase in foetal heart rate in the infant. In severely disturbed patients treatment with diazepam may result in paradoxical reactions provoking excitement instead of sedation. There is a risk of dependance of the barbiturate-alcohol type and withdrawal reactions including convulsions have been observed in patients receiving large doses for prolonged periods when the medicine was stopped abruptly. Patients taking diazepam should be cautioned against driving motor vehicles, operating machinery or performing tasks where a loss of mental alertness may lead to accidents.
The adverse effects most commonly encountered are drowsiness and oversedation. Drowsiness is more common in elderly and debilitated patients and in patients receiving high doses. Less commonly, the benzodiazepines may produce depression of mood and affect, disorientation or confusion, lethargy, and ataxia.
Paradoxical reactions such as acute hyperexcitable states with rage have been recorded. If these occur, the medicine should be discontinued.
The benzodiazepines have a moderate potential for abuse. Withdrawal symptoms (including convulsions) have occurred following abrupt cessation especially in patients receiving large doses for prolonged periods.
INJECTIONS: Respiratory depression due to a depressant effect on the respiratory centre and cardiovascular collapse may occasionally occur following intravenous and intramuscular administration of the benzodiazepines.
the benzodiazepines should be administered with particular care to the following patients:
the elderly and debilitated – who are at particular risk of oversedation, respiratory depression and ataxia. (The initial dosage should be reduced in these patients);
patients with pulmonary disease and limited pulmonary reserve;
patients suffering from impairment of renal or hepatic function, or from hypoalbuminaemia;
patients suffering from anxiety concomitant with an underlying depressive disorder;
patients receiving barbiturates or other central nervous system depressants concomitantly with the benzodiazepines. There is an additive risk of central nervous system depression when these medicines are taken together;
patients should be cautioned regarding the additive effect of alcohol when taken together with the benzodiazepines;
the benzodiazepines should be used judiciously during pregnancy and they are preferably avoided. Given during labour, benzodiazepines cross the placenta and may cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia and poor sucking. The benzodiazepines should not be administered to lactating mothers.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Coma, respiratory and cardiovascular depression. Treatment: No specific antidote is known. General supportive measures should be employed, such as administration of intravenous infusions. Adequate air passage control must be observed and oxygen can be administered.
Manifestations of overdosage with the benzodiazepines include somnolence, contusion and coma. Gastric aspiration and lavage should be performed, following with 50 g of activated charcoal which should be administed intragastrically. Careful respiratory and cardiovascular support is mandatory. An adequate airway should be maintained. Hypotension, when it occurs, may be controlled with sympathomimetic agents.
IDENTIFICATION: Clear colourless to pale yellow solution in 2 mL amber glass ampoules.
PRESENTATION: Amber glass ampoules of 10 mg diazepam per 2 mL packed in boxes of 10.
STORAGE INSTRUCTIONS: Protect from light. Keep below 25°C. Keep out of reach of children.
REFERENCE NUMBERS: K/2.6/220
NAME AND BUSINESS ADDRESS OF APPLICANT: INTRAMED (PTY) LTD. 6 Gibaud Road North End 6001
DATE OF PUBLICATION OF THIS LEAFLET:

Q-MED DIAZEPAM Injection 10 mg/2 mL
SCHEDULING STATUS: S5
PROPRIETARY NAME (and dosage form):
Q-MED DIAZEPAM Injection 10 mg/2 mL
COMPOSITION: Each 2 mL ampoule contains 10 mg of diazepam with 5% m/v benzoate buffer, 1,5% v/v benzyl alcohol and 19,2% v/v ethanol.
PHARMACOLOGICAL CLASSIFICATION: A 2.6 Tranquillizers
PHARMACOLOGICAL ACTION: The effect of diazepam, a benzodiazepine, results from its action on the central nervous system ie. sedation, hypnosis, decreased anxiety, muscle relaxation, anterograde amnesia and anticonvulsant activity. Elimination follows a biphasic pattern, with a rapid distribution phase, followed by a prolonged terminal elimination phase of 1 to 2 days. The half life of its principal metabolite, desmethyldiazepam, is 2 to 5 days. It is excreted in the urine. In addition to crossing the blood-brain barrier, diazepam and its metabolites also cross the placental barrier and are excreted in breast milk.
INDICATIONS: Diazepam is used in the treatment of anxiety and tension states as a sedative and pre- medication, in the control of muscle spasm as in tetanus, in the management of alcohol withdrawal syndrome. It can also be used for the control of status epilepticus. Diazepam is only indicated when the disorder is severe, disabling or subjecting the individual to extreme stress.
CONTRA-INDICATIONS: Diazepam is contra-indicated in patients with known hypersensitivity to benzodiazepines. Caution should be observed when giving diazepam to patients with impaired liver, kidney or respiratory function. Elderly and debilitated patients are specially sensitive to its side-effects. Infants may be unable to metabolize diazepam. The effects of diazepam may be enhanced by alcohol, barbiturates, narcotics, and other depressants of the central nervous system. Benzodiazepines should be avoided in psychotic patients unless there is a marked component of anxiety in their illness. The use of diazepam should be avoided in patients with pre-existing central nervous system depression or coma, acute pulmonary insufficiency, or sleep apnoea, and with care in those with chronic pulmonary insufficiency. Use of diazepam in the first trimester of pregnancy has been associated with various congenital malformations in infants but no clear relationship has been established. Diazepam should also be avoided in lactating mothers.
WARNINGS: When given intravenously in the undiluted form, the injection should be administered at a rate not exceeding 5 mg/minute. Because of drowsiness and impaired concentration, affected patient should not drive or operate machinery, where loss of concentration could lead to accidents. There is a potential for abuse and dependence, especially with prolonged use and high doses. Withdrawal symptoms may occur after long periods of ordinary therapeutic doses.
DOSAGE AND DIRECTIONS FOR USE: Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. Diazepam is given by deep intramuscular or slow intravenous injection. Absorption following intramuscular injection is erratic and provides lower blood concentrations than those following oral administration. Intravenous injection should be carried out slowly into a large vein of the antecubital fossa at are commended rate of no more than 1 mL of a 0,5 % solution (5 mg) per minute. It is advisable to keep the patient in the supine position for at least an hour after administration. Facilities for respiratory assistance must be available. In severe anxiety or acute muscle spasm, diazepam 10 mg may be given intramuscularly or intravenously and repeated after 4 hours. Higher doses may be required for treatment of delirium tremens. Patients with tetanus may be given 100 to 300 µg per kg body-mass intravenously and repeated every 1 to 4 hours; similar doses may be given by nasoduodenal tube. Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free. The overall duration of treatment generally should not be more than 8 to 12 weeks, including a tapering off process. In certain cases extension beyond the maximum treatment period may be necessary; it so, it should not take place without re-evaluation of the patient’s status. In status epilepticus 150 to 250 µg per kg is given by intramuscular or intravenous injection for adults and repeated if required after 30 to 60 minutes. Dose in minor surgical procedures and dentistry is 100 to 200 µg per kg by injection adjusted to patient’s requirements. Sedative dose for children is up to 200 µg per kg body-mass. A suggested parenteral regimen for children with status epilepticus or severe recurrent seizures or febrile convulsions is 200 to 300 µg per kg body-mass or 1 mg per year of age; if necessary these doses may be repeated 30 minutes or 1 hour later. Maintenance therapy may then follow. Elderly and debilitated patients should be given not more than one-half the usual adult dose. Dosage reduction may also be required in patients with liver or kidney dysfunction.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: Dizziness, vertigo, light-headedness, headache, confusion, mental depression, slurred speech or dysarthria, changes in libido, ataxia, tremor, blurred vision, urinary retention or incontinence, gastro-intestinal disturbances, changes in salivation, jaundice, and occasional blood disorders have been reported. The benzodiazepines can cause amnesia and paradoxical excitation. Respiratory depression and hypotension may occur with high dosage and parenteral administration. Overdosage can produce central nervous system depression and coma. Other agents with central nervous system depressant properties may enhance the sedation or respiratory and cardio-vascular depression eg. alcohol, antipressants, antihistamines, general anaesthetics, other hypnotics or sedatives, neuroleptics and opoid analgesics. Care should be taken in patients with personality disorders as diazepam-induced disinhibition may precipitate suicide or aggressive behaviour. Caution is required in patients with organic brain changes, particularly arteriosclerosis. In cases of bereavement, psychological adjustment may be inhibited by diazepam. Pain and thrombophlebitis may occur with some intravenous formulations of diazepam. Diazepam is not recommended for the primary treatment of psychotic illness. Diazepam should not be used alone to treat depression or anxiety with depression (suicide may be precipitated in such patients). Diazepam should be used with extreme caution in patients with history of alcohol or drug abuse. Dependence There is a potential for abuse and the development of physical and psychic dependence, especially with prolonged use and high doses. The risk of dependence is also greater in patients with a history of alcohol or drug abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyper-acusis, numbness and tingling of extremeties, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures. Rebound effects A transient syndrome whereby the symptoms that led to treatment with diazepam recur in an enhanced form may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment it is recommended that the dosage is decreased gradually. Duration of treatment The duration of treatment should be as short as possible (see Dosage), but should not exceed eight to twelve weeks in case of anxiety, including tapering of process. Extension beyond these periods should not take place without re-evaluation of the situation. It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms, should they occur while the product is being discontinued.
KNOWN SYMPTOMS OF OVERDOSAGE ITS TREATMENT: For symptoms see side-effects and special precautions. Treatment is intensive symptomatic and supportive measures should be employed, such as administration of intravenous infusions to maintain electrolytic balance. Cardiovascular, respiratory and renal functions must be maintained.
IDENTIFICATION: A clear, colourless to pale yellow solution in amber ampoules in boxes of 10.
PRESENTATION: Amber glass ampoules of 10 mg diazepam per 2 mL packed in boxes of 10.
STORAGE INSTRUCTIONS: Protect from light. Store below 25°C. Keep out of reach of children.
REGISTRATION NUMBER: 29/2.6/0603
NAME AND BUSINESS ADDRESS OF APPLICANT: Quatromed Limited 10 Lindley Street BETHLEHEM 9700
DATE OF PUBLICATION: September 1995         PDI0081/10-96