Zopiclone

Approved Uses

• Short-term treatment of insomnia in adults, including:
• Difficulty falling asleep
• Nighttime awakenings
• Early morning awakenings
• Poor sleep quality impacting daytime function
• Typical treatment duration: 7–14 days (maximum 4 weeks including tapering)

Clinically Accepted Off-label Uses

• Chronic insomnia (carefully monitored, with gradual tapering after prolonged use)
• Treatment of insomnia in psychiatric disorders (e.g., depression, anxiety), as adjunct
• Rare use in disorders of consciousness (e.g., vegetative states, though evidence is stronger for zolpidem)

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Adults (General Population)

• Initial Dose: 3.75 mg orally once daily at bedtime.
• Usual Dose: 7.5 mg once daily at bedtime.
• Administration:
• Take immediately before going to bed.
• Ensure at least 7–8 hours of uninterrupted sleep time available.
• Should be swallowed whole with water.

Elderly Patients (≥65 years)

• Initial and Maximum Dose: 3.75 mg once daily at bedtime.
• Use lowest effective dose to reduce risk of excessive sedation, falls, and cognitive impairment.

Hepatic Impairment

• Mild to Moderate:
• Initial dose: 3.75 mg once daily at bedtime.
• Monitor closely for signs of CNS depression.
• Severe hepatic impairment:
• Contraindicated due to risk of encephalopathy and prolonged sedation.

Renal Impairment

• Mild to Moderate:
• No dosage adjustment usually required.
• Start with 3.75 mg in sensitive patients.
• Severe Renal Impairment:
• Use with caution; reduced clearance may increase effects.

Patients with Respiratory Impairment

• Use with caution, especially in chronic obstructive pulmonary disease (COPD) or sleep apnea, as Zopiclone can worsen respiratory function.

Pediatric Use

• Not recommended in patients <18 years of age.
• Safety and efficacy have not been established.

Dependence or History of Substance Abuse

• Use the lowest effective dose for shortest duration.
• Avoid prolonged or unsupervised use.

Duration of Treatment

• Short-term use only (usually 2–4 weeks, including tapering off).
• Prolonged use requires periodic reassessment of benefits and risks.

Missed Dose

• Skip missed dose if not taken at bedtime.
• Do not take if unable to get a full night’s sleep (7–8 hours).
• Do not double the dose to make up for a missed dose.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Zopiclone is a non-benzodiazepine hypnotic that acts by binding to the benzodiazepine site of the GABAA receptor complex. It enhances GABAergic transmission by increasing the frequency of chloride channel opening, leading to neuronal hyperpolarization. This produces sedative, anxiolytic, muscle-relaxant, and anticonvulsant effects. It has a high affinity for the α1 subunit of GABAA receptors, which mediates sedative and hypnotic effects.

• Absorption: Rapid and well absorbed orally; bioavailability ~75–80%; peak plasma concentration (Tmax) occurs in 1–2 hours
• Distribution: Moderate plasma protein binding (~52–59%); widely distributed; crosses blood-brain barrier and placenta
• Metabolism: Primarily metabolized in the liver via CYP3A4 and CYP2E1 enzymes; major metabolites include N-desmethylzopiclone (active) and zopiclone-N-oxide (inactive)
• Elimination: Elimination half-life ~3.5–6.5 hours in adults (prolonged in elderly); ~80% excreted in urine (mostly as metabolites)
• Special Populations:
• Prolonged half-life in elderly and hepatic impairment
• No significant accumulation in renal impairment

• Pregnancy: Category C
• Animal studies suggest risk of fetal harm; limited human data
• Potential neonatal respiratory depression and withdrawal if used in late pregnancy
• Lactation:
• Excreted in breast milk
• May cause sedation or respiratory depression in nursing infants
• Breastfeeding not recommended or should be used with caution

• Primary Class: Hypnotic, sedative
• Subclass: Non-benzodiazepine ("Z-drug") cyclopyrrolone derivative

• Hypersensitivity to zopiclone or any component of the formulation
• Myasthenia gravis
• Severe respiratory insufficiency
• Sleep apnea syndrome
• Severe hepatic impairment
• History of complex sleep behaviors after zopiclone use
• Children and adolescents under 18 years of age
• Concomitant use with alcohol

• CNS Depression: Risk of daytime drowsiness, cognitive impairment, especially in elderly
• Dependence and Withdrawal: May develop after prolonged use (>4 weeks); abrupt discontinuation can cause rebound insomnia and withdrawal symptoms
• Complex Sleep Behaviors: Reports of sleepwalking, sleep-driving, eating during sleep—discontinue immediately if observed
• Anaphylaxis and Angioedema: Rare but serious hypersensitivity reactions reported
• Respiratory Depression: Risk increases when combined with CNS depressants or in patients with compromised respiration
• Depression and Suicidality: Use cautiously in patients with depression; monitor for mood worsening or suicidal ideation
• Impaired Driving: Residual sedation may affect driving or machinery operation, especially in older adults or those on higher doses

Common (≥1%):

• CNS: Drowsiness, dizziness, headache, fatigue, confusion
• GI: Bitter or metallic taste, dry mouth, nausea
• Neuropsychiatric: Memory disturbances, agitation, nightmares

Less Common/Serious:

• Hallucinations, anxiety, depression exacerbation
• Complex sleep behaviors (e.g., sleep-driving, sleep-eating)
• Anaphylaxis, angioedema
• Ataxia, falls in elderly
• Rebound insomnia after discontinuation

Dose-dependent Effects:

• Higher doses increase risk of CNS depression, confusion, and residual sedation

• CNS Depressants: Additive sedation with opioids, alcohol, benzodiazepines, antihistamines, antipsychotics, and antidepressants
• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin, ritonavir): Increase zopiclone plasma concentration and toxicity
• CYP3A4 Inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John's Wort): Reduce zopiclone levels and effectiveness
• Alcohol: Strongly potentiates sedative effects; increases risk of respiratory depression and fatal overdose

• Health authorities advise limiting use to 7–14 days, with gradual discontinuation
• Complex sleep behaviors have led to regulatory safety alerts and labeling changes in some countries
• Emphasis on next-day impairment and driving restrictions—patients should be warned not to engage in hazardous activities until fully alert
• Caution advised in elderly and patients with depression or respiratory compromise

• Store at 20–25°C (68–77°F); excursions permitted between 15–30°C (59–86°F)
• Protect from moisture and light
• Do not freeze
• Keep tablets in original blister pack until use
• No reconstitution or refrigeration required