Zopiclone

Oral
Insomnia
Adult: 7.5 mg once daily at bedtime for up to 4 weeks. Dose may be reduced to 3.75 mg according to clinical response.
Elderly: Initially, 3.75 mg once daily at bedtime, may increase dose to 7.5 mg once daily if necessary.
Renal impairment: Initially, 3.75 mg once daily at bedtime.
Hepatic impairment: Mild to moderate: Initially, 3.75 mg once daily at bedtime. Severe: Contraindicated.

May be taken with or without food.

Respiratory failure, severe sleep apnoea, myasthenia gravis, acute stroke. Severe hepatic impairment. Lactation.

Patient with psychiatric disorder (e.g. depression), chronic respiratory disease; personal or family history of sleepwalking or disorders that affect sleep (e.g. restless leg syndrome, periodic limb movement); history of drug abuse/dependence or alcoholism, risk of falls. Debilitated patients. Renal and mild to moderate hepatic impairment. Elderly. Pregnancy. Not indicated for long-term treatment of insomnia. Avoid abrupt withdrawal. Patient Counselling This drug may impair physical and mental abilities, if affected, do not drive or operate machinery. Monitoring Parameters Monitor for confusion, excessive drowsiness, and/or respiratory depression.

Significant: Psychiatric and paradoxical reactions (e.g. restlessness, aggression, bizarre behaviour, agitation, hallucinations, depersonalisation); rebound insomnia, anterograde amnesia, suicidal ideation and suicide attempts; drug dependence, drug abuse, somnambulism and associated behaviours (e.g. sleep-driving, cooking and eating food, making phone calls while asleep). Rarely, hypersensitivity reactions (e.g. angioedema). Gastrointestinal disorders: Dysgeusia, dry mouth, nausea, vomiting. General disorders and administration site conditions: Fatigue. Nervous system disorders: Somnolence, dizziness, headache.

Symptoms: Drowsiness, confusion, lethargy, ataxia, hypotonia, hypotension, methaemoglobinaemia, respiratory depression, coma. Management: Symptomatic and supportive treatment. Administer activated charcoal within 1 hour of ingestion, or gastric lavage within 1 hour of life-threatening overdose. May administer flumazenil in case of severe CNS depression. Maintain clear airway and monitor cardiac and vital signs until patient is stable.

Increased risk of profound sedation, respiratory depression, and coma with concomitant use of opioids. Enhanced central depressive effect with other CNS depressants (e.g. neuroleptics, hypnotics, sedatives, antidepressants, anaesthetics). Increased plasma concentration with CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, ritonavir). Decreased plasma concentrations with CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin).

Enhanced sedative effect with alcohol. Decreased plasma concentrations with St. John's wort.

Zopiclone is a cyclopyrrolone derivative with pharmacological properties similar to those of benzodiazepines. It binds to the benzodiazepine receptor component of GABA receptor complex, but at a different site to that of benzodiazepines, leading to enhanced GABA activity in the brain.
Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 77%. Time to peak plasma concentration: 1.5-2 hours.
Distribution: Rapidly distributed from the vascular compartment. Crosses the placenta, present in breast milk. Volume of distribution: Approx 91.8-104.6 L. Plasma protein binding: Approx 45-80%.
Metabolism: Extensively metabolised in the liver by CYP3A4 and to a lesser extent by CYP2C8 isoenzymes into less active metabolite zopiclone N-oxide and inactive metabolite N-desmethylzopiclone.
Excretion: Via urine (75%, approx 4-5% as unchanged drug); faeces (approx 16%). Elimination half-life: 3.5-6.5 hours.

Oral: Store below 30°C. Protect from light and moisture.

Hypnotics & Sedatives

N05CF01 - zopiclone ; Belongs to the class of benzodiazepine related agents. Used as hypnotics and sedatives.