Return To The Previous Page
Buy a Package
Number Of Visible Items Remaining : -4 Item

Zopiclone (United States: Not available): Drug information

Zopiclone (United States: Not available): Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Zopiclone (United States: Not available): Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: Canada
  • ACT Zopiclone;
  • AG-Zopiclone;
  • APO-Zopiclone;
  • BIO-Zopiclone;
  • DOM-Zopiclone [DSC];
  • Imovane;
  • JAMP-Zopiclone;
  • M-Zopiclone;
  • Mar-Zopiclone;
  • MINT-Zopiclone;
  • NRA-Zopiclone;
  • PMS-Zopiclone;
  • PRO-Zopiclone;
  • RATIO-Zopiclone [DSC];
  • RIVA-Zopiclone;
  • TARO-Zopiclone;
  • TEVA-Zopiclone
Pharmacologic Category
  • Hypnotic, Miscellaneous;
  • Nonbenzodiazepine Benzodiazepine Receptor Agonist
Dosing: Adult
Insomnia, sleep onset or sleep maintenance

Insomnia, sleep onset or sleep maintenance :

Note: Limit long-term use (>4 weeks) to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (Ref).

Oral: Initial: 3.75 mg once daily at bedtime, as needed; may increase to 5 or 7.5 mg based on response and tolerability (maximum: 7.5 mg/day).

Discontinuation of therapy: Reduce by ~25% of the original dose each week or every other week (zopiclone can be reduced by 1.875 to 2.5 mg each week or every other week). For patients taking higher doses of zopiclone (eg, 7.5 mg/day) for an extended period, tapering zopiclone even more slowly in conjunction with cognitive behavioral therapy for insomnia is encouraged (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: The manufacturer’s labeling recommends a maximum dose of 5 mg/day in patients with kidney impairment but does not specify the level of eGFR at which the dose reduction should occur. Zopiclone concentrations are either unchanged or slightly increased in patients with severe kidney impairment based on single-dose pharmacokinetic analyses, and no accumulation of zopiclone or its metabolites is expected (Ref).

Altered kidney function:

eGFR ≥30 mL/minute/1.73 m2: Oral: No dosage adjustment necessary (Ref).

eGFR <30 mL/minute/1.73 m2: Oral: Initial: 3.75 mg once daily at bedtime; may cautiously increase to 5 mg once daily at bedtime if clinically indicated (Ref). The maximum dose is 5 mg/day, as patients may be at increased risk of next-day driving impairment (Ref).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2) : Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).

Oral: No dosage adjustment necessary (Ref).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (Ref):

Oral: Dose as for eGFR<30 mL/minute/1.73 m2 (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzed (Ref):

Oral: Dose as for eGFR<30 mL/minute/1.73 m2 (Ref).

CRRT: Oral: Dose as for eGFR<30 mL/minute/1.73 m2 (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Oral: Dose as for eGFR<30 mL/minute/1.73 m2 (Ref).

Dosing: Liver Impairment: Adult

Mild-to-moderate hepatic impairment: Initial: 3.75 mg once daily at bedtime; may increase up to 5 mg once daily with caution if clinically indicated.

Severe hepatic impairment: Use is contraindicated.

Dosing: Older Adult

Avoid use (Ref).

Insomnia, sleep onset or sleep maintenance: Oral: Initial: 3.75 mg once daily at bedtime, as needed; may increase to 5 mg based on response and tolerability (maximum: 5 mg/day).

Discontinuation of therapy: Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

Frequency not defined:

Cardiovascular: Palpitations

Dermatologic: Diaphoresis, pruritus, skin rash

Endocrine & metabolic: Change in libido (including decreased libido), weight loss

Gastrointestinal: Anorexia, coated tongue, constipation, diarrhea, dysgeusia, halitosis, increased appetite, nausea, sialorrhea, vomiting, xerostomia

Hepatic: Increased serum alkaline phosphatase, increased serum transaminases

Nervous system: Aggressive behavior, agitation, anterograde amnesia, anxiety, asthenia, ataxia, bitter taste, chills, confusion, daytime sedation, depression, dizziness, drowsiness, drug abuse, euphoria, falling, fatigue, feeling of heaviness (limb), hallucination, headache, hostility, hypotonia, intoxicated feeling, irritability, memory impairment, nervousness, nightmares, paresthesia, speech disturbance, tremor

Neuromuscular & skeletal: Muscle spasm

Ophthalmic: Amblyopia

Respiratory: Dyspnea

Postmarketing:

Gastrointestinal: Dyspepsia

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Abnormal behavior, abnormality in thinking, complex sleep related disorder (including sleep driving, sleep talking, somnambulism), delirium, delusion, disturbance in attention, drug dependence, myasthenia, outbursts of anger, rebound insomnia, restlessness, withdrawal syndrome

Ophthalmic: Diplopia

Respiratory: Respiratory depression

Contraindications

Hypersensitivity to zopiclone or any component of the formulation; severe respiratory impairment (eg, significant sleep apnea syndrome); myasthenia gravis; severe hepatic insufficiency; history of complex sleep behaviors after taking any nonbenzodiazepine sedative/hypnotic.

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal thinking/behavioral changes: Increased daytime anxiety and/or restlessness have been observed with use; effects may be related to drug's short half-life. Hypnotics/sedatives have also been associated with abnormal thinking and behavior changes including decreased inhibition, aggression, bizarre behavior, agitation, hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

• Anterograde amnesia: Benzodiazepines and benzodiazepine-like agents have been associated with anterograde amnesia; zopiclone should not be administered unless a full night's sleep is possible.

• CNS depression: CNS depression impairing physical and mental capabilities may occur and in some cases may persist into the following day [driving performance may be impaired up to 11 hours following administration (Leufkens 2014)]. Risk of persistent effects is increased if taken without a full night's sleep, with higher dosages, and/or concomitant use of other CNS depressants or drugs that increase zopiclone. Some patients may experience persistent effects at recommended dosages. Advise patients to wait at least 12 hours after administration before engaging in activities which require mental alertness (operating machinery or driving).

• Complex sleep behaviors: [Canadian Boxed Warning]: Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of nonbenzodiazepine sedative-hypnotics. Some of these events may result in serious injuries, including death. Preparing and eating food, making phone calls, or having sex have also occurred during sleep and are usually not remembered. Events may occur at recommended doses and with or without concurrent alcohol or CNS depressant use. Discontinue zopiclone immediately if a patient experiences a complex sleep behavior. Use with caution in patients with personal or family history of sleep-walking or other disorders that may affect sleep (eg, periodic limb movement disorder, restless legs syndrome, sleep apnea) or with concomitant use of other CNS depressants.

• Hypersensitivity: Angioedema and signs of anaphylaxis have been reported (rarely) with administration, including after the initial dose. Patients developing angioedema should discontinue therapy and should not be rechallenged.

• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicidal ideation and suicide attempts, has been reported with the use of hypnotics in patients with or without depression. Intentional overdose may be an issue in this population; prescribe least amount of medication needed.

• Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment; dosage adjustment recommended. Use is contraindicated in severe hepatic insufficiency.

• Renal impairment: Accumulation of zopiclone or its metabolites is not anticipated; the manufacturer labeling however recommends a dose reduction and to use with caution.

• Respiratory disease: Use with caution in patients with chronic respiratory disease. Use is contraindicated in patients with severe respiratory insufficiency.

Concurrent drug therapy issues:

• Opioids: [Canadian Boxed Warning]: Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of zopiclone and opioids for use in patients for whom alternative treatment options are not possible. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Special populations:

• Debilitated patients: Use with caution in debilitated patients.

• Older adult: Use with caution in older adult patients; more susceptible to adverse reactions (eg, agitation, anorexia, anxiety, anterograde amnesia, confusion, falls).

• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.

Dosage forms specific issues:

• Lactose: Some formulations may contain lactose; avoid use in patients intolerant to galactose (eg, glucose-galactose malabsorption or galactosemia).

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Use should generally not exceed 7 to 10 days. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric and/or medical illness; complete re-evaluation of the patient should occur when treatment is required for >2 to 3 consecutive weeks.

• Rapid onset: Because of the rapid onset of action, administer immediately prior to bedtime or after the patient has gone to bed and is having difficulty falling asleep.

• Rebound insomnia: Following withdrawal of therapy, transient insomnia may recur accompanied by other reactions, including restlessness, anxiety, and mood changes (Bélanger 2009).

• Substance use disorder/abuse/misuse: [Canadian Boxed Warning]: Use can lead to addiction, abuse, and misuse, resulting in overdose and death, especially when used in combination with other medications (eg, opioids), alcohol, or illicit drugs. Assess each patient's risk prior to prescribing zopiclone and monitor all patients regularly for the development of these behaviors or conditions. Store securely to avoid theft or misuse. Risk of dependence increases with high doses and longer use, but can occur with any dose and treatment length. Increased risk for dependence is also greater in patients with a history of psychiatric disorders or substance (including alcohol) use disorder.

• Withdrawal: [Canadian Boxed Warning]: Severe or life-threatening withdrawal symptoms may occur with use. Avoid abrupt discontinuation or rapid dose reduction; discontinue treatment by gradually tapering the dose under close monitoring. Risk of withdrawal increases with high doses and longer use, but can occur with any dose and treatment length. A longer sleep-onset latency and increased awakenings during sleep may occur for 1 to 2 days following the discontinuation of GABA-mediated (GABAergic) medications. A more severe withdrawal syndrome may rarely occur following abrupt discontinuation or large decreases in dose after sustained use, and is characterized by abdominal pain, anxiety, confusion, delirium, disorientation, euphoria, hypertension, insomnia, irritability, restlessness, speech difficulties, seizures, and tremor. This withdrawal syndrome is generally mild and infrequent and resolves within weeks or upon reinitiation of the GABAergic medication. Intermittent dosing may reduce the risk of withdrawal symptoms (BAP [Wilson 2019]; Schifano 2019).

Product Availability

Not available in the US

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Imovane: 5 mg [DSC] [contains corn starch]

Imovane: 7.5 mg [contains fd&c blue #1 (brill blue) aluminum lake]

Generic: 3.75 mg, 5 mg, 7.5 mg

Administration: Adult

Oral: Administer just before bedtime.

Use: Labeled Indications

Note: Not approved in the United States.

Insomnia, sleep onset or sleep maintenance: Short-term and symptomatic relief of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings (typically treatment should not exceed 7 to 10 consecutive days).

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Based on pharmacologic class concerns for nonbenzodiazepine benzodiazepine-receptor agonist hypnotic agents in the Beers Criteria, zopiclone may be a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to adverse events similar to benzodiazepines in older adults (eg, delirium, falls, fractures) and an increase in emergency room visits, hospitalizations, and motor vehicle crashes. In addition, improvement in sleep latency and duration is minimal (Beers Criteria [AGS 2023]).

Other safety concerns:

ALERT: Canadian Boxed Warning: Health Canada-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.

Metabolism/Transport Effects

Substrate of CYP2C8 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alcohol (Ethyl): May increase CNS depressant effects of Zopiclone. Alcohol (Ethyl) may increase adverse/toxic effects of Zopiclone. Specifically, taking alcohol with zopiclone may increase the risk of complex sleep-related behaviors (eg, sleep-driving, eating food, making phone calls, leaving the house) Risk X: Avoid

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

CarBAMazepine: May increase CNS depressant effects of Zopiclone. CarBAMazepine may decrease serum concentration of Zopiclone. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

CYP3A4 Inducers (Moderate): May decrease serum concentration of Zopiclone. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Zopiclone. Risk C: Monitor

CYP3A4 Inhibitors (Moderate): May increase serum concentration of Zopiclone. Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider Therapy Modification

Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor

Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Grapefruit Juice: May increase serum concentration of Zopiclone. Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor

Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Melatonin: May increase sedative effects of Hypnotics (Nonbenzodiazepine). Risk C: Monitor

Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

PHENobarbital: May increase CNS depressant effects of Zopiclone. PHENobarbital may decrease serum concentration of Zopiclone. Risk C: Monitor

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor

Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification

Primidone: May increase CNS depressant effects of Zopiclone. Primidone may decrease serum concentration of Zopiclone. Risk C: Monitor

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Food Interactions

Effect/toxicity may be increased by grapefruit juice. Management: Do not exceed 3.75 mg as starting dose; monitor for signs and symptoms of zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression) with concomitant use.

Pregnancy Considerations

Zopiclone crosses the placenta.

Outcome data following maternal use of zopiclone during pregnancy are available (Ban 2014; Diav-Citrin 1999; Wikner 2011). Benzodiazepines may cause congenital malformations following first trimester exposure and neonatal CNS depression following exposure later in pregnancy; it is expected zopiclone may do the same. Newborns exposed to zopiclone in utero should be closely monitored for adverse events such as hypothermia, hypotonia, feeding difficulties, respiratory depression, and symptoms of withdrawal.

Although the manufacturer does not recommended use during pregnancy, short-term use may be considered in pregnant patients with intractable insomnia who require pharmacologic treatment, following consideration of risks and benefits of therapy (BAP [Wilson 2019]).

Breastfeeding Considerations

Zopiclone is present in breast milk.

Data related to the presence of zopiclone in breast milk are available following administration of zopiclone 7.5 mg orally to 3 lactating patients. Peak breast milk concentrations were observed 2 to 4 hours after the dose (Gaillot 1983). A second study administered zopiclone 7.5 mg orally to 12 lactating women 2 to 6 days postpartum. The median maximum maternal plasma concentration was 80 mcg/mL at 1.6 hours, compared to the median maximum breast milk concentration of 34 mcg/mL (range 23 to 57 mcg/mL) at 2.4 hours (Matheson 1990). Zopiclone breast milk concentrations may reach 50% of maternal plasma levels.

Breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

Monitor for confusion, excessive drowsiness (especially in elderly), and/or respiratory depression. Monitor patients with hepatic insufficiency or with chronic respiratory insufficiency closely.

Mechanism of Action

Zopiclone is a cyclopyrrolone derivative and has a pharmacological profile similar to benzodiazepines. Zopiclone reduces sleep latency, increases duration of sleep, and decreases the number of nocturnal awakenings.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid.

Distribution: Vd: ~92 to 105 L; occurs rapidly from vascular compartment.

Protein binding: ~45%.

Metabolism: Extensively hepatic via CYP3A4 and CYP2C8 (Becquemont 1999); metabolites have minimal or no activity.

Bioavailability: 77%; Elderly: 94%.

Half-life elimination: ~5 hours; Elderly: ~7 hours; Hepatic impairment: ~12 hours.

Time to peak, serum: <2 hours; Hepatic impairment: 3.5 hours.

Excretion: Urine (75%; ~4% to 5% as unchanged drug); feces (16%).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Zopiclone concentrations are either unchanged or slightly increased in patients with severe kidney impairment in single-dose pharmacokinetic analyses (Gaillot 1987, Marc-Aurele 1987, Viron 1990). After 7 days of dosing, no accumulation of zopiclone or its metabolites in patients with severe kidney impairment (CrCl ≤14 mL/minute) was observed (Viron 1990).

Hepatic function impairment: In patients with cirrhosis, clearance is decreased ~40%.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Imovane | Pms-zopiclone;
  • (AR) Argentina: Apo zopiclona | Cronus | Descanilona | Foltran | Imovane | Insomnium | Zopiclona Cevallos | Zopiclona vannier;
  • (AU) Australia: Apo zopiclone | Chemmart zopiclone | Imoclone | Imovane | Imrest | Pharmacor zopiclon | Terry White Chemists Zopiclone;
  • (BD) Bangladesh: Hypnoclone | Imovane;
  • (BE) Belgium: Imovane | Zopiclone ab | Zopiclone Eurogenerics | Zopiclone merck-generics | Zopiclone Ratiopharm | Zopiclone teva generics belgium;
  • (BG) Bulgaria: Ecodorm | Imovane | Zopiclon;
  • (BR) Brazil: Imovane | Neurolil | Zopiclona;
  • (CH) Switzerland: Imovane | Zopiclone zentiva;
  • (CL) Chile: Alpaz | Imovane | Losopil | Sonoesan | Zedax | Zetix | Zometic | Zoperil;
  • (CN) China: Apo zopiclone | Imovane | Jin meng | San chen;
  • (CO) Colombia: Expoclone | Imovane | Reply | Sedorm | Zetix | Zoiplon | Zopiclona | Zopiclona humax;
  • (CZ) Czech Republic: Imovane | Zopiclon | Zopitin;
  • (DE) Germany: Desizopiclon | Espa Dorm | Imovane | Optidorm | Somnosan | Ximovan | Zodurat | Zop | Zopi Puren | Zopicalm | Zopiclodura | Zopiclon | Zopiclon 1A Pharma | Zopiclon Actavis | Zopiclon al | Zopiclon Aristo | Zopiclon beta | Zopiclon CT | Zopiclon Heumann | Zopiclon Hexal | Zopiclon puren | Zopiclon ratiopharm | Zopiclon Sandoz | Zopiclon stada | Zopiclon Teva | Zopiclone Axcount | Zopiclonlich | Zopidorm | Zopidura;
  • (DK) Denmark: Imoclone | Zopiklon nm;
  • (DO) Dominican Republic: Insomin | Insomnium | Sedorm;
  • (EC) Ecuador: Adormin | Dormiclona | Ezleep | Farbio zoplic | Nocturlen | Sedorm | Zalepla | Zedupax | Zerenix | Zetix | Zonix | Zopiclona | Zopiclona la sante | Zopiclona mk | Zopicloxx | Zopizz | Zoplivid | Zoplix;
  • (EE) Estonia: Imovane | Somnols | Zopitin;
  • (EG) Egypt: Hypnor;
  • (ES) Spain: Datolan | Limovan | Siaten | Zopicalma | Zopiclona qualigen;
  • (FI) Finland: Imovane | Zopiclon generics | Zopiclone alpharma | Zopinox | Zopitabs | Zopitin;
  • (FR) France: Imovane | Noctirex | Zopiclone Alter | Zopiclone arrow | Zopiclone biogaran | Zopiclone g gam | Zopiclone gnr | Zopiclone irex | Zopiclone ivax | Zopiclone merck | Zopiclone Qualimed | Zopiclone Ranbaxy | Zopiclone Ratiopharm | Zopiclone rpg | Zopiclone Sandoz | Zopiclone teva | Zopiclone zydus;
  • (GB) United Kingdom: Zileze | Zimovane | Zopiclone almus | Zopiclone arrow | Zopiclone cox | Zopiclone kent | Zopiclone Sandoz;
  • (GR) Greece: Imovane;
  • (HK) Hong Kong: Amvey | Apo zopiclone | Bf-Zopiclone | Dopareel | Eurovan | Genclone | Good-Knight | Imolone | Imovane | Jecefarma zopiclone | Neo Cone | Neo Plicon | Pms-zopiclone | Qualivane | Sedivan | Synovane | Zolief | Zolium | Zomni | Zopicla | Zopiclon | Zopicon | Zopistad | Zopivane;
  • (HR) Croatia: Zonotte;
  • (HU) Hungary: Imovane | Somnol | Zopigen | Zopitidin;
  • (IE) Ireland: Zileze | Zimoclone | Zimovane | Zopitan | Zorclone;
  • (IL) Israel: Imovane | Nocturno;
  • (IN) India: Somna | Ziclone | Zolinox | Zolium | Zonap | Zopicon | Zopitran;
  • (IT) Italy: Imovane | Nenia | Zopiclone aristo;
  • (JP) Japan: Amoban | Amoban chugai | Amoban mitsubishi | Amobantes | Antomylin | Dopareel | Metrom | Slowheim | Zopiban | Zopiban choseido | Zopicool;
  • (KE) Kenya: Imovane;
  • (KR) Korea, Republic of: Imovane;
  • (LB) Lebanon: Imovane;
  • (LT) Lithuania: Imovan | Imovane | Somnols | Yzop lekarsky | Zopiclon ria | Zopitin;
  • (LU) Luxembourg: Imovane | Zopiclone Eurogenerics;
  • (LV) Latvia: Imolan | Imovan | Imovane | Somnols | Zopiclon | Zopitin;
  • (MA) Morocco: Imovane;
  • (MX) Mexico: Imovane;
  • (MY) Malaysia: Apo zopiclone | Imovane | Insopin | Zolon | Zopicon;
  • (NG) Nigeria: Nitress | Swiclone | Zop;
  • (NL) Netherlands: Imovane | Zopiclon | Zopiclon Actavis | Zopiclon Alpharma | Zopiclon aurobindo | Zopiclon ratiopharm;
  • (NO) Norway: Imovane | Imozop | Zopiclodura | Zopiclon | Zopiclon 1A Pharma | Zopiclon aurobindo | Zopiclon CT | Zopiclon neuraxpharm | Zopiclone actavis | Zopiclone arrow | Zopiclone orion | Zopiklon | Zopiklon Pilum | Zopitin;
  • (NZ) New Zealand: Apo zopiclone | Imovane | Zo-Tab | Zopiclone actavis;
  • (PE) Peru: Docilen | Dormex | Ezolin | Imovane | Ryvalzhir pd | Zopiclona;
  • (PH) Philippines: Imovane;
  • (PK) Pakistan: Imovane;
  • (PL) Poland: Apodream | Dobroson | Imovane | Senzop | Somnol | Zopiclon | Zopiratio | Zopitin;
  • (PY) Paraguay: Docilen;
  • (RO) Romania: Als zopiclon | Imovane;
  • (RU) Russian Federation: Imovan | Imovane | Piclodorm | Sleepwell | Somnol | Torson | Zopiclon;
  • (SE) Sweden: Imovane | Zopiclon Copyfarm | Zopiclon stada | Zopiclone actavis | Zopiclone jubilant | Zopiclone orion | Zopiklon | Zopiklon Merck NM | Zopiklon mylan | Zopiklon Pilum | Zopiklon scand pharm | Zopikon mylan;
  • (SG) Singapore: Apo zopiclone | Imovane;
  • (SK) Slovakia: Imovane | Sonlax | Zopiclon | Zopitin;
  • (SR) Suriname: Zopiclon | Zopiclon mylan;
  • (TN) Tunisia: Imovane;
  • (TR) Turkey: Imovane;
  • (TW) Taiwan: Apo zopiclone | Genclone | Imovane | Insopin | Pms-zopiclone | Uniclone | Zolon;
  • (UA) Ukraine: Imovan | Piklon | Somnol | Sonnat | Sonovan | Zopiclon;
  • (UY) Uruguay: Docilen | Imovane;
  • (VE) Venezuela, Bolivarian Republic of: Imovane | Zopiclona;
  • (VN) Viet Nam: Drexler;
  • (ZA) South Africa: Adco Zopimed | Alchera | Austell zopiclone | Bio zopiclone | Imovane | Rolab-zopiclone | Z-dorm | Zopimed | Zopisleep | Zopivane;
  • (ZW) Zimbabwe: Imovane
  1. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
  2. Ban L, West J, Gibson JE, et al. First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study. PLoS One. 2014;9(6):e100996. doi:10.1371/journal.pone.0100996 [PubMed 24963627]
  3. Becquemont L, Mouajjah S, Escaffre O, et al. Cytochrome P-450 3A4 and 2C8 Are Involved in Zopiclone Metabolism. Drug Metab Dispos. 1999;27(9):1068-1073. [PubMed 10460808]
  4. Bélanger L, Belleville G, Morin C. Management of hypnotic discontinuation in chronic insomnia. Sleep Med Clin. 2009;4(4):583-592. doi:10.1016/j.jsmc.2009.07.011 [PubMed 20607118]
  5. Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7. [PubMed 29441476]
  6. Diav-Citrin O, Okotore B, Lucarelli K, Koren G. Pregnancy outcome following first-trimester exposure to zopiclone: a prospective controlled cohort study. Am J Perinatol. 1999;16(4):157-160. doi:10.1055/s-2007-993850 [PubMed 10458526]
  7. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  8. Gaillot J, Heusse D, Hougton GW, Marc Aurele J, Dreyfus JF. Pharmacokinetics and metabolism of zopiclone. Pharmacology. 1983;27(suppl 2):S76-S91. doi:10.1159/000137914 [PubMed 6669634]
  9. Gaillot J, Le Roux Y, Houghton GW, Dreyfus JF. Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency. Sleep. 1987;10(suppl 1):7-21. [PubMed 3438645]
  10. Health Canada. Summary safety review - IMOVANE (zopiclone) - next-day impairment. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR00048. Published November 21, 2014. Accessed August 29, 2024.
  11. Imovane (zopiclone) [product monograph]. Toronto, Ontario, Canada: Sanofi-Aventis Canada Inc; September 2024.
  12. Leufkens TR, Vermeeren A. Zopiclone's residual effects on actual driving performance in a standardized test: a pooled analysis of age and sex effects in 4 placebo-controlled studies. Clin Ther. 2014;36(1):141-150. doi:10.1016/j.clinthera.2013.11.005 [PubMed 24360801]
  13. Marc-Aurele J, Caille G, Bourgoin J. Comparison of zopiclone pharmacokinetics in patients with impaired renal function and normal subjects. Effect of hemodialysis. Sleep. 1987;10(suppl 1):22-26. [PubMed 3438644]
  14. Matheson I, Sande HA, Gaillot J. The excretion of zopiclone into breast milk. Br J Clin Pharmacol. 1990;30(2):267-271. doi:10.1111/j.1365-2125.1990.tb03774.x [PubMed 2206788]
  15. NRA-Zopiclone (zopiclone) [product monograph]. Saint-Lamber, Quebec, Canada: Nora Pharma Inc; March 2022.
  16. pms-Zopiclone [product monograph]. Montreal, Quebec, Canada: Pharmascience Inc; April 2024.
  17. Pons G, Rey E, Matheson I. Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations. Clin Pharmacokinet. 1994;27(4):270-289. doi:10.2165/00003088-199427040-00003 [PubMed 7834964]
  18. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125-133. doi:10.7326/M15-2175 [PubMed 27136449]
  19. Refer to manufacturer's labeling.
  20. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675-700. doi:10.1111/jsr.12594 [PubMed 28875581]
  21. Schifano F, Chiappini S, Corkery JM, Guirguis A. An insight into Z-drug abuse and dependence: an examination of reports to the European Medicines Agency database of suspected adverse drug reactions. Int J Neuropsychopharmacol. 2019;22(4):270-277. doi:10.1093/ijnp/pyz007 [PubMed 30722037]
  22. Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000 [PubMed 20000886]
  23. Viron B, De Meyer M, Le Liboux A, et al. Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure. Int Clin Psychopharmacol. 1990;5(suppl 2):95-104. [PubMed 2387982]
  24. Wikner BN, Källén B. Are hypnotic benzodiazepine receptor agonists teratogenic in humans? J Clin Psychopharmacol. 2011;31(3):356-359. doi:10.1097/JCP.0b013e3182197055 [PubMed 21508851]
  25. Wilson S, Anderson K, Baldwin D, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: an update. J Psychopharmacol. 2019;33(8):923-947. doi:10.1177/0269881119855343 [PubMed 31271339]
Topic 10126 Version 313.0