film-coated scored tablets
Active ingredient: zopiclone. Each tablet contains 7.5 mg zopiclone.
Excipients: lactose, calcium hydrogen phosphate, wheat starch, sodium starch
glycolate, magnesium stearate. Film coating: hypromellose, titanium dioxide
Pharmaco-therapeutic class: HYPNOTICS and SEDATIVES (N: Nervous system)
Zopiclone is a cyclopyrrolone, related to the benzodiazepine drugs. Its
pharmacological properties are: hypnotic, sedative, anxiolytic, anti-convulsant,
muscle-relaxant. These effects are related to a specific agonist action at
central receptors belonging to the GABAA macromolecular complex, modulating
the opening of the chloride ion channel. Zopiclone reduces the time to onset
of sleep and the frequency of nocturnal awakenings, increases the duration
of sleep and improves both the quality of sleep and the quality of
In insomniac patients, zopiclone decreases stage I, increases stage II,
while preserving or prolonging the deep sleep stages (III and IV) and the
Zopiclone is rapidly absorbed. Peak concentrations are reached within 1.5-2
hours and they are approximately 60 ng/ml after administration of 7.5 mg.
Absorption is not modified by food. Plasma protein binding is weak
(approximately 45 %) and non saturable. After repeated administration, there
is no accumulation of zopiclone and its metabolites. Interindividual
variations appear to be low. An in vitro study indicates that cytochrome
P450 (CYP) 3A4 is the major isoenzyme involved in the metabolism of
zopiclone. The principal metabolites are the N-oxide derivative (active) and
the Ndemethyl metabolite (inactive). Their apparent half-lives evaluated
from urinary data are approximately 4.5 hours and 7.4 hours respectively. At
recommended doses, the elimination half-life of the unchanged zopiclone is
approximately 5 hours. Zopiclone is eliminated by the urinary route
(approximately 80 %) mainly in the form of free metabolites and in the
faeces (approximately 16 %). In renal insufficiency, no accumulation of
zopiclone or of its metabolites has been detected after prolonged
administration. In cirrhotic patients, the plasma clearance of zopiclone is
reduced by approximately 40 % in relation with the decrease of the
demethylation process. Therefore dosage will have to be modified in these
patients. In elderly patients, notwithstanding a slight decrease in hepatic
metabolism and lengthening of elimination half-life to approximately 7
hours, various studies have not shown plasma accumulation of drug substance
on repeated dosing.
When should this medicinal product be used (Therapeutic indications)
IMOVANE is intended for treatment of transient, short-term and chronic
insomnia in adults (including difficulties with falling asleep, nocturnal
awakening, and early wakening).
How should this medicinal product be used
Strictly follow the recommended dosage unless directed otherwise by the
Dosage and method of administration
Adults: the recommended dose is one 7.5 mg IMOVANE tablet by oral route.
This dose should not be exceeded. The product must be taken just before
retiring for the night.
Transient insomnia: 2 to 5 days.
Short term insomnia: 2 to 3 weeks.
Chronic insomnia: long term treatment should be considered only after a
consultation with a specialist.
The dosage should be gradually decreased before discontinuation of
treatment. Treatment should be as short as possible and should not exceed
four weeks including the period of tapering off. Extension beyond the
maximum treatment period should not take place without re-evaluation of the
In elderly and in patients with impaired liver function or chronic
respiratory insufficiency: a starting dose of 3.75 mg zopiclone (half a
tablet) is recommended initially. The dosage subsequently may be increased
to 7.5 mg.
In patients with renal insufficiency: although no accumulation of zopiclone
or of its metabolites has been detected In cases of renal insufficiency, it
is recommended that patients with impaired renal function should start
treatment with 3.75 mg. The safe and effective dose of zopiclone has not
been established in children and young adults less than 18 years.
When should this medicinal product not he used (contraindications)
should not be used in the following cases:
• myasthenia gravis (chronic
progressive muscle disease),
• hypersensitivity (allergy) to zopiclone or to
any of the excipients,
• respiratory failure,
severe sleep apnea syndrome (respiratory pauses during sleep),
• severe liver
Warnings and precautions
Use of sedative/hypnotics agents like zopiclone may lead to the development
of physical and psychological dependence or abuse. Risks of dependence or
abuse increase with: dose and duration of treatment, history of alcohol
and/or drug abuse, use with alcohol or other psychotropics. In case of
physical dependence, stopping the treatment suddenly may lead to withdrawal
symptoms: insomnia, headache, muscular pains, anxiety, tension, agitation,
confusion and irritability.
A transient syndrome whereby the symptoms that led to treatment with
sedative/hypnotic agents recur in an enhanced form, may occur on withdrawal
of hypnotic treatment. Since the risk of such phenomena is greater after
abrupt discontinuation of zopiclone, especially after prolonged treatment,
it is, therefore, recommended to decrease the dosage gradually and to advise
the patient accordingly. (see Undesirable effects).
Some loss of efficacy of other hypnotics may develop after repeated use.
However, there is an absence of marked tolerance with zopiclone for
treatment periods up to 4 weeks.
Anterograde amnesia (inability to remember recent events) may occur,
especially when sleep is interrupted or when retiring to bed is delayed
after the intake of the tablet. To reduce the possibility of memory
disturbances, patients should ensure that they take the tablet strictly when
retiring for the night and that they are able to have a full night sleep.
Other psychiatric and paradoxical reactions have been reported (see
Anaphylaxis (severe allergic reaction) and angioedema (severe facial
swelling) which can occur as early as the first time the product is taken.
Somnambulism and associated behaviours: Sleep walking and other associated
behaviours such as "sleep driving", preparing and eating food, or making
phone calls, with amnesia for the event, have been reported in patients who
have taken zopiclone and were not fully awake. The use of alcohol and other
CNS-depressants with zopiclone appears to increase the risk of such
behaviours, as does the use of zopiclone at doses exceeding the maximum
recommended dose. Discontinuation of zopiclone should be strongly considered
for patients who report such behaviours (See Interactions: Alcohol, and
Undesirable effects: Psychiatric reactions). As with other hypnotics,
zopiclone does not constitute a treatment of depression and may even mask
Patients intolerants to gluten or lactose should be warned of
the presence of wheat starch (gluten) and lactose in IMOVANE tablets.
Due to the risks of drowsiness, memory disturbances, difficulty in
concentrating, visual disturbances and muscle pain linked to the use of this
medicinal product, drivers and machine operators should be extremely
careful. These risks are increased by the concomitant intake of alcohol. If
you drink alcohol during the treatment, do not drive. The risk of impaired
vigilance is even greater when sleep duration is insufficient
The use of zopiclone during pregnancy is not recommended. If zopiclone is
used during the last three months of pregnancy or during labour, due to the
pharmacological action of the product, effects on the neonate, such as
hypothermia, hypotonia and respiratory depression can be expected.
Zopidone should not be used by nursing mothers.
In case of overdose, contact immediately your physician.
Overdose is usually manifested by varying degrees of central nervous system
depression ranging from drowsiness to coma according to the quantity
ingested. In mild cases, symptoms include drowsiness, confusion, and
lethargy; in more severe cases,
symptoms may include ataxia, hypotonia, hypotension, respiratory depression,
and coma. Overdose should not be life threatening unless combined with other
CNS depressants, including alcohol. Other risk factors, such as the presence
of concomitant illness and the debilitated state of the patient, may
contribute to the severity of symptoms and very rarely can result in fatal
outcome. Symptomatic and supportive treatment is recommended; attention
should be paid to respiratory and cardiovascular functions. Gastric lavage
or activated charcoal is only useful when performed soon after ingestion.
Hemodialysis is of no value due to the large volume of distribution of
zopiclone. Flumazenil may be a useful antidote.
In order to avoid possible interactions with other medicines inform your
physician or pharmacist about any other current treatment.
intake with alcohol or alcohol containing-medicinal products is not
recommended. The sedative effect of zopiclone may be enhanced when the
product is used in combination with alcohol, This affects the ability to
drive or use machines.
Enhancement of the central depressive effect may
occur in cases of concomitant use with CNS depressants: neuroleptics,
hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic
analgesics, antiepileptic drugs, anesthetics and sedative antihistaminics.
Since zopiclone is metabolized by the cytochrome P450 (CYP) 3A4 isoenzyme,
plasma levels of zopiclone may be increased when co-administered with CYP3A4
inhibitors. Conversely, plasma levels of zopiclone may be decreased when
co-administered with CYP3A4 inducers. In case of concomitant administration
with erythromycin the hypnotic effects of zopiclone may be enhanced.
Please tell your physician or pharmacist, if you experience any adverse
effect with the use of this product.
Bitter taste in the mouth is the most common side-effect observed with
Other adverse reactions which have been reported are: dizziness, headache,
residual somnolence, dyspepsia (gastric discomfort), nausea, dry mouth,
allergic or cutaneous reactions such as pruritus (itching) and rash.
Quincke's edema (swelling of the face, tongue, throat or larynx) and/or
anaphylactic reactions (severe rapid onset allergic reactions) have been
reported very rarely, Anterograde amnesia may occur.
paradoxical reactions such as nightmares, irritability, confusion,
hallucinations, aggressiveness, inappropriate behaviour possibly associated
with amnesia, sleep walking (see Warnings and Precautions: somnambulism and
associated behaviour), have been reported rarely. Withdrawal and rebound
insomnia have been occasionally observed at the discontinuation of the
treatment (see Warnings and precautions).
Mild to moderate increases in serum transaminases and/or alkaline
phosphatase have been reported very rarely.
Store below 25°C.
Keep out of the reach of children.
Do not use later than the date of expiry indicated on the outer packaging.
Box of 20 tablets in PVC/aluminium blisters.