Brand name
- Zopiclone®
Drug Class
- Zopiclone belongs to hypnotics family
- Similar to Benzodiazepine it is a GABA receptor agonist
- Similar to benzodiazepines, zopiclone has anti-anxiety, anticonvulsant, sedative, muscle relaxant and antiaggressive properties (Julou et al., 1983; Sanger et al., 1985).
Preparations
- Tablets: 5 mg and 7.5 mg
Indications
- It is used for the short-term and symptomatic relief of sleep disturbances.
- It is used to help with difficulty falling asleep, frequent wake-ups during the night, or early morning awakenings
Pharmacology
- reduces sleep latency, increases the duration of sleep and decreases the number of nocturnal awakenings.
- delays the onset of REM sleep but does not reduce consistently the total duration of REM periods.
- reduces stage 1 sleep and increase stage 3 sleep (Stone et al., 2002).
- prolongs the non-REM (rapid eye movement) stage 2 and 4 sleep and decreases the total REM sleep (Hemmeter et al., 2000).
Dosing
- 5 to 7.5 mg at bed time
- Should usually not be taken for more than 7 to 10 consecutive days
- Use for more than 2 to 3 consecutive weeks requires complete re-evaluation of the patient.
- Prescriptions for zopiclone should be written for short-term use (7 to 10 days) and it should not be prescribed in quantities exceeding a 1-month supply.
Drug Interactions
- Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like agents.
- Examples include cimetidine or erythromycin
Adverse Effects
- Bitter taste (10%) in mouth and dry mouth: Most frequently reported adverse effects (Wadworth 1993)
- Nausea and dizziness (Allain et al., 1991)
- Increase in sweating and headache (Allain et al., 2003)
- Agitation
- Dizziness
- Impaired vision
- Chills
- Constipation
- Decreased muscle tone
- Difficulty speaking
- Fast, irregular, or pounding heartbeat
- Feeling of heaviness of arms and legs
- Heartburn
- Increased appetite
- Indigestion
- Increase in the amount of saliva
- Increased sweating
- loss of appetite
- stomach upset
- tingling, burning, or prickly sensation
- trembling and shaking of fingers, hands, arms, feet, or legs
- vomiting
- weight loss
- Confusion
- Reduced concentration, attention and vigilance
- Asthenia and fatigue, ataxia,
- Impairment of concentration, and
- Somnolence can occur
- Paraesthesias
- Hyperkinesia
- Dyskinesia
- Involuntary muscle contractions
- Hallucinations, nightmares, and behavioural disturbancies, including agitation and aggression have been reported
- Irritability, confusion, depressed mood
- Abnormal vision
- Zopiclone as a sedative hypnotic reduces CNS functions, including memory.
- Amnesia which is dose dependent
- Withdrawal symptoms:
- Withdrawal symptoms similar to those occurring with related substances, including alcohol, have been observed after stopping the medication suddenly (after having taken it regularly over a period of time)
- These symptoms include:
- Abdominal cramps
- Agitation
- Confusion
- Diarrhea
- Extreme anxiety
- Headache
- Irritability
- Memory impairment
- Muscle pain
- Nervousness
- Restlessness
- Sleep problems
- Tension
- Tremors
- Vomiting
Contraindications
- History of allergic reactions to zopiclone or to the benzodiazepine
- Myasthenia gravis
- Sleep apnea
- Severe breathing difficulties
- Severe liver disease
Pregnancy and Breastfeeding
- A child born to a mother who is on benzodiazepines or benzodiazepine-like agents may be at risk for withdrawal symptoms from the drug during the postnatal period
- Zopiclone is excreted in human milk, and its concentration may reach 50% of the plasma levels. Therefore, the administration of zopiclone to nursing mothers is not recommended
Precautions
- The risk of dependence is increased in patients with a history of alcoholism, drug abuse, or in patients with marked personality disorders.
- Interdose daytime anxiety and rebound anxiety may increase the risk of dependency in zopiclone treated patients.
- Laboratory Tests:
- There have been sporadic reports of abnormal laboratory test values including increase in AST, ALT or alkaline phosphatase values
References
- Allain H, Bentué-Ferrer D, Tarral A, Ganon J-M (2003). Effects on postural oscillation and memory functions of a single dose of zolpidem 5 mg, zopiclone 3.75 mg and lormetazepam 1 mg in elderly healthy subjects. A randomized, cross-over, double-blind study versus placebo. Eur J Pharmacol 59: 179-188.
- Allain H, Delahaye C, Lecoz F (1991). Postmarketing surveillance of zopiclone in insomnia: analysis of 20513 cases. Sleep 14: 408-413.
- Dorian P, Sellers EM, Kaplan H, Hamilton C (1983). Evaluation of zopiclone physical dependence liability in normal volunteers. Pharmacology 27 (S2) 228-234.
- Dündar Y, Boland A, Strobl J, Dodd S, Haycox A, Bagust A, Bogg J, Dickson R, Walley T (2004). Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation. Health Technology Assessment 8 (24) 154 p.
- Hajak G (1999). A comparative assessment of the risks and benefits of zopiclone. Drug Saf 21: 459-467.
- Hemmeter U, Muller M, Bischof R, Annen B, Holsboer-Trachsler E (2000). Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers. Psychopharmacology 147: 384-396.
- Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM (1983). Pharmacological studies on zopiclone. Pharmacology (Basel) 27 (S2): 46-58.
- Lader M (1998a). The consequences of zopiclone use: rebound insomnia, development of tolerance, and abuse potential. Rev Contemp Pharmacother 9: 131-140.
- Lader M (1998b). Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs 10: 425-440.
- Sanger DJ, Joly D, Zivkovic B (1985). Behavioral effects of nonbenzodiazepine anxiolytic drugs: A comparison of CGS 9896 and zopiclone with chlordiazepoxide. J Pharmacol Exp Ther 232: 831-837.
- Wadworth AN, McTavish D (1993). Zopiclone. A review of its pharmacological properties and therapeutic efficacay as an hypnotic. Drugs Aging 3: 441-459.
- Wagner J, Wagner ML (2000). Non-benzodiazepines for the treatment of insomnia. Sleep Med Rev 4: 551-581.
Note
This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.