Consumer medicine information

Imrest

Zopiclone

BRAND INFORMATION

Brand name

Imrest

Active ingredient

Zopiclone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Imrest.

What is in this leaflet

This leaflet answers some common questions about Imrest.

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 Imrest 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 Imrest is used for

Imrest is used to help people with sleeping difficulties, also called insomnia. It can help you fall asleep and to reduce the number of times you wake up during the night. It is used for short term treatment (2-4 weeks) of insomnia. It is not recommended for use for more than 4 weeks at a time.

Your doctor, however, may prescribe Imrest for another purpose.

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

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

Before you take Imrest

When you must not take it

Do not take Imrest if you have:

  • been drinking alcohol or you believe that you may have alcohol in your bloodstream
  • sleep apnoea (a condition where you temporarily stop breathing while you sleep)
  • myasthenia gravis (a condition in which the muscles become weak and tire easily)
  • severe liver problems
  • acute and/or severe lung problems
  • had a stroke

Do not take Imrest if you are allergic to it or any of the ingredients listed at the end of this leaflet.

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

Do not give Imrest to children or adolescents. There is no experience with its use in children or adolescents.

Do not take it if you are pregnant or intend to become pregnant. It may affect your developing baby if you take it during pregnancy. Your doctor will discuss the risks and benefits of taking it if you are pregnant.

Do not take it if you are breastfeeding or planning to breastfeed. Imrest passes into breast milk and there is a possibility your baby may be affected. Your doctor will discuss the risks and benefits of using it if you are breastfeeding or planning to breastfeed.

Do not take Imrest after the expiry date (EXP) printed on the pack. If you take it after the expiry date has passed, it may not work as well.

Do not take Imrest if the packaging is damaged or shows signs of tampering.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to:

  • any of the ingredients listed at the end of this leaflet
  • any other substances such as foods, dyes or preservatives

Tell your doctor if you are pregnant or intend to become pregnant. Like most medicines of this kind, Imrest is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of taking it if you are pregnant.

Tell your doctor if you are breastfeeding or planning to breastfeed. Your doctor will discuss the risks of taking it if you are breastfeeding or planning to breastfeed.

Tell your doctor if you have any problems with your breathing or if you often snore while you are asleep.

Tell your doctor if you have ever been addicted to alcohol or any drug or medicine, or if you have ever suffered from a mental illness.

If you have, you may be at risk of getting into a regular pattern or habit of taking Imrest.

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

  • thyroid problems
  • depression psychosis or schizophrenia
  • epilepsy
  • addiction to drugs or medicines

Tell your doctor if you plan to have surgery.

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

Taking other medicines

You must 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 store.

Some medicines may interfere with the absorption of Imrest. These include:

  • medicines to treat depression, anxiety and mental illness
  • St John's wort, (hypericum),a herbal remedy for depression
  • other medications which may cause drowsiness
  • benzodiazepines (medicines used as sedatives or to treat anxiety)
  • pain relievers, such as opioids or narcotic analgesics
  • alcohol, (ethanol), contained in some medicines e.g. cough syrups
  • pain relievers
  • muscle relaxants
  • antihistamines
  • medicines used to treat epilepsy
  • antiviral medication
  • rifampicin, erythromycin or
  • clarithromycin (medicines used to
  • treat infections)
  • ketoconazole, or itraconazole (medicine to treat antifungal infections)

These medicines may be affected by Imrest or may affect how well it works. You may need to take different amounts of your medicine or different medicines. Your doctor or pharmacist will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while taking Imrest.

How to take it

How much to take

Imrest should only be taken when you are able to get a full night's sleep (7 to 8 hours) before you need to be active again.

The standard adult dose of Imrest is one tablet just before you go to bed.

If you are over 65 years of age the dose is half a tablet taken just before you go to bed.

Imrest should be taken in a single intake and not readministered during the same night.

If you have a liver problem, the usual recommended dose is half a tablet taken just before you go to bed.

Your doctor may have prescribed a different dose.

Ask your doctor if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, Imrest may not work as well.

Imrest should not be given to children or adolescents less than 18 years of age.

How to take it

Swallow the tablet with a full glass of water.

When to take it

Take Imrest immediately before you go to bed. This medicine should be taken as a single intake and not be readministered during the same night. It helps put you to sleep quite quickly. If you take Imrest on an empty stomach it may work more quickly.

If you are not sure when to take it, ask your doctor or pharmacist.

How long to take it

Usually, Imrest or any other medicines to treat sleeping disorders should only be used for short periods (e.g. 2 to 4 weeks). Continuous long term use is not recommended unless advised by your doctor.

Ask your doctor or pharmacist if you are not sure how long to take the medicine for.

If you forget to take it

If you forget to take the tablet before you go to bed, and you wake up late in the night or very early in the morning, do not take it. You may have trouble waking at your normal time.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (In Australia call 13 11 26 or New Zealand call 0800 POISON, 0800 764 766) for advice, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Imrest.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking it

Things you must do

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

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

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine.

If you become pregnant while you are taking this medicine, stop taking it and tell your doctor or pharmacist immediately.

Things you must not do

Do not take more than the recommended dose unless your doctor tells you to. This can increase the risk of side effects.

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

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

Do not drink alcohol before or after taking this medicine. This can increase the risk of side effects.

Things to be careful of

Because Imrest will make you sleepy, you should not operate dangerous machinery or drive motor vehicles for 8 hours after you take it. You should also be careful the next morning when you wake up. Make sure you know how you react to Imrest before you drive a car or operate machinery. This is very important if you are taking other drugs that also make you drowsy.

Be careful if you are over 65 and unwell or taking other medicines. You may be more sensitive to some of the side effects of Imrest.

You should not drink alcohol while you are taking Imrest. The effects of alcohol could be made worse while taking Imrest.

Side effects

All medicines have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor or pharmacist has weighed the risks of using this medicine against the benefits they expect it will have for you.

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

Tell your doctor as soon as possible if you do not feel well while you are taking Imrest.

It helps most people with insomnia, but it may have unwanted side effects in some people.

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

  • headaches
  • dry mouth
  • bitter taste in your mouth
  • drowsiness

These are the most common side effects of this medicine.

  • Less common side effects include:
  • heartburn
  • nausea, vomiting and/or diarrhoea
  • change in appetite
  • stomach pain
  • rash
  • agitation
  • depression
  • confusion
  • anxiety
  • dizziness
  • blurred vision
  • impotence
  • sleep walking or other behaviours whilst asleep

Alcohol can increase the risk of sleep walking or other behaviours such as driving or eating food whilst asleep. This risk is also increased if you take more than the recommended dose.

Some sleep medicines may cause a 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.

Sleep medicines should in most cases, be used only for short periods of time. If your sleep problems continue, consult your doctor.

Some medicines can cause dependence, especially when they are used regularly for longer than a few weeks. People who have been dependent on alcohol or other drugs in the past may have a higher chance of becoming addicted to sleep medicines. If you have been addicted to alcohol or drugs in the past, it is important to tell your doctor before starting Imrest.

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

  • swelling of the face, lips, mouth or throat, which may cause difficultly in swallowing or breathing
  • hives
  • fainting

These are very serious side effects. If you have them, you may have had a serious allergic reaction to Imrest. You may need urgent medical attention or hospitalisation.

These side effects are very rare.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you feel you are becoming depressed, having suicidal thoughts or are experiencing changes in your behaviour.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some consumers.

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.

After taking it

Sometimes when medicines are stopped suddenly, after being used for a long time, withdrawal symptoms may occur. Symptoms of withdrawal may include abdominal and muscle cramps, vomiting and sweating.

In some cases your insomnia may appear worse for a short time; speak to your doctor if this occurs.

Tell your doctor if you have any problems when you stop taking Imrest.

If you have any query about any aspect of your medicine, or any questions regarding the information in this leaflet, discuss them with your doctor or pharmacist.

Storage

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

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

Do not store it or any other medicine in the bathroom, near a sink or on a windowsill. Heat and dampness can destroy some medicines.

Do not leave it in the car. Heat and damp can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above ground is a good place to store medicines.

Disposal

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

Return any unused medicine to your pharmacist.

Product description

What it looks like

Imrest is an oval, white, film-coated tablet marked "Z|Z" on one side and "7.5" on the other. The tablets are scored.

Each pack contains 30 tablets.

Ingredients

The active ingredient in Imrest is zopiclone. Each tablet contains 7.5 mg of zopiclone.

The tablets also contain the following inactive ingredients:

  • lactose anhydrous
  • calcium hydrogen phosphate anhydrous
  • maize starch
  • povidone
  • magnesium stearate
  • Opadry White Y-1-7000.

The tablets are gluten free.

Supplier

Imrest is supplied in Australia by:

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

Australian registration number:
Imrest - AUST R 99794

This leaflet was prepared on 4 October 2019.

Imrest_cmi\Oct19/00

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Imrest

Active ingredient

Zopiclone

Schedule

S4

 

1 Name of Medicine

Zopiclone.

6.7 Physicochemical Properties

Zopiclone is a fine white or slightly cream crystalline powder with a melting point of 176° to 178°C. It is practically insoluble in acetone, soluble in dimethyl formamide and hydrochloric acid 0.1 N and freely soluble in chloroform and dichloromethane.

Chemical structure.


The chemical name for zopiclone is 6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl-4-methylpiperazine-1-carboxylate.
Molecular Formula: C17H17ClN6O3.
Molecular Weight: 388.8.

CAS number.

43200-80-2.

2 Qualitative and Quantitative Composition

Each Imrest tablet contains 7.5 mg of zopiclone as the active ingredient.
Imrest also contains the following excipients lactose, calcium hydrogen phosphate, maize starch, povidone, magnesium stearate and Opadry White Y-1-7000. The tablets are gluten free.

3 Pharmaceutical Form

Imrest tablets are white, film coated, oval tablets embossed with "Z" breakline "Z" on one side and "7.5" on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Benzodiazepine related drugs, ATC code: N05C F01.

Mechanism of action.

Zopiclone, a cyclopyrrolone derivative, is a short-acting hypnotic agent. Zopiclone belongs to a novel chemical class which is structurally unrelated to existing hypnotics. The pharmacological profile of zopiclone is similar to that of the benzodiazepines.
In sleep laboratory studies of 1 to 21 day duration in humans, zopiclone reduced sleep latency, increased the duration of sleep and decreased the number of nocturnal awakenings. Zopiclone delayed the onset of rapid eye movement (REM) sleep but did not reduce consistently the total duration of REM periods. The duration of stage 1 sleep was shortened and the time spent in stage 2 sleep increased. In most studies, stage 3 and 4 sleep tended to be increased, but no change and actual decreases have also been observed. The effect of zopiclone on stage 3 and 4 sleep differs from that of the benzodiazepines, which suppress slow wave sleep. The clinical significance of this finding is not known.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Zopiclone is rapidly absorbed and distributed after oral administration, the time of maximum observed plasma concentration being about 1.75 hours.

Distribution.

A study of 16 healthy volunteers receiving a single dose of zopiclone 7.5 mg intravenously demonstrated the apparent volume of distribution of zopiclone to be 104 ± 15.5 L. Autoradiographic studies in the rat showed rapid distribution into the blood and peak tissue levels at 0.5 hours in the liver, small intestine, stomach, kidneys and adrenals. After 24 hours the total residual radioactivity in the body of the rat was 8%.
The bioavailability of the 7.5 mg tablets in humans is 76.3 ± 9.6%. An hepatic first-pass effect has been demonstrated. In fresh human plasma, zopiclone is approximately 45% protein bound in the 25 to 100 nanogram/mL concentration range.

Metabolism.

Zopiclone is extensively and rapidly metabolised by the liver. A large number of metabolites have been isolated and characterised, with the two major ones being the N-oxide, produced by oxidation of the piperazine nitrogen, and the N-desmethyl, produced by oxidative demethylation of the N-methyl piperazine. Only the N-oxide analogue has weak pharmacological activity.

Excretion.

Zopiclone is rapidly eliminated, mainly by means of hepatic metabolism. The elimination half-life after a single oral dose is 5.57 ± 1.4 hours. The elimination half-life for the N-oxide metabolite is 4.44 ± 0.66 hours and that for the N-desmethyl metabolite is 7.28 ± 0.49 hours.
Renal clearance is 13.9 ± 7.0 mL/minute which further shows that the major elimination pathway is by hepatic metabolism.
The amount of renal excretion is also low: unchanged zopiclone 3.6%, the N-oxide metabolite 11.4% and the N-desmethyl metabolite 13.4%.

Elderly.

In elderly patients, the absolute bioavailability is increased (94% versus 77% in young subjects) and the elimination half-life prolonged (approximately 7 hours).

Hepatic insufficiency.

In patients with hepatic insufficiency, the elimination half-life is prolonged (11.9 hours) and the time to peak plasma levels is delayed (3.5 hours).

Renal insufficiency.

In patients with mild to moderate renal insufficiency, the pharmacokinetics of zopiclone are not altered. Haemodialysis does not appear to increase the plasma clearance of the drug.

5.3 Preclinical Safety Data

Genotoxicity.

Genotoxicity studies, using a standard battery of tests, showed no evidence of gene mutations or chromosomal damage.

Carcinogenicity.

Treatment with zopiclone by dietary administration for two years increased the incidence of thyroid carcinomas in male rats dosed with 100 mg/kg/day and increased the incidence of mammary carcinoma in female rats dosed with 100 mg/kg/day, probably due to interference with thyroid hormone and 17β-estradiol metabolism. Studies with mice treated with zopiclone at dietary doses up to 100 mg/kg/day showed no evidence of drug-related carcinogenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Short-term treatment of insomnia (two to four weeks).

4.3 Contraindications

Patients with known hypersensitivity to zopiclone or any excipient.
Prior or concomitant use of alcohol.
Myasthenia gravis.
Severe impairments of respiratory function.
Acute cerebrovascular accident.
Sleep apnoea syndrome.
Severe hepatic insufficiency.
Imrest is contraindicated in children.

4.4 Special Warnings and Precautions for Use

Prolonged use of hypnotics is not recommended, especially in the elderly.
The cause of insomnia should be identified wherever possible and the underlying factors treated before a hypnotic is prescribed.

Dependence.

Zopiclone should be prescribed for short periods only (2 to 4 weeks). Continuous long-term use is not recommended. Use of zopiclone may lead to the development of abuse and/or physical and psychological dependence. It is therefore recommended that after prolonged use the dose should be decreased gradually and the patient advised about such a possibility (see Section 4.8 Adverse Effects (Undesirable Effects)).
The risk of dependence or abuse increases with dose and duration of treatment. Cases of dependence have been reported more frequently in patients treated with zopiclone for longer than 4 weeks. The risk of abuse or dependence is also increased in patients with a history of psychiatric disorders and/or alcohol or drug abuse. The risk of dependence or abuse increases with the use of alcohol or other psychotropics. Zopiclone should be used with extreme caution in patients with current or a history of alcohol or drug abuse.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.

Rebound insomnia.

A transient syndrome whereby the symptoms that led to treatment with sedative-hypnotic agents recur in an enhanced form, may occur on withdrawal of hypnotic treatment. Since the risk of such phenomena is greater after abrupt discontinuation of zopiclone, especially after prolonged treatment, it is therefore recommended to decrease the dosage gradually and to advise the patient accordingly (see Section 4.8 Adverse Effects (Undesirable Effects)).

Amnesia.

Anterograde amnesia may occur, especially when sleep is interrupted or when retiring to bed is delayed after the intake of the tablet.
To reduce the possibility of anterograde amnesia, patients should ensure that:
they take the tablet strictly when retiring for the night; and
they are able to have a full night sleep.

Other psychiatric and paradoxical reactions.

Other psychiatric and paradoxical reactions have been reported (see Section 4.8 Adverse Effects (Undesirable Effects)), like restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, inappropriate behaviour and other adverse behavioural effects are known to occur when using sedative/ hypnotic agents like zopiclone. Should this occur, use of zopiclone should be discontinued. These reactions are more likely to occur in the elderly.

Somnambulism and associated behaviours.

Sleepwalking and other associated behaviours such as 'sleep driving', preparing and eating food, or making phone calls with amnesia for the event, have been reported in patients who have taken zopiclone and were not fully awake. The use of alcohol and other CNS-depressants with zopiclone appears to increase the risk of such behaviours, as does the use of zopiclone at doses exceeding the maximum recommended dose. Discontinuation of zopiclone would be strongly considered for patients who report such behaviours (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Alcohol; Section 4.8 Adverse Effects (Undesirable Effects)).

Depression, suicidality, psychosis and schizophrenia.

As with other hypnotics, zopiclone does not constitute a treatment of depression and may even mask its symptoms.
As with other sedative/hypnotic drugs, zopiclone should be administered with caution in patients exhibiting symptoms of depression, including those with latent depression. Suicidal tendencies may be present and protective measures may be required. Therefore, the lowest possible quantity of zopiclone should be supplied to these patients to reduce the risk of intentional overdosage by the patient.
Pre-existing depression may be unmasked during use of zopiclone.
Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists.
Several epidemiological studies show an increased incidence of suicide and suicide attempt in patients with or without depression, treated with benzodiazepines and other hypnotics, including zopiclone.

Epilepsy.

Patients with a history of seizures should not be abruptly withdrawn from any CNS depressant drug, including zopiclone.

Severe anaphylactic and anaphylactoid 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, including zopiclone. 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. Patients who develop angioedema after treatment with zopiclone should not be rechallenged with the drug.

Use in hepatic impairment.

In patients with severe hepatic insufficiency (serum albumin less than 30 g/L or presence of gross oedema), the elimination of zopiclone may be significantly reduced. Treatment should be initiated at a dose of 3.75 mg and, if necessary, may be increased to 7.5 mg.

Use in renal impairment.

Zopiclone is removed by dialysis.

Respiratory insufficiency.

Caution should be exercised in treating patients with chronic respiratory insufficiency. Treatment should be initiated at a dose of 3.75 mg and, if necessary, should be carried out at 7.5 mg.
As hypnotics have the capacity to depress respiratory drive, precautions should be observed if zopiclone is prescribed to patients with compromised respiratory function.

Hormonal systems.

Treatment of rats with zopiclone increases hepatic thyroid hormone metabolism of T4, resulting in increases in thyroid stimulating hormone (TSH) and T3 levels and decreases in T4 levels. It is suggested that zopiclone not be administered to individuals with impaired thyroid hormone homeostatic mechanisms or with conditions linked to hormonal imbalances.

Risks from concomitant use with opioids.

Concomitant use of opioids with benzodiazepines or other sedative-hypnotic drugs, including zopiclone, may result in sedation, respiratory depression, coma and death. Because of these risks, reserve concomitant prescribing of opioids and zopiclone for use in patients for whom alternative treatment options are inadequate.
If a decision is made to prescribe zopiclone concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Abuse.

Caution must be exercised in administering zopiclone to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative.

Use in the elderly.

Such patients may be particularly susceptible to the sedative effects of zopiclone and associated giddiness, ataxia and confusion, which may increase the possibility of a fall (see Section 4.2 Dose and Method of Administration).

Paediatric use.

The safe and effective dose in children and adolescents under 18 years of age has not been established (see Section 4.3 Contraindications).

Effects on laboratory tests.

No data available.

Use in debilitated patients.

Such patients may be particularly susceptible to the sedative effects of zopiclone and associated giddiness, ataxia and confusion, which may increase the possibility of a fall (see Section 4.2 Dose and Method of Administration).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Alcohol.

Concomitant intake with alcohol is not recommended. The sedative effect of Imrest may be enhanced when the product is used in combination with alcohol.

CNS depressants.

Additive CNS depressant effects should be expected if zopiclone is administered concomitantly with other medications which themselves produce CNS depression, e.g. barbiturates, benzodiazepines, alcohol, sedatives, tricyclic antidepressants, nonselective monoamine oxidase inhibitors (MAOIs) and other antidepressants, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines, narcotic analgesics, anaesthetics, neuroleptics, hypnotics, anxiolytics, antiepileptics (see Section 4.4 Special Warnings and Precautions for Use). In the case of narcotic analgesics, enhancement of euphoria may also occur leading to an increase in psychic dependence.

Other.

Erythromycin has been reported to significantly increase zopiclone concentrations at 30 minutes and 1 hour after ingestion of zopiclone. The total area under the curve (AUC) of zopiclone increased by 80% in 10 healthy volunteers which indicates that erythromycin can inhibit the metabolism of drugs metabolised by CYP3A4. Accelerated absorption of zopiclone in the presence of erythromycin may lead to enhanced hypnotic effects.
Plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors such as erythromycin, clarithromycin, ketoconazole, itraconazole, and ritonavir.
Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers, such as rifampicin, carbamazepine, phenobarbital (phenobarbitone), phenytoin, and St. John's wort.

Opioids.

The concomitant use of benzodiazepines and other sedative-hypnotic drugs, including zopiclone, and opioids increases the risk of sedation, respiratory depression, coma, and death because of additive CNS depressant effect. Limit dosage and duration of concomitant use of zopiclone and opioids (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Zopiclone has been shown to severely reduce fertility in male rats treated with 50 mg/kg/day or greater. The significance of this finding for humans is not known.
(Category C)
The use of Imrest during pregnancy is not recommended. Studies in animals have not shown evidence of an increased occurrence of foetal damage. However, zopiclone has been shown to cross the placenta and increase postnatal mortality in rats given 10 mg/kg/day and above. Although the significance of this for humans is not known, it is likely that zopiclone may be harmful to the neonate.
Cases of reduced foetal movement and foetal heart rate variability have been described after administration of benzodiazepines and other sedative-hypnotic drugs, such as zopiclone, during pregnancy.
Administration of zopiclone during the last three months of pregnancy or during labour, has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties and respiratory depression due to the pharmacological action of the product.
Treatment should be as short as possible and should not exceed four weeks including the period of tapering off. Moreover, infants born to mothers who took sedative/ hypnotics agents chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. Appropriate monitoring of the newborn in the postnatal period is recommended.
If zopiclone is prescribed to a woman of childbearing potential, she should be warned to contact her doctor regarding discontinuation of the product if she intends to become or suspects she is pregnant.
Zopiclone and/or its metabolites are excreted in breast milk, therefore should not be used in nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

The side-effect most commonly seen in clinical trials is taste alteration (bitter taste).

More common effects.

Nervous system disorders.

Drowsiness, headaches, fatigue.

Gastrointestinal disorders.

Bitter taste, dry mouth.

Less common effects.

Immune system disorders.

Angioedema and/or anaphylactic reactions have been reported very rarely.

Nervous system disorders.

Agitation, anxiety, loss of memory including retrograde amnesia, anterograde amnesia, confusion, dizziness, weakness, somnolence, asthenia, feeling of drunkenness, euphoria, depression, coordination abnormality, hypotonia, speech disorder, hallucinations (auditory and visual), behavioural disorders, aggression, tremor, rebound insomnia, nightmares, irritability, abnormal and/or inappropriate behaviour possibly associated with amnesia, sleepwalking (see Section 4.4 Special Warnings and Precautions for Use, Somnambulism and associated behaviours), restlessness, delusion, anger, dependence, ataxia, paresthesia, cognitive disorders such as memory impairment, disturbance in attention, speech disorder.
Withdrawal syndrome has been reported upon discontinuation (see Section 4.4 Special Warnings and Precautions for Use). Withdrawal symptoms vary and may include rebound insomnia, muscle pain, anxiety, tremor, sweating, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, hallucinations, and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations. In very rare cases, seizures may occur.

Eye disorders.

Blurred vision and diplopia.

Cardiac disorders.

Palpitations in elderly patients.

Respiratory, thoracic and mediastinal disorders.

Dyspnea and respiratory depression have been reported.

Gastrointestinal disorders.

Heartburn, constipation, diarrhoea, nausea, coated tongue, bad breath, anorexia or increased appetite, vomiting, epigastric pains, dyspepsia.

Hepatobiliary disorders.

Mild to moderate increases in serum transaminases and/or alkaline phosphatase have been reported very rarely.

Skin and subcutaneous tissue disorders.

Pruritus, rash, urticaria, and tingling have been rarely reported.

Musculoskeletal and connective tissue disorders.

Muscular weakness.

Renal and urinary disorders.

Micturition.

Reproductive system and breast disorders.

Impotence, ejaculation failure, libido disorder.

Injury, poisoning and procedural complications.

Falls, predominantly in elderly patients.

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

For oral use only. Use the lowest effective dose. Imrest should be taken in a single intake and not be readministered during the same night. Treatment should be as short as possible and should not exceed four weeks including the period of tapering off.

Adults.

One tablet (7.5 mg) by oral administration shortly before retiring for a maximum of 2 to 4 weeks. This dose should not be exceeded. Depending on clinical response, the dose may be lowered to 3.75 mg.
Zopiclone is not recommended for long-term use (i.e. periods of more than 4 weeks). If used for long periods, treatment should be withdrawn gradually (see Section 4.4 Special Warnings and Precautions for Use).

Elderly.

In elderly and/or debilitated patients an initial dose of 3.75 mg is recommended. The dose may be increased to a maximum of 7.5 mg if the starting dose does not offer adequate therapeutic effect, but in clinical trials, 25% of elderly patients treated with zopiclone experienced CNS side effects at the higher dose. Zopiclone should be used with caution in these patients (see Section 4.4 Special Warnings and Precautions for Use).

Paediatric.

Zopiclone is contraindicated in children. Dosage has not been established.

Hepatic insufficiency.

The recommended dose is 3.75 mg depending on acceptability and efficacy. Up to 7.5 mg may be used with caution in appropriate cases.

Renal impairment.

In patients with renal insufficiency: although no accumulation of zopiclone or of its metabolites has been detected in cases of renal insufficiency, it is recommended that patients with impaired renal function should start treatment with 3.75 mg.

Alternative therapy.

For long-term treatment of insomnia, alternative non-pharmacological methods should be considered. Effective practical management of insomnia must respond to the presenting characteristics of the complaint. Giving accurate information is a form of treatment; there is benefit in discussing some simple facts with the patient and relating them to the problem, thereby assisting the patient to place the sleep problem in its context. Sleep hygiene such as reduction of caffeine intake, should be exercised. Programs designed to establish an optimal sleeping pattern for the patient may also be useful as are relaxation techniques designed to assist the patient to deal with tension and intrusive thoughts in bed.

4.7 Effects on Ability to Drive and Use Machines

Zopiclone can impair daytime function in some patients even when taken as instructed. Some patients may still have zopiclone blood levels in the morning on the day following use that are high enough to produce impairment. Patients should be warned that impairment can occur despite feeling fully awake, in the absence of symptoms, or even with subjective improvement.
Zopiclone is not to be taken with alcohol or other sedative hypnotics (including other zopiclone products). If concomitant use of another CNS depressant or a drug that increases zopiclone blood levels is clinically warranted, dosage adjustments of zopiclone may be necessary.
The risk of psychomotor impairment, including impaired driving ability, is increased if:
zopiclone is taken within 12 hours of performing activities that require mental alertness;
zopiclone is taken with less than a full night sleep remaining;
a higher dose than recommended is taken; or
zopiclone is co-administered with other CNS depressants, alcohol, or with other drugs that increase the blood levels of zopiclone.
Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle following administration of zopiclone and in particular during the 12 hours following that administration.

4.9 Overdose

Overdose of zopiclone can be manifested by varying degrees of CNS depression ranging from drowsiness to coma according to the quantity ingested. In mild cases, symptoms include drowsiness, confusion and lethargy. In more severe cases, symptoms may include ataxia, hypotonia, hypotension, methaemoglobinaemia, respiratory depression and coma. Overdosage could be life threatening when combined with other CNS depressants, including alcohol. Other risk factors, such as the presence of concomitant illness and the debilitated state of the patient, may contribute to the severity of symptoms and very rarely can result in fatal outcome.

Treatment.

Symptomatic and supportive treatment in an adequate clinical environment is recommended, attention should be paid to respiratory and cardiovascular function. Activated charcoal may reduce absorption of the medicine if given within one or two hours after 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. Haemodialysis is of no value, due to large volumes of distribution of zopiclone. Flumazenil may be useful as an antidote. As in the management of overdosage with any medication, it should be borne in mind that multiple agents may have been taken.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Container type: Blister pack.
Pack sizes: 2, 10, 30 and 100 tablets.
Some pack sizes may not be marketed.

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