Ivadal - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 90.4 mg, microcrystalline cellulose 12.1 mg, hypromellose 2.5 mg, carboxymethyl starch sodium (sodium amylopectin glycolate) (type A) 3.8 mg, magnesium stearate 1.2 mg.

Shell

Hypromellose - 4.32 mg, titanium dioxide (E 171) - 1.26 mg, macrogol 400 - 0.42 mg.

Description:

Oblong tablets covered with white or almost white shell, with a fault line and engraving SN 10 on one side.

Pharmacotherapeutic group:Sleeping pills. Psychotropic substance listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

ATX: & nbsp

N.05.C.F.02 Zolpidem

Pharmacodynamics:

Zolpidem is a hypnotic from the group of imidazopyridines, similar in pharmacological activity to benzodiazepines, which has effects qualitatively similar to the effects of other drugs in this group: myorelaxing, anxiolytic, sedative, hypnotic, anticonvulsant, amnestic. The development of these effects is associated with a specific agonistic effect on the central omega receptors (benzodiazepine receptors I and II type), related to macromolecular GABA-receptor complexes, which causes the opening of neuronal anion channels for chlorine.

Zolpidem interacts selectively with central type I benzodiazepine receptors (omega-1 receptor subtype). Therefore, the sedative effect of the drug is observed at lower doses than the doses necessary for the development of myorelaxing, anticonvulsant and anxiolytic effects.

In humans: zolpidem shortens the period of falling asleep and reduces the number of awakenings, increases the overall duration and improves the quality of sleep. These effects are associated with a characteristic EEG profile of the drug, which differs from that of benzodiazepines. Zolpidem prolongs the II stage of sleep and deep sleep (III and IV stages). In recommended doses zolpidem does not affect the total duration of paradoxical (fast) sleep.

Pharmacokinetics:

Absorption

After oral administration, the bioavailability of zolpidem is 70%, the maximum plasma concentration of the drug is reached after 0.5 -3 hours after administration.

Distribution

In the therapeutic dosage range, the pharmacokinetics of zolpidem is linear. The connection with plasma proteins is about 92%. The volume of distribution in adults is 0.54 ± 0.02 l / kg.

Metabolism and excretion

Zolpidem is excreted in the form of inactive metabolites (metabolism occurs in the liver), mainly by the kidneys (about 60%) and through the intestine (about 40%). Zolpidem does not induce liver enzymes.

The half-life is about 2.4 h (0.7-3.5 h).

Pharmacokinetics in specific patient groups

In elderly patients, the hepatic clearance of the drug decreases. The maximum concentration (C_max) increases by approximately 50% with an insignificant increase in the half-life (on average up to 3 h). The volume of distribution is reduced to 0.34 ± 0.05 l / kg.

In patients with renal diseaseinsufficiency (regardless of receiving or not receiving hemodialysis procedures) there is a moderate decrease in the clearance of the drug. Other pharmacokinetic parameters do not change. Zolpidem is not excreted by hemodialysis and other types of dialysis.

In patients with insufficient liver function, bioavailability increases, clearance decreases and the half-life of zolpidem increases (up to about 10 hours).

Indications:

Treatment of transient and situational insomnia in adults with clinically significant (severe) sleep disturbance, including difficulties with falling asleep.

Contraindications:

Hypersensitivity to zolpidem or drug auxiliaries.
Acute and / or severe respiratory failure.
Severe acute or chronic hepatic insufficiency (more than 9 on the Child-Pugh scale) (risk of encephalopathy).
Sleep apnea syndrome.
Pseudo-paralytic myasthenia gravis (myasthenia gravis).
Age under 18 years (no clinical data).
Congenital galactosemia (galactose intolerance), glucose malabsorption syndrome or galactose, lactase deficiency.

Carefully:

With respiratory insufficiency (since hypnotics have the ability to depress respiration, caution should be used if Ivald® is used in patients with impaired breathing) (see "Side-Effects" section).
If the patient has symptoms of depression (see section "Special instructions").
In elderly patients (see sections "Special instructions", "Method of administration and dose").
In case of mild (5-6 points on the Child-Pugh scale) and moderately expressed (7-9 points on the Child-Pugh scale) of liver failure (see recommendations on the dosage regimen in the section "Method of administration and dose"),
In patients with alcoholism, drug addiction and other addictions (increased risk of dependence on zolpidem).

Pregnancy and lactation:

Pregnancy

Due to the lack of data on the use of the drug in pregnant women, it is preferable to avoid the use of Ivald® during pregnancy, although studies in animals have not revealed teratogenic effects in zolpidem.

When using the drug in women of childbearing age, they should be warned about the needconsultation with a doctor to stop taking the drug in case of pregnancy planning or with a suspicion of pregnancy.

In case of need of application of a preparation during pregnancy it is necessary to take into account a parity of expected benefit for mother and possible adverse influence on a fetus or the newborn.

When taking high doses of zolpidem in the second and third trimester of pregnancy, it is possible to reduce the mobility of the fetus and change its heart rate.

If zolpidem is taken at the end of pregnancy or during labor, it is possible to enter the fetus and, based on the pharmacodynamic effects of zolpidem, we can expect the development of a newborn hypothermia, a decrease in muscle tone, moderate respiratory depression. There have been reports of severe respiratory depression in the newborn when the mother receives zolpidem in the late pregnancy in combination with other drugs that depress the central nervous system (CNS).

In addition, children born to women who took long-term sedatives / hypnotics at the end of pregnancy may develop physical dependence, and there is a risk of developing a "cancellation" syndrome in the postnatal period.The time of onset of such events depends on the rate of excretion from the body of the newborn sedative / hypnotic drug that entered it before delivery from the mother through the placenta.

Breastfeeding period

Small amounts of zolpidem enter the breast milk. Therefore, it is not recommended to take zolpidem in the period of breastfeeding.

Dosing and Administration:

The drug is intended for oral administration.

Doses

The recommended adult dose is 10 mg per day. It should take a minimum effective dose and do not exceed a dose of 10 mg.

The drug Iwadal® is taken immediately before going to bed or in bed, since its action begins very quickly. The drug Ivadal® should be taken once and do not repeat the reception during the night.

Children

Safety and efficacy of zolpidem in children and adolescents under 18 years are not established. therefore zolpidem Do not use in children and adolescents under 18 years.

Elderly patients

Since elderly patients or weakened patients may be particularly sensitive to the effects of zolpidem, in such patients it is recommended to start treatment with a dose of 5 mg.The daily dose should never exceed 10 mg.

Patients with hepatic impairment

In severe hepatic insufficiency, the use of the drug is contraindicated.

Since patients with mild and moderate impairment of liver function reduce clearance and slow metabolism of zolpidem, treatment should begin with a dose of 5 mg, extra care should be taken in such elderly patients. In adults under the age of 65, the dose may be increased to 10 mg only if the clinical efficacy is not sufficient and the drug is well tolerated.

Duration of treatment

Long-term use of zolpidem, as well as other sleeping pills, is not recommended.

The duration of treatment should be as short as possible: from several days to four weeks, including the period of dose reduction. In some cases, prolongation of treatment beyond the maximum possible time may be required, but only after a second assessment of the patient's condition.

The following treatment duration is recommended:

2-5 days with transient insomnia (for example, while traveling);
2-3 weeks with situational insomnia (for example, due to the psychotraumatic situation).

Abolition of the drug

Very short periods of treatment do not require the gradual withdrawal of the drug.

In the case of prolonged use of the drug to reduce the possibility of development of ricochet insomnia, the abolition of zolpidem should be carried out gradually (first a reduction in daily doses and then the withdrawal of the drug).

Side effects:

The following undesirable effects are presented in accordance with the following gradations of their frequency: very often (≥10%); often (≥1% - <10%); infrequently (≥0.1% - <1%); rarely (≥0.01% - <0.1%); very rarely (<0.01%) (including individual cases); frequency is unknown (based on available data, the establishment of frequency of occurrence is not possible).

Adverse effects, especially from the central nervous system, depend on the dose and individual response of the patient. They are more often observed in elderly patients, and their severity should theoretically be less when taking the drug immediately before going to bed or already in bed (see section "Method of administration and dose").

Disturbances from the nervous system

Often: drowsiness, headache, dizziness, increased insomnia; anterograde amnesia (the effects of amnesia may be associated with behavioral disorders), which can also be observed with therapeutic doses of the drug, although the risk of its development increases in proportion to the dose.

Frequency unknown: lowering the level of consciousness.

Disorders of the psyche

Often: hallucinations, agitation, nightmares.

Infrequently: confusion, irritability.

Frequency unknown: anxiety, aggressiveness, delirium, anger, psychosis, behavioral deviations from the norm, somnambulism (walking in a dream, etc.) (see "Special instructions", subsection "Somnambulism and associated complex behavior"), a relationship that can develop even with the use of therapeutic doses of the drug (after the cessation of treatment can develop a syndrome of "withdrawal" or "bounce" effects), violations of libido (sexual desire), depression (see section "Special instructions").

Most of these side effects from the psyche relate to paradoxical reactions (see section "Special instructions").

General disorders

Frequency unknown: gait disturbance, addiction to the drug, falls (mainly in elderly patients and failure to comply with the prescribed recommendations for admission).

Disturbances on the part of the organ of sight

Infrequently: diplopia.

Disturbances from the respiratory system, chest and mediastinal organs

Frequency unknown: respiratory depression (see the sections "With caution" and "Special instructions").

Disorders from the gastrointestinal tract

Often: diarrhea, nausea, vomiting, abdominal pain.

Disturbances from the skin and subcutaneous tissues

Frequency unknown: rash, itching, hives, hyperhidrosis (increased sweating).

Immune system disorders

Frequency unknown: angioedema.

Disturbances from the liver and bile ducts

Frequency unknown: an increase in the activity of "hepatic" enzymes in the blood.

Disturbances from musculoskeletal and connective tissue

Often: backache.

Frequency unknown: muscle weakness.

Infectious and parasitic diseases

Often: upper respiratory tract infections, lower respiratory tract infections.

Overdose:

Manifestations

In case of an overdose of one zolpidem or zolpidem in combination with other substances depressing the central nervous system (including ethanol), reported the development of mental disorders up to coma and more severe symptoms, including death.

Treatment

If, after taking an excessive dose, less than one hour has passed and the patient is conscious, vomiting should be attempted. If it is not possible to induce vomiting, or in the case of an unconscious patient, gastric lavage is recommended. In the event that after an accidental or deliberate administration of an excessive dose of the drug, more than one hour has elapsed, the patient should be admitted or injected through a probe (unconscious) Activated carbon to reduce the absorption of zolpidem. In case of an overdose, symptomatic therapy and treatment aimed at maintaining the basic functions of the body, in particular the functions of respiration and the cardiovascular system, are performed. In case of severe overdose, the administration of flumazenil (a benzodiazepine receptor antagonist) should be considered, but administration of flumazenil may cause neurologic disorders (seizures), especially in patients with epilepsy.

Zolpidem is not excreted by hemodialysis and other types of dialysis.

Interaction:

With ethanol

Simultaneous reception of zolpidem and ethanol is not recommended. Ethanol potentiates the sedative effect of the drug, which disrupts the ability of the patient to drive vehicles and work with mechanisms. Avoid simultaneous use with zolpidem of alcoholic beverages and medicines containing ethanol.

With drugs, depressing the central nervous system (neuroleptics, barbiturates, other hypnotics, anxiolytics / sedatives, antidepressants, morphine derivatives (narcotic analgesics; antitussives); antiepileptics, agents for general anesthesia; antihistamine with a sedative effect; antihypertensives central action; baclofen; thalidomide; pisotifen).

While the use of zolpidem may increase inhibitory action on the central nervous system and, accordingly, increase the risk of respiratory depression which can be fatal overdose (particularly when combined with morphine derivatives, barbiturates), drowsiness and psychomotor development disorders including reduced ability to drive vehicles.

In the case of simultaneous use of narcotic analgesics, there may also be an increase in euphoria, leading to an increase in psychological dependence.

With inhibitors or inductors of cytochrome P450 isoenzymes

Substances that inhibit cytochrome P450 isoenzymes can enhance the action of certain hypnotic sleepworms like zolpidem. Zolpidem is metabolized with the participation of several cytochrome P450 isoenzymes, the main one being the isoenzyme CYP3A4. In addition to this isoenzyme, the isoenzyme CYP1A2 is involved in the metabolism of zolpidem.

The pharmacodynamic effect of zolpidem decreases with its simultaneous use with rifampicin (inducer of the isoenzyme CYP3A4). With the combined use of zolpidem and itraconazole (an inhibitor of the isoenzyme CYP3A4), the pharmacokinetics and pharmacodynamics of zolpidem changed insignificantly.

The clinical significance of this data is not known. Simultaneous reception of zolpidem and a strong inhibitor of the isoenzyme CYP3A4 ketoconazole (200 mg twice daily) prolonged the half-life, increased the AUC (area under the pharmacokinetic curve "concentration-time") and decreased clearance, compared with zolpidem and placebo.The AUC value for zolpidem when taken concomitantly with ketoconazole increased 1.83 times, in comparison with monotherapy with zolpidem. Usually, this combination of zolpidem with ketoconazole does not require correction of the dosage regimen of zolpidem, but patients should be warned that the sedative effect of zolpidem may worsen when taking zolpidem simultaneously with ketoconazole.

With buprenorphine

Increased risk of respiratory depression, even fatal. The benefit / risk ratio of such a combination requires careful evaluation. The patient should be warned that strict adherence to the doctor's recommendations for the dosing regimen is necessary.

With warfarin, digoxin, ranitidine or cimetidine

Absence of significant pharmacokinetic interaction.

With fluvoxamine

Fluvoxamine is a potent inhibitor of the CYP1A2 isoenzyme and a moderate or weak inhibitor of the CYP2C9 and CYP3A4 isoenzymes. With the simultaneous use of fluvoxamine and zolpidem, the concentration of zolpidem in the blood may increase, so the purpose of this combination is not recommended.

With ciprofloxacin

Ciprofloxacin is a moderate inhibitor of the isoenzymes CYP1A2 and CYP3A4. With the simultaneous use of ciprofloxacin and zolpidem, the concentration of zolpidem in the blood can increase, so the appointment of this combination is not recommended.

Special instructions:

In all cases, before the use of a hypnotic drug, it is necessary, whenever possible, to establish the causes of sleep disorders and to correct (including, medicamentous) the underlying causes.

Preservation of insomnia within 7-14 days of treatment indicates the presence of primary mental disorders and / or disorders of the nervous system. Therefore, to assess these disorders, it is necessary to regularly assess the patient's condition.

Patients should always be warned about the recommended duration of treatment, which is determined by the type of insomnia (see section "Method of administration and dose").

Psychotic diseases

Sleeping pills, such as zolpidem, are not recommended as a primary treatment for psychotic illnesses.

Depression

The use of zolpidem, as well as other drugs with a sedative / hypnotic effect,In patients with symptoms of depression, special care is required. Such patients should be treated for depression, but should not be prescribed to them zolpidem in monotherapy. The manifestation of pre-existing latent depression is possible during the use of zolpidem. Since such patients may have suicidal tendencies, they should be given the minimum amount of zolpidem necessary to avoid the possibility of his deliberate overdose by the patient.

Due to the fact that insomnia can be a symptom of depression, in the case of insomnia, a reassessment of the patient's condition should be conducted in order to identify possible depression.

Amnesia

Sedatives / hypnotics, such as zolpidem, can cause anterograde amnesia, which is most often observed a few hours after taking the drug, and therefore, to reduce the risk of its development, patients should have the conditions for a continuous 7-8-hour sleep.

Other psychic and "paradoxical" reactions

As is known, with the use of sedative / hypnotic drugs like zolpidem, other psychic and "paradoxical" reactions may occur,such as anxiety, increased insomnia, agitation, irritability, aggressiveness, delirium, anger, nightmares, hallucinations, psychosis, behavioral abnormalities and other undesirable behavioral effects.

The appearance of these symptoms can be accompanied by the following potentially dangerous for the patient or others behavioral disorders:

- unusual behavior for the patient;

- self-aggression or aggression towards other persons who are trying to prevent the patient's dangerous actions;

- automatic behavior with its subsequent amnesia.

If these effects occur, zolpidem should be discontinued.

The probability of occurrence of these effects is higher in elderly patients.

Somnambulism and related complex behavior

In some patients, benzodiazepines and related drugs can cause a syndrome of combined disorders of consciousness, behavior and memory of varying severity.

Patients who took zolpidem and not fully awake, there was walking in the dream and other related complex behavior: driving in a sleepy state, cooking and eating,calls on the phone, the commission of sexual intercourse with incomplete awakening with amnesia of these actions. The intake of alcoholic beverages and other drugs with CNS depressant effect in conjunction with zolpidem, and the use of zolpidem in doses exceeding the maximum recommended dose, apparently, increases the risk of such behavior. If the patient reports an episode (s) of such behavior (eg driving in a sleepy state), zolpidem should be discontinued because of the risk to both the patient and the people around him (see "Interaction with Other Drug Users" means "subsection" With ethanol "and in the section" Side effect "subsection" Disorders of the psyche ").

Psychomotor disorders

The risk of developing psychomotor disorders, including impaired ability to drive transport increases:

- when taking zolpidem in less than 7-8 hours before performing actions that require concentration of attention and rapid speed of psychomotor reactions;

- when taking a dose that exceeds the recommended dose;

- with the simultaneous administration of zolpidem with other drugs that depress the central nervous system (CNS), ethanol or drugs that increase the concentration of zolpidem in the blood.

Decrease in efficacy (development of tolerance to the drug)

After a course of taking sedative / hypnotic drugs like zolpidem for several weeks, some reduction in the hypnotic effect is possible.

Formation of drug dependence

The use of sedative / hypnotic drugs like zolpidem can lead to the formation of physical and / or mental dependence. Dependence may also occur with the use of therapeutic doses and / or in patients without individual risk factors.

The risk of dependence increases with increasing dose of the drug and the duration of treatment, it is also higher in patients with anamnesis on mental disorders, alcohol or other drugs and non-drug substances. Such patients with the use of sleeping pills should be under very careful observation.

In the case of physical dependence on the drug with a sharp discontinuation of its reception may develop a syndrome of "cancellation", of which frequent manifestations are: insomnia, headache, myalgia, severe anxiety, muscle tension, anxiety, confusion and irritability.In cases of severe withdrawal, derealization, depersonalization, hyperacusia (pathologically increased perception of ordinary sounds), numbness and paresthesia of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures are observed.

There are reports of drug abuse cases.

Reflective insomnia

With the cancellation of sedative / hypnotic drugs, there may be a transient syndrome in the form of a return of insomnia in a strengthened form. It can be combined with other reactions, including mood changes, anxiety and anxiety. It is important that the patient be warned about the possibility of a "rebound" phenomenon, which will reduce his anxiety about the occurrence of such symptoms when the drug is discontinued.

In the case of a short-acting sedative / hypnotic, there may be symptoms of "cancellation" in the interval between doses.

Risk of cumulation

In elderly patients or patients with insufficient liver function, a significant increase in the half-life (see the section "Pharmacokinetics") can occur, which can lead to accumulation of the drug when it is repeated.Based on the characteristics of zolpidem pharmacokinetics, with renal failure, cumulation of the drug is not expected.

Use in elderly patients

When using zolpidem in elderly patients, care must be taken because of the danger of developing sedative and / or muscle relaxant effects, which can lead to falls with serious consequences for this group of patients (see the section "Method of administration and dose" Patients of advanced age ").

Use in children

The safety and effectiveness of zolpidem in children and adolescents under 18 years is not established.

In an 8-week study in children and adolescents (aged 6-17 years) with insomnia associated with attention deficit hyperactivity disorder, the most common adverse reactions that arose with the use of zolpidem compared with placebo were mental disorders and disorders of the nervous system, such as dizziness (23.5% vs. 1.5%), headache (12.5% vs 9.2%) and hallucinations (7.4% vs. 0%), see " Method of administration and dose ".

Severe injury

Due to its pharmacological properties zolpidem may cause drowsiness and a decrease in the level of consciousness, which can lead to patient falls and, as a result, severe injuries.

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

Drivers of vehicles and persons working with mechanisms or dealing with other potentially hazardous activities should be warned about the possible risk of developing side effects including drowsiness, slowing of reactions, dizziness, drowsiness, blurred vision, reduced focus and speed of psychomotor reactions, violation ability to drive vehicles in the morning after taking zolpidem.

In order to minimize the risk of such reactions, it is recommended to provide the patient with a continuous night sleep for 7-8 hours.

The above reactions can be significantly enhanced by the use of zolpidem in combination with other drugs that depress the central nervous system and alcohol (ethanol) (see section "Interaction with other drugs"). Patients should be warned that alcohol should not be taken (ethanol) and drugs that depress the central nervous system, against the background of zolpidem.

Form release / dosage:

Tablets, film-coated, 10 mg.

Packaging:

For 7, 10 or 20 tablets in a blister of PVC / aluminum. 1 blister for 7 or 20 tablets or 2 blisters for 10 tablets together with instructions for use in a cardboard box.

Storage conditions:

In accordance with the rules for storage of psychotropic substances listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

4 years.

Do not take the medicine after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014944 / 01

Date of registration:27.10.2008

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: & nbsp14.09.2015

Illustrated instructions

Instructions

Iwadal® (Ivadal®)