Zimoclone 7.5 mg Film-coated Tablets

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Updated on 29 January 2019 PIL

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  • Change to section 6 - marketing authorisation holder

Updated on 29 January 2019 SmPC

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  • Change to section 8 - Marketing authorisation number(s)

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 14 January 2019 PIL

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  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 14 January 2019 SmPC

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  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

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Updated on 4 January 2016 SmPC

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  • New SmPC for new product

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Updated on 4 January 2016 SmPC

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  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 2:

Excipients with known effect:
Each film-coated tablet contains 30.8 mg lactose anhydrous


Section 4.1:

Zimoclone is indicated for the short-term treatment of insomnia

 

in adults.

 




Section 4.2:
The lowest effective dose should be used.
Zopiclone should be taken in a single dose and not re-administered during the
same night.
Method of administration:
Zimoclone is for oral use only.
Treatment duration
Treatment with Zimoclone zopiclone should be as short as possible. Generally
the duration of treatment varies from a few days to two weeks with a maximum,
including the tapering off, of four weeks.

In certain cases an extension beyond the maximum treatment period may be
necessary; if so it should take place after re-evaluation of the patient’s status.
(see section 4.4).

The recommended dose for adults is 1 tablet (7.5 mg Zimoclonezopiclone). This dose should not be exceeded. The tablet should be taken just before retiring.

Impaired hepatic function

 

and chronic respiratory insufficiency:

 

A dose of 3.75 mg is recommended in patients with impaired hepatic function

since elimination of zopiclone As elimination of zopiclone

 

 

may be reduced in

 

these

 

 

patients with hepatic dysfunction, a lower dose of 3.75 mg zopiclone

 

nightly is recommended

 

 

.

 

The

 

standard doseage of may be increased to 7.5 mg zopiclone may be used

 

with caution

 

in some cases if considered clinically necessary, depending on

 

effectiveness and patient

 

 

acceptability.

 

Chronic respiratory insufficiency:

In patients with chronic respiratory insufficiency, a starting dose of 3.75 mg

zopiclone is recommended initially. The dosage subsequently may be increased

to 7.5 mg.

Elderly:

A starting dose of 3.75 mg is recommended, this dose may consequently be

increased to 7.5 mg if considered

 

clinically necessary depending on patient

 

effectiveness and

 

 

acceptability. (see section 4.4).

 

Paediatric population:

 

 

 

Zopiclone should not be used in children

 

or and adolescents younger less than

 

18 years

 

of age. The safety and efficacy of zopiclone in children and

 

adolescents aged less than 18 years have not been established.

Method of administration

Zopiclone is for oral use only.



Section 4.4:

 

Special warnings and

 

special precautions for use

 

 

 

 

Risk of dependence:

 

 

 

Clinical experience to date suggests that the risk of dependence is minimal when

the duration of treatment is limited to not more than 4 weeks, however, as with

the benzodiazepines and other benzodiazepine-like drugs

 

(even at therapeutic

 

doses)

 

 

, there is a risk of physical and psychological dependence or abuse. This

 

risk increases with dose and length of treatment

 

and use with alcohol or other

 

psychotropics

 

 

. Patients with a history of alcohol and/or drug abuse or those with

 

personality disorders are more at risk of dependence and this should be

considered when prescribing

 

Zimoclonezopiclone. If a patient does become

 

dependent, abrupt cessation of treatment may result in withdrawal symptoms

including:

 

extreme anxiety, headaches, muscle pain, tension, confusion and

 

restlessness and irritability. In severe cases symptoms may also include

 

 

 

depersonalisationpersonality disturbances

 

 

, derealisation, numbness and tingling

 

 

 

 

 

of the extremities, hypersensitivity to noise, light and physical contact,

hallucinations or epileptic seizures.

Rare cases of abuse have been reported.

 

 

 

Withdrawal:

 

 

 

 

The termination of treatment with Zimoclonezopiclone is unlikely to be

associated with withdrawal effects when the duration of treatment is limited to

4 weeks.

Patients may benefit from tapering off the dose before discontinuation (see also

section 4.8).

 

 

 

 

Rebound insomnia:

 

 

 

On cessation of treatment with Zimoclone, there may be a transient, and often

enhanced, recurrence of insomnia which may be accompanied by some of the

withdrawal symptoms described above. Abrupt discontinuation of treatment

should be avoided, instead, the dosage should be reduced gradually.

 

 

 

 

Withdrawal:

 

 

 

The termination of treatment with Zimoclone is unlikely to be associated with

withdrawal effects when the duration of treatment is limited to 4 weeks.

Patients may benefit from tapering off the dose before discontinuation (see also

section 4.8).

 

 

 

 

Patients with a history of depression, anxiety or psychotic disorders:

Depression:

 

 

 

 

Benzodiazepines and benzodiazepine-like substances, such as zopiclone, are not

recommended as the primary treatment of psychoses.

Zopiclone does not constitute a treatment for depression (or anxiety linked with

depression) and may even mask its symptoms (suicide may be precipitated in

such patients).

Zopiclone does not constitute a treatment for depression and may even mask its

symptoms (suicide may be precipitated in such patients).

 

 

Any underlying cause

 

 

 

 

of the insomnia should also be addressed before symptomatic treatment to avoid

under treating potentially serious effects of depression.

 

 

Tolerance:

 

 

Some loss of efficacy to the hypnotic effects of benzodiazepines and

benzodiazepine-like agents may develop after repeated use for a few weeks.

However with

 

Zimoclone zopiclone no marked tolerance occurred during

 

treatment periods of up to four weeks.

 

 

 

Rebound insomnia:

 

 

 

 

A transient syndrome where the symptoms which led to treatment with a

benzodiazepine or benzodiazepine-like agent recur in an enhanced form on

discontinuation of therapy. It may be accompanied by other reactions including

mood changes, anxiety and restlessness. Since the risk of withdrawal/rebound

phenomena may be increased after prolonged treatment, or abrupt

discontinuation of therapy, it is therefore, recommended to decrease the dosage

gradually and to advise the patient accordingly.

A course of treatment should employ the lowest effective dose for the minimum

length of time necessary for the effective treatment. See section 4.2 for guidance

on possible treatment regimen. A course of treatment should not continue for

longer than 4 weeks including any tapering off (see section 4.8).

 

 

 

 

Amnesia:

 

 

 

Amnesia is rare, but anterograde amnesia may occur, especially iI

 

 

f sleep is

 

interrupted or

 

when retiring to bed is delayed after taking the tablet., the patient

 

may suffer anterograde amnesia, sS

 

 

ituations when this might occur should

 

therefore be avoided

 

and the patient should ensure that they are able to have a

 

full night’s sleep (uninterrupted sleep of about 7 to 8 hours).

.

 

 

 

 

Psychomotor impairment

 

 

 

 

Like other sedative/hypnotic drugs, zopiclone has CNS-depressant effects. 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, a dose higher than the recommended dose is taken, or zopiclone is coadministered

with other CNS depressants, alcohol or with other drugs that

increase the blood levels of zopiclone (see section 4.5). 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.

 

 

 

 

Specific patient groups:

 

 

For

 

 

theUse in elderly:

 

 

 

 

Hypnotics should be avoided in the elderly who are at risk of becoming ataxic

and confused and so liable to fall and injure themselves. If, based on clinical

need, a decision to treat is nevertheless taken, treatment should be initiated at a

lower dose (see section 4.2) and co-administration of

 

Zimoclone zopiclone with

 

CYP3A4 inhibitors should be avoided (see section 4.5).

 

 

 

Use in respiratory insufficiency

 

 

 

 

As hypnotics have the capacity to depress respiratory drive, precautions should

be observed if zopiclone is prescribed to patients with compromised respiratory

function (see section 4.8).

 

 

 

 

Use in hepatic insufficiency

 

 

 

 

A reduced dosage is recommended, (see section 4.2).

 

 

Benzodiazepines and

 

benzodiazepine-like substances are not suitable for the treatment of patients

with severe hepatic insufficiency, since they may promote the occurrence of

encephalopathy

 

(see section 4.3).

 

 

 

 

Use in renal insufficiency

 

 

 

 

A reduced dosage is recommended (see section 4.2).

Benzodiazepines and benzodiazepine-like substances are not recommended as

the primary treatment of psychoses. Benzodiazepines and benzodiazepine-like

substances should not be used as the sole treatment of depression or anxiety

linked with depression (suicide may be triggered in such patients).

Benzodiazepines and benzodiazepine-like substances should be administered

with extreme caution to patients with a previous history of alcohol and drug

abuse.

Before starting treatment with Zimoclone any underlying cause of insomnia

should be addressed carefully.

 

 

 


 

Paediatric population:

 

 

 

 

Zopiclone should not be used in children and adolescents less than 18 years. The

safety and efficacy of zopiclone in children and adolescents aged less than 18

years have not been established.

 

 

 

Section 4.5:


 

Alcohol may enhance the sedative effect of zopiclone, this may persist to the

following morning and could affect the patient’s ability to drive or use

machinery.

 

Concurrent use is therefore not recommended.

 

 

 

 

 

The effect of erythromycin on the pharmacokinetics of zopiclone has been

studied in 10 healthy subjects. The AUC of zopiclone is increased by 80% in

presence of erythromycin which indicates that erythromycin can inhibit the

metabolism of drugs metabolised by CYP3A4. As a consequence, the hypnotic

effect of zopiclone may be enhanced.

 

 

 

 

Since zopiclone is metabolised by

 

the cytochrome P450 (CYP) P4503A4

 

isoenzyme

 

(see section 5.2), plasma levels of zopiclone may be increased when

 

co-administered with CYP3A4 inhibitors

 

, such as erythromycin,

 

clarithromycin, ketoconazole, itraconazole, fluconazole, tacrolimus and

ritonavir.

 

This may result in an increased risk of adverse effects, particularly in

 

the elderly. Consequently, cC

 

 

o-administration of zopiclone with CYP3A4

 

inhibitors should be avoided in the elderly (see section 4.4)

 

.; fFor all other

 

 

 

 

patients

 

, a dose reduction for zopiclone may be required when it is coadministered

 

with CYP3A4 inhibitorsconsidered

 

 

.

 

Conversely, plasma levels of zopiclone may be decreased

 

, therefore reducing

 

the sedative effects of zopiclone

 

 

when co-administered with CYP3A4 inducers,

 

 

 

 

such as rifampicin, nefazodone, phenobarbital, phenytoin and St John’s wort.

 

A

 

dose increase for zopiclone may be required Ww

 

 

hen it is co-administered with

 

CYP3A4 inducers

 

or inhibitors a dose adjustment may be considered.

 

 

 

 

The interaction between erythromycin and zopiclone results in accelerated

absorption which may lead to a faster hypnotic effect.

 

 

Metoclopramide

 

increases and atropine decreases concentration of zopiclone in plasma.

 

 

Section 4.6:

 

If

 

, for compelling medical reasons zopiclone is administered during the last

 

three months late phase

 

 

of pregnancy or during labour, effects on the neonate

 

such as hypothermia, hypotonia, moderate respiratory depression, decreased

muscle tone and suckling reflex (“floppy infant syndrome”) can be expected.

Infants born to mothers who took benzodiazepines or benzodiazepine-like

agents chronically during the later stages of pregnancy may have developed

physical dependence and may be at some risk of developing withdrawal

symptoms in the postnatal period.


Section 4.7:

 

It has been reported that the risk that zopiclone adversely affects driving ability

is increased by the concomitant intake of alcohol. Therefore, it is recommended

not to drive while taking zopiclone and alcohol concomitantly. This may also

Use of zopiclone with alcohol may enhance the sedative effect and

 

 

affect the

 

patient’s ability to drive and use machinery the following morning.

Section 4.8;

 

 

 

 

Psychiatric disorders

 

 

 

 

Uncommon:

 

Nightmares, agitation

 

 

 

 

 

Rare:

 

Confusional state, numbed emotions, irritability, aggressiveness,

 

hallucinations, psychoses,

 

changes in libido disorder

 

 

 

 

 

 

Not known:

 

Dependency, restlessness, delusion, anger, depressed mood,

 

 

 

 

 

somnambulismsleepwalking

 

 

and other abnormal behaviour

 

 

 

 

 

(possibly associated with amnesia)

 

 

 

 

 

See below under ‘Depression’, ‘Psychiatric and paradoxical reactions’,

 

 

 

 

‘withdrawal syndrome’,

 

 

‘Somnambulism and associated behaviours’ and

 

‘Dependency’.

Nervous system disorders

 

 

 

 

Common:

 

Somnolence (residual)Drowsiness during the following day,

 

reduced alertness

 

, dysguesia (bitter taster)

 

 

 

 

 

 

Uncommon:

 

Headaches, dizziness, drowsiness

 

 

 

 

 

 

Rare:

 

Anterograde aAmnesia

 

See below under ‘Amnesia’.

 

 

 

 

Not known:

 

Ataxia (predominantly at the start of therapy and usually

 

disappears with repeated administration)

 

, paraesthesia

 

 

 

 

 

 

Eye disorders

 

 

 

 

Not known:

 

DiplopiaDouble vision (predominantly at the start of therapy and

 

usually disappears with repeated administration)

 

 

 

 

Respiratory, thoracic and mediastinal disorders

Rare: dyspnoea (see section 4.4)

Not known: respiratory depression (see section 4.4)

 

 

 

 

 

Gastrointestinal disorders

 

 

 

Common:

 

Bitter taste, dDry mouth

 

 

 

 

 

Uncommon:

 

Nausea, vomiting, drowsiness

 

 

 

 

 

 

Not known

 

 

: Dyspepsia

 

 

 

 

 

 

Skin and subcutaneous tissue disorders

 

 

 

Rare:

 

uUrticaria or rash, pruritis

 

 

 

 

 

Injury, poisoning and procedural complications

 

 

 

Rare:

 

Fall (predominantly in elderly patients)

 

Withdrawal syndrome has been reported upon discontinuation of zopiclone

(see section 4.4). Withdrawal symptoms vary and may include rebound

insomnia, muscle pain, anxiety, tremor, sweating, agitation, confusion,

headache, palpitations, tachycardia, delirium, nightmares,

 

hallucinations, panic

 

attacks, muscle aches/cramps, gastrointestinal disturbances 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.

 

 

 

Psychiatric and “paradoxical” reactions:

 

 

 

Reactions like restlessness, agitation, irritability, aggressiveness, delusion,

rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other

adverse behavioural effects are known to occur when using benzodiazepines or

benzodiazepine-like products. They are more likely to occur in

 

children and the

 

elderly.

 

 

 

Somnambulism and associated behaviours:

 

 

 

There is an increased risk of sleepwalking and other associated behaviours with

amnesia for the event in patients who have taken zopiclone and were not fully

awake

 

(see section 4.4). It appears that there is an increased risk of such

 

behaviour with the concomitant use of alcohol, other CNS depressants and the

use of zopiclone at doses exceeding the maximum recommended dose (see

section 4.4).

Section 4.9:

 

Fatal dose not known.

Symptoms

 

 

 

 

Symptoms of central nervous system

........

Management

Treatment of overdose should be symptomatic

.......

Section 5.1:

Pharmacotherapeutic group: Hypnotic and sedatives; benzodiazepine related

drugs,

 

 

ATC code: N05C F01. Hypnotic and sedatives; benzodiazepine related

 

drugs

Section 5.2:


 

Biotransformation

 

:

 

 

 

 

The most important metabolites are the N-oxide derivative (pharmacologically

active in animals) and the N-desmethyl metabolite (pharmacologically inactive

in animals). Their apparent half-life times are approximately 4.5 hours and 7.4

hours respectively. No significant accumulation of the compound as seen

following repeat dosing. (15 mg) for 14 days.

 

In animals, no enzyme

 

induction has been observed even at high doses.

 

Special patient groups:

 

 

In various trials with elderly patients, no accumulation of zopiclone was

observed in the plasma after repeated doses, in spite of a slight reduction in the

 

renal hepatic

 

 

function and extension of the eliminated half-life to

 

approximately 7 hours.



Section 6.3:

2

 

Yyears.

 



Section 6.5:

Also available in bulk packs of 100

 

and 500 tablets in a polypropylene container.

 

Section 6.6:

Special precautions for disposalInstructions for use/handling

Section 8:

PA

 

0405/044/001

 


Updated on 21 December 2015 PIL

Reasons for updating

  • New PIL for new product

Updated on 21 December 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to further information section
  • Change to date of revision
  • Change to dosage and administration

Updated on 22 July 2015 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 1:

Zimoclone 7.5 mg Film-coated Tablets

Section 2:

Excipients with known effect:
Each film-coated tablet contains 30.8 mg lactose anhydrous/film-coated tablet

For a the full list of excipients, see section 6.1.


Section 3:

White, film- coated, oval tablet having with a breakline, marked with “ZZ” on one side and “7.5” on the other.


Section 4.1:

Zopiclone Zimoclone Tablets 7.5mg are is indicated for the short-term treatment of insomnia.

Benzodiazepines and benzodiazepine-like agents are only indicated when the disorder is severe, disabling or subjecting the individual to extreme distress. Long term continuous use is not recommended. A course of treatment should employ the lowest effective dose.

Section 4.2:
Method of administration:
Zimoclone is for oral use only. Treatment with Zimoclone should be as short as possible. Generally the duration of treatment varies from a few days to two weeks with a maximum, including the tapering off, of four weeks.

In certain cases an extension beyond the maximum treatment period may be necessary; if so it should take place after re-evaluation of the patient’s status. (see section 4.4)

Posology
Adults:
The recommended dose for adults is 1 tablet (7.5 mg Zimoclone).

Children and adolescentsPaediatric population:

Section 4.3:
Zimoclone is contraindicated in patients with any of the following:

• Hypersensitivity to zopiclone or to any of the excipients listed in section 6.1
• Myasthenia gravis
• Severe hepatic impairment
• Sleep apnoea syndrome
• Respiratory failure


Section 4.4:
Clinical experience to date suggests that the risk of dependence is minimal when the duration of treatment is limited to not more than 4 weeks, however, aAs with the benzodiazepines and other benzodiazepine-like drugs, there is a risk of physical and psychological dependence. This risk increases with dose and length of treatment. Patients with a history of alcohol and/or drug abuse or those with personality disorders are more at risk of dependence and this should be considered when prescribing zopicloneZimoclone.


Rare cases of abuse have been reported.

Withdrawal:
The termination of treatment with Zimoclone is unlikely to be associated with withdrawal effects when the duration of treatment is limited to 4 weeks.
Patients may benefit from tapering off the dose before discontinuation (see also section 4.8).

Depression:
Zopiclone does not constitute a treatment for depression
and may even mask its symptoms (suicide may be precipitated in such patients).
Any underlying cause of the insomnia should also be addressed before symptomatic treatment to avoid under treating potentially serious effects of depression.


Psychiatric and ‘Pparadoxical’ reactions:
It is known that reactions such as restlessness, agitation, irritability, aggression, delusion, outbursts of rage, nightmares, hallucinations, psychoses, unsuitable behaviour and other behavioural disturbances may occur during the use of benzodiazepines and benzodiazepine-like substances. If this is the case administration of the medicinal product should be discontinued.
These reactions are more likely to occur in the elderly.


Section 4.6:
Pregnancy

Zopiclone should not be used during pregnancy unless clearly necessary.

To date zopiclone has not produced injurious effects in animal studies except at very high maternally toxic doses.



LactationBreast-feeding
Zopiclone is excreted in breast milk, although the concentration of zopiclone in the breast milk is low, use in nursing mothers must be avoided

Fertility
Double-blind long-term studies (7.5 mg zopiclone for 84 days) in healthy volunteers revealed no changes in ejaculate volume, sperm concentration, sperm motility or morphology.


Section 4.8:

Exstensive updates throughout this section.

Section 4.9:
Symptoms of central nervous system depression which can range 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. The effects of overdose may be magnified if combined with alcohol or any other CNS depressants and in severe cases may be life-threatening. 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 of overdose should be symptomatic and supportive paying particular attention to respiratory and cardiac functions. Consider activated charcoal if an adult has ingested more than 150 mg or a child more than 1.5 mg/kg within an hour. Alternatively, consider gastric lavage in adults within one hour of a potentially life- threatening overdose. If CNS depression is severe consider the use of flumazenil. It has a short half-life (about an hour). NOT TO BE USED IN MIXED OVERDOSE OR AS A ‘DIAGNOSTIC’ TEST. Haemodialysis does not have any therapeutic effect in cases of zopiclone overdose.


Section 5.2:

Biotransformation:
The most important metabolites are the N-oxide derivative (pharmacologically active in animals) and the N-desmethyl metabolite (pharmacologically inactive in animals). Their apparent half-life times are approximately 4.5 hours and 7.4 hours respectively. No significant accumulation of the compound as seen following repeat dosing. (15 mg) for 14 days.


Updated on 6 July 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to further information section
  • Change to date of revision
  • Change to dosage and administration
  • Addition of manufacturer

Updated on 8 December 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to how the medicine works
  • Change to date of revision
  • Change to dosage and administration
  • Correction of spelling/typing errors

Updated on 8 December 2011 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 2: Excipients: 30.8mg lactose anhydrous/film-coated tablet

Section 4.4:

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. It appears that there is an increased risk of such behaviour with the concomitant use of alcohol, other CNS depressants or the use of zopiclone at doses exceeding the maximum recommended dose. If such behaviours are reported, administration of zopiclone should be discontinued (see Section 4.5).

Section 4.5:

Since zopiclone is metabolised by CYPP4503A4 isoenzyme, plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors, such as erythromycin, clarithromycin, ketoconazole, itraconazole, fluconazole, tacrolimus and ritonavir.  This may result in an increased risk of adverse effects, particularly in the elderly.  Consequently, co-administration of zopiclone with CYP3A4 inhibitors should be avoided in the elderly (see section 4.4); for all other patients a dose reduction may be considered.

Section 4.6:

Zopiclone should not be used during pregnancy unless clearly necessary.

 

Any woman of child-bearing potential prescribed zopiclone, should be advised to consult her physician about discontinuing use of zopiclone in the event that she wishes to, or suspects that she has, become pregnant.

 

If, for compelling medical reasons zopiclone is administered during the late phase of pregnancy or during labour, effects on the neonate such as hypothermia, hypotonia, moderate respiratory depression, decreased muscle tone and suckling reflex (“floppy infant syndrome”) can be expected. Infants born to mothers who took benzodiazepines or benzodiazepine-like agents chronically during the later stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.

 

To date zopiclone has not produced injurious effects in animal studies except at very high maternally toxic doses.

 

Zopiclone should not be used in nursing mothers since zopiclone and its metabolites are excreted in breast milk

Double-blind long-term studies (7.5mg zopiclone for 84 days) in healthy volunteers revealed no changes in ejaculate volume, sperm concentration, sperm motility or morphology.

Section 4.7: Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines.
Section 4.8:

The following undesirable effects have been reported at the approximate frequencies shown:  very common (³1/10), common (³1/100 to < 1/10), uncommon (³1/1,000 to <1/100), rare (³1/10,000 to <1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data)

 

Immune system disorders

 

Rare:                Allergic reactions including skin reactions

 

Very rare:        Anaphylactic reactions and/or angioedema

 

Psychiatric disorders

 

Rare:                Confusion, numbed emotions, depression, restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, sleepwalking and other adverse behaviour

 

Very rare:        Changes in libido

 

Not known:     Dependency

 

See below under ‘Depression’,  ‘Psychiatric and paradoxical reactions’, ‘Somnambulism and associated behaviours’ and ‘Dependency’.

 

Nervous system disorders

 

Common:        Drowsiness during the following day, reduced alertness, headaches, dizziness

 

Rare:                Amnesia, ataxia (predominantly at the start of therapy and usually disappears with repeated administration)

 

See below under ‘Amnesia’.

 

Eye disorders

 

Rare:                Double vision (predominantly at the start of therapy and usually disappears with repeated administration)

 

Gastrointestinal disorders

 

Very common: Bitter taste

 

Common:        Other gastrointestinal complaints

 

Musculoskeletal and connective tissue disorders

 

Rare:                Muscle weakness

 

General disorders and administration site conditions

 

Uncommon:    Fatigue

 

Investigations

 

Rare:                Mild to moderate increases in serum transaminases and/or alkaline phosphatase

 

 

 

Amnesia:

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesiac effects may be associated with inappropriate behaviour (see Section 4.4).


Somnambulism and associated behaviours:

There is an increased risk of sleepwalking and other associated behaviours with amnesia for the event in patients who have taken zopiclone and were not fully awake. It appears that there is an increased risk of such behaviour with the concomitant use of alcohol, other CNS depressants and the use of zopiclone at doses exceeding the maximum recommended dose (see Section 4.4) 

 

Dependence:

Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena (see Section 4.4).  Psychological dependence may occur.  Abuse has been reported.

Section 4.9:

Treatment of overdose should be symptomatic and supportive paying particular attention to respiratory and cardiac functions.    If overdose is detected soon after ingestion, gastric lavage may be useful. If CNS depression is severe consider the use of flumazenil. It has a short half-life (about an hour). NOT TO BE USED IN MIXED OVERDOSE OR AS A ‘DIAGNOSTIC’ TEST.  Haemodialysis does not have any therapeutic effect in cases of zopiclone overdose.

Section 5.2: Zopiclone is swiftly absorbed.  Maximum plasma concentrations are achieved after 1½ - 2 hours and are approximately 30 and 60ng/ml after administration of 3.75mg and 7.5mg respectively. 

Section 5.3: Foetal developmental retardations and foetotoxic effects in rats and rabbits were observed only at doses well above the maximum human dosage. There was no evidence of a teratogenic potential.


Updated on 10 June 2011 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 6.4 - Special precautions for storage
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

          Section 2: Excipients: 30.8mg lactose/film-coated tablet

 

 For a full list of excipients, see section 6.1
Section 3: The tablet can be divided into equal halves.

Section 4.2:

In certain cases an extension beyond the maximum treatment period may be necessary; if so it should take place after re-evaluation of the patient’s status. (see warnings on dependence and tolerance in section 4.4)

Section 4.7: Patients should be advised not to  drive or operate machinery the day after treatment until it is established that their performance is unimpaired.

 

Section 6.4:

Store in the original package, in order to protect from light.

Section 9:

            Date of first authorisation: 28th April 2000

Date of latest renewal: 8th December 2008

Section 10:

April 2011

Updated on 9 June 2011 PIL

Reasons for updating

  • Change to storage instructions
  • Change to further information section
  • Change to date of revision

Updated on 14 August 2009 PIL

Reasons for updating

  • Change due to user-testing of patient information

Updated on 5 January 2007 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.5: the following paragraph was added
A single dose study has indicated that when zopiclone and carbamazepine are taken in combination, their sedative effects are additive.  However, as carbamazepine is a potent inducer of CYP3A4, it is predicted that long term use of carbamazepine could result in a reduction of zopiclone plasma levels and reduce its hypnotic effects accordingly.

Updated on 24 August 2006 SmPC

Reasons for updating

  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 14 August 2006 PIL

Reasons for updating

  • Change of active ingredient
  • Change to side-effects
  • Change to storage instructions
  • Change to drug interactions
  • Change to warnings or special precautions for use

Updated on 27 July 2006 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SmPC updated to current guidelines.
 
Main changes are to section 4.4, 4.5 and 4.8.
 
Section 4.8: arranging effects according to frequency/system organ class.

Updated on 16 September 2004 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 19 August 2003 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 19 June 2003 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)