Imovan - instructions for use, dose, side effects, contraindications

Active substanceZopicloneZopiclone

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Imovan®

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Sanofi-Aventis France France

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Dosage form: & nbspFilm-coated tablets.

Composition:

One tablet contains: active substance: zopiclone - 7.5 mg;

Excipients: wheat starch - 60,000 mg, calcium hydrophosphate dihydrate - 60,000 mg, lactose monohydrate - 31,575 mg, sodium carboxymethyl starch (type A) - 4.950 mg, magnesium stearate - 0.975 mg.

The composition of the shell *: hypromellose - 4.950 mg, titanium dioxide (E 171) - 1,650 mg, macrogol-6000 - 1,650 mg.

* - A ready-made mixture can be used to apply the coating to the Oadry Oy-S-38906 tablet, 8.250 mg (Opaprai OY-S-38906 composition: hypromellose 60%, titanium dioxide (E 171) 20%, macrogol- 6000 - 20%).

Description:

Oval tablets covered with a film shell, white, with a risk on one side.

Pharmacotherapeutic group:Sleeping pills.

ATX: & nbsp

N.05.C.F.01 Zopiclone

Pharmacodynamics:

The drug belongs to the LIST No. 1 of potent BACC substances.

Zopiclone is a hypnotic from the group of cyclopyrrolones. It has the following pharmacological properties: hypnotic, sedative, tranquilizing, anticonvulsant and muscle relaxant.These effects of zopiclone are associated with a specific agonistic effect on the omega receptors (known earlier as benzodiazepine receptors of type I and type II) related to the macromolecular GABA-omega complex that modulates the opening of neuronal ion channels for chlorine.

Zopiclone has the property of reducing the time to sleep and the frequency of nocturnal and early awakenings, increasing the duration of sleep and improving the quality of sleep and awakening. These effects when using the drug in recommended doses are combined with a characteristic electroencephalographic profile, which differs from that recorded when taking benzodiazepines. Polysomnography data showed that in patients with insomnia zopiclone reduces phase I and prolongs II phase of sleep, along with maintaining or prolonging the stage of deep sleep (III and IV) and paradoxical (fast) sleep.

Objective study of withdrawal syndrome with the help of polysomnogram registration did not reveal significant ricochet insomnia after 28 days of taking the drug. Other studies have demonstrated a lack of escape of the hypnotic effect when taking the drug for up to 17 weeks.

Pharmacokinetics:

Absorption

Zopiclone is rapidly absorbed. Food intake does not affect its absorption. The maximum plasma concentrations are achieved within 1.5-2 hours and are approximately 30 and 60 ng / ml after ingestion of 3.75 mg and 7.5 mg, respectively. Absorption of zopiclone does not depend on sex.

Distribution

Linkage to blood plasma proteins is weak (approximately 45%) and unsaturated. The risk of interaction with other drugs at the level of communication with plasma proteins is very low. Zopiclone quickly distributed from the systemic blood flow. The volume of distribution is 91.8-104.6 liters. Zopiclone concentrations in breast milk are similar to those in plasma. According to calculations, the entry of zopiclone into the body of a baby with breast milk will not exceed 1% of the dose taken by the mother within 24 hours.

Metabolism

After repeated administration of the drug cumulation of zopiclone and its metabolites does not occur.

Individual differences are insignificant.

In the human body zopiclone Intensively metabolized to two main metabolites: zopiclon-N-oxide and N-demethyl-isopiclone. In vitro studies have shown that cytochrome P450 (CYP) 3A4 is the main isoenzyme by which zopiclone metabolism occurs and both metabolites are formed.In addition, zoziclone metabolism involves the isoenzyme CYP2C8, which also produces a second metabolite (N-demethyl-isopylone). The half-life of these metabolites according to urinary excretion is approximately 4.5 and 7.4 hours, respectively.

Excretion

At recommended doses, the final half-life of the unchanged zopiclone is approximately 5 hours. Low values of renal clearance of unchanged zopiclone (8.4 ml / min) in comparison with its plasma clearance (232 ml / min) indicate that zopiclone clearance is predominantly metabolic. Zopiclone is excreted in the urine mainly in the form of free metabolites (zopiclon-N-oxide derivatives and N-demethylpsilicon), (approximately 80%) and with fecal masses (approximately 16%).

Individual patient groups

Elderly patients

Despite a slight decrease in the metabolism in the liver and an elongation of the half-life to about 7 hours, even with repeated administration, no cumulation of zopiclone in the blood plasma was detected.

Patients with renal insufficiency

Even after prolonged use, no cumulation of zopiclone or its metabolites was detected. Zopiclone penetrates through the dialysis membrane, however, in the treatment of overdose hemodialysis is ineffective due to the large volume distribution of zopiclone

Patients with hepatic insufficiency

In patients with cirrhosis of the liver, zopiclone clearance decreases by approximately 40%, in accordance with a decrease in the demethylation process. Therefore, these patients require a dose adjustment.

Indications:

Treatment of transient, situational and chronic insomnia in adults (including difficulties with falling asleep, night and early awakenings).

Contraindications:

Hypersensitivity to zopiclone or other components of the drug.
Severe pseudo-paralytic myasthenia gravis (myasthenia gravis).
Severe respiratory failure.
Severe hepatic insufficiency (acute and chronic) (risk of encephalopathy).
Severe sleep apnea syndrome.
Age to 18 years.
Hypersensitivity or intolerance to gluten, since the composition contains wheat starch.
Intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption

Carefully:

In persons with alcohol, drug or drug dependence in history, patients who simultaneously take alcohol (ethanol) or other psychotropic substances or drugs (increased risk of dependence or abuse), in patients with respiratory function disorders.

Pregnancy and lactation:

Insufficient data are available to assess the safety of Imovan® in pregnant women and women during lactation.

The reproductive toxicity of zopiclone was studied in 3 species of animals, and no adverse effect of zopiclone on the fetus was detected.

Since reproductive studies in animals do not always predict a response to a drug during pregnancy in humans, the use of Imovan® in pregnancy is not recommended.

If zopiclone is used during the third trimester of pregnancy or during childbirth, then in connection with the pharmacological effects of the drug in the newborn, you can expect the emergence of hypothermia, muscle hypotension and respiratory depression.

Treatment with Imovan® during pregnancy should be as short as possible and not exceed 4 weeks, including a period of gradual dose reduction. In addition, it should be remembered that in children born to mothers,long-term sedatives / hypnotics on late pregnancy, it is possible to develop physical dependence, and they have a risk of developing a "cancellation" syndrome in the postnatal period.

If Imovan® is used in women of childbearing age, they should be warned that in the case of pregnancy planning or suspected pregnancy, they should consult their doctor in order to stop taking the drug.

Although the concentration of zopiclone in breast milk is very low, breast-feeding women should not take imovan®

Dosing and Administration:

The drug is intended only for oral administration.

Treatment should be as short as possible and not exceed four weeks, including a period of gradual dose reduction. Prolongation of treatment periods beyond the maximum allowable is only performed after a second assessment of the patient's condition. Treatment should always begin with the lowest effective dose and never exceed the maximum dose. The drug is taken immediately before going to sleep at night.

Duration of treatment

Transient insomnia: 2 to 5 days (for example, caused by a change of place during a trip).

Situational insomnia: 2 to 3 weeks.

Chronic insomnia: prolonged treatment is prescribed after consultation with a specialist.

Recommended doses

For adults (younger than 65 years): the recommended daily dose is 7.5 mg.

For patients of advanced age (over 65 years), patients with impaired liver function or with respiratory failure of moderate severity: the recommended The daily dose is 3.75 mg. The daily dose can be further increased to 7.5 mg.

For patients with renal insufficiency: despite the fact that with renal failure, there is no accumulation of the drug or its metabolites, treatment of patients with renal failure should begin with a dose of 3.75 mg per day.

In all cases, the daily dose of Imovan® should not exceed 7.5 mg

Side effects:

The following side effects are given using the following gradations of the incidence of side effects: very often ≥10%; often ≥1% and <10%; infrequently ≥0.1% and <1%; rarely ≥0.01% and <0.1%; very rarely <0.01%; unknown frequency (according to available data it is impossible to determine the incidence of side effect).

Immune system disorders

Very rarely: angioedema, anaphylactic reactions.

Disorders of the psyche

Infrequently: nightmares, agitation. Rarely: confusion, violations (decrease) of libido, irritability, aggression, hallucinations. Unknown frequency: anxiety, delirium, anger, inappropriate behavior (possibly combined with amnesia) and somnambulism (walking in a dream) (see "Special instructions"), dependence, withdrawal syndrome (see below "Physical psychic dependence"), depressed mood, depressed state.

Disturbances from the nervous system

Often: dysgeusia (bitter taste in the mouth), residual drowsiness after awakening. Infrequent: dizziness, headache. Rarely: anterograde amnesia. Unknown frequency: ataxia, paresthesia.

Disturbances on the part of the organ of sight

Unknown frequency: diplopia.

Disturbances from the respiratory system, chest and mediastinal organs

Rarely: dyspnea (shortening of breath, subjective difficulty or respiratory failure) (see section "Special instructions"). Unknown frequency: respiratory depression (see section "Special instructions").

Disorders from the gastrointestinal tract

Often: dryness of the oral mucosa. Infrequently: nausea. Unknown frequency: indigestion.

Disturbances from the liver and bile ducts

Very rarely: increased activity of "hepatic" transaminases and / or alkaline phosphatase concentrations in the blood (from mild to moderate).

Disturbances from the skin and subcutaneous tissues

Often: rash, itching.

Disturbances from musculoskeletal and connective tissue

Unknown frequency: muscle weakness.

General disorders and disorders at the site of administration

Unknown frequency: a feeling of fatigue.

Injuries, intoxications, complications of manipulation

Rarely: falls (mainly elderly patients)

Physical and mental dependence (even when used in therapeutic doses)

At the termination of treatment there was a syndrome of "cancellation" (see also "Special instructions"). His symptoms are different and can manifest as "ricochet" insomnia, muscle pain, anxiety, tremor, excessive sweating, agitation, confusion, headache, palpitation, tachycardia, delirium, nightmares, irritability.In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis (pathologically increased perception of ordinary sounds), numbness and tingling in the extremities, hypersensitivity to light, noise, tactile hyperesthesia, hallucinations. In very rare cases, convulsive seizures may develop.

Overdose:

Signs and Symptoms Overdose usually manifests itself in the form of symptoms of varying degrees of depression of the central nervous system from drowsiness to coma, depending on the amount of the drug taken. In mild cases, symptoms are expressed in drowsiness, confusion, lethargy. In more serious cases, it is possible to develop ataxia, muscle hypotension, lower blood pressure, methemoglobinemia, respiratory depression and coma. Overdosing does not pose a threat to life unless it is combined with the administration of other agents that depress the central nervous system (including ethanol). Other risk factors, such as concomitant disease and a weakened patient, may exacerbate symptoms and even (very rarely) cause death.

Treatment If necessary, symptomatic and supportive therapy in a hospital is recommended. Particular attention should be paid to the functions of the respiratory and cardiovascular systems. Gastric lavage or the use of activated carbon is effective only if performed shortly after taking the drug.

Hemodialysis is of low significance because of the large volume distribution of zopiclone. As an antidote can be applied flumazenil.

Interaction:

With ethanol

Ethanol can enhance the sedative effect of zopiclone. It is not recommended simultaneous reception of zopiclone and ethanol.

With drugs depressing the central nervous system: neuroleptics, barbiturate, hypnotic drugs, tranquilizers, sedatives, antidepressants with a sedative effect (amitriptyline, doxepin, mianserin, mirtazapine, Trimipramine), narcotic analgesic and antitussive drugs (buprenorphine addition, interaction with buprenorphine see below), antiepileptic drugs, anesthetics, gistamtovyh blockers H1-receptors with a sedative effect, hypotensive drugs central action, baclofen, thalidomide, pizotifenom.

When these drugs are combined with zopiclone, the oppressive effect on the central nervous system, including respiratory depression (especially with the use of morphine derivatives and barbiturates) can be intensified.

With the simultaneous use of narcotic analgesics, euphoria can increase, which leads to an increase in mental dependence.

With trimipramine

In addition to the above, zopiclone reduces the concentration of trimipramine in the plasma and its effect.

With buprenorphine

Increased risk of respiratory depression, up to a lethal outcome.

With inhibitors of the isoenzyme SUR FOR 4, such as erythromycin, clarithromycin, ketoconazole, itraconazole and ritonavir.

As zopiclone is metabolized by the CYP3A4 isoenzyme, inhibitors of the CYP3A4 isoenzyme can increase the plasma concentrations of zopiclone. With their simultaneous administration, a dose reduction of zopiclone may be required.

The effect of erythromycin on the pharmacokinetics of zopiclone was studied in 10 healthy volunteers. The area under the pharmacokinetic curve "concentration-time" of zopiclone increased by 80% in the presence of erythromycin.

With inducers of the isoenzyme CYP3A4: such as rifampicin, carbamazepine, phenobarbital, phenytoin, preparations of St. John's wort perfumed.

As zopiclone is metabolized by the CYP3A4 isoenzyme, then the inducers of the CYP3A4 isoenzyme may reduce the plasma concentrations of zopiclone. With their simultaneous administration, an increase in the dose of zopiclone may be required.

Special instructions:

The use of sedative (hypnotics) drugs, such as zopiclone, may lead to the development of physical and mental dependence or abuse of the drug.

The risk of dependence or abuse increases:

with increasing dose and prolonged treatment;
with alcohol abuse (ethanol) and / or other medicinal products;
when used in conjunction with alcohol (ethanol) or other psychotropic substances or preparations.

In the event of physical dependence, a sharp cessation of treatment can cause the development of the "withdrawal" syndrome (see the "Side effect" section).

"Ricochet" insomnia

In response to the cancellation of the treatment with hypnotic drugs, a temporary syndrome may develop, when the symptoms that lead to the need for the appointment of sedative (hypnotics) drugs arise with increased strength.

Since the risk of developing this phenomenon is higher in the case of a sharp discontinuation of zopiclone, especially after prolonged treatment, it is necessary to reduce the dose of the drug gradually and inform the patient about the possible occurrence and measures to prevent the development of "ricochet" insomnia.

Slipping Effect

With the use of other sleeping pills, some escape of their effect may develop. However, when using Imovan® for no more than 4 weeks, the effect of the drug was not eluded.

Amnesia

Anterograde amnesia can occur, especially with interruption of sleep or after a considerable time between taking the drug and going to sleep. To reduce the risk of anterograde amnesia:

take the pill just before going to sleep at night;
ensure a sufficient duration of night sleep.

Depression

The drug is not indicated for the treatment of depression, and can even mask its symptoms.

Use in children

A safe and effective dose of zopiclone in children and adolescents under the age of 18 years is not established.

Other psychic and paradoxical reactions

As is known, with the use of sedative / hypnotic drugs, such as zopiclone, there are paradoxical reactions (see the section "Side effects"), such as anxiety, agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, inadequate behavior and other side effects of behavior. If they occur, the reception of zopiclone should be discontinued. More likely the development of these reactions in elderly patients.

Sleepwalking and related behavior

Somnambulism and related behavior: sleeping and other related behavior, for example, "driving in a dream", cooking and eating food, talking on the phone with amnesia about what happened, was described in patients who used zopiclone and not completely awake.

The use of alcohol (ethanol) and other drugs that depress the central nervous system, together with zopiclone, seems to increase the risk of this disorder, similar to how it occurs when zopiclone is used at doses exceeding the maximum recommended dose. In the development of such behavioral disorders, it is strongly recommended to discontinue zopiclone therapy.

Patients with impaired respiratory function

Since hypnotic drugs have the ability to inhibit the activity of the respiratory center of the brain, caution should be exercised when using zopiclone in patients with impaired respiratory function (see section "Side effect").

Effect on the ability to drive transp. cf. and fur:

Because of their pharmacological properties and effects on the central nervous system zopiclone can have an adverse effect on the ability to drive and engage in other potentially hazardous activities. This effect increases with the simultaneous reception of alcoholic beverages, so during the treatment period it is necessary to refrain from driving and practicing other potentially hazardous activities.

Form release / dosage:

Tablets, film-coated 7.5 mg

Packaging:

For 10 tablets in a blister of PVC / aluminum foil. Two blisters together with instructions for use are placed in a cardboard box.

For 20 tablets in a blister of PVC / aluminum foil. The blister, along with the instructions for use, are placed in a cardboard box.

Storage conditions:

In a dry place, at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

List 1 of the strong BACC.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015904 / 01

Date of registration:11.08.2009

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp04.09.2015

Illustrated instructions

Instructions

Imovan® (Imovane®)