Consumer medicine information

APO-Lorazepam

Lorazepam

BRAND INFORMATION

Brand name

APO-Lorazepam

Active ingredient

Lorazepam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Lorazepam.

What is in this leaflet

This leaflet answers some common questions about this medicine. It does not contain all 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 this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What this medicine is used for

APO-Lorazepam tablets contain the active ingredient lorazepam.

Lorazepam is used to relieve anxiety or used before surgery to help you relax. However, anxiety or tension associated with the normal stress of everyday life usually does not require treatment with medicines.

Lorazepam belongs to a group of medicines called benzodiazepines, thought to work by their action on brain chemicals.

In general, benzodiazepines such as lorazepam, should be taken for short periods only (e.g. 2 to 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 this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

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

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

  • any medicine containing lorazepam
  • any other medicine from the benzodiazepine group of medicines
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine if you have any of the following medical conditions:

  • severe and chronic lung disease
  • sleep apnoea, a condition where you have breathing problems when you sleep
  • depression with or without anxiety problems.

Do not take this medicine if you are pregnant. It may affect your developing baby if you take it during pregnancy.

APO-Lorazepam may affect the development of newborn babies and cause breathing difficulty, muscle stiffness, a drop in body temperature or yellowing of the skin.

Babies born to mothers who take APO-Lorazepam throughout their pregnancy may be at risk of withdrawal symptoms. The baby may require ventilation at birth.

Do not breastfeed if you are taking this medicine. Lorazepam passes into breast milk and there is a possibility that your baby may be affected.

Do not give this medicine to a child under the age of 16 years. Safety and effectiveness in children younger than 16 years have not been established.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • 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

Tell your doctor if you drink alcohol regularly. Alcohol may increase the effects of lorazepam.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

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

Some medicines and lorazepam may interfere with each other. 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 be affected by lorazepam or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take this medicine

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the directions, ask your doctor or pharmacist for help.

How much to take

The dose of lorazepam 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 lorazepam 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 the tablets with a full glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take this medicine before or after food.

How long to take it

Do not take this medicine for longer than your doctor says.

Lorazepam is usually used for short periods only (e.g. 2 to 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.

If you forget to take it

If it is almost time to take 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 your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

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 this medicine for insomnia due to anxiety and forget to take it before you go to bed, do not take it if you wake up late in the night or early morning. Taking lorazepam late at night or early in the morning may make it hard for you to wake in the morning.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include feeling drowsy, confused, tired, dizzy, weak, having difficulty breathing, or becoming unconscious.

While you are using this medicine

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine.

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.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

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

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.

Things you must not do

Do not drive or operate machinery until you know how this medicine 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 lorazepam 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 lorazepam at night, you may still be drowsy or dizzy the next day.

Do not take this medicine to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or change the dosage without checking with your doctor.

Stopping this medicine suddenly may cause some unwanted withdrawal effects. This is more common in patients that have taken high doses over longer periods of time.

Withdrawal symptoms may include insomnia, anxiety, unusual mood, fast heartbeat, panic attacks, dizziness, lack of normal movement, light sensitivity, increased sound and touch sensitivity, abnormal body sensations (e.g. feels of motion, metallic taste), confusion, hallucinations, vomiting, sweating and loss of short-term memory.

Your doctor will slowly reduce your dose before you can stop taking it completely. This will minimise these unwanted withdrawal symptoms.

Do not suddenly stop taking this medicine if you suffer from epilepsy. Stopping this medicine suddenly may make your epilepsy worse.

Do not take this medicine for a longer time than your doctor has prescribed. Lorazepam should be taken for short periods only (e.g. 2 to 4 weeks), unless advised otherwise by your doctor.

Things to be careful of

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, symptoms such as dizziness and drowsiness may be worse.

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

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 taking this medicine.

This medicine helps most people with anxiety, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

Tell your doctor or pharmacist if you notice any of the following and they worry you:

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

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

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

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • symptoms of an allergic reaction including cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

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

Storage and Disposal

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack, they may not keep well.

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

Do not store this medicine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. 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 this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

APO-Lorazepam 1 mg

White, round, flat, bevelled, scored tablets, with the inscription “1.0” on one side. AUST R 304306.

Available in blister packs of 50 tablets.

APO-Lorazepam 2.5 mg

White, round, flat, bevelled, scored tablets. AUST R 304307.

Available in blister packs of 50 tablets.

*Not all strengths are available.

Ingredients

This medicine contains 0.5, 1 or 2.5 mg of lorazepam as the active ingredient.

This medicine also contains the following:

  • maize starch
  • microcrystalline cellulose
  • sodium starch glycollate (Type A)
  • lactose monohydrate
  • povidone
  • crospovidone
  • magnesium stearate
  • polacrillin potassium

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

Distributor

This medicine is distributed in Australia by:

Arrotex Pharmaceuticals
15 – 17 Chapel St
Cremorne VIC 3121

This leaflet was prepared in September 2024.

Published by MIMS October 2024

BRAND INFORMATION

Brand name

APO-Lorazepam

Active ingredient

Lorazepam

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Lorazepam.

2 Qualitative and Quantitative Composition

APO-Lorazepam immediate release tablets contain the active ingredient lorazepam.
Each APO-Lorazepam 1 mg tablet contains 1 mg of lorazepam.
Each APO-Lorazepam 2.5 mg tablet contains 2.5 mg of lorazepam.
Lorazepam is a white or almost white crystalline powder.
APO-Lorazepam contains lactose, for the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Lorazepam 1 mg immediate release tablets are white, round, flat, beveled and scored with the inscription "1.0" on one side.
APO-Lorazepam 2.5 mg immediate release tablets are white, round, flat, beveled and scored tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

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.
Presurgical medication taken the night before surgery and/or 1-2 hours prior to the surgical procedure.

4.2 Dose and Method of Administration

APO-Lorazepam 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 APO-Lorazepam 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, Duration of treatment).
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 APO-Lorazepam in patients who have been taking medication for several weeks should be evaluated, periodically.
For presurgical medication, a dosage of 2-4 mg of APO-Lorazepam is recommended the night before surgery and/or 1-2 hours prior to the surgical procedure.
APO-Lorazepam is not recommended for children.

4.3 Contraindications

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

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

Use in renal or hepatic impairment.

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.

Depression, psychosis and schizophrenia.

Lorazepam 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 behaviour;
Confusional states: disorientation, derealisation, depersonalization and/or clouding of consciousness; and
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, lorazepam should be discontinued.

Geriatric 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.

Impaired respiratory function.

Caution in the use of lorazepam 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.

Use in the elderly.

Lower doses should be used in elderly patients (see Section 4.2 Dose and Method of Administration).

Abuse.

Caution must be exercised in administering lorazepam 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, hyperreflexia 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, Lorazepam 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 cardio-vascular depression (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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 lorazepam, 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 lorazepam and, unlike many benzodiazepines, pharmacokinetic interactions involving the P450 system have not been observed with lorazepam.
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 preimplantation 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 childbearing 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.

Nonteratogenic 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 lorazepam is given to breastfeeding women. Lorazepam 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 lorazepam should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from lorazepam therapy. Abilities may be impaired on the day following use.

4.8 Adverse Effects (Undesirable Effects)

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).

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

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.
Following overdosage with oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airways protected if the patient is comatose. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. 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.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

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 presynaptic inhibition mediated by gamma-aminobutyric acid or by directly affecting the action potential generating mechanisms.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Lorazepam is readily absorbed when given orally. Peak concentrations in plasma occur approximately 2 hours following administration. The half-life of lorazepam in human plasma is approximately 12-16 hours. At clinically relevant concentrations, lorazepam is approximately 90% bound to plasma proteins.

Distribution.

The plasma levels of lorazepam are proportional to the dose given. There is no evidence of excessive accumulation of lorazepam on administration up to 6 months nor is there any indication of induction of drug-metabolising enzymes under these conditions. Lorazepam is not a substrate for N-dealkylating enzymes of the cytochrome P450 system nor is it hydroxylated to any significant extent.

Metabolism.

Lorazepam is metabolised in the liver, mainly to the inactive glucuronide of lorazepam.

Excretion.

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 lorazepam.
Studies comparing young and elderly subjects have shown that the pharmacokinetics of lorazepam 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

Lorazepam 1 mg and 2.5 mg tablets contain the following inactive ingredients: maize starch, microcrystalline cellulose, sodium starch glycollate type A, lactose monohydrate, povidone, crospovidone, magnesium stearate, polacrilin potassium.

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. Protect from light and store in original container.

6.5 Nature and Contents of Container

Lorazepam tablets are available in PA/Al/PVC/Al blister packs.
1 mg and 2.5 mg in blister packs of 50 tablets.

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

Chemical structure.


Chemical name: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one.
Molecular formula: C15H10Cl2N2O2.
Molecular weight: 321.2.

CAS number.

846-49-1.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes