Composition, form of production and packaging
Tablets covered with a film shell white or almost white, oblong, with a fault line and engraving "SN 10" on one side.
zolpidem tartrate 10 mg
Excipients: lactose monohydrate, microcrystalline cellulose, hypromellose, sodium carboxymethyl starch (type A), magnesium stearate.
Composition of the membrane: hypromellose, titanium dioxide (E171), macrogol 400.
7 pcs. - blisters (1) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.
20 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
A hypnotic drug from the group of imidazopyridines, which are close in pharmacological activity to benzodiazepines. It has effects that are 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 central ОІ-receptors (benzodiazepine type I and II receptors) related to macromolecular GABA receptor complexes that cause the opening of neuronal anion channels for chlorine.
Zolpidem selectively interacts with the central benzodiazepine type I receptors (subtype of ОІ-receptors of type 1). 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.
After ingestion C max in the blood plasma is observed after 0.5-3 hours. Bioavailability is about 70%.
In the therapeutic dosage range, the pharmacokinetics of zolpidem is linear.
Binding to plasma proteins - 92%. V d is 0.54 В± 0.02 l / kg.
Metabolism and excretion
Zolpidem is metabolized in the liver and in the form of inactive metabolites is excreted in the urine (about 60%) and feces (about 40%). Does not induce microsomal liver enzymes.
T 1/2 is about 2.4 h (0.7-3.5 h).
Pharmacokinetics in special clinical cases
In elderly patients, the clearance of zolpidem in the blood plasma can be reduced, while T 1/2 increases insignificantly (on average 3 hours), C max increases by 50%, V d decreases to 0.34 В± 0.05 l / kg.
In patients with renal failure (regardless of receiving hemodialysis procedures) there is a moderate decrease in zolpidem clearance, other pharmacokinetic parameters do not change. Zolpidem is not excreted by hemodialysis.
In patients with insufficient liver function, the bioavailability of zolpidem increases, the clearance decreases slightly, T 1/2 increases to 10 hours.
- treatment of transient and situational insomnia in adults, including difficulties with falling asleep, night and early awakenings.
The drug is intended for oral administration.
Treatment should always begin with a minimum effective dose, while never exceeding the maximum dose.
The recommended dose for adults is 10 mg / day. The drug is taken immediately before going to bed or in bed.
For elderly or debilitated patients, in patients with impaired hepatic function, the initial dose is 5 mg. The dose can be increased to 10 mg only in case of insufficient clinical effect and good tolerability of the drug.
The maximum daily dose is 10 mg.
Duration of treatment should be minimal: from several days to 4 weeks, including the period of dose reduction. Prolongation of treatment beyond the maximum allowable period is carried out with extreme caution after a second clinical assessment of the patient's condition.
The recommended duration of taking the drug in case of transient insomnia (for example, during a trip) is 2-5 days, with situational insomnia (for example, due to the psychotraumatic situation) - within 2-3 weeks.
In the case of a very short period of treatment, gradual withdrawal of the drug is not required.
In case of long reception to reduce the possibility of development of ricochet insomnia, the abolition of zolpidem should be carried out gradually: first - a decrease in the daily dose and only then - complete withdrawal of the drug.
Side effects, especially from the side of the central nervous system, depend on the dose and individual response of the patient. They are more often observed in elderly patients, their severity should theoretically be less when taking the drug immediately before going to bed or already in bed.
Determination of the frequency of side effects: very often (? 10%, often (? 1%, <10%), sometimes (? 0.1%, <1%), rarely (0.01% to 0.1%), very rarely (<0.01% ), including individual cases, it is not known - based on available data, the definition of frequency of occurrence is impossible.
From the side of the central nervous system: often - drowsiness, a sense of intoxication, headache, dizziness, increased insomnia, anterograde amnesia (can occur with the drug in therapeutic doses, and the risk of its development increases in proportion to the dose) sometimes in combination with behavioral disorders, hallucinations, excitement, nightmarish dreams; sometimes confusion, irritability; unknown, impairment of consciousness, dysphoria, aggressiveness, visual and auditory hallucinations, excitability, behavioral abnormalities, sleep walking (somnambulism), dependence, which can develop even when the drug is used in therapeutic doses (after the cessation of treatment, withdrawal or rebound syndrome may develop insomnia), decreased sexual desire, gait disturbance, ataxia, falls (mainly in elderly patients and failure to comply with prescribed recommendations for admission), addiction to prep aratus (reduction of sedative and hypnotic effects when applied for several weeks).
Most side effects from the psyche are related to paroxysmal reactions.
From the side of the organ of vision: sometimes - diplopia.
From the digestive system: often - diarrhea, nausea, vomiting, abdominal pain; unknown - increased activity of liver enzymes.
From the osteo-muscular system: unknown - muscle weakness.
Dermatological reactions: unknown - rash, itching, hyperhidrosis (profuse sweating).
Allergic reactions: unknown - hives, angioedema.
Other: often - a feeling of fatigue.
acute and / or severe respiratory failure;
- sleep apnea syndrome;
- severe acute or chronic liver failure (risk of encephalopathy);
- children's and adolescence under 18 years (lack of clinical data);
- I trimester of pregnancy;
- congenital galactosemia, glucose malabsorption syndrome or galactose, lactase deficiency;
- Hypersensitivity to the components of the drug.
With caution should be used in severe pseudo-paralytic myasthenia (asthenic bulbar paralysis), violations of liver function, chronic alcoholism, drug addiction and other types of dependence (increased risk of dependence on zolpidem).
PREGNANCY AND LACTATION
IwadalВ® is contraindicated for use in the first trimester of pregnancy.
In connection with the lack of data on the use of Iwadala in pregnant women, it is not recommended to prescribe the drug in the II and III trimesters of pregnancy.
Women of childbearing age who receive the drug should be warned about the need to see a doctor in the case of a planned or onset of pregnancy.
If it is necessary to prescribe the drug in the II and III trimesters of pregnancy, the expected benefit of therapy for the mother and the potential risk to the fetus and newborn should be carefully evaluated.
When taking zolpidem in high doses in the II and III trimesters of pregnancy, there may be a decrease in mobility and a change in heart rate in the fetus.
In the case of benzodiazepines at the end of pregnancy or at the time of delivery (even at low doses), active substances may enter the fetus and develop newborn hypothermia, transient respiratory depression or apnea, axial hypotension, arterial hypotension, and sucking disorders. Based on this, as well as the known pharmacodynamic effects of zolpidem, it is impossible to exclude the possibility of developing such phenomena when it is taken at the end of pregnancy or during childbirth. In addition, children born to mothers who took long-term sedatives / hypnotics at the end of pregnancy may become physically addicted, and there is a risk of developing a withdrawal syndrome in the postnatal period, which is manifested primarily by the increased excitability and tremor of the newborn arising after some time after delivery. The time of onset of such events depends on the rate of excretion of the sedative / hypnotic from the body.
Small amounts of zolpidem are excreted in human breast milk. Therefore, it is not recommended to take zolpidem during breastfeeding.
In experimental studies on animals, there was no teratogenic effect of the drug.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe acute or chronic liver failure (risk of encephalopathy).
With caution should be used for violations of liver function.
APPLICATION FOR CHILDREN
Contraindication: children and adolescence under 18 years (lack of clinical data).
APPLICATION IN ELDERLY PATIENTS
For elderly or debilitated patients, the initial dose is 5 mg. The dose can be increased to 10 mg only in case of insufficient clinical effect and good tolerability of the drug.
In all cases, before the appointment of a sleeping pill, one should establish the cause of sleep disorders and correct (including medicamental) causes underlying them.Preservation of insomnia within 7-14 days of treatment indicates the presence of primary mental disorders and / or disorders of the nervous system. Therefore, in order to identify these disorders, the patient's condition must be reassessed regularly.
Sleeping pills, such as zolpidem, are not recommended as the main treatment for mental illness.
The use of zolpidem in patients with symptoms of depression, as well as other drugs with sedative / hypnotic effects, requires special care. Such patients should be treated for depression and should not prescribe benzodiazepines and their similar drugs in monotherapy, because these drugs can mask the symptoms of depression, which against their background can continue to develop with the preservation or strengthening of suicidal tendencies.
In connection with the fact that the cause of insomnia may be depression, then in case of persistent insomnia persistence, a repeated assessment of the patient's mental state should be conducted in order to identify possible depression.
Sedatives / hypnotics, such as zolpidem, can cause anterograde amnesia. This condition 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 an uninterrupted 7-8-hour sleep.
Mental and paradoxical reactions: as is known with the use of sedatives / hypnotics, incl. and zolpidem, may occur, increased insomnia, nightmares, agitation, nervousness, delirium, hallucinations, confusion and onyricism, psychotic symptoms, disinhibition with impulsiveness, euphoria, excitability, anterograde amnesia, increased suggestibility, aggressiveness. This syndrome can be accompanied by the following potentially behaviorally dangerous for the patient or others: behavior unusual for the patient, self-aggression or aggression towards other persons who try 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 people, benzodiazepines and related drugs can cause a syndrome of combined disorders of consciousness of behavior and memory of varying severity. In patients receiving zolpidem, there was walking in sleep and other related complex behavior: driving in a sleepy state, cooking and eating, phone calls, the commission of sexual intercourse with incomplete awakening with amnesia of these actions. The use of alcohol and other drugs with CNS depressant effects in conjunction with zolpidem, and the use of zolpidem in doses exceeding the recommended dose, seem to increase the risk of such behavior. If the patient reports an episode (s) of such behavior, Iwadal's treatment should be discontinued.
After a course of taking sedative / hypnotic drugs like zolpidem for several weeks, some reduction in their sedative and hypnotic effects is possible.
The use of benzodiazepines and related drugs, especially prolonged ones, can lead to the formation of physical and / or mental dependence. The risk of dependence is increased with an increase in the dose of the drug and the duration of treatment, it is also higher in patients with a history of alcohol or other drug abuse and non-drug substance abuse. Such patients should be monitored carefully when receiving sleeping pills.
However, dependence can also occur when the drug is administered at therapeutic doses and / or in patients without individual risk factors.
When Ivadal is used in therapeutic doses, the state of dependence on the drug is extremely rare.
In the case of dependence on the drug, when it is stopped, withdrawal syndrome can develop, often with symptoms such as insomnia, headache and myalgia, dysphoria, anxiety, muscle tension and irritability. Less often (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.
The withdrawal syndrome can be observed for several days after discontinuation of treatment. When taking zolpidem (as well as other short-acting benzodiazepines), withdrawal symptoms may occur in the interval between the two doses, especially in high doses.
Regardless of the indications for use, the combination of zolpidem with benzodiazepines increases the risk of dependence.
There are reports of drug abuse cases.
Ricochet insomnia is a transient syndrome with the withdrawal of sleeping pills in the form of a return of insomnia in a strengthened form. It can be combined with other reactions, including mood changes, anxiety and dysphoria. It is important that the patient be warned about the possibility of a bounce phenomenon, which will reduce the anxiety about the occurrence of such symptoms when the drug is discontinued.
Risk of cumulation: benzodiazepines and related compounds remain in the body for approximately five half-lives. In elderly patients or in patients with liver failure, a significant increase in T 1/2 is possible, which can lead to accumulation of the drug upon its repeated administration. Based on the characteristics of zolpidem pharmacokinetics, with renal failure, cumulation of the drug is not expected.
When prescribing benzodiazepines and related compounds, elderly patients need to be cautious about 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 is not established.
Impact on the ability to drive vehicles and manage mechanisms
Patients engaged in driving vehicles and working with mechanisms should be warned about the risk of drowsiness and dizziness in the face of Ivadal treatment, which can be significantly intensified when the drug is used in combination with other drugs with sedative action and / or with alcohol.
If, after taking Iwadal, the duration of sleep was not sufficient, the risk of disturbances in psychomotor reactions increases, which may pose an additional risk when driving transport and other potentially hazardous activities.
Overdosing with the use of one zolpidem or zolpidem in combination with other substances that depress the central nervous system (including alcohol) may be life threatening.
Symptoms are mainly caused by depression of the central nervous system: there are possible disorders of consciousness from mild forms (confusion, inhibition) to severe (up to coma), ataxia, arterial hypotension, respiratory depression dangerous for the patient's life.
Treatment: if after taking an excessive dose less than 1 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. If after an accidental or deliberate administration of an excessive dose of the drug, more than 1 hour has elapsed, the patient should be allowed to take or inject through the probe (in the unconscious state) activated charcoal 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 the case of severe overdose for differential diagnosis and / or treatment should consider the introduction of flumazenil (antagonist of benzodiazepine receptors), but it should be remembered that inhibition of benzodiazepine receptors can cause neurological disorders (seizures), especially in patients with epilepsy. Zolpidem is not displayed by hemodialysis.
Ethanol potentiates the sedative effect of the drug, which affects the ability to drive and use machines. It should avoid the simultaneous use of zolpidem with alcoholic beverages and medicines containing ethyl alcohol.
Combinations requiring caution when using
Drugs that suppress the CNS: neuroleptics, barbiturates and other hypnotics, anxiolytics / sedatives, antidepressants with sedative, morphine derivatives (opioid analgesics, antitussives), antiepileptics, agents for anesthesia, antihistamine with a sedative effect, antihypertensives central action, baclofen, thalidomide; pizotifen - while the appointment of zolpidem may increase depressant effects on the central nervous system and, accordingly, the risk of respiratory depression, which can lead to fatal overdose (especially when combined with a derivative of morphine, barbiturates), the weakening of psychomotor reactions and decrease in transportation management capabilities.
Buprenorphine: increased risk of respiratory depression or death. Benefit / risk ratio of this combination requires careful assessment. Patients should be warned of the need to adhere strictly to medical recommendations on dosing regimen.
Ketoconazole (a potent inhibitor of CYP3A4): Zolpidem is metabolized with the participation of several isoenzymes CYP450, chief among which is CYP3A4, except that contribute to metabolism contributes CYP1A2. When simultaneous administration of zolpidem and ketoconazole (200 mg, 2 times / day) increased T 1/2zolpidem, AUC, and clearance is reduced, and therefore slightly increases the sedative effect of zolpidem.
Itraconazole (an inhibitor of CYP3A4): slight, clinically insignificant change in the pharmacokinetics and pharmacodynamics of zolpidem.
Interaction that should be taken into account
rifampicin (inducer of CYP3A4): decrease the effectiveness of zolpidem, zolpidem is associated with decreased plasma concentrations due to the acceleration of the metabolism of zolpidem in the liver.
Warfarin, digoxin, ranitidine or cimetidine: no significant pharmacokinetic interaction.
Selective serotonin reuptake inhibitors - fluoxetine and sertraline: no clinically significant pharmacokinetic and pharmacodynamic interaction.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 4 years.