Your activity: 6 p.v.

Zopiclone (United States: Not available): Drug information

Zopiclone (United States: Not available): Drug information
(For additional information see "Zopiclone (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: Canada
  • ACT Zopiclone;
  • AG-Zopiclone;
  • APO-Zopiclone;
  • BIO-Zopiclone;
  • DOM-Zopiclone;
  • Imovane;
  • JAMP-Zopiclone;
  • M-Zopiclone;
  • Mar-Zopiclone;
  • MINT-Zopiclone;
  • NRA-Zopiclone;
  • PMS-Zopiclone;
  • PRO-Zopiclone;
  • RATIO-Zopiclone;
  • RIVA-Zopiclone;
  • SANDOZ Zopiclone [DSC];
  • 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 (ACP [Qaseem 2016]; ESRS [Riemann 2017]).

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 (Bélanger 2009).

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

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

Dosing: Hepatic 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 (Beers Criteria [AGS 2019]).

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.

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

Product Availability

Not available in the US

Administration: Adult

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 2019]).

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.

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

Dermatological: 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:

• Addiction/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.

• 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).

• 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).

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): May enhance the adverse/toxic effect 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, etc.) Alcohol (Ethyl) may enhance the CNS depressant effect of Zopiclone. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: May enhance the CNS depressant effect of Zopiclone. CarBAMazepine may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

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

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

CYP3A4 Inhibitors (Strong): May increase the 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

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect 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 enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect 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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

HydrOXYzine: May enhance the CNS depressant effect 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

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect 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

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect 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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

PHENobarbital: May enhance the CNS depressant effect of Zopiclone. PHENobarbital may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy

Primidone: May enhance the CNS depressant effect of Zopiclone. Primidone may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

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

Suvorexant: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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

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

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

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

Brand Names: International
  • Amoban (JP);
  • Datolan (ES);
  • Docilen (PE, PY, UY);
  • Dopareel (HK);
  • Dormex (PE);
  • Eurovan (HK);
  • Genclone (TW);
  • Hypnoclone (BD);
  • Hypnor (EG);
  • Imoclone (AU);
  • Imovane (AR, AU, BB, BE, BM, BR, BS, BZ, CH, CL, CN, CO, CZ, DK, EE, FI, FR, GR, GY, HK, HN, HU, IL, IS, IT, JM, KR, LT, LU, LV, MX, MY, NL, NO, NZ, PL, RO, RU, SE, SG, SR, TR, TT, TW, UA, UY, VE, VN, ZW);
  • Imrest (AU);
  • Insopin (MY);
  • Nestacoran (EG);
  • Nocturno (IL);
  • Optidorm (DE);
  • Piklon (UA);
  • Sedolox (AT);
  • Sedorm (CO);
  • Siaten (ES);
  • Sleepez (EG);
  • Sleepil (BD);
  • Somnol (HN, UA);
  • Somnols (EE, LV);
  • Somnosan (DE);
  • Sonlax (BG);
  • Sono (BD);
  • Ticlon (BD);
  • Ximovan (DE);
  • Z-Dorm (ZA);
  • Zetix (CL, EC);
  • Zileze (IE);
  • Zimoclone (IE);
  • Zimovane (GB, IE);
  • Zolinox (IN);
  • Zolon (MY, TW);
  • Zometic (CL);
  • Zomianne (TW);
  • Zopic (EG);
  • Zopimed (ZA);
  • Zopinox (FI);
  • Zopistad (HK, VN);
  • Zopitan (IE);
  • Zopitin (LV);
  • Zopitran (IN);
  • Zopivane (ZA);
  • Zorclone (IE)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]
  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. 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]
  6. 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]
  7. Imovane (zopiclone) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; April 2022.
  8. 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]
  9. 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]
  10. NRA-Zopiclone (zopiclone) [product monograph]. Saint-Lamber, Quebec, Canada: Nora Pharma Inc; March 2022.
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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 259.0