Imovan

Imovane is a sedative-hypnotic drug.

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Indications Imovana

Indicated for severe forms of sleep disorders: in case of temporary or situational insomnia.

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Release form

Available in tablets, on a blister of 20 pieces. One package contains 1 blister plate.

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Pharmacodynamics

Zopiclone belongs to the cyclopyrrolone category and has an affinity for the pharmaceutical group of benzodiazepines. The pharmacodynamics of the substance are similar in their properties to the effects of other compounds of this group: the drug acts as a tranquilizer, muscle relaxant, hypnotic and sedative, and also an anticonvulsant and amnestic (for memory disorders).

These properties are due to its action (specific receptor agonist), which extends to the macromolecular complex of GABA-ω receptors within the central nervous system (these are BZ1, as well as BZ2, which modulate the process of opening the channels necessary for the passage of Cl ions).

According to established data, it is known that the use of zopiclone in humans prolongs sleep, and also improves its quality and reduces the frequency of premature or night awakenings. Such an effect is due to characteristic electroencephalographic properties that differ from the functions inherent in benzodiazepines.

Polysomnographic testing has shown that the active substance of the drug shortens the duration of stage I and prolongs stage II sleep. In addition, it maintains or prolongs the stages of so-called "deep sleep" (stages III and IV) and promotes the stages of paradoxical sleep or REM.

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Pharmacokinetics

The absorption of the active component is very fast: its plasma peak is reached after 1.5-2 hours, and it is equal to 30, 60, and 115 ng / ml when administered, respectively, 3.75, 7.5, and 15 mg. The level of bioavailability is approximately 80%. The absorption rates are not affected by the frequency and time of use, as well as the gender of the person taking the drug.

The distribution of the substance occurs through the vessels and is very fast. Synthesis with plasma protein is quite low (approximately 45%) and also unsaturated. Therefore, the risk of drug interactions due to substitution in the area of protein synthesis is minimal.

The decrease in plasma parameters in the dosage range of 3.75-15 mg does not depend on the dose itself. The half-life is approximately 5 hours.

Benzodiazepines and similar elements pass through the placenta and the BBB, and can also be excreted in breast milk. There are similarities in the pharmacokinetics of the substance in plasma and breast milk. In percentage terms, the portion of the dosage that is consumed by the child during breastfeeding is equal to 0.2% of the substance consumed by the mother in 24 hours.

Extensive hepatic metabolism of the substance is also carried out. The two main breakdown products are the N-oxide (pharmacoactive in animals) and the N-demethylated derivative (inactive in animals). The apparent half-lives of these substances, which were detected during urinary excretion, are approximately 4.5 and 7.5 hours, respectively. This observation is fully consistent with the fact that repeated administration of 15 mg over 2 weeks does not result in significant accumulation of metabolites. No increase in enzyme activity was observed in animal testing, even with high doses.

The low renal clearance of unchanged drug (mean 8.4 ml/min) compared to plasma clearance (232 ml/min) indicates that zopiclone is excreted primarily as breakdown products. Approximately 80% of the compound is excreted via the kidneys as free breakdown products (N-oxide with N-demethylated derivative) and approximately 16% is excreted in the faeces.

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Dosing and administration

The medicine is intended for oral administration. Therapy should be started with the lowest effective dosage, and the maximum permissible dose should not be exceeded. Also, you should not take pills before bedtime.

A daily dose of 3.75 mg is prescribed only to people in a special risk category (renal failure, chronic pulmonary failure, liver dysfunction) or elderly patients (over 65 years old; in this case, increasing the dose to 7.5 mg is allowed only if absolutely necessary). The standard daily dose for adults under 65 is 7.5 mg. Exceeding this value is prohibited.

It is recommended that the duration of the therapeutic course be short. The maximum period is 1 month, including the period of gradual withdrawal of the drug.

Recommended duration of taking tablets in different situations:

• for situational insomnia – 2-5 days (for example, during travel);
• for transient insomnia – for 2-3 weeks.

In some cases, it is necessary to extend the period of therapy. In such circumstances, it is necessary to carefully weigh and evaluate the patient's condition.

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Use Imovana during pregnancy

Animal testing has shown that zopiclone has no teratogenic effects. At present, there is insufficient information regarding the effects of this drug on the body of a pregnant woman and the condition of the fetus. When compared with the effects of similar substances (benzodiazepines):

• a decrease in motor activity is possible, as well as a change in the heart rate of the fetus (in the case of taking the drug in large doses in the 2nd or 3rd trimester);
• In case of using benzodiazepines in late pregnancy, even in low doses, absorption symptoms (sucking disorder and axial hypotonia) were observed in babies after birth, which resulted in insufficient weight gain. Such manifestations are reversible, but can last 1-3 weeks (the period depends on the half-life of the benzodiazepine). In case of using high doses in newborns, reversible suppression of the respiratory process or hypothermia and apnea may develop. There is also a risk of developing withdrawal syndrome in the baby (this can occur even in the absence of absorption symptoms). This syndrome manifests itself in babies in the following form: a short period of time after birth, tremors, severe excitability, and a state of psychomotor agitation occur. The time of development of these symptoms depends on the half-life of the drug.

Given this information, the use of the drug during pregnancy is not recommended, regardless of its duration.

If the use of drugs during pregnancy is necessary, it is necessary to prescribe it in small doses, and in addition, monitor the fetus during treatment to prevent the development of the above-mentioned reactions.

It is also prohibited to prescribe Imovan during the lactation period.

Contraindications

The drug is contraindicated in the following cases:

• in case of intolerance to zopiclone or any of the additional components of the drug;
• in case of respiratory failure;
• in case of sleep apnea syndrome developing during sleep;
• in case of liver failure (acute, severe or chronic stage of the pathology), since in this case there is a risk of developing encephalopathy;
• for myasthenia;
• in children, since this drug has not been used for the designated category of patients;
• in case of an allergic reaction to wheat food (except for cases of wheat intolerance due to celiac disease).

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Side effects Imovana

Adverse effects depend on the individual characteristics of the person, as well as the dosage of the drug. The main side effect after taking the drug, observed most often, is bitterness in the mouth. Among the mental and neurological manifestations:

• anterograde form of amnesia, which can develop even when taking drugs in therapeutic doses (the likelihood of its occurrence increases in accordance with the increase in dose);
• changes in consciousness, behavioral disturbances, feelings of aggression, irritability, restless or delusional behavior, development of somnambulism;
• after completion of therapy, psychological and physical dependence may develop (even if recommended doses are used) with signs of withdrawal syndrome or insomnia;
• headaches, feeling of euphoria or intoxication, development of paresthesia, tremor, muscle spasms, coordination or speech disorders, dizziness, appearance of depressive mood; ataxia is rare;
• development of hallucinations or confusion, the appearance of nightmares during sleep, the occurrence of insomnia, a feeling of tension, an excited state, attention may deteriorate or drowsiness may be observed (especially concerns the elderly);
• sexual desire disorder.

Other side effects include:

• cardiovascular system organs: heart palpitations;
• skin: itching, rashes (may be signs of hypersensitivity), increased sweating, development of erythema multiforme, as well as Lyell's or Stevens-Johnson syndromes. If the patient has such symptoms, the use of the drug should be stopped immediately;
• systemic manifestations: asthenia, muscle hypotonia, feeling of fatigue, profuse sweating, chills;
• immune system organs: Quincke's edema, urticaria, anaphylactic reactions;
• visual organs: lazy eye or diplopia;
• respiratory organs: development of dyspnea;
• gastrointestinal tract: bad breath, white coating on the tongue, vomiting, constipation, dyspeptic symptoms, nausea, diarrhea, dry mouth, increased appetite or anorexia;
• changes in laboratory test values: occasionally the transaminase or alkaline phosphatase levels increase, as a result of which a clinical picture of liver dysfunction sometimes occurs;
• metabolic processes: weight loss;
• Muscles and skeleton: weakness in the muscles, as well as a feeling of heaviness in the limbs.

Older people often suffer from vomiting, feelings of restlessness or agitation, heart palpitations, tremors, as well as ptyalism and anorexia.

Post-marketing testing has shown that reactions such as behavioral disorder associated with the development of amnesia and anger may occur.

After completion of treatment, withdrawal syndrome may develop, which manifests itself in muscle pain, rebound insomnia, tremor, a feeling of irritability, anxiety or strong agitation. In addition, increased sweating, palpitations, headaches, tachycardia, confusion, nightmares during sleep and delirium. In severe reactions, allopsychic depersonalization, simple depersonalization, and hyperacusis may develop; hallucinations, a tingling sensation with numbness in the extremities, intolerance to noise, light, and physical contact also appear.

Occasionally, patients may develop seizures.

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Overdose

An overdose can be life-threatening, especially if the drug is taken in large doses in combination with several CNS depressants (including alcohol).

If the recommended dose is exceeded, the CNS functions may be suppressed, causing drowsiness, which may reach a state of coma (depending on the size of the dose taken). With weak overdoses, lethargy or confusion of consciousness occurs.

More severe cases were accompanied by the development of muscle hypotonia, ataxia, methemoglobinemia, respiratory depression, and decreased blood pressure. In some cases, it resulted in death.

If an overdose after taking the tablets orally occurs within 1 hour, induction of vomiting is recommended, in other cases gastric lavage is required. Then it will be useful to give the patient activated carbon - to reduce the absorption of the drug.

It is necessary to carefully monitor the functioning of the respiratory and cardiac organs (this is carried out in a department specialized for such procedures).

During the therapy, hemodialysis procedure will not be advisable, since the active component of Imovana has a high distribution volume index.

To diagnose or treat accidental/intentional overdose of benzodiazepine, flumazenil may be administered to the patient. This component has an effect opposite to benzodiazepines, so it can provoke the development of neurological disorders (feelings of anxiety or excitement, emotional instability, and seizures). This applies especially to epileptics.

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Interactions with other drugs

Alcoholic beverages enhance the sedative effect of benzodiazepines and related components. Due to the weakening of concentration with such a combination, it is not recommended to work with various mechanisms or drive a car.

It is recommended not to combine the medicine with alcoholic beverages or drugs containing alcohol.

Combination with rifampicin reduces the effectiveness and plasma level of zopiclone, as it increases its hepatic metabolism. For this reason, the above substances should be used together only under constant clinical observation of the patient. If necessary, another sleeping pill may be prescribed.

Other drugs that depress the function of the central nervous system: morphine derivatives (such as antitussives, painkillers, and drugs used in substitution treatment during the period of elimination of drug addiction (in addition to buprenorphine)), barbiturates with neuroleptics, tranquilizers, other hypnotics, anticonvulsants, hypnotic antidepressants, as well as anesthetics, hypotensive drugs (with central action), thalidomide with baclofen and pizotifen, and in addition antihistamines (H1) drugs. All of the above substances in combination with Imovane enhance the depressant effect on the function of the central nervous system.

At the same time, the simultaneous use with morphine derivatives, as well as barbiturates, increases the likelihood of suppression of respiratory function (when taking medications in excessive doses, this combination can provoke the death of the patient).

Opioid analgesics can increase the feeling of euphoria, which can cause a person to develop a stronger psychological dependence on the substances they take.

The process of zopiclone metabolism is carried out with the participation of hemoprotein P450 (CYP) 3A4, as a result of which, as a result of combination with inhibitors of the CYP3A4 element, the substance levels in plasma can increase. Use together with inducers of the CYP3A4 component, on the contrary, reduces the zopiclone level in plasma.

When combined with buprenorphine, which is used in substitution treatment for drug addiction, the likelihood of respiratory depression increases, which can ultimately lead to death. The risks and effectiveness of this drug combination must be carefully assessed. The patient must be warned to strictly adhere to the dosages prescribed by the doctor.

Concomitant use with clozapine increases the risk of the patient developing collapse, which is accompanied by cardiac or respiratory arrest.

The combination of zopiclone with erythromycin, clarithromycin, nelfinavir or telithromycin, as well as with voriconazole, ritonavir, itraconazole, and ketoconazole slightly enhances the sedative properties of the active component of Imovane.

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Storage conditions

The medicine is stored in a place inaccessible to small children. The temperature values cannot exceed 25°C.

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Shelf life

Imovan is approved for use for 3 years from the date of release of the drug.

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