ZOPIVANE Film-coated tablet Ref.[115177] Active ingredients: Zopiclone

ZOPIVANE should be used with extreme caution in patients with a history of drug or alcohol abuse.

Drowsiness and inco-ordination on waking may occur. Patients should be cautioned about driving motor vehicles or operating machinery, until it has been established that their performance is not affected (see section 4.7).

Specific patient groups

Use in hepatic insufficiency

A reduced dosage is recommended, (see Posology). Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy (see section 4.3).

Use in renal insufficiency

A reduced dosage is recommended, (see Posology).

Use in respiratory insufficiency

If ZOPIVANE is prescribed to patients with compromised respiratory function (see section 4.8), precautions should be observed because hypnotics have the capacity to depress respiratory drive. A lower dose is recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

Use in paediatric population

ZOPIVANE should not be used in children and adolescents less than 18 years. The safety and efficacy of ZOPIVANE in children and adolescents aged less than 18 years have not been established.

Use in elderly patients

ZOPIVANE should be given with care to the elderly or debilitated patients who may be more prone to adverse effects.

Dependence

The development of dependence or abuse cannot be excluded and should be kept in mind when zopiclone is prescribed. Dependence is particularly likely in patients with a history of alcohol and/or drug abuse and in patients with marked personality disorders. The risk of dependence or abuse increases with dose and duration of treatment and the use with alcohol and other psycotropics.

Once physical dependence has developed, abrupt termination of therapy will result by withdrawal symptoms (see section 4.8).

Withdrawal

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

Suicidal ideation/suicide attempt/suicide depression

Some epidemiological studies show an increased incidence of suicidal ideation, suicide attempt and suicide in patients with or without depression, and treated with benzodiazepines and other hypnotics, including zopiclone (e.g. ZOPIVANE). However, a causal relationship has not been established.

ZOPIVANE does not constitute a treatment for depression and may even mask its symptoms (suicide may be precipitated in such patients).

ZOPIVANE is not recommended for primary treatment of psychotic illness.

ZOPIVANE should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present therefore the least amount of ZOPIVANE that is feasible should be supplied to these patients to avoid the possibility of intentional overdosage by the patient. Pre-existing depression may be unmasked during use of ZOPIVANE. Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists.

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 effect of benzodiazepines and benzodiazepine-like medicines may develop after repeated use for a few weeks.

However, with ZOPIVANE there is an absence of any marked tolerance during treatment periods of up to 4 weeks.

Rebound insomnia and withdrawal phenomena

A transient syndrome where the symptoms which led to treatment with a benzodiazepine or benzodiazepine-like medicine recur in an enhanced form on discontinuation of therapy. It may be accompanied by other reactions including mood changes, anxiety and restlessness. The risk of such phenomena is greater after abrupt discontinuation of ZOPIVANE, especially after prolonged treatment. It is, therefore, recommended to decrease the dosage gradually and to advise patient accordingly. (see section 4.8).

A course of treatment should employ the lowest effective dose for the minimum length of time necessary for effective treatment. See Posology 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).

Some loss of efficacy may develop after repeated use.

Amnesia

Amnesia is rare, but anterograde amnesia may occur, especially when sleep is interrupted or when retiring to bed is delayed after taking the tablet. To minimise the risk of anterograde amnesia and mental confusion, ZOPIVANE should be taken only when the patient’s schedule will allow for a full night’s sleep (7 to 8 hours).

Psychomotor impairment

ZOPIVANE has central nervous system depressant effects. The risk of psychomotor impairment, including impaired driving ability, should be taken into account (see sections 4.5 and 4.7).

Risks from concomitant use with opioids

Concomitant use of opioids with benzodiazepines or other sedative-hypnotic medicines, including zopiclone may result in sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of opioids and benzodiazepines for use in patients for whom alternative treatment options are inadequate.

If a decision is made to prescribe ZOPIVANE 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).

Other psychiatric and paradoxical reactions

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

Somnambulism and associated behaviours

Sleep walking 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 as contained in ZOPIVANE and were not fully awake. The use of alcohol and other CNS-depressants with ZOPIVANE appears to increase the risk of such behaviours, as does the use of ZOPIVANE at doses exceeding the maximum recommended dose.

Discontinuation of ZOPIVANE should be strongly considered for patients who report such behaviours (see section 4.5).

ZOPIVANE contains lactose monohydrate

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption should not take ZOPIVANE.

• The concomitant use of alcohol is not recommended since the sedative effect of zopiclone may be enhanced.
• Caution is advised when prescribing zopiclone to patients using central depressant medication such as neuroleptics, anxiolytic/sedatives, hypnotics, antidepressant medicines, antiepileptic medication, anaesthetics, narcotic analgesics and sedative antihistaminics as the central depressive effects of zopiclone may be enhanced by these medicines.
• In the case of narcotic analgesics, enhancement of euphoria may also occur leading to an increase in psychic dependence. Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like medicines.
• Hepatic enzyme inhibitors including erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and cimetidine: Inhibitors of cytochrome P450 enzymes may increase the effects of ZOPIVANE. A dose reduction for ZOPIVANE may be required when it is co-administered with CYP3A4 inhibitors.
• Hepatic enzyme inducers such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John’s wort.: CYP3A4 inducers may decrease the plasma concentrations of ZOPIVANE. Therefore, a dose increase for ZOPIVANE may be required when it is co-administered with CYP3A4 inducers.
• Opioids: The concomitant use of benzodiazepines and other sedative-hypnotic medicines, including ZOPIVANE, 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 benzodiazepines and opioids (see section 4.4).
• Sedative effects of zoplicone may be enhanced by cisapride.
• Zopiclone may be removed by dialysis.

Women of childbearing potential/Contraception in males and females

If ZOPIVANE is prescribed to a woman of childbearing potential, she should be warned to contact her medical practitioner regarding discontinuation of ZOPIVANE if she intends to become or suspects that she is pregnant.

Pregnancy

Insufficient data are available on ZOPIVANE to assess its safety during human pregnancy and lactation. If ZOPIVANE is used during the last three months of pregnancy or during labour, due to pharmacological action of the product, effects on the neonate, such as hypothermia, hypotonia, and respiratory depression can be expected. The use of ZOPIVANE during pregnancy is not recommended. (see section 4.3).

Breastfeeding

Although the concentration of ZOPIVANE in the breast milk is very low, ZOPIVANE should not be used by breastfeeding mothers. (see section 4.3).

Because of its pharmacological properties and its effect on central nervous system, ZOPIVANE may adversely affect the ability to drive or to use machines (see section 4.4). The risk of psychomotor impairment, including impaired driving ability, is increased if:

• ZOPIVANE is taken within 12 hours of performing activities that require mental alertness,
• a dose higher than the recommended dose is taken, or
• is co-administered with other CNS depressants, alcohol, or with other medicines that increase the blood levels of ZOPIVANE.

Summary of the safety profile

Sedation, ataxia, drowsiness and inco-ordination on waking, are the most frequent side-effects. They generally decrease on continued administration of zopiclone.

Tabulated summary of adverse reactions

The following adverse reactions have been classified according to the following categories, frequent, less frequent and frequency unknown.

Other

Rebound effects: Discontinuation of treatment of ZOPIVANE may result in a transient syndrome of restlessness and mood changes, as well as an enhancement of symptoms that led to the treatment with ZOPIVANE (see section 4.2).

Withdrawal syndrome has been reported upon discontinuation of ZOPIVANE (see section 4.4.). Withdrawal symptoms vary and may include rebound insomnia, muscle pain, extreme 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 (abnormal acute hearing), numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8 and to Cipla Medpro (Pty) Ltd at drugsafetysa@cipla.com or telephone 080 222 6662 (toll free).

Not applicable.