Zopiclone

Registered South African indications: 

• Insomnia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Myasthenia gravis
• Respiratory failure
• Severe hepatic insufficiency
• Sleep apnoea syndrome
• Pre-existing CNS depression or coma
• Safety in pregnancy has not been established
• Should not be prescribed to breastfeeding mothers
• Should not be prescribed to children younger than 18 years old

Cautions

• Moderate to severe renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Compromised respiratory function
• Chronic respiratory insufficiency
• History of substance abuse
• Marked personality disorders
• Depression
• Prolonged use
• Abrupt withdrawal
• Galactose intolerance  
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Insomnia

• Oral (tab): 7.5mg, dly at night; Max duration: 4 weeks

Treatment duration: Transient insomnia: 2-5 days; Short term insomnia: 2-3 weeks

Tablets are to be swallowed whole

Patients may benefit from tapering of the dose before discontinuation

See additional prescribing points 

Not established for use in children below 18 years (see Contraindications)

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Fertility

• If the product is prescribed to a woman of child bearing potential, she should be advised to contact her physician about stopping the product if she intends to become pregnant, or suspects that she is pregnant
• Double-blind long-term studies (7.5 mg zopiclone for 84 days) in healthy volunteers revealed no changes in ejaculate volume, sperm concentration, sperm motility or morphology

Renal Impairment

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended

Hepatic Impairment

• Child-Pugh Class A and B: Caution; dose adjustment recommended
  Initial: 3.75mg, daily at night; Up-titrate to 7.5mg daily at night if there are no changes in LFT over 8-12 weeks
• Child-Pugh Class C: Contraindicated

Elderly

• Caution; dose adjustment recommended
  Initial: 3.75mg, daily at night
  Limit the duration of therapy for a maximum of 4-6 weeks
  In the elderly, all benzodiazepine, benzodiazepine-like, agonists or analogues are to be avoided without consideration of the duration of use because of their association with harm balanced with their minimal efficacy in treating insomnia
• Presence of renal and/or hepatic impairment: Contraindicated

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Light headedness
• Headache
• Anterograde amnesia
• Nightmare
• Agitation
• Confusional state
• Libido disorder
• Irritability
• Aggression
• Hallucinations
• Drowsiness
• Restlessness
• Delusion
• Anger
• Depressed mood
• Abnormal behaviour
• Somnambulism
• Somnolence
• Dependence
• Withdrawal syndrome
• Rebound insomnia
• Ataxia
• Paraesthesia
• Cognitive disorders
• Memory impairment   
• Disturbance in attention
• Incoordination
• Speech disorder
• Fatigue

Respiratory Disorders

• Dyspnoea
• Respiratory depression

Gastrointestinal Disorders

• Dry mouth
• Nausea and vomiting
• Dyspepsia

Hepatobiliary Disorders

• Increased transaminases
• Increased blood alkaline phosphatase

Musculoskeletal Disorders

• Muscular weakness

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Pruritis

Immune, Blood and Lymphatic System Disorders

• Angiooedema
• Anaphylactic reaction

Sensory Disorders

• Dysgeusia (bitter taste)
• Diplopia

Other

• Increased fall risk, predominantly in elderly patients

• Central nervous system depressants
• Alcohol
• Antipsychotics (neuroleptics)
• Hypnotics
• Anxiolytics/sedatives
• Antidepressant agents
• Narcotic analgesics (opioids)
• Anti-epileptic drugs
• Anaesthetics
• Sedative antihistamines
• CYP3A4 inducers
• Rifampicin
• Carbamazepine
• Phenobarbital
• Phenytoin
• St John's Wort
• CYP3A4 inhibitors
• Erythromycin
• Clarithromycin
• Ketoconazole
• Itraconazole
• Ritonavir

None routine

Risk of dependence

• The use of benzodiazepines and benzodiazepine-like agents (even at therapeutic doses) may lead to the development of physical and psychological dependence or abuse upon these products
• The risk of dependence or abuse increases with:
  - Dose and duration of treatment
  - Use with alcohol or other psychotropics
  - A history of alcohol and/or drug abuse
  - Patients with marked personality disorders
• Clinical experience suggests that risk of dependence is minimal when the duration of treatment is limited to 4 weeks

Withdrawal symptoms

• Termination of treatment is unlikely to be associated with withdrawal symptoms if the duration is limited to 4 weeks
• Patients may benefit from tapering off the dose before discontinuation
• If physical dependence has developed, withdrawal symptoms of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability may occur
• In severe cases, symptoms may include derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures

Use in depression

• As with other hypnotics, zopiclone does not constitute a treatment for depression and may mask its symptoms (suicide may be precipated in such patients)
• Suicidal tendencies may be present, thus the least amount of tablets (that is feasible) should be supplied to these patients to avoid the possibility of intentional overdosage by the patient
• Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists. Any underlying cause of the insomnia should also be addressed before symptomatic treatment to avoid under treating potentially serious effects of depression

Tolerance

• Some loss of efficacy to the hypnotic effect of benzodiazepines and benzodiazepine-like agents may develop after repeated use for a few weeks
• However, with zopiclone, there is an absence of any marked tolerance during treatment periods of up to 4 weeks

Rebound insomnia

• Rebound insomnia may occur on discontinuation of therapy accompanied by other reactions including mood changes, anxiety and restlessness
• Since the risk of withdrawal/ rebound phenomena may be increased after prolonged treatment or abrupt discontinuation of therapy, it is recommended to decrease the dosage gradually and to advise the patient accordingly. A course of treatment should employ the lowest effective dose for the minimum length of time necessary for effective treatment

Zopiclone, a hypnotic agent, is a member of the cyclopyrrolone group of compounds. Zopiclone displays high affinity and specific agonist action at central receptors of the GABA macromolecular receptor complex, modulating the opening of the chloride ion channel. It has been shown that zopiclone and other cyclopyrrolones act on a different site to those of benzodiazepines including different conformational changes in the receptor complex. Zopiclone rapidly initiates and sustains sleep without reduction of total REM sleep and with preservation of slow wave sleep. Negligible residual effects are seen the following morning.

Tablet 7.5mg

• Adco-Zopimed (Adcock) 
• Alchera (Pharmacare)
• Austell-Zopiclone (Camox)
• Bio Zopiclone (Biotech)
• Imovane (Sanofi) originator
• Sandoz Zopiclone (Sandoz)
• Z-Dorm (Kiara Health)
• Zopiclone Unicorn (Camox)
• Zopigen (Xixia)
• Zopisleep (iPharma)
• Zopivane (Cipla Medpro)