BREVINAZE INJECTION 10 mg/mL; BREVINAZE INJECTION 50 mg/mL; BREVINAZE INJECTION 100 mg/mL

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

BREVINAZE INJECTION 10 mg/mL
BREVINAZE INJECTION 50 mg/mL
BREVINAZE INJECTION 100 mg/mL

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

BREVINAZE INJECTION 10 mg/mL
BREVINAZE INJECTION 50 mg/mL
BREVINAZE INJECTION 100 mg/mL

COMPOSITION:
Each 1 mL contains 10, 50 or 100 mg Ketamine as the hydrochloride salt.
Preservative: Benzethonium chloride 0,01% m/v
Brevinaze Injection 10 mg/mL has been made isotonic with sodium chloride.

PHARMACOLOGICAL CLASSIFICATION:
A. 2.1 Anaesthetics

PHARMACOLOGICAL ACTION:
Brevinaze (ketamine) produces dissociative anaesthesia which is characterised by a state of sedation, immobility, amnesia and marked analgesia as well as a strong feeling of dissociation.

It acts on the cortex and the limbic system.

Muscular relaxation is poor and muscle tone may be increased. Respiration is maintained, although transient depression may occur. Pharyngeal and laryngeal reflexes are partially retained, but the cough reflex is depressed. Airway resistance is decreased.

Arterial blood pressure increases by as much as 25% and cardiac output and rate increase. Cerebral metabolism and blood flow increase, leading to a potential increase in intracranial pressure. It has a half life of about 3½ hours. Intense analgesia and amnesia are established rapidly.

INDICATIONS:
Induction of anaesthesia, or, in combination with oxygenated nitrous oxide, for the maintenance of general anaesthesia.

Brevinaze (ketamine) may be used in children for the management of minor surgical and diagnostic procedures or for repeated procedures that required intense analgesia, such as changing burn dressings.

CONTRA-INDICATIONS:
Hypersensitivy to ketamine hydrochloride. Patients with cardiovascular disease including hypertension. It is best avoided in patients with eclampsia or pre-eclampsia and should be used with caution in patients with a history of convulsive disorders or psychiatric disease. It should not be given to patients with increased intra-ocular or cerebro-spinal fluid pressure or those with intracranial space-occupying lesions. Alternative anaesthetics should be considered in patients with penetrating wounds of the eye. It is not suitable for ophthalmic procedures or pharyngeal surgery. Safety during pregnancy and lactation has not been established.

WARNINGS:

Intracranial pressure may increase

DOSAGE AND DIRECTIONS FOR USE:
Doses should be individualised.

Administration should be preceded by atropine or another suitable antimuscarinic agent.

A benzodiazepine, such as diazepam 2,5 to 5 mg intravenously (0,05 to 0,1 mg/kg) decrease the incidence of hallucinations during Brevinaze (ketamine) anaesthesia and decrease the incidence of emergence reactions.

A.	Brevinaze (ketamine) may be administered by intravenous or intramuscular injection. Intravenous injection should be over a period of 60 seconds.

Route	Dose mg/kg	Onset of anaesthesia	Duration time
IV	1-2	30 seconds	5 to 10 minutes
IM	5-10	3 to 4 minutes	12 to 25 minutes

Alternative method
An Intravenous infusion solution (1 mg/mL) is prepared by mixing 500 mg of Brevinaze (ketamine) in 500 mL of glucose or saline solution.
Induction is accomplished by infusing the solution until induction is complete. In general the induction dose will be approximately 1 mg/kg.
Maintenance intravenous infusion rates need to be individualised to prevent nystagmus and response to surgical stimuli, 1 to 5 mg/kg/hour being the usual dose. Upon termination of surgery, the Brevinaze (ketamine) is discontinued.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Emergence reactions in recovery are common including vivid and often unpleasant dreams, confusion, hallucinations and irrational behaviour. Increased muscle tone (sometimes resembling seizures). Children and elderly appear to be less sensitive than other adult patients.
Increase in blood pressure and heart rate are common, but hypotension, arrhythmias and bradycardia have occurred.
Respiration may be depressed especially during too rapid intravenous injection. Apnoea, laryngospasm, diplopia, nystagmus, nausea, vomiting, dizziness, headache, lachrymation, hypersalivation, raised intraocular and cerebrospinal fluid pressure as well as skin rashes and pain at the injection site have occurred.

Special Precautions
The necessary equipment for airway support, intubation and resuscitation should always be readily available.
Special caution should be taken when administering Brevinaze (ketamine) to patients with a history of epilepsy, psychiatric illnesses or porphyria. Cardiac function should be monitored in patients with mild hypertension or cardiac decompensation.
Patients should be intubated if there is a risk of aspiration as laryngeal reflexes are not necessarily maintained.
Incompatibility exists with soluble barbiturates, and these should not be combined in the same syringe. It is also not recommended that Brevinaze (ketamine) be combined with ergometrine.
Verbal, tactile and visual stimuli should be kept to a minimum during recovery in an attempt to reduce the risk of emergence reactions.
Dosage may need to be decreased in the event of renal and liver impairment.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Respiratory depression. Supportive ventilation and resuscitation equipment should always be available when general anaesthesia is administered. Treatment is symptomatic and supportive.

IDENTIFICATION:
A clear, colourless solution in amber vials.

PRESENTATION:
Brevinaze Injection (ketamine) 10 mg/mL in 20 mL amber glass vials packed in tens and singles.
Brevinaze Injection (ketamine) 50 mg/mL in 10 mL amber glass vials packed in tens and singles.
Brevinaze Injection (ketamine) 100 mg/mL in 10 mL amber glass vials packed in tens and singles.

STORAGE INSTRUCTIONS:
Store below 25°C.
Keep out of the reach of children.

REGISTRATION NUMBERS:
Brevinaze Injection 10 mg/mL –Y/2.1/373
Brevinaze Injection 50 mg/mL –Y/2.1/273
Brevinaze Injection 100 mg/mL –V/2.1/274

NAME AND BUSINESS ADDRESS OF APPLICANT:
INTRAMED (Pty) Ltd.
6 Gibaud Road
Port Elizabeth
6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
May 1992

12-067/11-92