Consumer medicine information

Imovane

Zopiclone

BRAND INFORMATION

Brand name

Imovane

Active ingredient

Zopiclone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Imovane.

SUMMARY CMI

Imovane®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Imovane?

Imovane contains the active ingredient zopiclone. Imovane is used to help people over 18 years of age 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 (7-14 days) of insomnia. For more information, see Section 1. Why am I using Imovane? in the full CMI.

2. What should I know before I use Imovane?

Do not use if you have ever had an allergic reaction to Imovane or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Imovane? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Imovane and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Imovane?

  • Imovane 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 Imovane is one tablet just before you go to bed.

More instructions can be found in Section 4. How do I use Imovane? in the full CMI.

5. What should I know while using Imovane?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Imovane.
  • If you become pregnant while you are taking this medicine, stop taking it and tell your doctor or pharmacist immediately.
Things you should not do
  • Do not take more than the recommended dose unless your doctor tells you to.
Driving or using machines
  • Because Imovane will make you sleepy, you should not operate dangerous machinery or drive motor vehicles for 12 hours after you take it. You should also be careful the next morning when you wake up.
Drinking alcohol
  • You should not drink alcohol while you are taking Imovane.
  • The effects of alcohol could be made worse while taking Imovane.
Looking after your medicine
  • Follow the instructions in the carton on how to take care of your medicine properly.
  • Keep your tablets in the blister pack until it is time to take them.
  • Store below 25°C, in a cool dry place away from moisture, heat or sunlight.
  • Keep it where young children cannot reach it.

For more information, see Section 5. What should I know while using Imovane? in the full CMI.

6. Are there any side effects?

  • Common side effects include headache, bitter taste in your mouth, dry mouth and drowsiness. Serious side effects include allergic reaction symptoms such as swelling of the face, lips, mouth or throat, which may cause difficultly in swallowing or breathing. Other serious side effects include fainting, depression, suicidal thoughts or changes in your behaviour.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Imovane®

Active ingredient: zopiclone


Consumer Medicine Information (CMI)

This leaflet provides important information about using Imovane. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Imovane.

Where to find information in this leaflet:

1. Why am I using Imovane?
2. What should I know before I use Imovane?
3. What if I am taking other medicines?
4. How do I use Imovane?
5. What should I know while using Imovane?
6. Are there any side effects?
7. Product details

1. Why am I using Imovane?

Imovane contains the active ingredient zopiclone.

Imovane belongs to the class of medications called sedative-hypnotics.

Imovane is used to help people over 18 years of age 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 (7-14 days) of insomnia.

Your doctor, however, may prescribe Imovane for another purpose. Ask your doctor if you have any questions about why Imovane has been prescribed for you.

2. What should I know before I use Imovane?

Warnings

Do not use Imovane if you:

  • are allergic to zopiclone, 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.
    Always check the ingredients to make sure you can use this medicine.
  • have been drinking alcohol or you believe that you may have alcohol in your bloodstream
  • have sleep apnoea (a condition where you temporarily stop breathing while you sleep)
  • have myasthenia gravis (a condition in which the muscles become weak and tire easily)
  • have severe liver problems
  • have acute and/or severe lung problems
  • have had a stroke
  • have ever experienced sleep-walking or other unusual behaviour (such as driving, eating, making a phone call or having sex etc.) while not being fully awake after taking Imovane.
  • Do not take Imovane as a long term treatment
  • Do not take Imovane if the packaging is damaged or shows signs of tampering.
  • Do not give Imovane to children or adolescents.
  • Do not take it if you are pregnant or intend to become pregnant.
  • Do not take it if you are breastfeeding or planning to breastfeed.

Check with your doctor if you:

  • take any medicines for any other condition.
  • have allergies to any of the ingredients listed at the end of this leaflet or any other substances such as foods, dyes or preservatives.
  • have any problems with your breathing or if you often snore while you are asleep.
  • 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 Imovane.
  • ever had a history of sleep-walking or other unusual behaviour (such as driving, eating, making a phone call, or having sex etc.) while not being fully awake after taking Imovane.

Imovane may cause sleep walking or other unusual behaviour (such as driving, eating, making a phone call, or having sex etc.) while not being fully awake, some of which have been associated with serious injuries and death. The next morning, you may not remember that you did anything during the night. These activities may occur whether or not you drink alcohol or take other medicines that make you drowsy with Imovane. If you experience any of the above, stop the treatment with Imovane immediately and contact your doctor or health-care provider.

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 Imovane.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

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.

Imovane 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.

Use in children

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

3. What if I am taking other medicines?

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

Some medicines may interfere with the absorption of Imovane. 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 eg cough syrups
  • muscle relaxants
  • antihistamines
  • medicines used to treat epilepsy
  • antiviral medication
  • rifampicin, erythromycin or clarithromycin (medicines used to treat infections)
  • ketoconazole or itraconazole (medicines used to treat fungal infections)

These medicines may be affected by Imovane 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 Imovane.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Imovane.

4. How do I use Imovane?

How much to take

  • Imovane 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 Imovane is one tablet just before you go to bed.
  • Imovane should be taken in a single intake and not readministered during the same night.
  • If you are over 65 years of age the dose is half a tablet taken just before you go to bed.
  • If you have a liver or kidney 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, Imovane may not work as well.
  • Imovane should not be given to children or adolescents less than 18 years of age.

When to take Imovane

  • Take Imovane immediately before you go to bed. Imovane 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 Imovane 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 Imovane

  • Imovane should only be used for short periods (e.g.7-14 days). Continuous long term use is not recommended.
  • Ask your doctor or pharmacist if you are not sure how long to take the medicine for.

How to take Imovane

  • Swallow the tablet with a full glass of water.

If you forget to use Imovane

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.

After taking Imovane

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 Imovane.

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

If you use too much Imovane

If you think that you have used too much Imovane, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 in Australia or 0800 764 766 in New Zealand), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Imovane?

Things you should do

  • Tell all the doctors, dentists and pharmacists who are treating you that you are taking Imovane.
  • If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Imovane.
  • 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 should 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.

Driving or using machines

Because Imovane will make you sleepy, you should not operate dangerous machinery or drive motor vehicles for 12 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 Imovane before you drive a car or operate machinery. This is very important if you are taking other drugs that also make you drowsy.

Impairment can occur despite feeling fully awake, in absence of symptoms or if you are feeling better.

Use in Elderly (over 65 years)

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 Imovane.

Drinking alcohol

You should not drink alcohol while you are taking Imovane.

The effects of alcohol could be made worse while taking Imovane.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

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.

Store below 25°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
General
  • headaches
  • dry mouth
  • bitter taste in your mouth
  • drowsiness

These are the most common side effects of this medicine.

Less common side effects include:

Gut related
  • heartburn
  • nausea, vomiting and/or diarrhoea
  • change in appetite
  • stomach pain
General
  • rash
  • blurred vision
Sexual health
  • impotence
Central nervous system-related
  • agitation
  • depression
  • confusion
  • anxiety
  • dizziness
  • sleep walking or other unusual behaviours (such as driving, eating, making a phone call, or having sex etc.) while not being fully awake, some of which have been associated with serious injuries and death
  • delirium (a sudden and severe change in mental state that can cause a combination of confusion, disorientation and/or attention deficit)
Speak to your doctor if you have any of these less serious side effects and they worry you.

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 sleep 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 Imovane.

Serious side effects

Serious side effectsWhat to do
Allergy related
  • swelling of the face, lips, mouth or throat, which may cause difficultly in swallowing or breathing
  • hives
General
  • fainting
Central nervous system-related
  • suicidal thoughts or are experiencing changes in your behaviour
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

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

These side effects are very rare.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

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

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems in Australia or in New Zealand at https://nzphvc.otago.ac.nz/reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Imovane contains

Active ingredient
(main ingredient)
  • Zopiclone 7.5 mg
Other ingredients
(inactive ingredients)
  • calcium hydrogen phosphate dihydrate
  • wheat starch (gluten)
  • sodium starch glycollate
  • lactose monohydrate
  • magnesium stearate

Coating (Opadry white OY-S-38906):

  • hypromellose
  • titanium dioxide
  • macrogol 6000

Do not take this medicine if you are allergic to any of these ingredients.

What Imovane looks like

Imovane is a white, elliptical biconvex film-coated tablet with a score line on one side.

Australia: Imovane is available in blister packs of 2, 10, 14 and 30 tablets.

New Zealand: Imovane is available in blister packs of 10, 14 and 30 tablets.

** Not all pack sizes marketed.

AUST R 165934.

New Zealand Ref: TT50-3976

Who distributes Imovane

Distributed in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806
Email: [email protected]

Distributed in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
PO Box 62027
Sylvia Park Auckland 1644
Freecall: 0800 283 684
Email: [email protected]

This leaflet was prepared in October 2022.

® Registered Trademark

Imovane-ccdsv13-cmiv18-06oct22

Published by MIMS November 2023

BRAND INFORMATION

Brand name

Imovane

Active ingredient

Zopiclone

Schedule

S4

 

1 Name of Medicine

Zopiclone.

2 Qualitative and Quantitative Composition

Imovane tablets contain 7.5 mg of the active ingredient zopiclone.
Zopiclone is a fine white or slightly cream crystalline powder with a melting point of 176-178°C. It is practically insoluble in acetone, soluble in dimethyl formamide and 0.1 N hydrochloric acid and freely soluble in chloroform and dichloromethane.
The tablets also contain lactose monohydrate, calcium hydrogen phosphate dihydrate, wheat starch (gluten), sodium starch glycollate, magnesium stearate, hypromellose, macrogol 6000 and titanium dioxide.

3 Pharmaceutical Form

The tablets are scored white or almost white, elliptical, biconvex, film coated tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Short-term treatment of insomnia (7 - 14 days).

4.2 Dose and Method of Administration

For oral use only. Use the lowest effective dose for short term treatment (7-14 days). Extension beyond the maximum treatment period should not take place without re-evaluation of the patient's status, since the risk of abuse and dependence increases with the duration of treatment.
Imovane should be taken in a single intake and not be readministered during the same night.

Adults.

7.5 mg by oral administration shortly before retiring. This dose should not be exceeded. Depending on clinical response, the dose may be lowered to 3.75 mg.
Zopiclone is for short-term treatment (7 - 14 days). See Section 4.4 Special Warnings and Precautions for Use, Dependence for advice of gradual dose decrease after prolonged use.

Elderly patients.

In the elderly and/or debilitated patient 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 deal with tension and intrusive thoughts in bed.

4.3 Contraindications

Patients with known hypersensitivity to zopiclone or any of the excipients.
Prior or concomitant use of alcohol.
Myasthenia gravis.
Severe impairments of respiratory function.
Acute cerebrovascular accident.
Sleep apnoea syndrome.
Severe hepatic insufficiency.
Patients who have previously experienced complex sleep behaviours after taking zopiclone.
Zopiclone 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 (7-14 days). 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, abnormal behaviour, delirium 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.

Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake, may occur following the first or any subsequent use of zopiclone. Patients can be seriously injured or injure others during complex sleep behaviors. Such injuries may be fatal. Other complex sleep behaviors (e.g. preparing and eating food, making phone calls, or having sex, with amnesia for the event) have also been reported. Patients usually do not remember these events. Postmarketing reports have shown that complex sleep behaviors may occur with zopiclone alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Discontinue Imovane immediately if a patient experiences a complex sleep behavior. (See Section 4.3 Contraindications).

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 on 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 on 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 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 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 of zopiclone 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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Alcohol.

Concomitant intake with alcohol is not recommended. The sedative effect of zopiclone 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, for example barbiturates, benzodiazepines, alcohol, sedatives, tricyclic antidepressants, non-selective MAO inhibitors 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.

CYP450 inhibitors and inducers.

Erythromycin has been reported to increase significantly zopiclone concentrations at 0.5 and 1 hour after ingestion of zopiclone. The total AUC of zopiclone increased by 80% in 10 healthy volunteers which indicates that erythromycin can inhibit the metabolism of drugs metabolised by CYP 3A4. 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 zopiclone 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/d 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.
Zopiclone is for short term treatment of insomnia (7-14 days). 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 physician 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 so therefore should not be used in nursing mothers.

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.

4.8 Adverse Effects (Undesirable Effects)

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

More common reactions.

Nervous system disorders.

Drowsiness, headaches, fatigue.

Gastrointestinal disorders.

Bitter taste, dry mouth.

Less common reactions.

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, co-ordination 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, complex sleep behaviours, including sleep walking (see Section 4.4 Special Warnings and Precautions for Use, Somnambulism and associated behaviours), restlessness, delirium, 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 (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

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 functions. 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 the large volume 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 general advice on overdose management, contact the Poisons Information Centre, telephone number 13 11 26 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

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 man, zopiclone reduced sleep latency, increased the duration of sleep and decreased the number of nocturnal awakenings. Zopiclone delayed the onset of 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 7.5 mg of zopiclone 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 intestines, stomach, kidneys and the adrenals. After twenty four hours the total residual radioactivity in the body of the rat was 8%.
The bioavailability of the 7.5 mg tablets in man is 76.3 ± 9.6%, a hepatic first pass effect has been demonstrated. In fresh human plasma, zopiclone is approximately 45% protein bound in the 25-100 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 5.26 ± 0.76 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/min 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 metabolites 11.4% and the N-desmethyl metabolite 13.4%.

Elderly.

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

Hepatic insufficiency.

In patients with hepatic insufficiency, elimination half-life is prolonged (11.9) and time to peak plasma levels 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 2 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 17 β-estradiol metabolism. Studies with mice treated with zopiclone at dietary doses up to 100 mg/kg/day showed no evidence of drug-related carcinogenicity.

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

Imovane tablets containing 7.5 mg of zopiclone and are available in packs of 10s, 14s and 30s.
*Not all pack sizes are marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

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.

7 Medicine Schedule (Poisons Standard)

Schedule 4.

Summary Table of Changes