Learn a Drug a Day - Zopiclone

Today's drug is zopiclone. It is selling as Insopin in Malaysia.
What is zopiclone indicated for?
INDICATIONS : 

• It is used in short-term treatment of insomnia (2-4 weeks).
• It is not normally taken for more than 2-4 weeks. This is because our body gets used to this medicine and after a time it is unlikely to have the same effect. Our body may also become dependent on it when it is taken for longer periods of time.

How does zopiclone work?

MECHANISMS OF ACTION : 

• Zopiclone, a cyclopyrrolone derivative, is a short-acting hypnotic that belongs to a novel chemical class which is structurally unrelated to existing hypnotics.
• It reduces the time it takes to fall asleep, increases the length of time spent sleeping and decreases the number of nocturnal awakenings.
• Zopiclone delayed the onset of REM(rapid eye movement) sleep but did not reduce consistently the total duration of REM periods.
• Dependence potential appears to be less pronounced with zopiclone than with benzodiazepines.

How is zopiclone being used?
ROUTE OF ADMINISTRATION : 

• It is taken orally as tablets.
• Treatment should be as short as possible and should not exceed four weeks including the period of tapering off. 
• Extension beyond the maximum treatment period should not take place without re-evaluation of the patient’s status. 
• The product should be taken just before retiring for the night.

Is there any contraindication?

CONTRAINDICATIONS : 

• Myasthenia gravis (autoimmune neuromuscular disease leading to fluctuating voluntary muscle weakness and fatiguability.)
• Hypersensitivity to zopiclone
• Respiratory failure
• Severe sleep apnoea syndrome
• Severe hepatic insufficiency
• Use in children
• Prior or concomitant use of alcohol

Are there any possible side effects?
SIDE EFFECTS : 
(i) Common possible side effects : 

• Bitter or metallic taste in the mouth.
• Drowsiness can sometimes occur and, more rarely, inco-ordination; patients should be cautioned about driving or operating machinery until it has been established that their performance is not affected.
• Dry mouth.
• Headaches. 
• Fatigue.

(ii) Rare possible side effects : 

• Gastrointestinal - heartburn, constipation, diarrhoea, nausea, coated tongue, bad breath, anorexia or increased appetite, vomiting, epigastric pains.
• Nervous System - agitation, anxiety, loss of memory including retrograde amnesia, confusion, dizziness, weakness, somnolence, asthenia, feeling of drunkenness, euphoria, depression, hypotonia, speech disorder, hallucinations, behavioural disorders, aggression, tremor, rebound insomnia, nightmares.
• Cardiovascular - palpitations, particularly in elderly patients.
• Dermatological - urticaria, tingling
• Other - blurred vision, altered micturition, impotence, ejaculation failure.

(iii) Withdrawal symptoms : 

• A withdrawal syndrome has been reported upon discontinuation of zopiclone. 
• Withdrawal symptoms vary and may include: rebound insomnia, anxiety, tremor, sweating, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, hallucinations, panic attacks, muscle aches/cramps, gastrointestinal disturbances and irritability. 
• In very rare cases seizures may occur.

What precautions are necessary?
PRECAUTIONS :  

Risk of Dependence : 

• Clinical experience to date with zopiclone suggests that the risk of dependence is minimal when the duration of treatment is limited to 4 weeks or less. 
• Patients with a history of drug abuse or alcoholism, are using alcohol or psychotropics, or who have marked personality disorders, are at most risk of dependence. The decision to use zopiclone in such patients should be taken only with this clearly in mind. 
• Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.

Rebound and Withdrawal : 

• A greater risk of such phenomena cannot be excluded after abrupt discontinuation of zopiclone, especially in those whom physical dependence is suspected. 
• It is therefore recommended to decrease the dosage gradually and advise the patient accordingly. The recommendation for tapering the dose is particularly important in patients with a history of seizures.

Anterograde Amnesia: (a selective memory deficit, resulting from brain injury, in which the individual is severely impaired in learning new information. )

• 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. 
• Anterograde amnesia is a dose-related phenomenon and elderly subjects may be at particular risk.

Abnormal Thinking and Psychotic Behavioural Changes : 

• Particular caution is warranted in patients with a history of violent behaviour and a history of unusual reactions to sedatives including alcohol and the benzodiazepines or benzodiazepine-like agents. 
• Psychotic behavioural changes reported include bizarre behaviour, hallucinations and depersonalisation. The emergence of any new behavioural sign or symptom of concern requires careful and immediate evaluation.

Depression : 

• Caution should be exercised if zopiclone is prescribed to patients with signs and symptoms of depression that could be intensified by hypnotic drugs. 
• The potential for self-harm (e.g.: intentional overdose) is high in patients with depression and thus the least amount of drug that is feasible should be available to them at any one time.
• Patients should be closely monitored for any signs or symptoms of psychiatric disorders.
• Patients should be advised to seek medical assistance immediately if they notice they are becoming depressed or have suicidal thoughts or change in behaviour. 
• Patients may wish to consider asking a family member or close friend to help them stay alert to signs of depression or behavioural changes.

Confusion : 

• The benzodiazepines and benzodiazepine-like agents affect mental efficiency e.g.: concentration, attention and vigilance. 
• The risk of confusion is greater in the elderly and in patients with cerebral impairment.

Effects on ability to drive and use machines : 

• Because of its pharmacological properties, zopiclone may adversely affect the ability to drive or to use machines.

DRUG INTERACTIONS : 

• barbiturates 
• benzodiazepines 
• alcohol
• sedatives
• tricyclic antidepressants
• nonselective MAOIs (monoamine oxidase inhibitors)
• phenothiazines & other antipsychotics
• skeletal muscle relaxants
• antihistamines 
• narcotic analgesics
• anaesthetics
• More drug interactions --> click here! 

Pregnancy and breastfeeding:  

• the use of zopiclone during pregnancy is not 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.
• Moreover, if zopiclone is used during the last three months of pregnancy or during labour, due to the pharmacological action of the product, effects on the neonate such as hypothermia, hypotonia and respiratory depression can be expected.
• Although the concentration of zopiclone in the breast-milk is very low, zopiclone should not be used by nursing mothers.

References : 

1. Zopiclone by APOTEX NZ Ltd.

2. Zopiclone by Patient.co.uk.

3. Zopiclone by MIMS Malaysia.