zopiclone
non-benzodiazepine hypnotic· Brands: Zimovane, Imovane, Imrest, AmobanPO
Mechanism of action
Zopiclone is a cyclopyrrolone hypnotic that acts at the benzodiazepine binding site of the GABA-A receptor, enhancing the inhibitory effect of GABA. It increases the frequency of chloride ion channel opening, leading to neuronal hyperpolarisation, sedation, anxiolysis, and muscle relaxation.
Pharmacokinetics
Plasma protein binding is weak, approximately 45% and non-saturable, and it is metabolised by CYP3A4 to inactive metabolites.
Indications & dosing
Short-term treatment of insomnia (difficulty falling asleep, waking during the night, or early morning waking)
Short-term use only, max 4 weeks. Avoid alcohol.
- adult · PO: 7.5 mg once at bedtime · Short-term use only, max 4 weeks. Avoid alcohol.
Short-term treatment of insomnia in elderly patients
Use lower initial dose; short-term use only.
- elderly · PO: 3.75 mg once at bedtime · Use lower initial dose; short-term use only.
Short-term treatment of insomnia in hepatic impairment
Reduce dose in hepatic impairment; use with caution.
- adult · PO: 3.75 mg once at bedtime · Reduce dose in hepatic impairment; use with caution.
Contraindications & precautions
- Hypersensitivity to zopiclone or any component of the formulation
- Severe respiratory insufficiency (including sleep apnoea)
- Severe hepatic impairment
- Myasthenia gravis
- Children under 18 years · Safety and efficacy not established
- Avoid concurrent use of alcohol or other CNS depressants as they increase sedative effects and respiratory depression.
- Use the lowest effective dose for the shortest possible duration (maximum 4 weeks) to minimise risk of dependence.
- Caution in elderly patients due to increased risk of falls, cognitive impairment, and dependence.
- Caution in patients with a history of substance abuse or dependence.
- Caution in patients with hepatic or renal impairment; consider dose reduction in moderate impairment.
- Advise patients not to drive or operate machinery if they feel drowsy; the drug can impair alertness the next day.
Adverse effects
- Taste disturbance (bitter or metallic taste)
- Drowsiness
- Dizziness
- Headache
- Anterograde amnesia
- Paradoxical reactions (agitation, confusion)serious
- Complex sleep behaviours (sleepwalking, sleep driving)serious
- Respiratory depressionserious
- Dependence and withdrawal symptoms on discontinuationserious
Renal & hepatic adjustment
- eGFR 0+: No specific dose adjustment required in mild to moderate renal impairment. Use caution in severe renal impairment; consider reducing the dose to 3.75 mg.
- Hepatic impairment (mild): Initiate at 3.75 mg at night; increase if necessary. Monitor for excessive sedation.
- Hepatic impairment (moderate): Reduce dose to 3.75 mg; monitor for excessive sedation and cognitive impairment.
- Hepatic impairment (severe): Avoid use; contraindicated due to risk of encephalopathy and excessive sedation. (avoid)
Monitoring, pregnancy & toxicity
- Excessive sedation or drowsiness · At each review or dose change
- Cognitive and psychomotor impairment · At each review or dose change
- Signs of dependence or abuse · Periodically during long-term use
- Rebound insomnia on discontinuation · On dose reduction or withdrawal
- Respiratory depression (in at-risk patients) · During initiation and dose titration
- Pregnancy: Zopiclone is not recommended during pregnancy. If used, use the lowest effective dose for the shortest duration. Avoid in late pregnancy due to risk of neonatal sedation and withdrawal symptoms.
- Toxicity: CNS depression: drowsiness, ataxia, confusion · Supportive care, monitor vital signs. Activated charcoal if within 1 hour and airway secure.
- Toxicity: Respiratory depression · Airway management and ventilatory support. Consider flumazenil with caution, balancing risk of withdrawal seizures.
- Toxicity: Hypotension and bradycardia · Intravenous fluids and cardiovascular support as needed.
- Toxicity: Coma and unconsciousness · Admission to intensive care. Monitor for aspiration and provide supportive care. Consider flumazenil in selected cases.
Clinical notes
Zopiclone is indicated for the short-term treatment of insomnia, including difficulty in falling asleep and early awakening. It should be used at the lowest effective dose and for the shortest possible duration, usually not exceeding four weeks. It causes dependence and tolerance with prolonged use, so discontinuation should be gradual. Concomitant alcohol use is contraindicated. Caution is needed in elderly patients, who are more susceptible to falls and cognitive impairment. Dose reduction may be necessary in hepatic impairment. Zopiclone is not recommended during pregnancy or breastfeeding. Tolerance and withdrawal effects are similar to benzodiazepines.
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BNF; local formulary