Panado Paediatric Alcohol Free – Grape Flavour 120 mg/5 ml Syrup

ZOPIVANE is indicated for the short-term treatment of insomnia in adults.

Posology

Adults: 7,5 mg (one tablet) taken orally shortly before retiring at night. This dose should not be exceeded. Treatment should be started with the lowest recommended dose and the maximum dose should not be exceeded.

Special populations

• Elderly patients and patients with hepatic and chronic respiratory insufficiency: 3,75 mg taken orally shortly before retiring at night, initially. This may be increased to 7,5 mg depending on the effectiveness and tolerance of the tablets.
• Renal insufficiency: Although accumulation of zopiclone has not been observed in patients with renal insufficiency, it is recommended that treatment should be initiated with 3,75 mg.
• Paediatric population: ZOPIVANE should not be prescribed to children younger than 18 years old.

ZOPIVANE is contraindicated in patients with:

• hypersensitivity to zopiclone or to any other excipients of ZOPIVANE (see section 6.1)
• myasthenia gravis
• respiratory failure
• severe hepatic insufficiency
• sleep apnoea syndrome
• patients with pre-existing CNS depression or coma.

Safety in pregnancy has not been established (see section 4.6). ZOPIVANE should not be prescribed to breastfeeding mothers (see section 4.6). ZOPIVANE should not be prescribed to children younger than 18 years old.

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 psychotropics. 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 patientu2019s schedule will allow for a full nightu2019s 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).

• 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. Johnu2019s 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.

MedDRA system organ Class

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.

Symptoms of overdose: Overdosage usually presents with varying degrees of central nervous system depression, ranging from drowsiness to coma, according to the quantity ingested. In mild cases, symptoms include drowsiness, confusion, and lethargy; in more serious cases, symptoms may include ataxia, hypotonia; hypotension, respiratory depression and coma. When the overdosage is combined with alcohol or other CNS depressants, it 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 the symptoms and can result in fatal outcome.

Treatment of overdose: Symptomatic and supportive treatment in an adequate clinical environment, is recommended, with special attention to respiratory and cardiovascular functions. Gastric lavage is of value only if performed soon after ingestion. Flumazenil may be useful as an antidote. Haemodialysis is of no value due to the large volume of distribution of ZOPIVANE.