Consumer medicine information

Hypnodorm

Flunitrazepam

BRAND INFORMATION

Brand name

Hypnodorm

Active ingredient

Flunitrazepam

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Hypnodorm.

What is in this leaflet

This leaflet answers some common questions about Hypnodorm.

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 Hypnodorm against the benefits they expect it will have 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 Hypnodorm is used for

Hypnodorm is used to treat severe cases of insomnia (trouble sleeping).

Hypnodorm belongs to a group of medicines called benzodiazepines. These medicines are thought to work by their action on brain chemicals.

In general, benzodiazepines such as Hypnodorm need only be taken for a few nights and then discontinued by gradually decreasing the dosage. Continuous long term use of Hypnodorm is not recommended. The use of benzodiazepines may lead to dependence on the medicine.

Hypnodorm is not recommended as a first choice of treatment in patients with depression and/or psychosis as it can increase your risk of suicide.

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

Hypnodorm is available only with a doctor's prescription.

Before you take Hypnodorm

When you must not take it

Do not take Hypnodorm if you are allergic to medicines containing flunitrazepam, any other benzodiazepine or 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 Hypnodorm if you have:

  • severe and chronic lung disease
  • myasthenia gravis, condition where there is severe muscle weakness
  • sleep apnoea, condition where you temporarily stop breathing while you are asleep
  • severe liver disease.

Do not take Hypnodorm if you are breastfeeding. Hypnodorm passes into breast milk and may affect your baby.

Do not take Hypnodorm 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 Hypnodorm to children.

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. Your doctor will discuss the risks and benefits of taking Hypnodorm during pregnancy.

Tell your doctor if you plan to breastfeed. Hypnodorm passes into breast milk and is not recommended for use when breastfeeding.

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

  • hypotension (low blood pressure)
  • myasthenia gravis (severe muscle weakness)
  • liver or kidney problems
  • lung problems
  • a blood disorder
  • glaucoma (increased pressure in the eye)
  • depression, psychosis or schizophrenia
  • epilepsy (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 Hypnodorm and should be avoided while you are being treated with Hypnodorm.

Tell your doctor if you need to drive, operate dangerous machinery, or are involved in activities requiring concentration. Hypnodorm may cause drowsiness or dizziness up until the next day.

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 Hypnodorm.

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 Hypnodorm, or may affect how well it works. These include:

  • other sleeping tablets, sedatives or tranquillisers
  • medicines for depression
  • medicines used to treat mental illness
  • medicines to treat epilepsy
  • antihistamines, medicines for allergies or colds
  • muscle relaxants
  • cimetidine, medicine used to treat stomach ulcers
  • cisapride, medicine used to treat reflux
  • strong pain relievers
  • disulfiram, medicine used in the treatment of alcohol dependence
  • anticholinergics, medicines for travel sickness, stomach cramps or Parkinson's Disease.

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

Hypnodorm may produce additive depressant effects when using together with other medications, such as., alcohol, sedatives, antidepressants, antipsychotics drugs, epilepsy drugs, hypnotics, relaxants, antihistamines, severe pain relievers and anaesthetics. This has the potential to significantly increase the effects on HYPNODORM and may lead to addiction or result in death from overdose.

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 Hypnodorm.

How to take Hypnodorm

How much to take

The dose varies from patient to patient. Your doctor will decide the right dose for you.

The usual dose is 1 mg to 2 mg (one to two tablets) at bedtime.

The usual dose for elderly patients is 0.5 mg to 1 mg (half to one tablet) at bedtime.

Follow all directions given to you by your doctor and pharmacist carefully.

How to take it

Swallow the tablets with a glass of water.

Hypnodorm tablets can be broken in half if your doctor has prescribed half a tablet.

When to take it

Hypnodorm should be taken when you go to bed. Only take Hypnodorm if you feel you will need help sleeping.

Hypnodorm can be taken with or without food.

Withdrawal
If you have taken Hypnodorm for a long period of time and suddenly stop taking it, you may experience withdrawal symptoms. Withdrawal symptoms may last for weeks or months and symptoms may include: extreme anxiety, shaking (tremor) including involuntary movements, difficulty sleeping (insomnia), depression, problems with your perception, confusion, fits (convulsions), muscle cramps, headaches, tension, restlessness, irritability, stomach problems, being sick (vomiting) and sweating. More severe withdrawal symptoms include: a feeling of loss of identity/ feeling detached from yourself (depersonalisation or derealisation), sensitivity to light, noise (including tinnitus) and physical contact, numbness or tingling in the hands or feet (paraesthesia), seeing or hearing things that are not real (hallucinations). Hypnodorm should be stopped gradually to reduce withdrawal symptoms.

If you forget to take it

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

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

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

How long to take it

Take Hypnodorm only for as long as your doctor recommends.

Usually, Hypnodorm need only be taken for a few nights and then discontinued by gradually decreasing the dosage. 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 Hypnodorm. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Hypnodorm, you may feel drowsy, confused, tired, unsteady when walking, weak in muscle strength, dizzy, lightheaded, have trouble breathing or become unconscious.

While you are taking Hypnodorm

Things you must do

Use Hypnodorm exactly as prescribed by your doctor.

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

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

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

Hypnodorm crosses the placenta and may cause poor muscle tone, slowed breathing, feeding problems and low body temperature in the newborn infant if used in high doses during labour. Withdrawal symptoms in newborn infants have been reported with long term use of this class of drugs

If you are depressed and/or have anxiety disorders, you can sometimes have thoughts of harming or ending your life. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

If you plan to have surgery, including dental surgery, tell your doctor or dentist that you are taking Hypnodorm.

If you have to have any clinical tests such as an EEG, tell your doctor that you are taking Hypnodorm. Hypnodorm may affect the results of some tests.

Visit your doctor regularly so they can check on your progress. Your doctor needs to check your progress and see whether you need to continue taking Hypnodorm.

Tell your doctor, if for any reason, you have not taken Hypnodorm exactly as prescribed. Otherwise, your doctor may think that your medicine is not working properly and change your treatment unnecessarily.

Things you must not do

Do not drive or operate machinery until you know how Hypnodorm affects you. Hypnodorm may cause drowsiness, dizziness or lightheadedness in some people. If any of these occur, do not drive, 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.

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

Do not take Hypnodorm for a longer time than your doctor has prescribed. Hypnodorm should be taken for short periods only unless advised otherwise by your doctor.

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

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

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

Do not give Hypnodorm 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 when drinking alcohol while taking Hypnodorm. Combining Hypnodorm and alcohol can make you more sleepy, 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 while you are taking Hypnodorm.

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 Hypnodorm.

Hypnodorm helps most people with insomnia, 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.

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

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

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

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

  • tiredness or drowsiness
  • hangover feeling in the morning, headache, confusion
  • dizziness, unsteadiness when walking
  • stomach upsets
  • dry mouth
  • slurred speech.

The above list includes the more common side effects.

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

  • skin rash
  • fast heart beat
  • muscle weakness
  • aggressive behaviour
  • delusions, hallucinations
  • sudden excitation or anxiety
  • severe sleep disturbances, nightmares
  • loss of memory
  • swelling of the face, lips mouth, tongue or throat which may cause difficulty swallowing or breathing.

These are serious side effects and you may need urgent medical attention. Serious side effects are rare.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything that is making you feel unwell.

After taking Hypnodorm

Storage

Keep Hypnodorm 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.

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.

Keep your tablets in a cool dry place where the temperature stays below 30 degrees C.

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

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

Disposal

If your doctor tells you to stop taking Hypnodorm, 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

Hypnodorm is a green, oval film-coated tablet with "FM|1" on one side and "a" on the other.

Each bottle contains 30 tablets.

Ingredients

The active ingredient in Hypnodorm is flunitrazepam.

Each Hypnodorm tablet contains 1 mg of flunitrazepam.

The tablets contain the following inactive ingredients:

  • lactose monohydrate
  • maize starch
  • pregelatinised maize starch
  • magnesium stearate
  • Indigo carmine CI73015
  • Opadry Green OY-LS-21051.

Hypnodorm also contains sugars (as lactose and galactose) and trace amounts of sulfites. The tablets are gluten free.

Manufacturer

Hypnodorm 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:

Hypnodorm 1 mg - AUST R 78344

This leaflet was prepared in August 2022.

Hypnodorm_cmi\Aug22/00

Published by MIMS October 2022

BRAND INFORMATION

Brand name

Hypnodorm

Active ingredient

Flunitrazepam

Schedule

S8

 

1 Name of Medicine

Flunitrazepam.

6.7 Physicochemical Properties

Chemical name: 5-(2-fluorophenyl)-1,3- dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin 2 one.
Molecular formula: C16H12FN3O3.
Molecular weight: 313.3.
Flunitrazepam is a pale yellow crystalline solid, sparingly soluble in water, slightly soluble in alcohol.

Chemical structure.


CAS number.

1622-62-4.

2 Qualitative and Quantitative Composition

Each Hypnodorm tablet contains 1 mg flunitrazepam.
Hypnodorm also contains sugars (as lactose and galactose) and trace amounts of sulfites. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Flunitrazepam 1 mg tablets: green, oval, normal convex, scored, film coated tablet debossed "FM/1" on one side and "α" on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Flunitrazepam is a member of the benzodiazepine group of drugs and is closely related to nitrazepam, flurazepam and clonazepam. It has marked sedative and hypnotic properties with a rapid onset of action. In experimental animals, flunitrazepam has also been shown to possess anticonvulsant, anxiolytic and muscle relaxant properties.
Given orally, flunitrazepam induces sleep and maintains and deepens it. The intensity of the effect depends both on the dose taken and on the aetiology of the sleep disturbance.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, flunitrazepam is almost completely absorbed. Peak blood levels of flunitrazepam occur usually 45 minutes after ingestion. 10% to 15% is metabolised by a liver first-pass effect, resulting in bioavailability of 64-77%.
Chronic oral administration of flunitrazepam leads to slight accumulation of flunitrazepam in the plasma. The accumulation ratio of flunitrazepam given once daily is approximately 2. Steady-state concentrations are reached after 3 to 5 days for flunitrazepam, and after 5 to 7 days for N-desmethyl- flunitrazepam. Subsequently, the minimum and maximum concentrations remain constant, even on prolonged administration.

Distribution.

The distribution of flunitrazepam is rapid and extensive. About 77 to 80% of absorbed flunitrazepam is bound to plasma proteins over a concentration range of 1 to 20 nanogram/mL.

Metabolism.

Flunitrazepam is extensively metabolised, and both the major metabolites, 7- amino- flunitrazepam and N-desmethyl- flunitrazepam, are pharmacologically active in humans but less so than the parent drug. Both metabolites are eliminated as glucuronides, largely through the kidneys.

Excretion.

Following intravenous administration, the elimination half-life for flunitrazepam is 20 to 30 hours, 10 to 16 hours for 7-amino-flunitrazepam and 23 to 33 hours for N-desmethyl-flunitrazepam. However, due to extensive distribution of the drug and metabolites out of the plasma into body tissues, the long elimination half-lives are not reflected in the duration of clinical effect.

5.3 Preclinical Safety Data

Genotoxicity.

Studies have not been performed to assess the mutagenic potential of flunitrazepam.

Carcinogenicity.

Studies have not been performed to assess the carcinogenic potential of flunitrazepam.

4 Clinical Particulars

4.1 Therapeutic Indications

Severe cases of insomnia.

4.3 Contraindications

Hypnodorm is contraindicated in:
patients with known hypersensitivity to flunitrazepam or to any other components of Hypnodorm;
patients with known hypersensitivity to benzodiazepines;
patients with chronic obstructive airways disease with incipient respiratory failure;
myasthenia gravis;
sleep apnoea;
children;
severe hepatic insufficiency.

4.4 Special Warnings and Precautions for Use

Severe allergic reactions.

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. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal.

Withdrawal reactions.

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

Tolerance.

In general, benzodiazepines should be prescribed for short periods only (e.g. 2 to 4 weeks). Continuous long-term use of Hypnodorm 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).

Hypotension.

Although hypotension has occurred only rarely, Hypnodorm 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.

Memory impairment.

Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines. On rare occasions, especially when flunitrazepam was taken with alcohol or CNS active drugs, patients developed unusual or disturbed behaviour of which they had no recollection.

Myasthenia gravis.

Hypnodorm could increase the muscle weakness in myasthenia gravis and is, therefore, contraindicated in this condition.

Glaucoma.

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

Hypnodorm 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.

Hypnodorm should be discontinued if paradoxical reactions such as acute rage, stimulation or excitement occur. These reactions are more common in the elderly.

Impaired respiratory function.

Caution in the use of Hypnodorm 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 Hypnodorm 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. Tolerance, as defined by a need to increase the dose in order to achieve the same therapeutic effect, seldom occurs in patients receiving the recommended doses under medical supervision. Tolerance to sedation may occur with benzodiazepines, especially in those with drug seeking behaviour.
Withdrawal symptoms similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuation of benzodiazepines. These symptoms can range from headache, tension, muscle pain, restlessness, irritability, 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), numbness and tingling of the extremities, 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, Hypnodorm 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 pretreatment 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.
It is important to warn against changing to a benzodiazepine with a short duration of action when benzodiazepines with a long half-life are used, as withdrawal symptoms may develop.

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.

Paediatric use.

Contraindicated in children.

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

CNS depressant drugs.

The benzodiazepines, including flunitrazepam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression, e.g. barbiturates, alcohol, sedatives, antidepressants, nonselective MAO inhibitors, phenothiazines and other antipsychotics, antiepilectic drugs, hypnotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anaesthetics (see Section 4.7 Effects on Ability to Drive and Use Machines).

Disulfiram and cimetidine.

Flunitrazepam undergoes oxidative metabolism and consequently may interact with disulfiram or cimetidine, resulting in increased plasma levels of flunitrazepam. 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.

Anticholinergics.

The anticholinergic effects of other drugs, including atropine and similar drugs, antihistamines and antidepressants may be potentiated.

Anticonvulsants.

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.

Alcohol.

The mutual potentiation between alcohol and flunitrazepam may produce unforeseeable reactions in certain patients. Alcoholic drinks should, therefore, be avoided while under the influence of this drug.

Cisapride.

Cisapride may lead to a temporary increase in the serum levels, and thus sedative effects, of orally administered benzodiazepines due to faster absorption.

Narcotic analgesics.

In the case of narcotic analgesics, enhancement of euphoria may also occur, leading to an increase in psychological dependence.

Anticoagulants and antidiabetics.

There appears to be no interaction with coumarin anticoagulants or oral diabetic agents.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies have not been performed to assess the potential of flunitrazepam to impair fertility.
(Category C)
Benzodiazepines cross the placenta and may cause hypotonia, respiratory depression and hypothermia in the newborn infant if used in high doses during labour. 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 prolonged use of this class of drugs.
 Flunitrazepam is excreted in human breast milk and, therefore, should not be used when breastfeeding.

4.8 Adverse Effects (Undesirable Effects)

Note.

Percentages indicate the incidence of adverse reactions in clinical trials.
About 13% of patients experience adverse effects, usually due to the persistence or accentuation of the pharmacological effects of the drug. They are more frequent at higher doses (over 4 mg) and in sensitive or elderly persons.

Body as a whole.

Common: headache, falling. Uncommon: asthenia, malaise, collapse, unsteadiness.

Cardiovascular.

Common: hypotension. Uncommon: tachycardia, orthostatic hypotension.

Gastrointestinal.

Common: gastrointestinal upsets, dry mouth. Uncommon: hiccups.

Musculoskeletal.

Uncommon: muscle weakness.

Nervous system.

Common: hangover, tiredness, drowsiness, sleepiness, dizziness, ataxia, confusion, tremor, amnesia, excitation. Uncommon: daytime sedation, disorientation, slurred speech. Rare: anxiety, hallucinations, agitation, sleep disturbances, unusual dreams.

Dermatological.

Uncommon: skin reactions, sweating, rash, angioedema.
In rare cases, paradoxical reactions, such as acute excitation, confusion, agitation, sleep disturbances including unusual dreams, anxiety and hallucinations may occur. If this happens, treatment must be stopped. These reactions may be quite severe with flunitrazepam, and are more likely to occur in the elderly.
Daytime sedative effects, particularly in elderly people, may cause serious domestic accidents.

Post-marketing experience.

Paradoxical reactions.

Restlessness, irritability, nightmares, inappropriate behaviour, delusions, aggressiveness and psychoses.

Special senses.

Double vision.

Urogenital system.

Changes in libido.

Central nervous system.

Pre-existing depression may be unmasked during benzodiazepine 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 www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

In most patients, Hypnodorm need only be administered for a few nights. Treatment should be discontinued gradually by decreasing the dosage.
Dosage should be selected carefully, due consideration being given to the patient's age and general condition, as well as the type of sleep disturbance.
The drug should be taken immediately before going to bed. In general, the following dosages are recommended.

Adults.

1 to 2 mg on going to bed.

Elderly patients.

0.5 to 1 mg.

In impaired renal or hepatic function.

Elimination of metabolites will be impaired. For these patients, commence treatment with small doses which are increased slowly until the desired response is attained.

4.7 Effects on Ability to Drive and Use Machines

Complex behaviours such as “sleep-driving” (i.e. driving while not fully awake after taking a sedative-hypnotic, with amnesia for the event) 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. Due to the risk to the patient and the community, discontinuation of sedative-hypnotics should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviours (e.g. preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with “sleep-driving”, patients usually do not remember these events.
As with all patients taking CNS depressant medications, patients receiving Hypnodorm should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from Hypnodorm 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 Hypnodorm.
Due to the slight accumulation of flunitrazepam in the plasma, a 2 mg dose of flunitrazepam should not be administered on a daily basis to patients involved in activities requiring concentration during the early part of the day.

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.
Following overdosage with flunitrazepam tablets, activated charcoal should be given to reduce absorption. General symptomatic and supportive measures are recommended. 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.
If excitation occurs in patients following overdosage, barbiturates should not be used.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S8.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following excipients: lactose monohydrate, maize starch, pregelatinised maize starch, magnesium stearate, indigo carmine CI73015 and Opadry Green OY-LS-21051.

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 30°C.

6.5 Nature and Contents of Container

Available in HDPE bottles of 30 tablets.

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.

Summary Table of Changes