Active ingredients: Zopiclone
IMOVANE 7.5 mg film-coated tablets
Indications Why is Imovane used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Benzodiazepine-like substance with hypnotic action.
THERAPEUTIC INDICATIONS
Short-term treatment of insomnia in adults.
Benzodiazepines and benzodiazepine-like substances are indicated only when the disorder is severe, disabling, or makes the subject very uncomfortable.
Contraindications When Imovane should not be used
Myasthenia gravis. Hypersensitivity to the active substance or to any of the excipients. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome.
Administration to children.
Precautions for use What you need to know before taking Imovane
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines and benzodiazepine-like substances may develop after repeated use for a few weeks. However, the absence of marked tolerance for treatments up to 4 weeks was noted with zopiclone.
Dependence
The use of hypnotic sedatives such as zopiclone can lead to the development of physical and mental dependence on these drugs. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse or when used in conjunction with alcohol or other psychotropics.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body aches, extreme anxiety, tension, restlessness, confusion and irritability.In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
Rebound insomnia and anxiety
A transient syndrome may occur on discontinuation of treatment in which symptoms leading to treatment with benzodiazepines and hypnotic sedatives recur in an aggravated form. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disturbances.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, especially in prolonged treatments, it is suggested that the dosage be gradually decreased and the patient be warned (see "Undesirable Effects").
Duration of treatment
The duration of treatment should be as short as possible (see also "Dose, method and time of administration") depending on the indication, but should not exceed four weeks including a gradual withdrawal period. The extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation.It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.
Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about such symptoms should they occur when the drug is discontinued.
There is evidence that, in the case of benzodiazepines and benzodiazepine-like substances with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses. .
Amnesia
Benzodiazepines and benzodiazepine-like substances can induce anterograde amnesia which can arise especially when sleep is abruptly interrupted or when the patient delays bedtime after taking the tablets; this occurs most often several hours after ingestion of the drug and, therefore, , to reduce the risk, it should be ensured that patients take the tablets immediately before bedtime and that they can have an uninterrupted sleep of 7-8 hours (see "Undesirable effects").
Psychiatric and paradoxical reactions
When using benzodiazepines and benzodiazepine-like substances, such as zopiclone, reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes are known to occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in the elderly.
Sleepwalking and associated behaviors:
Sleepwalking and other associated behaviors such as sleep driving, preparing and eating food, making phone calls, with amnesia for the event have been reported in patients taking zopiclone who were not fully awake. It appears that both alcohol and other use are reported. CNS depressants together with zopiclone and the use of zopiclone at doses exceeding the maximum recommended dose increase the risk of such behaviors. Careful consideration should be given to discontinuing zopiclone treatment in patients exhibiting such behaviors (see "Interactions - Alcohol "and" Undesirable effects - Psychiatric and paradoxical reactions).
Psychomotor alterations
Like other sedative / hypnotic drugs, zopiclone has CNS depressant effects. The risk of psychomotor impairment, including impaired ability to drive, increases if: zopiclone is taken less than 12 hours before performing activities requiring mental alertness, a higher than recommended dose is taken, or zopiclone is co-administered with other drugs with central nervous system (CNS) depressant effect, with alcohol or with other drugs that increase blood levels of zopiclone (see "Interactions"). Patients should be cautioned not to engage in hazardous occupations requiring full mental alertness or motor coordination, such as operating machinery or driving vehicles, after administration of zopiclone and particularly during the 12 hours following its administration (see section Special warnings).
Particular groups of patients
The elderly should take a reduced dose (see "Dose, method and time of administration"). Since hypnotics have the ability to reduce respiratory activity, caution should be exercised when prescribing zopiclone to patients with impaired respiratory function. A lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression (see " Dose, method and time of administration "). Benzodiazepines and benzodiazepine-like substances are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy.
Benzodiazepines and benzodiazepine-like substances are not recommended for the primary treatment of psychotic illness.
Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of drug or alcohol abuse.
Pediatric population
Zopiclone should not be used in children and adolescents under the age of 18. The safety and efficacy of zopiclone in children and adolescents below 18 years of age have not been established.
Depression
As with other hypnotics, Imovane should not be used alone to treat depression or anxiety associated with depression (suicide can precipitate in such patients) and may mask their symptoms.
Interactions Which drugs or foods may change the effect of Imovane
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines.
In the case of narcotic analgesics, an increase in euphoria can occur, leading to an increase in psychic dependence.
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines and benzodiazepine-like substances.
The effect of erythromycin on zopiclone pharmacokinetics was studied in 10 healthy subjects. In the presence of erythromycin, the AUC of zopiclone was increased by 80%, indicating that erythromycin can inhibit the metabolism of drugs, metabolised by CYP3 A4; therefore, as a consequence, the hypnotic effect of zopiclone may be increased .
Since zopiclone is metabolised by the isoenzyme P450 (CYP) 3A4, plasma levels of zopiclone may increase with concomitant administration of CYP3A4 inhibitors such as erythromycin, clarithromycin, ketoconazole, itraconazole and ritonavir. When co-administered with CYP3A inhibitors. a reduction in the dosage of zopiclone may be necessary.
Conversely, plasma levels of zopiclone may be reduced during concomitant administration of CYP3A4 inducers, such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John's wort. Concomitant administration with CYP3A4 inducers may require an increase in the dosage of zopiclone.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There are insufficient data on zopiclone to assess its safe use during pregnancy and lactation.
The use of Imovane during pregnancy is not recommended.
If the drug is prescribed to a woman of childbearing age, she should contact her doctor regarding discontinuation of the drug, whether she is planning to become pregnant or if she suspects that she is pregnant.
If Imovane is administered during the last three months of pregnancy or during labor or delivery, effects on the newborn such as hypothermia, hypotonia and respiratory depression may occur due to the drug's pharmacological action.
In addition, infants born to mothers who have taken benzodiazepines and benzodiazepine-like substances chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since benzodiazepines and benzodiazepine-like substances are excreted in breast milk, zopiclone should not be given to breastfeeding mothers.
Effects on ability to drive and use machines
Due to its pharmacological properties and its effect on the central nervous system (sedation, amnesia, impaired concentration and muscle function) Imovane may adversely affect the ability to drive or use machines.
The risk of psychomotor impairment, including impaired ability to drive, increases if:
- zopiclone is taken less than 12 hours before performing activities that require mental alertness,
- a higher dose than recommended is taken, or
- zopiclone is co-administered with other central nervous system (CNS) depressant drugs, alcohol or other drugs that increase the blood levels of zopiclone.
Patients should be cautioned not to engage in hazardous occupations requiring full mental alertness or motor coordination, such as operating machinery or driving motor vehicles after administration of zopiclone and particularly during the 12 hours following its administration.
It is recommended not to take zopiclone and alcohol at the same time if you have to drive.
If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see "Interactions"). If your doctor has diagnosed you with an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine can be given to people with celiac disease. People with wheat allergy (other than celiac disease) should not take this medicine.
Dosage and method of use How to use Imovane: Dosage
Treatment should be as short as possible. The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period. In certain cases, extension beyond the maximum treatment period may be necessary; if so, this should not occur without reassessment of the patient's condition.
The drug should be taken at bedtime.
Dosage
Use the drug at the lowest effective dose. Imovane should be taken as a single dose and should not be re-administered during the same night (should not be taken less than 12 hours before performing activities requiring mental alertness. See "Special warnings"). Treatment should be initiated with the dose lowest recommended. The recommended dose for adults is 7.5 mg. This dose must not be exceeded.
Elderly patients and patients with impaired hepatic function or chronic respiratory failure should start with a dose of 3.75 mg.
Although no accumulation of zopiclone or its metabolites has been shown in renal insufficiency, treatment with 3.75 mg is recommended in patients with impaired renal function.
Pediatric population
Zopiclone should not be used in children and adolescents under the age of 18. The safety and efficacy of zopiclone in children and adolescents below 18 years of age have not been established.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Imovane
In case of accidental ingestion / intake of an excessive dose of Imovane, notify your doctor immediately or go to the nearest hospital.
Signs and symptoms:
As with other benzodiazepines and other benzodiazepine-like substances, overdose should not be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
As in the treatment of overdosing of any drug, the possibility that other substances have been taken at the same time should be considered.
Overdosing of benzodiazepines and benzodiazepine-like substances usually manifests itself with varying degrees of CNS depression, ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, methemoglobinemia, respiratory depression, rarely coma. Other risk factors such as the presence of concomitant diseases and a state of debility can contribute to the severity of symptoms and can very rarely be fatal.
Treatment:
Supportive and symptomatic treatment conducted in an appropriate hospital setting with particular attention to the patient's respiratory and cardiovascular functions is recommended.
Gastric lavage or activated charcoal are only effective when used immediately after drug ingestion. Hemodialysis is not useful for drug removal due to the high volume of distribution of zopiclone.
Flumazenil can be useful as an antidote.
In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Imovane
Like all medicines, this can cause side effects, although not everybody gets them.
The most common side effect observed with zopiclone is bitter taste.
Other reported side effects are daytime sleepiness, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, paraesthesia, double vision. These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances (dyspepsia, nausea, dry mouth), changes in libido and allergic and skin reactions such as pruritus and rash Angioedema and / or anaphylactic reactions have been reported very rarely.
Cases of moderate elevation of transaminases and / or blood alkaline phosphatase have been reported very rarely.
Cases of falls have also been reported (mainly in elderly patients).
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects can be associated with behavioral changes. to see. "Precautions for use").
Depression
A pre-existing state of depression may be unmasked during the use of benzodiazepines and benzodiazepine-like substances.
Psychiatric and paradoxical reactions
Restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, behavioral changes associated with amnesia and sleepwalking have been reported (see "Precautions for" use "- sleepwalking and associated behaviors). quite severe They are more likely in the elderly.
Dependence
The use of benzodiazepines and benzodiazepine-like substances (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see Precautions for use). Cases of withdrawal syndrome have been reported with discontinuation of Imovane. Symptoms of this syndrome can vary and include rebound insomnia, anxiety, tremors, sweating, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, hallucinations and irritability. In very rare cases, seizures can occur.
Psychic dependence can occur. Cases of abuse have been reported.
Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea (see "Precautions for use")
Not known: respiratory depression (see "Precautions for use").
Nervous system disorders
Not known: cognitive disturbances such as memory deficit, attention disturbance, language disturbances.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Italian Medicines Agency, Website: http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this product. medicinal
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
Keep this medicine out of the reach and sight of children.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
COMPOSITION
One scored film-coated tablet contains:
Active ingredient: zopiclone 7.5 mg
Excipients: wheat starch; dibasic calcium phosphate dihydrate; lactose monohydrate; sodium carboxymethyl starch; magnesium stearate; hypromellose; titanium dioxide, macrogol 6000.
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets.
Carton containing 20 divisible tablets in blister packs.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
IMOVANE 7.5 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
One scored film-coated tablet contains:
Active principle: zopiclone 7.5 mg.
Excipients: wheat starch 60.0 mg, lactose 31.575 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Film-coated tablets.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Short-term treatment of insomnia.
Benzodiazepines and benzodiazepine-like substances are indicated only when the disorder is severe, disabling, or makes the subject very uncomfortable.
04.2 Posology and method of administration -
Treatment should be as short as possible. The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period. In certain cases, extension beyond the maximum treatment period may be necessary; if so, this should not occur without reassessment of the patient's condition.
The drug should be taken at bedtime.
Dosage
Treatment should be started with the lowest recommended dose. The recommended dose for adults is 7.5 mg. This dose must not be exceeded.
Elderly patients and patients with impaired hepatic function or chronic respiratory failure should start with a dose of 3.75 mg.
Although no accumulation of zopiclone or its metabolites has been shown in renal insufficiency, treatment with 3.75 mg is recommended in patients with impaired renal function.
In young adults below 18 years of age, the safe and effective dose has not been established.
04.3 Contraindications -
Myasthenia gravis.
Hypersensitivity to the active substance or to any of the excipients.
Severe respiratory insufficiency.
Severe hepatic insufficiency.
Sleep apnea syndrome.
Administration to children.
04.4 Special warnings and appropriate precautions for use -
The medicine contains lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
This medicine contains Wheat starch which may contain gluten, but only in trace amounts, and is therefore considered safe for people with celiac disease.
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines and benzodiazepine-like substances may develop after repeated use for a few weeks. However, the absence of marked tolerance for treatments up to 4 weeks was noted with zopiclone.
Dependence
The use of hypnotic sedatives such as zopiclone can lead to the development of physical and mental dependence on these drugs. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse or when used with alcohol or other psychotropics.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body aches, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
Rebound insomnia and anxiety
A transient syndrome in which symptoms leading to treatment with hypnotic sedatives recur in an aggravated form may occur upon discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disturbances.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, especially in prolonged treatments, it is suggested that the dosage be gradually decreased and the patient be warned (see section 4.8).
Duration of treatment
The duration of treatment should be as short as possible (see also section 4.2) depending on the indication, but should not exceed four weeks including a gradual withdrawal period. Extension of therapy beyond these periods should not occur without reassessment of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.
Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about such symptoms should they occur when the drug is discontinued.
There is evidence that, in the case of benzodiazepines and benzodiazepine-like substances with a short duration of action, withdrawal symptoms may become manifest within the dosing interval between doses, particularly for high doses. .
Amnesia
Anterograde amnesia can arise especially when sleep is abruptly interrupted or when the patient delays bedtime after taking the tablets; this happens more often several hours after ingestion of the drug and, therefore, to reduce the risk one should make sure that patients take the tablets immediately before bedtime and can have 7-8 hours of uninterrupted sleep (see section 4.8).
Psychiatric and paradoxical reactions
When using benzodiazepines and benzodiazepine-like substances, such as zopiclone, reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes are known to occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in the elderly.
Sleepwalking and associated behaviors:
Sleepwalking and other associated behaviors such as sleep driving, preparing and eating food, making phone calls, with amnesia for the event have been reported in patients taking zopiclone who were not fully awake. It appears that both alcohol and other use are reported. CNS depressants together with zopiclone and the use of zopiclone at doses exceeding the maximum recommended dose increase the risk of such behaviors. Careful consideration should be given to stopping zopiclone in patients exhibiting such behaviors (see section "Interactions" - Alcohol "and section" Undesirable effects - Psychiatric and paradoxical reactions).
Particular groups of patients
The elderly should take a reduced dose (see section 4.2).
Since hypnotics have the ability to reduce respiratory activity, caution should be exercised when prescribing zopiclone to patients with impaired respiratory function. A lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression (see section 4.2).
Benzodiazepines and benzodiazepine-like substances are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy.
Benzodiazepines and benzodiazepine-like substances are not recommended for the primary treatment of psychotic illness.
Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of drug or alcohol abuse.
Use in children.
Safety and effective dose are not established in children and adolescents under 18 years of age.
Depression
As with other hypnotics, Imovane should not be used alone to treat depression or anxiety associated with depression (suicide can precipitate in such patients) and may mask their symptoms.
04.5 Interactions with other medicinal products and other forms of interaction -
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines.
In the case of narcotic analgesics, an increase in euphoria can occur, leading to an increase in psychic dependence.
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines and benzodiazepine-like substances.
The effect of erythromycin on zopiclone pharmacokinetics was studied in 10 healthy subjects. In the presence of erythromycin, the AUC of zopiclone was increased by 80%, indicating that erythromycin may inhibit the metabolism of drugs metabolised by CYP3 A4; therefore, as a consequence, the hypnotic effect of zopiclone may be elevated.
Since zopiclone is metabolised by the isoenzyme P450 (CYP) 3A4 (see section 5.2), plasma levels of zopiclone may increase with concomitant administration of CYP3A4 inhibitors such as erythromycin, clarithromycin, ketoconazole, itraconazole and ritonavir. concomitant with CYP3A4 inhibitors, a reduction in zopiclone dosage may be necessary.
Conversely, plasma levels of zopiclone may be reduced during concomitant administration of CYP3A4 inducers, such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John's wort. Concomitant administration with CYP3A4 inducers may require an increase in the dosage of zopiclone.
04.6 Pregnancy and breastfeeding -
There are insufficient data on zopiclone to assess its safe use during pregnancy and lactation.
The use of Imovane during pregnancy is not recommended.
If the drug is prescribed to a woman of childbearing age, she should contact her doctor regarding discontinuation of the drug, whether she is planning to become pregnant or if she suspects that she is pregnant.
If Imovane is administered during the last three months of pregnancy or during labor or delivery, effects on the newborn such as hypothermia, hypotonia and respiratory depression may occur due to the drug's pharmacological action.
In addition, infants born to mothers who have taken benzodiazepines and benzodiazepine-like substances chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since benzodiazepines and benzodiazepine-like substances are excreted in breast milk, zopiclone should not be given to breastfeeding mothers.
04.7 Effects on ability to drive and use machines -
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive or operate machinery. The risk is increased by the concomitant use of alcohol (see section 4.5) therefore it is recommended not to take zopiclone and alcohol at the same time if you have to drive. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section 4.5).
04.8 Undesirable effects -
The most common side effect observed with zopiclone is bitter taste.
Other reported side effects are: daytime sleepiness, dulling of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, paraesthesia, double vision. These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations. Other adverse reactions have occasionally been reported including: gastrointestinal disturbances (dyspepsia, nausea, dry mouth), changes in libido and allergic and skin reactions such as pruritus and rash Angioedema and / or anaphylactic reactions have been reported very rarely.
Cases of moderate elevation of transaminases and / or blood alkaline phosphatase have been reported very rarely. Cases of falls have also been reported (mainly in elderly patients).
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects can be associated with behavioral changes. (see section 4.4).
Depression
A pre-existing state of depression may be unmasked during the use of benzodiazepines and benzodiazepine-like substances.
Psychiatric and paradoxical reactions
Restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, confusion, hallucinations, psychosis, behavioral changes associated with amnesia and sleepwalking have been reported (see section "Special warnings and precautions for use" - sleepwalking and associated behaviors These reactions can be quite severe and are more likely in the elderly.
Dependence
The use of benzodiazepines and benzodiazepine-like substances (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see section 4.4). cases of withdrawal syndrome reported. Symptoms of this syndrome can vary and include rebound insomnia, anxiety, tremors, sweating, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, hallucinations and irritability. In very rare cases they may check for seizures.
Psychic dependence can occur. Cases of abuse have been reported.
Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea (see section 4.4)
Not known: respiratory depression (see section 4.4)
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the Italian Medicines Agency, Website: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Signs and symptoms:
As with other benzodiazepines and other benzodiazepine-like substances, an overdose should not be life-threatening unless concomitant intake of other CNS depressants (including alcohol) is present.
As in the treatment of overdosing of any drug, the possibility that other substances have been taken at the same time should be considered.
Overdosing of benzodiazepines and benzodiazepine-like substances usually manifests itself with varying degrees of CNS depression, ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, methemoglobinemia, respiratory depression, rarely coma.Other risk factors such as the presence of concomitant diseases and a state of debility can contribute to the severity of symptoms and can very rarely be fatal.
Treatment:
symptomatic and supportive treatment conducted in an adequate hospital setting with particular attention to the patient's respiratory and cardiovascular functions is recommended.
Gastric lavage or activated charcoal are only effective when used immediately after drug ingestion. Hemodialysis is not useful for drug removal due to the high volume of distribution of zopiclone.
Flumazenil can be useful as an antidote.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: hypnotics and sedatives, benzodiazepine-like substances.
ATC code: N05CF01.
Zopiclone is a hypno-inducing benzodiazepine-like substance belonging to compounds of the cyclopyrrolone group. Its pharmacological properties are: anxiolytic, sedative, hypnotic, anticonvulsant, muscle relaxant.
These effects are related to a specific agonist action on the central receptors belonging to the GABA-omega receptor complex (BZ1 and BZ2) which regulates the opening of the chlorine ion channels.
05.2 "Pharmacokinetic properties -
Absorption
Absorption of zopiclone is rapid; peak blood concentrations are 30, 60 and 115 ng / ml respectively at doses of 3.75 mg, 7.5 mg and 15 mg and are achieved in 90 to 120 minutes.
Absorption does not undergo sex-related changes and is not altered by food intake.
Distribution
Distribution of the product is rapid starting from the vascular compartment. Plasma protein binding is weak, with binding rates close to 45%, and non-saturable. The risk of drug interactions due to protein binding is very low.
In case of breastfeeding, the kinetics of the drug in breast milk is comparable to that in plasma. The dose that can be ingested through milk is estimated to be around 1% of the dose administered to the mother in 24 hours.
Metabolism
After repeated administration there is no accumulation. Inter-individual variations are negligible.
Zopiclone is extensively metabolised in humans with the formation of two major metabolites, zopiclone N-oxide (pharmacologically active in animals) and N-demethyl zopiclone (pharmacologically inactive in animals). A study in vitro indicated that the main isoenzyme involved in the metabolism of the drug to the two metabolites is cytochrome P450 (CYP) 3A4 and that CYP2C8 is also involved in the formation of N-desmethyl zopiclone. The apparent half-lives of the two metabolites assessed by urinary assay are 4.5 and 7.4 hours, respectively. No enzymatic induction phenomena have been reported in the animal, even at high doses.
Elimination
At recommended dosages, the elimination half-life of unchanged drug is approximately 5 hours.
The low renal clearance of unchanged zopiclone (mean 8.4 ml / min) compared to plasma clearance (232 ml / min) indicates that the drug is eliminated mainly by metabolism.
Elimination occurs for 80% via the urine (in the form of free metabolites) and 16% via the faeces.
Particular groups of patients
In the elderly subject, despite a slight decrease in hepatic metabolism and a lengthening of the half-life (about 7 hours), the various studies carried out did not show plasma accumulation of zopiclone after repeated administration.
In case of renal insufficiency, no accumulation of zopiclone or metabolites in the blood was noted, even after prolonged administration. Zopiclone passes through dialysis membranes; however, hemodialysis is not useful in case of overdose due to the high volume of distribution of the drug (see section 4.9).
In patients with severe hepatic insufficiency (cirrhotic), plasma clearance of zopiclone is decreased by approximately 40% due to the slowing of demethylation: the dosage in these patients will therefore need to be adjusted.
05.3 Preclinical safety data -
Acute and chronic toxicity tests have shown that the drug is well tolerated even after long periods of treatment. The LD50 in the various animal species, per os, is 1150 mg / kg in the mouse, 2310 mg / kg in the rat and has reached even higher values in the cat, dog and monkey (> 4500 mg / kg).
Furthermore, zopiclone did not cause morphological and behavioral abnormalities and was neither fetotoxic nor teratogenic.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Wheat starch, dibasic calcium phosphate, lactose, sodium carboxymethyl starch, magnesium stearate, hypromellose, titanium dioxide.
06.2 Incompatibility "-
At the moment there are no known chemical-physical incompatibilities of zopiclone with other substances.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package -
PVC and aluminum blisters.
Packaging: 20 divisible tablets of 7.5 mg.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Sanofi S.p.A. - Viale L. Bodio 37 / B - 20158 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
Imovane 7.5 mg film-coated tablets: AIC n. 028299016
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
05.03.1993/16.03.2008
10.0 DATE OF REVISION OF THE TEXT -
March 2015
