(and dosage form):
Each tablet contains: Zopiclone 7,5 mg
A.2.2 Sedatives, hypnotics.
Zopiclone is a hypnotic agent, a member of the cyclopyrrolone group of compounds. Its pharmacological properties are: hypnotic, sedative, anxiolytic, anticonvulsant, muscle-relaxant. These effects are related to a specific agonist action at central receptors belonging to the GABAa macromolecular complex, modulating the opening of the chloride ion channel.
Zopiclone is rapidly absorbed. Peak concentrations of 30 to 60 ng/mL are reached within 1,5 to 2 hours after the administration of 3,75 mg and 7,5 mg respectively. Absorption is not modified by food.
Zopiclone is rapidly distributed from the vascular compartment. Plasma protein binding is weak (approximately 45%) and non saturable. There is very little risk of drug interactions due to protein-binding. The distribution volume is 91,8 to 104,6 litres.
After repeated administration there is no accumulation of zopiclone and its metabolites.
Individual variations appear to be low.
At recommended doses, the elimination half-life of the unchanged zopiclone is approximately 5 hours.
The low renal clearance value of unchanged zopiclone (mean 8,4 mL/min) compared with plasma clearance (232 mL/min) indicates that zopiclone clearance is mainly metabolic. Zopiclone is eliminated by the urinary route (approximately 80%) mainly in the form of free metabolites (N-oxide and N-demethyl derivatives) and in the faeces (approximately 16%).
In elderly patients, notwithstanding a slight decrease in hepatic metabolism and lengthening of the elimination half-life to approximately 7 hours, various studies have not shown plasma accumulation of the drug substance on repeated dosing.
In renal insufficiency, no accumulation of zopiclone or its metabolites has been detected after prolonged administration. Zopiclone is removed by haemodialysis.
In cirrhotic patients, the plasma clearance of zopiclone is reduced by approximately 40% in relation with the decrease of the demethylation process. Therefore dosage will have to be modified in these patients.
Short-term treatment of insomnia in adults.
Zopiclone is contra-indicated in patients with a hypersensitivity to zopiclone, myasthenia gravis, respiratory failure, severe sleep apnoea syndrome and severe hepatic insufficiency.
Zopiclone should not be used in children under the age of 18.
Safety in pregnancy and lactation has not been established.
Drowsiness and inco-ordination on waking can occur. Patients should be cautioned about driving motor vehicles or operating machinery until it has been established that their performance is not affected.
DOSAGE AND DIRECTIONS FOR USE:
One tablet (7,5 mg zopiclone) orally, shortly before retiring. This dose should not be exceeded.
Elderly patients, and patients with impaired liver function or chronic respiratory insufficiency:
A lower dose of 3,75 mg zopiclone (half a tablet) should be employed to start treatment in these patients, and if necessary the dose may be increased to 7,5 mg.
Accumulation of zopiclone or its metabolites has not been seen during the treatment of insomnia in patients with renal insufficiency. However, it is recommended that patients with impaired renal function should start treatment with 3,75 mg.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The side-effect most commonly observed with zopiclone is a bitter after-taste. Other effects which have been reported are dizziness, headache, residual somnolence, digestive disturbances such as dyspepsia, nausea and dry mouth, allergic or cutaneous reactions such as pruritus and rash.
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 that they are able to have a full night's sleep.
Nightmares, irritability, confusion, hallucinations, aggressiveness and inappropriate behaviour possibly associated with amnesia, have also been reported. When they occur, these reactions may be severe. They are more likely to occur in the elderly.
Withdrawal symptoms and transient rebound insomnia have been observed after abrupt discontinuation, especially after prolonged treatment with zopiclone. It is therefore recommended that the dosage be decreased gradually and that the patient be advised accordingly.
Drowsiness and inco-ordination on waking can occur.
The development of pharmacodependence or abuse cannot be excluded and should be borne in mind when zopiclone is prescribed. Risk of dependence or abuse increases with dose and duration of treatment, history of alcohol and/or drug abuse, and use with alcohol or other psychotropics.
Some loss of efficacy of zopiclone may develop after repeated use.
Zopiclone does not constitute a treatment for depression and may even mask its symptoms.
Concomitant intake with alcohol is not recommended since the sedative effect of zopiclone may be enhanced.
Caution should be exercised with the concomitant use of central depressant medicines such as neuroleptics, hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, antiepileptic drugs, anaesthetics, and sedative antihistaminics, as the central depressive effect of zopiclone may be enhanced in these cases.
Zopiclone should not be used by nursing mothers.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdose is usually manifested by varying degrees of central nervous system depression ranging from drowsiness to coma according to the quantity ingested. Overdosage may be life-threatening especially when combined with central nervous system depressants (including alcohol). Symptomatic and supportive treatment in an adequate clinical environment is recommended; attention should be paid to respiratory and cardiovascular functions. Gastric lavage is only useful when performed soon after ingestion. Haemodialysis is of no value due to the large volume of distribution of zopiclone. Flumazenil may be a useful antidote.
Round, white, film-coated, biconvex tablet with a breakline.
Blister packs of 30 tablets.
Store below 25°C and protect from light.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OF APPLICANT:
7 Fairclough Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
5 March 1999
New addition to this site: December 2004
Source: Pharmaceutical Industry
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