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

Logo 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:

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