Consumer medicine information

Ativan

Lorazepam

BRAND INFORMATION

Brand name

Ativan Tablets

Active ingredient

Lorazepam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ativan.

What is in this leaflet

This leaflet answers some common questions about ATIVAN. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking ATIVAN against the benefits this medicine is expected to have for you.

Ask your doctor or pharmacist if you have any concerns about taking this medicine.

Keep this leaflet with the medicine.

You may need to read it again.

What ATIVAN is used for

ATIVAN contains lorazepam as the active ingredient which belongs to a group of medicines called benzodiazepines. They are thought to work by their action on brain chemicals.

ATIVAN is used to relieve anxiety. However anxiety or tension associated with the normal stress of everyday life usually does not require treatment with medicines.

It is also used before surgery to help relax you.

In general, benzodiazepines such as ATIVAN should be taken for short periods only (for example 2-4 weeks). Continuous long term use is not recommended unless advised by your doctor. The use of benzodiazepines may lead to dependence on the medicine.

Ask your doctor if you have any questions about why ATIVAN has been prescribed for you.

Your doctor may have prescribed it for another purpose.

This medicine is available only with a doctor’s prescription.

Before you take it

When you must not take it

Do not take ATIVAN if:

  1. you are allergic to:
  • lorazepam or any of the ingredients listed at the end of this leaflet
  • any other medicine from the benzodiazepine group of medicines.
  1. you have severe and chronic lung disease
  2. you have sleep apnoea, a condition where you have breathing problems when you sleep.
  3. you are depressed with or without anxiety problems.
    Lorazepam can increase thoughts of death or suicide.

Do not take ATIVAN if the packaging is torn or shows signs of tampering.

Do not take ATIVAN after the expiry date (EXP) printed on the pack.

If you take it after the expiry date has passed, it may not work as well or have no effect at all.

Do not give this medicine to children unless advised by the child’s doctor.

The safety and effectiveness of ATIVAN in children under 16 years has not been established.

Before you take it

You must tell your doctor if:

  1. you have any allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. you are pregnant or planning to become pregnant
    Do not take ATIVAN if you are pregnant or planning to become pregnant unless you and your doctor have discussed the risks and benefits involved.
  2. you are breast-feeding or plan to breast-feed
    Do not take ATIVAN if you are breast-feeding or planning to breast-feed unless you and your doctor have discussed the risks and benefits involved.
  3. you have or have had any other medical conditions including:
  • liver, kidney or lung disease
  • blood disorders
  • fits or convulsions
  • severe muscle weakness known as myasthenia gravis
  • low blood pressure
  • glaucoma (high pressure in the eye)
  • depression, psychosis or schizophrenia.
  1. you drink alcohol regularly.
    Alcohol may increase the effects of ATIVAN.

If you have not told your doctor about any of the above, tell them before you take any ATIVAN.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interfere with ATIVAN. These include:

  • other sleeping tablets, sedatives or tranquillisers
  • medicines for depression
  • medicines for allergies for example antihistamines or cold tablets
  • pain relievers
  • muscle relaxants
  • medicines to control fits.

These medicines may increase the effects of ATIVAN. You may need to take different amounts of your medicine or you may need to take different medicines. Your doctor will advise you.

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while taking ATIVAN.

How to take it

How much to take

The dose of ATIVAN may be different for each person. Your doctor will decide the right dose for you.

For anxiety, the usual daily dose is 2 to 3 mg administered in divided doses. However, the daily dose can range from 1 to 10 mg.

For sleeping problems (insomnia) due to anxiety, a dose of 1 to 2 mg taken at bedtime is usually prescribed.

If you are taking ATIVAN before surgery the usual dose is 2 to 4 mg the night before surgery. Another dose of 2 to 4 mg may also be given 1 to 2 hours before surgery.

Elderly people may need a lower dose.

How to take it

Swallow ATIVAN with a glass of water.

It may be taken with or without food.

When to take it

Your doctor will tell you how many times during the day you need to take ATIVAN.

How long to take it

Do not take ATIVAN for longer than your doctor says.

ATIVAN is usually used for short periods only (for example 2-4 weeks). Continuous long term use is not recommended unless advised by your doctor. The use of benzodiazepines may lead to dependence on the medicine.

Continue taking ATIVAN as long as your doctor recommends it.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the dose that you missed.

If you have missed more than two doses in a row, speak to your doctor or pharmacist.

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

If you are taking ATIVAN for insomnia due to anxiety and forget to take ATIVAN before you go to bed, do not take any ATIVAN if you wake up late in the night or early morning.

Taking ATIVAN late at night or early in the morning may make it hard for you to wake in the morning. If you have any questions about this, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (in Australia telephone 13 11 26, in New Zealand telephone 0800 764 766) for advice, or go to casualty at your nearest hospital, if you think that you or anyone else may have taken too much ATIVAN. Do this even if there are no signs of discomfort or poisoning. Also report any other medicine or alcohol which has been taken.

You may need urgent medical attention.

If you take too much ATIVAN you may feel drowsy, confused, tired, dizzy, have difficulty breathing, feel weak or become unconscious.

While you are taking it

Things you must do

Take ATIVAN exactly as your doctor has prescribed.

Tell all doctors, dentists and pharmacists who are treating you that you are taking ATIVAN.

If you become pregnant while you are taking ATIVAN, tell your doctor immediately.

Tell your doctor if you feel ATIVAN is not helping your condition.

If you are being treated for anxiety, be sure to discuss with your doctor any problems you may have and how you feel, especially if your anxiety attacks are getting worse or more frequent.

This will help your doctor to determine the best treatment for you.

Visit your doctor regularly.

Your doctor needs to check your progress and see whether you need to keep taking ATIVAN.

Always discuss with your doctor any problems or difficulties you have during or after taking ATIVAN.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Otherwise your doctor may think that it was not effective and change your treatment unnecessarily.

Keep enough ATIVAN to last weekends and holidays.

Things you must not do

Do not drive or operate machinery until you know how ATIVAN affects you.

This medicine may cause drowsiness or dizziness in some people and therefore may affect alertness.

Make sure you know how you react to ATIVAN before you drive a car, operate machinery, or do anything else that could be dangerous if you are drowsy, dizzy or not alert.

Even if you take ATIVAN at night, you may still be drowsy or dizzy the next day.

Do not take ATIVAN for a longer time than your doctor has prescribed.

ATIVAN should be taken for short periods only (for example 2 to 4 weeks), unless advised otherwise by your doctor.

Do not change your dose without first checking with your doctor.

Do not stop taking ATIVAN or lower the dose, without first checking with your doctor.

Stopping this medicine suddenly may cause some unwanted effects. Your doctor will slowly reduce your dose before you can stop taking it completely.

Do not suddenly stop taking ATIVAN if you suffer from epilepsy.

Stopping this medicine suddenly may make your epilepsy worse.

Do not use this medicine to treat any other complaints unless your doctor says to.

Do not give ATIVAN to anyone else, even if their symptoms seem similar to yours.

Things to be careful of

Be careful when drinking alcohol while taking ATIVAN.

Combining ATIVAN and alcohol can make you more sleepy, dizzy or lightheaded.

Your doctor may suggest that you avoid alcohol or reduce the amount of alcohol you drink while you are taking ATIVAN.

Be careful if you are elderly, unwell or taking other medicines.

Some people may experience side effects such as drowsiness, confusion, dizziness and unsteadiness, which may increase the risk of a fall.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using ATIVAN.

ATIVAN helps most people with anxiety but it may have unwanted side effects in some people.

All medicines may have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

If side effects do happen, they are more likely to happen when you first start taking ATIVAN. These side effects may go away during treatment as your body adjusts to the dose.

However, tell your doctor if you notice any of the following and they worry you:

  • drowsiness
  • dizziness
  • sleepiness
  • clumsiness or unsteadiness
  • weakness
  • loss of memory.

These are the more common side effects of ATIVAN.

Other less common or rare side effects include:

  • skin rashes
  • feeling sick or vomiting
  • outbursts of anger and increased excitement
  • confusion or depression
  • headache
  • sleep disturbances
  • blurred vision
  • low blood pressure
  • dry mouth
  • excessive salivation
  • changes in appetite
  • nausea.

Tell your doctor if you notice anything else that is making you feel unwell when you are taking, or soon after you have finished taking, ATIVAN.

Other side effects not listed above may occur in some people.

Ask your doctor or pharmacist if there is anything you don’t understand.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After taking it

Storage

Keep ATIVAN in a cool dry place where the temperature stays below 25°C.

Keep your tablets in their blister pack until it is time to take them.

If you take the tablets out of the box or the blister pack they may not keep well.

Do not store it or any other medicines, in a bathroom or near a sink. Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking ATIVAN or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets left over.

Product description

What it looks like

ATIVAN 1 mg tablets are white with a score to make them easy to split. They are plain on the back and with “1 L” debossed on the front face, the break bar separating the ‘1’ and ‘L.’

ATIVAN 2.5 mg tablets are yellow with a deep score to make them easy to split. They are plain on the back and debossed “2.5 L” on the front face, the break bar separating the ‘2.5’ and ‘L’.

To break tablet, place on a hard surface with score facing upwards and press gently on the tablet with your thumb.

ATIVAN 1 mg and 2.5 mg tablets are supplied in blister packs or glass bottles in Australia. Each pack contains 50 tablets.

ATIVAN 1 mg and 2.5 mg tablets are supplied in glass bottles in New Zealand. ATIVAN 1 mg bottles contain 250 tablets and ATIVAN 2.5 mg bottles contain 100 tablets.

Ingredients

Active ingredient:

Each ATIVAN 1 mg tablet contains 1 mg lorazepam.

Each ATIVAN 2.5 mg tablet contains 2.5 mg lorazepam.

Inactive ingredients:

  • magnesium stearate
  • cellulose-microcrystalline
  • polacrilin potassium
  • lactose
  • iron oxide yellow (2.5 mg only)
  • quinoline yellow (2.5 mg only).

ATIVAN does not contain gluten, sucrose, tartrazine or any other azo dyes.

BRAND INFORMATION

Brand name

Ativan Tablets

Active ingredient

Lorazepam

Schedule

S4

 

1 Name of Medicine

Lorazepam.

2 Qualitative and Quantitative Composition

Tablets are available in 1 mg and 2.5 mg strengths with lorazepam as the active ingredient.

Excipient with known effect.

Lactose monohydrate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablets.
1 mg (white, round scored tablet, plain on one side and debossed '1 L' on the scored face with break bar between the 1 and L).
2.5 mg (yellow, round, plain on one side and debossed with '2.5 L' on scored face, with E.Z split break bar separating the 2.5 and L).
E.Z. split tablets have enlarged score bar for easy breaking. To break tablet, place on hard surface with score facing upwards and press gently on tablet with thumb.

4 Clinical Particulars

4.1 Therapeutic Indications

Ativan is indicated for:
1. Management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms.
Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The physician should periodically reassess the usefulness of the drug for the individual patient.
2. Pre-surgical medication taken the night before surgery and/or 1-2 hours prior to the surgical procedure.

4.2 Dose and Method of Administration

Ativan is administered orally. For optimal results, dose, frequency of administration and duration of therapy should be individualised according to patient response. Dosage should be individualised for maximum beneficial effect. In patients previously treated with anxiolytic agents, higher initial dosages of Ativan may be indicated.
The average daily dosage for treatment of anxiety is 2-3 mg administered in divided doses, however, this may range between 1 and 10 mg.
For insomnia due to anxiety or transient situational stress, a single daily dose of 1-2 mg may be given, usually at bedtime.
For patients with anxiety and/or insomnia, the duration of treatment should not exceed 4 weeks, including tapering off process (see Section 4.4 Special Warnings and Precautions for Use).
For elderly or debilitated patients, an initial dosage of 1 or 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated.
The need for continued therapy with Ativan in patients who have been taking medication for several weeks should be evaluated, periodically.
For pre-surgical medication, a dosage of 2-4 mg of Ativan is recommended the night before surgery and/or 1-2 hours prior to the surgical procedure.
Ativan is not recommended for children.

4.3 Contraindications

Ativan is contraindicated in:
Patients with a known hypersensitivity to benzodiazepines.
Patients with chronic obstructive airways disease with incipient respiratory failure.
Patients with sleep apnoea.
Lorazepam should not be used as monotherapy in patients with depression, or symptoms of anxiety associated with depression, due to a risk of suicide (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Following the prolonged use of Ativan at therapeutic doses withdrawal from the medication should be gradual. An individualised withdrawal timetable needs to be planned for each patient in whom dependence is known or suspected. Periods from four weeks to four months have been suggested. As with other benzodiazepines, when treatment is suddenly withdrawn, a temporary increase of sleep disturbance can occur after use of Ativan (see Dependence).

Duration of treatment.

In general, benzodiazepines should be prescribed for short periods only (e.g. 2-4 weeks).
For patients with anxiety and/or insomnia the duration of treatment should not exceed 4 weeks (including tapering off process).
Continuous long-term use of Ativan is not recommended.

Tolerance.

There is evidence that tolerance develops to the sedative effects of benzodiazepines. Tolerance as defined by a need to increase the dose in order to achieve the same therapeutic effect seldom occurs in patients receiving recommended doses under medical supervision. Tolerance to sedation may occur with benzodiazepines especially those with drug seeking behaviour.
After as little as one week of therapy withdrawal symptoms can appear following the cessation of recommended doses (e.g. rebound insomnia following cessation of a hypnotic benzodiazepine).
Although hypotension has occurred only rarely, Ativan should be administered with caution to patients in whom a drop in blood pressure might lead to cardiac or cerebral complications. This is particularly important in elderly patients.
Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines.
Ativan could increase the muscle weakness in myasthenia gravis and should be used with caution in this condition.
Caution should be used in the treatment of patients with acute narrow-angle glaucoma (because of atropine-like side effects).

Depression, psychosis and schizophrenia.

Ativan is not recommended as primary therapy in patients with depression and psychosis. In such conditions, psychiatric assessment and supervision are necessary if benzodiazepines are indicated. Benzodiazepines may increase depression in some patients, and may contribute to deterioration in severely disturbed schizophrenics with confusion and withdrawal. Suicidal tendencies may be present or uncovered and protective measures may be required. Therefore, benzodiazepines should be used with caution and the prescription size should be limited, in patients with signs and symptoms of a depressive disorder or suicidal tendencies.

CNS and/or paradoxical reactions.

As with other benzodiazepines and CNS active drugs, three idiosyncratic symptom clusters, which may overlap, have been described.

Amnestic symptoms.

Anterograde amnesia with appropriate or inappropriate behavior.

Confusional states.

Disorientation, derealisation, depersonalization and/or clouding of consciousness.

Agitational states.

Sleep disturbances, restlessness, irritability, aggression and excitation.
Lorazepam should be discontinued if confusion or agitation occurs.
Paradoxical reactions such as acute rage, stimulation or excitement may occur. Should such reactions occur, Ativan should be discontinued.

Impaired respiratory function.

Caution in the use of Ativan is recommended in patients with respiratory depression. In patients with chronic obstructive pulmonary disease, benzodiazepines can cause increased arterial carbon dioxide tension and decreased arterial oxygen tension.

Epilepsy.

Abrupt withdrawal of benzodiazepines in patients with convulsive disorders may be associated with a temporary increase in the frequency and/or severity of seizures.

Abuse.

Caution must be exercised in administering Ativan to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative. It is desirable to limit repeat prescription without adequate medical supervision.

Dependence.

The use of benzodiazepines may lead to dependence as defined by the presence of a withdrawal syndrome on discontinuation of the drug. Withdrawal symptoms similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuation of benzodiazepines. These symptoms can range from insomnia, anxiety, dysphoria, palpitations, panic attacks, vertigo, myoclonus, akinesia, hypersensitivity to light, sound and touch, abnormal body sensations (e.g. feelings of motion, metallic taste), depersonalisation, derealisation, delusional beliefs, hyper-reflexia and loss of short term memory, to a major syndrome which may include convulsions, tremor, abdominal and muscle cramps, confusional states, delirium, hallucinations, hyperthermia, psychosis, vomiting and sweating. Such manifestations of withdrawal, especially the more serious ones, are more common in those patients who have received excessive doses over a prolonged period. However, withdrawal symptoms have also been reported following abrupt discontinuation of benzodiazepines taken continuously at therapeutic levels. Accordingly, Ativan should be terminated by tapering the dose to minimise occurrence of withdrawal symptoms. Patients should be advised to consult with their physician before either increasing the dose or abruptly discontinuing the medication.
Rebound phenomena have been described in the context of benzodiazepine use. Rebound insomnia and anxiety mean an increase in the severity of these symptoms beyond pre-treatment levels following cessation of benzodiazepines. Rebound phenomena in general possibly reflect re-emergence of pre-existing symptoms combined with withdrawal symptoms described earlier. Some patients prescribed benzodiazepines with very short half-lives (in the order of 2 to 4 hours) may experience relatively mild rebound symptoms in between their regular doses. Withdrawal/rebound symptoms may follow high doses taken for relatively short periods.

Concomitant use with alcohol/CNS depressants.

The concomitant use of lorazepam with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of lorazepam which may include severe sedation, clinically relevant respiratory and/or cardiovascular depression (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic and renal impairment.

Impaired renal/liver function and blood dyscrasias.

Patients with impaired renal or hepatic function should use benzodiazepine medication with caution and dosage reduction may be advisable. In rare instances some patients taking benzodiazepines have developed blood dyscrasias, and some have had elevations of liver enzymes. As with other benzodiazepines, periodic blood counts and liver function tests are recommended.

Use in the elderly or debilitated patients.

Such patients may be particularly susceptible to the sedative effects of benzodiazepines and associated giddiness, ataxia and confusion which may increase the possibility of a fall.
Lower doses should be used in elderly patients (see Section 4.2 Dose and Method of Administration).

Paediatric use.

The safety and effectiveness of lorazepam has not been established in children less than 16 years of age.

Paediatric neurotoxicity.

Some published studies in children have observed cognitive deficits after repeated or prolonged exposures to anaesthetic agents early in life. These studies have substantial limitations, and it is not clear if the observed effects are due to the anaesthetic/analgesic/sedation drug administration or other factors such as the surgery or underlying illness.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy. The clinical significance of these nonclinical finding is yet to be determined.
Depending on the drug and patient characteristics, as well as dosage, the elimination phase may be prolonged relative to the period of administration resulting in longer exposure to the drug.

Effects on laboratory tests.

No interference with laboratory tests have been identified or reported with the use of lorazepam.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The benzodiazepines, including Ativan, produce additive CNS depressant effects when coadministered with other medications which themselves produce CNS depression, e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, nonselective MAO inhibitors, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anaesthetics.
The cytochrome P450 system has not been shown to be involved in the disposition of Ativan and, unlike many benzodiazepines, pharmacokinetic interactions involving the P450 system have not been observed with Ativan.
The anticholinergic effects of other drugs including atropine and similar drugs, antihistamines and antidepressants may be potentiated.
Interactions have been reported between some benzodiazepines and anticonvulsants, with changes in the serum concentration of the benzodiazepine or anticonvulsant. It is recommended that patients be observed for altered responses when benzodiazepines and anticonvulsants are prescribed together, and that serum level monitoring of the anticonvulsant be performed more frequently.
Minor EEG changes, usually low voltage fast activity, of no known clinical significance, have been reported with benzodiazepine administration.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A pre-implantation study in rats was performed with oral lorazepam at a 20 mg/kg dose which showed no impairment of fertility.
(Category C)
Benzodiazepines cross the placenta and may cause hypotonia, reduced respiratory function and hypothermia in the newborn infant. Continuous treatment during pregnancy and administration of high doses in connection with delivery should be avoided. Withdrawal symptoms in newborn infants have been reported with this class of drugs.
The use of benzodiazepines during the first trimester of pregnancy should almost always be avoided. If the drug is prescribed to a woman of child-bearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant.
Neonates appear to conjugate lorazepam slowly, the glucuronide being detectable in the urine for more than seven days. Glucuronidation of lorazepam may competitively inhibit the conjugation of bilirubin, leading to hyperbilirubinaemia in the newborn.

Non-teratogenic effects.

The use of benzodiazepines during the late phase of pregnancy or at delivery may require ventilation of the infant at birth.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy.
Published studies in pregnant and juvenile animals demonstrate that the use of anaesthetic/analgesic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of rapid brain growth or synaptogenesis may result in neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis when used for longer than 3 hours. These studies included anaesthetic agents from a variety of drug classes.
Caution should be exercised when Ativan is given to breastfeeding women. Ativan is excreted in human breast milk and may cause drowsiness and feeding difficulties in the infant.

4.7 Effects on Ability to Drive and Use Machines

As with all patients taking CNS-depressant medications, patients receiving Ativan should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from Ativan therapy. Abilities may be impaired on the day following use.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

More common reactions.

The more common adverse reactions, if they occur, are usually observed at the beginning of therapy and generally decreases in severity or disappears on continued medication or upon decreasing the dose.

Nervous system.

Anterograde amnesia, dizziness, sedation.

Musculoskeletal.

Unsteadiness, weakness.

Less common reactions.

Autonomic manifestations.

Dry mouth, hypersalivation.

Dermatological.

Rash.

Gastrointestinal.

Nausea, vomiting.

Miscellaneous.

Change in appetite.

Nervous system.

Disorientation, headache, sleep disturbances.

Ocular.

Eye function disturbances.

Psychiatric.

Agitation, depression.
Paradoxical reactions such as stimulation, excitement or rage rarely occur (see Section 4.4 Special Warnings and Precautions for Use).

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Overdosage of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy. In more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, coma, and very rarely proves fatal.

Treatment.

In the management of overdosage with any medication, it should be borne in mind that multiple agents may have been taken.
Treatment of overdose is supportive and symptomatic. If an overdose of oral benzodiazepines has been taken within 1 - 2 hours, consider activated charcoal which may reduce absorption. In patients who are not fully conscious or who have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Hypotension and respiratory depression should be managed according to general principles. Haemoperfusion and haemodialysis are not useful in benzodiazepine intoxication. The benzodiazepine antagonist flumazenil may be used in hospitalised patients for the reversal of acute benzodiazepine effects. Please consult the flumazenil product information prior to usage.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The exact mechanism of action of benzodiazepines has not yet been elucidated; however, benzodiazepines appear to work through several mechanisms. Benzodiazepines presumably exert their effects by binding to specific receptors at several sites within the central nervous system either by potentiating the effects of synaptic or pre-synaptic inhibition mediated by gamma-aminobutyric acid or by directly affecting the action potential generating mechanisms.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Ativan is readily absorbed when given orally. Peak concentrations in plasma occur approximately 2 hours following administration. The half-life of Ativan in human plasma is approximately 12-16 hours. At clinically relevant concentrations, Ativan is approximately 90% bound to plasma proteins.
Lorazepam is metabolised in the liver, mainly to the inactive glucuronide of lorazepam. Seventy to seventy-five per cent of the dose is excreted as the glucuronide in the urine. The glucuronides of lorazepam have no demonstrable CNS activities in animals, and there are no active metabolites of Ativan.
The plasma levels of Ativan are proportional to the dose given. There is no evidence of excessive accumulation of Ativan on administration up to 6 months nor is there any indication of induction of drug-metabolising enzymes under these conditions. Ativan is not a substrate for N-dealkylating enzymes of the cytochrome P450 system nor is it hydroxylated to any significant extent.
Studies comparing young and elderly subjects have shown that the pharmacokinetics of Ativan remain unaltered with advancing age. No changes in absorption, distribution, metabolism and excretion were reported in patients with hepatic disease (hepatitis, alcoholic cirrhosis). As with other benzodiazepines, the pharmacokinetics of lorazepam may change in patients with impaired renal function and the medication should be used with caution.

5.3 Preclinical Safety Data

Genotoxicity.

An investigation of the mutagenic activity of lorazepam on Drosophila melanogaster indicated that it was mutationally inactive.

Carcinogenicity.

No evidence of carcinogenic potential emerged in rats or mice during an 18-month study with oral lorazepam.

6 Pharmaceutical Particulars

6.1 List of Excipients

Cellulose-microcrystalline, lactose, magnesium stearate and polacrillin potassium. The 2.5 mg also contains iron oxide yellow and quinolone yellow.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

1 mg.

5's* and 50's available in blister packs (PVC/PVDC/Al or aluminium/aluminium) or amber glass bottles with child resistant caps.

2.5 mg.

50's available in PVC/PVDC/Al or Aluminium/Aluminium blister packs or amber glass bottles with child resistant caps.
*Not all presentations are actively marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Lorazepam is a nearly white powder which is almost insoluble in water and slightly soluble in alcohol and chloroform.
Lorazepam is a 1,4 benzodiazepine with the chemical name 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one. The molecular weight is 321.2.

Chemical structure.


CAS number.

CAS: 846-49-1.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes