Usage
- Zopiclone is primarily prescribed for the short-term treatment of insomnia in adults. This includes difficulty falling asleep, frequent nocturnal awakenings, and early morning awakenings. It is typically used for 7-14 days.
- Pharmacological Classification: Nonbenzodiazepine hypnotic, also categorized as a cyclopyrrolone.
- Mechanism of Action: Zopiclone enhances the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system. It binds to a specific site on the GABAA receptor complex, distinct from the benzodiazepine binding site, facilitating GABA’s inhibitory effects and promoting sleep.
Alternate Names
- No widely recognized alternate names exist for Zopiclone itself.
- Brand Names: Imovane, Zimovane, Dopareel
How It Works
- Pharmacodynamics: Zopiclone produces hypnotic effects, including sedation, muscle relaxation, and anticonvulsant activity, via its action on the GABAA receptor.
- Pharmacokinetics:
- Absorption: Zopiclone is rapidly and almost completely absorbed after oral administration, reaching peak plasma concentrations within 1.5-2 hours. Food does not significantly affect absorption.
- Metabolism: Extensively metabolized in the liver primarily by CYP3A4 and CYP2C8 enzymes into two major metabolites: N-desmethylzopiclone (active) and N-oxide zopiclone (inactive).
- Elimination: Eliminated primarily through hepatic metabolism, with metabolites excreted mainly in urine and a smaller amount in feces. Its elimination half-life is approximately 5 hours.
- Mode of Action: Zopiclone binds to a specific site on the GABAA receptor complex, increasing the frequency of chloride channel opening. This enhances GABA’s inhibitory effects, leading to neuronal hyperpolarization and reduced neuronal excitability, promoting sleep.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Binds to a site on the GABAA receptor complex, modulating GABAergic neurotransmission. It does not directly inhibit or induce CYP enzymes, although its metabolism is CYP-dependent.
- Elimination Pathways: Primarily hepatic metabolism with renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- The recommended dose is 7.5 mg orally, taken immediately before bedtime. This dose should not be exceeded.
Children:
- Zopiclone is contraindicated in children and adolescents under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: An initial dose of 3.75 mg is recommended, which may be increased to 7.5 mg if necessary, based on clinical response and tolerability.
- Patients with Renal Impairment: An initial dose of 3.75 mg is recommended.
- Patients with Hepatic Dysfunction: A lower initial dose of 3.75 mg is recommended due to potentially reduced clearance. The dose may be cautiously increased to 7.5 mg if needed and tolerated.
- Patients with Comorbid Conditions: Use with caution in patients with respiratory insufficiency. An initial lower dose of 3.75 mg is recommended.
Clinical Use Cases
- Zopiclone is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is short-term treatment of insomnia. For these clinical use cases, other agents, such as benzodiazepines and propofol, are generally preferred.
Dosage Adjustments
- Dose adjustments are necessary for elderly patients, those with renal or hepatic impairment, and those with respiratory insufficiency, as described above.
Side Effects
Common Side Effects
- Bitter or metallic taste
- Dry mouth
- Drowsiness
- Dizziness
- Headache
- Nausea
Rare but Serious Side Effects
- Angioedema
- Anaphylaxis
- Hepatic dysfunction
- Complex sleep behaviors (sleepwalking, sleep-driving, sleep-eating)
Long-Term Effects
- Tolerance and dependence can develop with prolonged use beyond the recommended duration.
- Rebound insomnia may occur upon discontinuation.
- Cognitive impairment
Adverse Drug Reactions (ADR)
- Severe allergic reactions
- Complex sleep behaviors
- Worsening of depression
- Suicidal ideation
Contraindications
- Hypersensitivity to zopiclone or any component of the formulation
- Severe respiratory insufficiency
- Severe hepatic insufficiency
- Myasthenia gravis
- Sleep apnea syndrome
- Pregnancy and breastfeeding
Drug Interactions
- CNS depressants (alcohol, opioids, antihistamines): Additive sedative effects
- CYP3A4 inhibitors (erythromycin, ketoconazole, itraconazole): Increased zopiclone plasma levels and risk of adverse effects.
- CYP3A4 inducers (rifampicin, carbamazepine, phenytoin): Decreased zopiclone plasma levels and efficacy.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Evidence of fetal risk in animals; no adequate or well-controlled studies in pregnant women).
- Zopiclone crosses the placenta and is excreted in breast milk. Use during pregnancy and breastfeeding is contraindicated due to potential risks to the fetus/infant.
Drug Profile Summary
- Mechanism of Action: Enhances GABAergic neurotransmission by binding to the GABAA receptor complex.
- Side Effects: Bitter taste, dry mouth, drowsiness, dizziness, headache, nausea; rarely, complex sleep behaviors, hepatic dysfunction, allergic reactions.
- Contraindications: Hypersensitivity, severe respiratory or hepatic insufficiency, myasthenia gravis, sleep apnea, pregnancy, breastfeeding.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors and inducers.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 7.5 mg orally before bedtime; elderly/hepatic/renal impairment: initial 3.75 mg.
- Monitoring Parameters: Respiratory rate, liver function tests (if used long-term).
Popular Combinations
- Zopiclone is not typically used in combination with other drugs for insomnia. Concomitant use of other CNS depressants should be avoided.
Precautions
- Assess patients for history of substance abuse, respiratory or hepatic impairment.
- Avoid alcohol and other CNS depressants.
- Caution patients about the risk of complex sleep behaviors.
- Advise against driving or operating machinery after taking zopiclone.
- Taper dose gradually to avoid rebound insomnia upon discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Zopiclone?
A: The standard adult dose is 7.5mg taken orally immediately before bedtime. Elderly patients or those with hepatic or renal impairment should start with 3.75mg.
Q2: How long can a patient take Zopiclone?
A: Zopiclone should be prescribed for short-term use only, typically 7-14 days, not exceeding four weeks, including the tapering off period.
Q3: What are the common side effects of Zopiclone?
A: Common side effects include a bitter or metallic taste in the mouth, dry mouth, drowsiness, dizziness, and headache.
Q4: What are the serious side effects of Zopiclone?
A: Rare but serious side effects include complex sleep behaviors (sleepwalking, sleep-driving, and preparing and eating food), allergic reactions (angioedema, anaphylaxis), and hepatic dysfunction.
Q5: Is Zopiclone safe to use in patients with liver disease?
A: Zopiclone should be used with caution in patients with hepatic impairment due to potentially reduced clearance. A lower initial dose of 3.75 mg is recommended.
Q6: Can Zopiclone be used during pregnancy or breastfeeding?
A: No, Zopiclone is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus and infant. It crosses the placenta and is present in breast milk.
Q7: Does Zopiclone interact with other medications?
A: Yes, Zopiclone can interact with other CNS depressants, like alcohol and opioids, leading to additive sedative effects. It also interacts with drugs that inhibit or induce CYP3A4, affecting zopiclone’s metabolism and therefore plasma levels.
Q8: How should Zopiclone be discontinued?
A: To minimize the risk of rebound insomnia, Zopiclone should be tapered gradually rather than abruptly stopped, especially after prolonged use.
Q9: What should I do if a patient experiences complex sleep behaviors while taking Zopiclone?
A: Discontinue Zopiclone immediately and evaluate the patient. Complex sleep behaviors, like sleepwalking, sleep-driving, and engaging in other activities while not fully awake, can be dangerous.
Q10: Can Zopiclone be used in children?
A: No, Zopiclone is contraindicated in children and adolescents under 18 years of age, as its safety and effectiveness have not been established in this population. Alternative treatments for insomnia should be considered for pediatric patients.
