Consumer medicine information

Alodorm

Nitrazepam

BRAND INFORMATION

Brand name

Alodorm

Active ingredient

Nitrazepam

Schedule

What is in this leaflet

This leaflet answers some common questions about Alodorm.

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 benefits and risks. Your doctor has weighed the risks of you taking Alodorm against the benefits expected for you.

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

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

What Alodorm is used for

Alodorm is used to treat insomnia (sleeping problems).

Alodorm contains the active ingredient nitrazepam, which belongs to a group of medicines called benzodiazepines. These medicines are thought to work by their action on brain chemicals.

Ask your doctor if you have any questions about why Alodorm has been prescribed for you. Your doctor may have prescribed Alodorm for another reason.

In general, benzodiazepines such as Alodorm should be taken for short periods only (for example 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.

Alodorm is available only with a doctor's prescription.

Before you take Alodorm

When you must not take it

Do not take Alodorm if you are allergic to:

nitrazepam
any other benzodiazepine medicines such as diazepam, temazepam, oxazepam, alprazolam and clonazepam
any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

Do not take Alodorm if you have:

severe and chronic lung disease (e.g. chronic obstructive airway disease) and difficulty breathing
severe liver disease.

Do not take Alodorm 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.

Do not give Alodorm to a child unless advised by the child's doctor. The safety and effectiveness of this medicine in children have not been established.

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 are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Like other benzodiazepine medicines, Alodorm may cause unwanted effects in the newborn baby if used during pregnancy. Your doctor will discuss the risks and benefits of taking Alodorm during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. Alodorm passes into breast milk and may cause drowsiness and/or feeding problems in the baby. Your doctor will discuss the risks and benefits of taking Alodorm when breastfeeding.

Tell your doctor if you have any medical conditions, especially the following:

liver, kidney or lung disease
high or low blood pressure
glaucoma (increased pressure in the eye)
myasthenia gravis, a condition where there is severe muscle weakness
depression, psychosis or schizophrenia
epilepsy, fits or convulsions.

Your doctor may want to take special care if you have any of these conditions.

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

Tell your doctor if you have a history of fall or are unsteady when walking.

Tell your doctor if you plan to have surgery.

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

Taking other medicines

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

Some medicines may be affected by Alodorm, or may affect how well it works. These include:

other sleeping tablets, sedatives or tranquillisers
medicines for depression
medicines used to treat epilepsy
antihistamines, medicines for allergies, colds or travel sickness
muscle relaxants
pain relievers such as opioid medicines
cimetidine, a medicine used to treat reflux and stomach ulcers
disulfiram, a medicine used to deter alcohol consumption.

These medicines may increase the effects of Alodorm or be affected by it. You may need to take different amounts of your medicine or you may need to take different medicines.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Alodorm.

How to take Alodorm

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

If you do not understand the instructions on the label, ask your doctor or pharmacist.

How much to take

The dose may vary from person to person.

Your doctor will tell you how many tablets you need to take each day.

The usual adult dose is 5 mg to 10 mg (one to two tablets) at bedtime.

For the elderly, the recommended dose is 2.5 mg to 5 mg (half to one tablet) at bedtime.

Alodorm is not recommended for children.

How to take it

Swallow the tablets with a glass of water.

If you forget to take it

If you forget to take Alodorm before you go to bed and you wake up late in the night or early in the morning, do not take Alodorm as you may have trouble waking in the morning.

If you have any questions about this, check with your doctor or pharmacist.

How long to take it

Take Alodorm only for as long as your doctor recommends.

Usually, Alodorm should be taken for short periods only (for example 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 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 you or anyone else may have taken too much Alodorm.

Do this even if there are no signs of discomfort or poisoning. Also report if any other medicine or alcohol has been taken. You may need urgent medical attention.

If you take too much Alodorm, the mild symptoms are drowsiness, mental confusion and lethargy. In more serious cases, symptoms are inability to move, loss of muscle tone, hypotension, breathing difficulties, coma and very rarely death.

While you are taking Alodorm

Things you must do

Take Alodorm exactly as your doctor has prescribed.

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

If you plan to have surgery that requires a general anaesthetic, tell your doctor or dentist that you are taking Alodorm.

Before starting any new medicine, tell your doctor or pharmacist that you are taking Alodorm.

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

Visit your doctor regularly. Your doctor needs to check your progress to see whether you need to keep taking Alodorm. You may also need to have tests to check your blood and liver function.

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

Things you must not do

Do not drive or operate machinery until you know how Alodorm affects you. Alodorm may cause drowsiness or dizziness in some people. Even though you take Alodorm at night, you may still be drowsy or dizzy the next day. Make sure you know how you react to Alodorm before you drive a car, operate machinery or do anything else that could be dangerous. This is very important if you are taking other drugs that also make you drowsy.

Do not take Alodorm for a longer time than your doctor has prescribed. Alodorm should be taken for short periods only (for example 2 to 4 weeks) unless advised otherwise by your doctor.

Do not stop taking Alodorm, or change the dose, without checking with your doctor. Stopping Alodorm suddenly may cause some unwanted effects. Your doctor may want you to gradually reduce the amount of Alodorm you are taking before stopping completely.

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

Do not use Alodorm to treat any other conditions unless your doctor tells you to.

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

Things to be careful of

Some sleep medicines may cause short-term memory loss. When this occurs, a person may not remember what has happened for several hours after taking the medicine. This is usually not a problem since most people fall asleep after taking the medicine. To reduce this risk, ensure that you are able to get a full night's sleep (7 to 8 hours) before you need to be active again.

Be careful drinking alcohol while taking Alodorm. Combining alcohol with Alodorm can make you more drowsy, dizzy or lightheaded, or increase the risk of sleep-walking and some other related sleep behaviours, which may include sleep-driving, making phone calls or preparing and eating food whilst asleep.

This risk is also increased if you take more than the recommended dose.

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

You should not take Alodorm if you experience complex sleep behaviours such as sleep walking, sleep driving or any other bizarre sleep-related behaviours.

Be careful if you are elderly, unwell or taking other medicines. You may have an increased chance of getting 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 Alodorm. Alodorm helps most people with insomnia and is usually well tolerated, but it may have unwanted side effects in some people.

All medicines can 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.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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

drowsiness
dizziness
fatigue
confusion
unsteadiness when walking
impairment of memory
headache
hangover feeling in the morning
slurred speech
clumsiness, lack of coordination
numbed emotions
reduced alertness
muscle weakness
double vision
inattention
unpleasant dreams
reoccurrence of insomnia

The above list includes the milder side effects of your medicine.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

swelling of the tongue or throat
difficulty in breathing.

The side effects listed above are very serious and require urgent medical attention or hospitalisation.

Like other medicines, Alodorm can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious, such as complex sleep behaviours, and need medical attention.

Tell your doctor if you notice any unusual changes in your sleep behaviour.

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

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

After using Alodorm

Storage

Keep Alodorm where children cannot reach it.

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

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

Keep your tablets in a cool dry place where the temperature stays below 25°C. Protect from light.

Do not store Alodorm or any other medicine in the bathroom or near a sink.

Do not leave Alodorm in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

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

Product description

What it looks like

Alodorm is a round white tablet marked NM/5 on one side and G on the other.

Each bottle contains 25 tablets.

Ingredients

The active ingredient in Alodorm is nitrazepam. Each Alodorm tablet contains 5 mg of nitrazepam.

The tablets also contain the following inactive ingredients:

lactose monohydrate
maize starch
pregelatinised maize starch
purified talc
colloidal anhydrous silica
magnesium stearate.

Alodorm also contains sugars (as lactose), traces of galactose and sulfites. The tablets are gluten free.

Manufacturer

Alodorm is made in Australia by:

Alphapharm Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration number:
AUST R 54009

This leaflet was prepared in
December 2020.

Alodorm_cmi\Dec20/00

Published by MIMS February 2021

BRAND INFORMATION

Brand name

Alodorm

Active ingredient

Nitrazepam

Schedule

1 Name of Medicine

Nitrazepam.

2 Qualitative and Quantitative Composition

Each tablet contains 5 mg of nitrazepam as the active ingredient.

Excipients with known effect.

Sugars (as lactose). Also contains traces of galactose and sulfites. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Nitrazepam 5 mg tablet: white, flat bevelled edged, marked NM/5 on one side, G on reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Insomnia, organic and inorganic in origin.

4.2 Dose and Method of Administration

Adults.

1 to 2 tablets (5 to 10 mg) before retiring. This average dosage may be increased if necessary up to 20 mg for in-patients.

Elderly patients.

½ to 1 tablet.

Children.

Not approved for use as a hypnotic in children.

4.3 Contraindications

Alodorm is contraindicated in:
patients with known hypersensitivity to benzodiazepines;
patients with chronic obstructive airway disease with incipient respiratory failure;
severe liver insufficiency.

4.4 Special Warnings and Precautions for Use

Hypotension.

Although hypotension has occurred only rarely, Alodorm 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 (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).

Amnesia.

Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines.

Myasthenia gravis.

Nitrazepam could increase the muscle weakness in myasthenia gravis and should be used with caution in this condition.

Acute narrow angle glaucoma.

Caution should be used in the treatment of patients with acute narrow-angle glaucoma (because of atropine-like side effects).

Bronchial hypersecretion and excessive salivation.

In infants and young children, as well as in elderly, bedridden patients, bronchial hypersecretion and excessive salivation leading to aspiration/pneumonia may occur (see Section 4.8 Adverse Effects (Undesirable Effects)).

Blood dyscrasias.

In rare instances some patients taking benzodiazepines have developed blood dyscrasias. As with other benzodiazepines, periodic blood counts are recommended.

Depression, psychosis and schizophrenia.

Alodorm is not recommended as primary therapy in patients with depression and/or 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.

Paradoxical reactions.

Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, nightmares, psychoses, inappropriate behaviour and other adverse behavioural effects, acute rage and stimulation or excitement may occur; should such reactions occur, Alodorm should be discontinued.

Impaired respiratory function.

Caution in the use of Alodorm 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 Alodorm 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 and tolerance.

The use of benzodiazepines may lead to dependence, as defined by the presence of a withdrawal syndrome on discontinuation of the drug. 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 in those with drug seeking behaviour.

Duration of treatment.

In general, benzodiazepines should be prescribed for short periods only (e.g. 2 to 4 weeks) (see Section 4.2 Dose and Method of Administration). Continuous long-term use of Alodorm is not recommended. There is evidence that tolerance develops to the sedative effects of benzodiazepines. 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).

Withdrawal.

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, Alodorm 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.

Dose tapering.

Following the prolonged use of Alodorm 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 Alodorm (see Section 4.4 Special Warnings and Precautions for Use, Dependence and tolerance).

Somnambulism and associated behaviours.

Complex behaviours have been reported with sedative hypnotics. These events can occur in sedative-hypnotic naive as well as in sedative-hypnotic experienced persons. These events can occur at normal therapeutic doses, and the risk appears to be increased when sedative-hypnotics are combined with alcohol or other CNS depressants or used at doses exceeding the maximum recommended dose. Discontinuation of sedative-hypnotics should be strongly considered for patients who reported complex behaviours whilst not fully awake after taking a sedative-hypnotic.

Angioedema.

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics. Some patients have had additional symptoms such as dyspnoea, throat closing, or nausea and vomiting that suggest anaphylaxis. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal and patients should be advised to contact the emergency department of their nearest hospital as soon as possible.

Concomitant use of opioids.

Concomitant use of nitrazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of nitrazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe nitrazepam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see Section 4.2 Dose and Method of Administration).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Lactose intolerance.

Alodorm contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Alodorm.

Use in hepatic impairment.

Patients with impaired hepatic function should use benzodiazepine medication with caution and dosage reduction may be advisable. In rare instances some patients have had elevation of liver enzymes. As with other benzodiazepines, periodic liver function tests are recommended.

Use in renal impairment.

Patients with impaired renal function should use benzodiazepine medication with caution and dosage reduction may be advisable.

Use in the elderly.

Geriatric or debilitated 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. (Also see Section 4.4 Special Warnings and Precautions for Use, Bronchial hypersecretion and excessive salivation).

Paediatric use.

Not approved for use as a hypnotic in children (See Section 4.8 Adverse Effects (Undesirable Effects)).

Effects on laboratory tests.

Minor EEG changes, usually low voltage fast activity, of no known clinical significance, have been reported with benzodiazepine administration.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The benzodiazepines, including nitrazepam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression, e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, non-selective MAO inhibitors, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anaesthetics (see Section 4.4 Special Warnings and Precautions for Use).
The concomitant use of nitrazepam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see Section 4.4 Special Warnings and Precautions for Use).
Nitrazepam undergoes oxidative metabolism, and consequently may interact with disulfiram or cimetidine, resulting in increased plasma levels of nitrazepam. Patients should be observed closely for evidence of enhanced benzodiazepine response during concomitant treatment with either disulfiram or cimetidine; some patients may require a reduction in benzodiazepine dosage.
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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Benzodiazepines cross the placenta and may cause hypotonia, respiratory depression and hypothermia in the newborn infant. Continuous treatment during pregnancy and administration of high doses in conjunction with delivery should be avoided. Withdrawal symptoms in newborn infants have been reported with prolonged use of this class of drugs.

Australian categorisation definition of category C.

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Caution should be exercised when Alodorm is given to a breastfeeding woman. Nitrazepam 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 Alodorm should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from Alodorm therapy. Abilities may be impaired on the day following use. Patients should be advised that their tolerance for alcohol and other CNS depressants will be diminished and that these medications should either be eliminated or given in reduced dosage in the presence of Alodorm (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.8 Adverse Effects (Undesirable Effects)

Alodorm is usually well tolerated.

More common reactions.

CNS depression including drowsiness, dizziness, fatigue, impairment of memory, ataxia, headache, confusion, vertigo, hangover feeling in the morning, slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, double vision and inattention have been reported. Unpleasant dreams and rebound insomnia have also been reported.

Less common reactions.

Rarely, hypotension, faintness, palpitation, rash or pruritus, gastrointestinal disturbances, changes in libido.
Very infrequently, paradoxical reactions may occur, e.g. excitement, stimulation, hallucinations, hyperactivity and insomnia. Also depressed or increased dreaming, disorientation, severe sedation, retrograde amnesia, headache, hypothermia, delirium tremens.
Hypersecretion of saliva and bronchial mucus has occurred with doses of 0.7 mg/kg/day. In infants and young children, as well as in the elderly, bed-ridden patients, bronchial hypersecretion and excessive salivation leading to aspiration/ pneumonia may occur.

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.

4.9 Overdose

Symptoms.

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, death.

Treatment.

In the management of overdosage with any medication, it should be borne in mind that multiple agents may have been taken.
Activated charcoal may reduce absorption of the drug if given within one to two hours of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Cardiac and vital signs monitoring is recommended, along with general symptomatic and supportive measures. 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 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Nitrazepam is a member of the group of benzodiazepine agonists and exhibits sedative, anxiolytic, anticonvulsant and muscle relaxant effects. This is presumed to be the result of facilitating the action in the brain of gamma-aminobutyric acid (GABA), an endogenous inhibitor neurotransmitter.
Taken in the evening in recommended doses, nitrazepam induces sleep lasting 6 to 8 hours.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Nitrazepam is well and fairly rapidly absorbed from the gastrointestinal tract. There is considerable interindividual variation in the rate of absorption with the time to reach peak plasma concentrations following oral administration about 2 hours (0.5 to 5 hours). The drug crosses the blood-brain barrier, the placenta, and is excreted in milk.
Peak plasma levels following a 10 mg single oral dose are about 68 to 108 nanogram/mL and following a 5 mg single oral dose about 25 to 50 nanogram/mL. Twelve hours after oral administration of 5 mg of nitrazepam, blood levels are about 12 to 38 nanogram/mL.

Bioavailability.

In one study comparing oral with intravenous administration, bioavailability varied from 53 to 94% (average 78%).

Distribution.

Nitrazepam is lipophilic and readily crosses body membranes.
Cerebrospinal fluid (CSF) concentration of nitrazepam is about 10% total plasma level and similar to the protein free fraction in plasma. One study observed accumulation of nitrazepam in CSF.
Nitrazepam is found in saliva at lower concentrations than protein free levels in serum.
Nitrazepam has been shown to cross the placenta and reach concentrations between 50 and 90% of the concentration in maternal plasma. It is excreted in breast milk.
The volume of distribution has been found to be significantly higher in elderly immobilised patients than in young controls, whereas the volume of distribution in healthy elderly subjects was found to be similar to young healthy subjects.

Protein binding.

Nitrazepam is approximately 87% bound to plasma protein.

Metabolism.

Nitrazepam is metabolised to a significant extent by the liver and the primary route of elimination is urinary excretion of these metabolites. Thus, hepatic or renal disease may require alteration of nitrazepam dosage.
The major pathway is conversion to 7-aminonitrazepam and then to 7-acetamidonitrazepam with subsequent hydroxylation. Opening of the diazepine ring to form 2-amino-5-nitrobenzophenone has also been reported. These metabolites have very weak pharmacological activity.
There is no evidence of nitrazepam dependent enzyme induction or inhibition during long-term treatment.
Total plasma clearance has been estimated as 4.1 ± 2.0 L/hour in young and 4.7 ± 1.5 L/hour in elderly patients.

Excretion.

Nitrazepam is mainly excreted as urinary metabolites. During the first 120 hours after a single radiolabelled 10 mg oral dose, the total renal elimination was 70%. Only 1% or less of the administered dose is excreted as unchanged nitrazepam.
The main urinary excretion products are free or conjugated 7-aminonitrazepam and 7-acetamidonitrazepam. Individual variation of the total excreted metabolites is high, ranging between 17 and 99% of the administered dose. Of this, the conjugated metabolites made up an average of 57%.
One faecal excretion study indicates the possibility of limited biliary excretion of the metabolites.

Half-life.

Nitrazepam is eliminated relatively slowly from the body. Following oral administration, half-life has been estimated to be from 16 to 48 hours (average 27 hours). The half-life in CSF appears to be about twice as long as that in plasma.
Elimination half-life has been estimated to be significantly higher in elderly debilitated patients as opposed to healthy elderly subjects and young subjects.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following inactive ingredients: lactose monohydrate, maize starch, pregelatinised maize starch, purified talc, colloidal anhydrous silica, magnesium stearate.

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.

6.5 Nature and Contents of Container

Available in HDPE bottles with PP child resistant screw caps (25's*, 50's, 1000's) and PVC/PVDC/Al blister packs (30's, 1000's).
* Marketed in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Chemical name: 7-nitro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one.
Structural formula:

Molecular formula: C₁₅H₁₁N₃O₃.
Molecular weight: 281.3.
Nitrazepam is a yellow, crystalline powder which is odourless and tasteless. It is almost insoluble in water, soluble in 120 parts of alcohol (95%), in 45 parts of chloroform, and in 900 parts of ether. Nitrazepam has a melting point of 226°-229°C.

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Alodorm

Nitrazepam

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BRAND INFORMATION

Alodorm 5 mg Tablets