Ivadal

Ivadal®

In all cases, before using a sleeping pill, it is necessary, whenever possible, to establish the causes of sleep disturbances and carry out correction (including medication) of the underlying causes.

The persistence of insomnia for 7-14 days of treatment indicates the presence of primary mental disorders and/or disorders of the nervous system. Therefore, to identify 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 "Dosage and Administration").

Psychotic illnesses

Hypnotics such as zolpidem are not recommended as primary treatment for psychotic illness.

Depression

The use of zolpidem, like other sedative/hypnotic drugs, in patients with symptoms of depression requires extreme caution. These patients should be treated for depression but should not be given zolpidem alone. Manifestation of pre-existing latent depression is possible while taking zolpidem. Since these patients may have suicidal tendencies, they should be given the minimum amount of zolpidem required to avoid the possibility of deliberate overdose by the patient.

Because insomnia can be a symptom of depression, if insomnia persists, the patient should be re-evaluated to identify possible depression.

Amnesia

Sedative/hypnotic drugs such as zolpidem can cause anterograde amnesia, which is most often observed several hours after taking the drug, and therefore, to reduce the risk of its development, patients should have conditions for 7-8 hours of uninterrupted sleep.

Other mental and "paradoxical" reactions

It is known that when using sedative/hypnotic drugs like zolpidem, other mental 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 may be accompanied by the following behavioral disorders that are potentially dangerous for the patient or others:

- unusual behavior for the patient;

— self-injury 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.

These effects are more likely to occur in older patients.

Somnambulism and associated challenging 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 were not fully awake experienced sleep walking and other associated complex behaviors: driving while half asleep, preparing and eating food, making phone calls, and engaging in sexual intercourse while not fully awake with amnesia for these activities. Taking alcoholic beverages and other CNS depressants with zolpidem, as well as taking zolpidem in doses greater than the maximum recommended dose, appears to increase the risk of these behaviors. If the patient reports episode(s) of such behavior (for example, driving while drowsy), zolpidem should be discontinued due to the risk to both the patient and those around him (see Interactions with Other Drugs). means" subsection "With ethanol" and in the section "Side effects" subsection "Mental disorders").

Psychomotor disorders

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

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

- when taking a dose exceeding the recommended dose;

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

Decreased effectiveness (development of drug tolerance)

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

Formation of dependence on the drug

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

The risk of dependence increases with increasing dosage of the drug and duration of treatment, and is also higher in patients with a history of mental disorders, abuse of alcohol or other drugs and non-drug substances. Such patients should be especially closely monitored when taking sleeping pills.

In the case of the use of short-acting sedative/hypnotic drugs, “oPharmacokinetics” symptoms may occur, which can lead to accumulation of the drug when it is repeated. Based on the pharmacokinetics of zolpidem, drug accumulation is not expected in patients with renal failure.

Use in elderly patients

When using zolpidem in elderly patients, caution must be exercised due to the risk of developing sedative and/or muscle relaxant effects, which can lead to falls with serious consequences for this group of patients (see section "Method of administration and dosage" subsection " Elderly patients").

Use in children

The safety and effectiveness of zolpidem in children and adolescents under 18 years of age have not been established.

In an 8-week study in children and adolescents (ages 6–17 years) with insomnia associated with attention deficit hyperactivity disorder, the most common adverse reactions reported with zolpidem, compared with placebo, were psychiatric disorders and Nervous system disorders such as dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%) and hallucinations (7.4% vs. 0%), see section " Method of administration and dosage."

Severe injuries

Due to its pharmacological properties, zolpidem can cause drowsiness and decreased level of consciousness, which can lead to patient falls and, as a result, serious injuries.

Use during pregnancy and breastfeeding

Ivadal® is contraindicated for use in the first trimester of pregnancy.
Due to insufficient data on the use of Ivadal in pregnant women, it is not recommended to prescribe the drug in the second and third trimesters of pregnancy.

Women of childbearing age receiving the drug should be warned about the need to consult a doctor in the event of a planned or actual pregnancy.

If it is necessary to prescribe the drug in the second and third trimesters of pregnancy, the expected benefits of therapy for the mother and the potential risk for the fetus and newborn should be carefully assessed.

When taking zolpidem in high doses in the second and third trimesters of pregnancy, a decrease in mobility and a change in heart rate in the fetus is possible.

If benzodiazepines are taken at the end of pregnancy or during childbirth (even in low doses), it is possible for active substances to enter the fetus’s body and develop hypothermia, transient respiratory depression or apnea, axial hypotension, arterial hypotension, and sucking disorders in the newborn. Based on this, as well as the known pharmacodynamic effects of zolpidem, the possibility of similar phenomena occurring when taken at the end of pregnancy or during childbirth cannot be excluded. In addition, children born to mothers who took sedative/hypnotic drugs for a long time at the end of pregnancy may develop physical dependence, and there is a risk of developing withdrawal syndrome in the postnatal period, which is manifested primarily by increased excitability and tremor of the newborn, which occurs after some time. time after childbirth. The time of onset of such phenomena depends on the rate at which the sedative/hypnotic drug is eliminated from the mother’s body.

Small amounts of zolpidem are excreted in human breast milk. Therefore, it is not recommended to take zolpidem during breastfeeding.

Experimental studies on animals did not reveal a teratogenic effect of the drug.

Use for liver dysfunction

Use is contraindicated in severe acute or chronic liver failure (risk of developing encephalopathy).

Use with caution in case of liver dysfunction.

Use in children

Contraindication: children and adolescents under 18 years of age (lack of clinical data).

Use in elderly patients

For elderly or debilitated patients, the initial dose is 5 mg. The dose can be increased to 10 mg only if the clinical effect is insufficient and the drug is well tolerated.

special instructions

In all cases, before prescribing a sleeping pill, the cause of sleep disturbances should be established and correction (including medication) of the underlying causes should be carried out. The persistence of insomnia for 7-14 days of treatment indicates the presence of primary mental disorders and/or disorders of the nervous system. Therefore, to identify these disorders, it is necessary to regularly reassess the patient's condition.

Sleeping pills such as zolpidem are not recommended as primary treatment for mental illness.

The use of zolpidem in patients with symptoms of depression, like other drugs with sedative/hypnotic effects, requires extreme caution. Such patients should be treated for depression and should not be prescribed benzodiazepines and drugs similar in their effects in monotherapy due to the fact that these drugs can mask the symptoms of depression, which against their background can continue to develop with the preservation or intensification of suicidal tendencies.

Because depression can be a cause of insomnia, if persistent insomnia persists, the patient's mental state should be re-evaluated to identify possible depression.

Sedative/hypnotic drugs such as zolpidem may cause anterograde amnesia. This condition is most often observed several hours after taking the drug and therefore, to reduce the risk of its development, patients should have conditions for uninterrupted 7-8 hours of sleep.

Mental and paradoxical reactions: as is known with the use of sedatives/hypnotics, incl. and zolpidem may occur, increased insomnia, nightmares, agitation, nervousness, delusions, hallucinations, confusion and onirism, psychotic symptoms, disinhibition with impulsivity, euphoria, excitability, anterograde amnesia, increased suggestibility, aggressiveness. This syndrome may be accompanied by the following potentially dangerous behavioral disorders for the patient or others: behavior unusual for the patient, self-injury 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. These effects are more likely to occur in older patients.

Somnambulism and associated complex behavior: in some individuals, benzodiazepines and related drugs can cause a syndrome of combined disorders of consciousness, behavior and memory of varying severity. Sleepwalking and other associated complex behaviors have been observed in patients receiving zolpidem: sleep-driving, preparing and eating food, making phone calls, and engaging in sexual intercourse while not fully awake with amnesia for these activities. The use of alcohol and other CNS depressants with zolpidem, as well as the use of zolpidem in doses higher than the recommended dose, appears to increase the risk of such behavior. If the patient reports episode(s) of such behavior, Ivadal should be discontinued.

After a course of taking sedative/hypnotic drugs like zolpidem for several weeks, there may be some reduction in their sedative-hypnotic effects.

The use of benzodiazepines and drugs similar to them in their effects, especially long-term, can lead to the formation of physical and/or mental dependence. The risk of dependence increases with increasing dosage and duration of treatment, and is also higher in patients with a history of abuse of alcohol or other drugs and non-drug substances. Such patients should be especially closely monitored when receiving sleeping pills.

However, dependence can also occur when the drug is used in therapeutic doses and/or in patients without individual risk factors.

When Ivadal is used in therapeutic doses, a state of dependence on the drug is extremely rare.

If dependence on the drug occurs when you stop taking it, withdrawal syndrome may develop, the most common symptoms of which are: insomnia, headache and myalgia, dysphoria, anxiety, muscle tension and irritability. Less commonly (in more severe cases of withdrawal syndrome) agitation or even episodes of confusion, derealization, depersonalization, numbness and paresthesia of the extremities, excessive sensitivity to light, noise, physical contact, hallucinations and convulsions are observed.

Withdrawal syndrome may occur for several days after stopping treatment. When taking zolpidem (as with other short-acting benzodiazepines), withdrawal symptoms may occur between two doses, especially at high doses.

Regardless of the indication for use, the combination of zolpidem with benzodiazepines increases the risk of developing dependence.

There are reports of cases of drug abuse.

Rebound insomnia is a transient syndrome upon discontinuation of treatment with sleeping pills in the form of a return of insomnia in an intensified form. It may be associated with other reactions including mood changes, anxiety and dysphoria. It is important that the patient be warned about the possibility of rebound phenomena, which will reduce anxiety about the occurrence of such symptoms when stopping the drug.

Risk of accumulation: Benzodiazepines and related compounds remain in the body for approximately five half-lives. In elderly patients or in patients with insufficient liver function, a significant increase in T1/2 is possible, which can lead to accumulation of the drug when it is repeated. Based on the pharmacokinetics of zolpidem, drug accumulation is not expected in patients with renal failure.

When prescribing benzodiazepines and related compounds to elderly patients, caution must be exercised due to the risk of developing sedative and/or muscle relaxant effects, which can lead to falls with serious consequences.

Patients should always be warned about the recommended duration of treatment, which is determined by the type of insomnia.

Use in pediatrics

The safety and effectiveness of Ivadal in children and adolescents under 18 years of age have not been established.

Impact on the ability to drive vehicles and operate machinery

Patients who drive vehicles or operate machinery should be warned about the risk of drowsiness and dizziness during treatment with Ivadal, which may be significantly increased when the drug is used in combination with other medicinal products with sedative effects and/or alcohol.

If, after taking Ivadal, the duration of sleep was not sufficient, then the risk of disturbances in psychomotor reactions increases, which may pose an additional danger when driving vehicles and other potentially hazardous activities.

Zolpidem

In all cases, before using a sleeping pill, it is necessary, whenever possible, to establish the causes of sleep disturbances and carry out correction (including medication) of the underlying causes.

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

Psychomotor disorders

The risk of developing psychomotor disorders, including impairment of the ability to drive vehicles, increases:

when taking zolpidem less than 7-8 hours before performing activities that require concentration and rapid psychomotor reactions;
when taking a dose exceeding the recommended dose;
while taking zolpidem with other drugs that depress the central nervous system (CNS), ethanol, or drugs that increase the concentration of zolpidem in the blood;

Respiratory failure

Sleeping pills have the ability to depress the respiratory center; caution should be exercised when using the drug in patients with impaired respiratory function.

Liver failure

Zolpidem is contraindicated in patients with severe hepatic impairment, as it may contribute to the development of hepatic encephalopathy (see sections "Contraindications", "Dosage and Administration" and "Side Effects").

Use in elderly patients

Risk of accumulation

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

Psychotic illnesses

Hypnotics such as zolpidem are not recommended as primary treatment for psychotic illness.

Suicidal behavior and depression

Some epidemiological studies have shown an increased incidence of suicide and suicide attempts in patients with or without depression and who were taking benzodiazepines or other hypnotics, including zolpidem. A cause-and-effect relationship between the use of these drugs and the development of suicide and suicide attempts has not been established.

The use of zolpidem, like other sedative/hypnotic drugs, in patients with symptoms of depression requires extreme caution. These patients should be treated for depression but should not be given zolpidem alone. Manifestation of pre-existing latent depression is possible while taking zolpidem. Because these patients may be suicidal, they should be given the minimum amount of zolpidem required to avoid the possibility of the patient intentionally overdosing.

Because insomnia can be a symptom of depression, if insomnia persists, the patient should be re-evaluated to identify possible depression.

Decreased effectiveness (development of drug tolerance)

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

Formation of dependence on the drug

If physical dependence on the drug develops, if the drug is abruptly stopped, the patient may develop “oricochete” syndrome, which will reduce his anxiety about the occurrence of such symptoms when stopping the drug. In the case of the use of short-acting sedative/hypnotics, symptoms of “paradoxical” reactions may occur

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

unusual behavior for the patient;
self-injury or aggression towards others who are trying to prevent the patient from dangerous actions;
automatic behavior with its subsequent amnesia.

If these effects occur, zolpidem should be discontinued. These effects are more likely to occur in older patients.

Somnambulism and associated challenging behavior

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

Taking alcoholic beverages and other CNS depressants with zolpidem, as well as taking zolpidem in doses greater than the maximum recommended dose, appears to increase the risk of these behaviors. If the patient reports episode(s) of such behavior (for example, driving while drowsy), zolpidem should be discontinued due to the risk to both the patient and those around him (see Interactions with Other Drugs). means" subsection "With ethanol" and in the section "Side effects" subsection "Mental disorders").

Severe injuries

Due to its pharmacological properties, zolpidem can cause drowsiness and decreased level of consciousness, which can lead to patient falls and, as a result, serious injuries.

Patients with long QT syndrome

An in vitro study of the electrophysiological functions of cardiac muscle showed that, under experimental conditions, using very high concentrations and pluripotent stem cells, zolpidem can reduce the flow of potassium ions through hERG potassium channels. The possible consequences in patients with congenital long QT syndrome are unknown. As a precaution, the benefit/risk ratio should be carefully considered when treating patients with congenital long QT syndrome with zolpidem.

Use in children

The safety and effectiveness of zolpidem in children and adolescents under 18 years of age have not been established.

In an 8-week study in children and adolescents (ages 6–17 years) with insomnia associated with attention deficit hyperactivity disorder, the most common adverse reactions reported with zolpidem, compared with placebo, were psychiatric disorders and Nervous system disorders such as dizziness (23.5% vs 1.5%), headache (12.5% vs 9.2%) and hallucinations (7.4% vs 0%), see section " Method of administration and dosage."