INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ATIVAN® INJECTION

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

ATIVAN^® INJECTION

COMPOSITION:
Each mL of ATIVAN^®INJECTION contains 4 mg lorazepam, compounded with 80% propylene glycol, 18% polyethylene glycol and 2% benzyl alcohol. Lorazepam is a benzodiazepine derivative developed through original WYETH research.
Chemically, lorazepam is: 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4- benzodiazepin-2-one.
It is a nearly white powder, insoluble in water.

PHARMACOLOGICAL CLASSIFICATION:
A 2.6 Tranquillisers.

PHARMACOLOGICAL ACTION:
ATIVAN INJECTION is readily absorbed when given intramuscularly. Peak plasma concentrations occur approximately 60-90 minutes following intramuscular administration. The half-life of ATIVAN (lorazepam) is approximately 12-16 hours. Steady state blood levels are reached within 3 days upon multiple dosing of ATIVAN INJECTION given intravenously or intramuscularly.
At clinically relevant concentrations, lorazepam is approximately 90% bound to plasma proteins.
Conjugation with glucuronic acid to form the inactive glucuronide of lorazepam is the major metabolic pathway for ATIVAN (lorazepam). Seventy to seventy five percent of the dose is excreted as the glucuronide in the urine. The glucuronides of lorazepam have no demonstrable central nervous system activities, and there are no active metabolites of ATIVAN (lorazepam).
ATIVAN INJECTION has anti-anxiety, anti-convulsant and sedative effects. The pharmacological action of ATIVAN (lorazepam) appears to be directed mainly to the limbic system.

INDICATIONS:

i.	As premedication to relieve anxiety and tension, and to diminish recall of events associated with major or minor surgical and diagnostic procedures.
ii.	Symptomatic relief of acute anxiety (IV administration preferred)
iii.	Treatment of status epilepticus caused by various partial and generalised types. Among the seizures known to respond to ATIVAN INJECTION are : generalised (tonic-clonic, "grand-mal") seizures, generalised absence ("petit mal") seizures or spike-wave stupor, partial elementary (focal motor) seizures, partial complex (psychomotor) seizures, and combinations such as generalised seizures with focal onset.
iv.	Initial treatment with ATIVAN INJECTION results in prolonged cessation of seizure activity.

ATIVAN (lorazepam) is not recommended for maintenance treatment of epilepsy. After seizures are controlled, agents useful in the prevention for the prevention of further seizures should be administered. In the treatment of status epilepticus due to reversible metabolic derangement (e.g. Hypoglycaemia, hypocalcaemia, hyponatraemia, etc.), immediate efforts should be made to correct the specific defect.

CONTRA-INDICATIONS:

i.	Safety in pregnancy has not been established.
ii.	History of hypersensitivity to benzodiazepines, or to the vehicle (polyethylene glycol, propylene glycol and benzyl alcohol).

WARNINGS:
There is a potential for abuse. Withdrawal symptoms, including convulsions, have occurred following abrupt cessation of ATIVAN (lorazepam) treatment, especially in patients receiving high dosages for prolonged periods.
Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines.
Disturbance behaviour and/or thought has been reported.
Respiratory depression due to depressant effect on the respiratory centre, and cardiovascular collapse may occur following intravenous and intramuscular administration.

DOSAGE AND DIRECTIONS FOR USE:
To facilitate withdrawal of solution from the ampoule of ATIVAN INJECTION, 1 mL of sterile water for injection or normal saline for injection may be added to the ampoule immediately before injection (i.e. 1:1 dilution). For IM administration, inject deeply into the upper outer quadrant of the gluteal region with a 21 gauge needle. For IV administration, inject with a 21-23 gauge needle.
Intravenous injection should be made slowly and with repeated aspiration. Partial airway obstruction may occur in heavily sedated patients. Intravenous ATIVAN (lorazepam), when given alone in greater than the recommended dose, or at the recommended dose and accompanied by other drugs used during the administration of anaesthesia, may produce heavy sedation; therefore, equipment necessary to maintain a patent airway and to support respiration/ventilation should be available.
ATIVAN INJECTION should not be injected intra-arterially since, as with other injectable benzodiazepines, intra-arterial injection may produce arteriospasm resulting in gangrene, which may require amputation. The addition of scopolamine to ATIVAN INJECTION is not recommended, since their combined effect may result in increased incidence of sedation, hallucination and irrational behaviour.

i.	Premedication

For maximum beneficial effect, dosage should be based on mass (usual dose will be 2-4 mg) and administration as follows :

A.	IV - 0,044 mg/kg fifteen to twenty minutes before the anticipated operative procedure for optimum effect, measured as lack of recall. This dose will suffice for sedating most adult patients, and should not ordinarily be exceeded in patients over 50 years of age. In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0,05 mg/ kg up to a total of 4 mg may be administered.
B.	IM - 0,05 mg/kg at least two hours before the anticipated operative procedure for optimum effect, measured as a lack of recall.
	Note : In the elderly and/or debilitated patients, and in those with serious respiratory or cardiovascular disease, a reduction of dosage is recommended.
	In the case of local anaesthesia and diagnostic procedures requiring patient co-operation, concomitant use of an analgesic is recommended.
	It is recommended that any concomitant medications be administered in separate syringes. Administering ATIVAN (lorazepam) 1-2,5 mg orally is recommended on the evening before surgery to relieve anxiety and promote sleep.

ii.

Psychiatry:

In acute cases of anxiety with or without psychomotor agitation (and depending on its aetiology, severity, and the mass of the patient), the recommended initial dose is 2-4 mg IV or IM, i.e. 0,05 mg/kg (IV administration preferred). If indicated, the dose may be repeated in two hours. Once the acute symptomology has beep controlled, the patient should be placed on oral ATIVAN (lorazepam) if further treatment is required.

iii.	Status Epilepticus
	Status epilepticus due to various partial and generalised seizure types:
	The usual recommended initial dose of ATIVAN (lorazepam) is 4 mg given by slow intravenous injection (2 mg/min) for patients 18 years and older. If seizures continue or recur after a ten to fourteen minute observation period, an additional intravenous dose of 4 mg may be administered. If the second dose does not result in seizure control after another ten to fifteen minute observation period, other measures to control status epilepticus should be employed. A maximum of 8 mg only of ATIVAN (lorazepam) should be administered during a 12-hour period.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects
The side-effects most commonly encountered are drowsiness and oversedation. Drowsiness is most common in elderly and debilitated patients and in patients receiving high dosages. Less common are depression of mood and affect, disorientation or confusion, lethargy and ataxia. Nausea, vomiting, hypertension and vertigo have been observed. Paradoxical reactions such as acute hyperexcitable states with rage may occur, if these occur, ATIVAN (lorazepam) should be discontinued.
A transient stinging or painful sensation at the injection site has sometimes been noted.
Use during pregnancy
Safety in pregnancy has not been established.
ATIVAN (lorazepam) should be used judiciously during pregnancy and preferably avoided. Given during labour, it crosses the placenta and may cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia and poor sucking. It should not be administered to lactating mothers.
Precautions

i.	Care is advised in the concomitant use of ATIVAN INJECTION and CNS depressant drugs such as barbiturates, alcohol, etc. There is an additive risk of central nervous system depression when these medicines are taken together.
ii.	Patients should not drive or undertake activities requiring maximum attentiveness. In these situations, impaired decision making could lead to accidents.
	(a)		When ATIVAN (lorazepam) is used for short procedures on an outpatient basis, the patient should be accompanied when discharged from the institution;
	(b)		Patients receiving the product should remain under observation for at least 24 hours after the last injection.
iii.		A reduction in the dose of narcotics and/or analgesics may be required when used in combination with ATIVAN (lorazepam).
iv.		ATIVAN (lorazepam) should not be administered to nursing mothers. Evidence to date indicates that ATIVAN (lorazepam) is excreted in breast milk.
v.		Patients with pulmonary disease and limited pulmonary reserve should be treated with caution.
vi.		Caution should be exercised in the treatment of patients with acute narrow-angle glaucoma.
vii.		Caution should be exercised in treating patients suffering from anxiety accompanied by an underlying depressive disorder.
viii.		Patients suffering from impairment of renal or hepatic function should be treated with caution.
ix.		Lack of clinical experience with ATIVAN (lorazepam) precludes its use in patients less than 12 years of age.
x.		ATIVAN (lorazepam) is not recommended for obstetrical use.
xi.		Particular caution should be exercised with the elderly and/or debilitated who are at particular risk of over-sedation, respiratory depression and ataxia. (Initial dosage should be reduced in these patients).
xii.		Care should be exercised when administering ATIVAN (lorazepam) with status epilepticus, especially when the patient has received other central nervous system depressants or is severely ill. The possibility that respiratory arrest may occur or that the patient may have partial airway obstruction, should be considered. Proper resuscitation equipment should be available.
xiii.		Some patients on ATIVAN (lorazepam) have developed blood dyscrasias, and some have had elevations in liver enzymes. Periodic blood counts and liver function tests are recommended for patients on long-term therapy.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Manifestations of overdosage include somnolence, confusion, coma, respiratory and cardiovascular depression, and hypotension. Symptomatic treatment is recommended, intravenous fluids should be administered, and an open airway maintained.

IDENTIFICATION:
A 2 mL clear glass ampoule containing 1 mL of a solution of ATIVAN (lorazepam).

PRESENTATION:
Boxes of 10 or 5 glass 2 mL ampoules, each containing 1 mL of ATIVAN (lorazepam) solution, equivalent to 4 mg lorazepam.

STORAGE INSTRUCTIONS:
Protect from light.
Keep refrigerated at 2°C to 8°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
JX/2.6/295

NAME AND BUSINESS ADDRESS OF APPLICANT:
AKROMED PRODUCTS (PTY) LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton        2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
5 March 1985.

Trademark and product under licence of WYETH-AYERST LABORATORIES, U.S.A.

308429        030801
Harry's Printers-K00000 H03

Updated on this site: January 2005
Source: Pharmaceutical Industry
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2005