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

Excipients: citric acid monohydrate 20.0 mg, sodium benzoate 0.25 mg, sodium hydroxide to pH 4.0, hydrochloric acid to pH 4.0, purified water to 1 ml.

Description:A clear, colorless or pale yellow solution.

Pharmacotherapeutic group:Sleeping pills.

ATX: & nbsp

N.05.C.F.02 Zolpidem

Pharmacodynamics:

Zolpidem is a hypnotic, which belongs to the group of imidazopyridines. Differing in structure from benzodiazepines, zolpidem has a sedative effect, while anxiolytic, anticonvulsant and central muscle relaxant effect is expressed only slightly.

The effect comes quickly. Zolpidem quickly absorbed from the gastrointestinal tract (GIT).

According to the classification, the allosteric sections of the γ-aminobutyric acid complex (GABA) to which the benzodiazepines bind are referred to as © -modulating regions or receptors. To date, three subtypes have been identified: ω1, ω2 and ω3. Unlike benzodiazepines, which non-selectively bind and activate all three subtypes of ω-receptors, zolpidem selectively binds to the ω1 receptor, therefore, the sedative effect of the drug is observed at lower doses than the doses necessary for the development of myorelaxing, anticonvulsant and anxiolytic effect.

ω1 receptors are mainly located in the fourth layer of the sensory cortex of the cerebral hemispheres, in the cerebellum, the variolium bridge and the lower tubercles of the quadruple.

Zolpidem showed a low affinity for ω2 receptors (lumbar spine, hippocampus) and ω3 receptors (certain peripheral regions).

The pharmacological action of zolpidem differs from that of benzodiazepines. Interaction with ω-receptors leads to the discovery of neuronal ion channels of chlorine.

Shortens the time of falling asleep, reduces the number of nocturnal awakenings, increases the total duration of sleep and improves its quality. Lengthens the II stage of sleep and the stage of deep sleep (III and IV).

Pharmacokinetics:

After taking a dose of 5 mg and 10 mg the maximum concentration in the blood plasma (C_max) are 59 ng / ml and 121 ng / ml, respectively, the time to reach the maximum concentration (TC_max) from 0.5-3 hours (mean TC_max 1.6 h).

When there is food in the stomach, the absorption of zolpidem slightly slows down. To accelerate the onset of sleep zolpidem Do not take it concurrently or immediately after a meal. The pharmacokinetics of zolpidem remains unchanged for several weeks of use.

Bioavailability of zolpidem reaches 70%, the connection with plasma proteins - 92 %.

There is a linear relationship between the dose of the drug and the concentration of zolpidem in the plasma.

Metabolized in the liver with the formation of three inactive metabolites, which are excreted by the kidneys (about 60%) and through the intestine (about 40%).

The half-life (T_1/2) of zolpidem is from 0.7-3.5 h (an average of about 2.4 h). The total clearance of zolpidem is 0.26 l / h / kg, the volume of distribution is 0.54 l / kg.

Does not induce microsomal liver enzymes. Do not cumulate.

In elderly people, clearance in the blood plasma can decrease without a significant increase in T_1/2, (an average of 3 hours), while C_max increases by 50 %.

In patients with severe renal failure, the clearance does not increase significantly. In patients with hepatic impairment, bioavailability increases, T_1/2increases to 10 hours.

Indications:

Sleep disorders: difficulty falling asleep, early and nocturnal awakenings.

Contraindications:

increased sensitivity to zolpidem and other auxiliary components of the drug;
severe acute or chronic liver failure;
sleep apnea syndrome;
severe respiratory failure;
I trimester of pregnancy and lactation;
age to 18 years (efficacy and safety not established).

Carefully:

Hepatic insufficiency of mild and moderate severity, depression, alcoholism, drug addiction and other addictions, II and III trimesters of pregnancy, respiratory failure of mild and moderate degree, severe gravis gravis, patients with mental illness.

Pregnancy and lactation:

A drug Onyria contraindicated in the first trimester of pregnancy.If it is necessary to prescribe the drug Onyria in II and III trimesters of pregnancy should carefully evaluate the expected benefit of therapy for the mother and the potential risk to the fetus and newborn. In studies on animals, the teratogenic and embryotoxic effect of the drug was not detected.

Women of reproductive age who take the drug should be warned about the need to see a doctor in the case of a planned or onset of pregnancy, and during treatment with the drug Onyria patients should use reliable methods of contraception.

In the case of zolpidem at the end of pregnancy or during labor (even at low doses), hypothermia may develop in the newborn, transient respiratory depression or apnea, axial hypotension, lower blood pressure, and sucking disorders.

In addition, children born to mothers who took sedatives / hypnotics for a long time at the end of pregnancy can become physically addicted, and there is a risk of developing a "cancellation" syndrome in the postnatal period.

Zolpidem penetrates into breast milk, therefore it is contraindicated for use during breastfeeding. If it is necessary to use the drug Onyria During lactation breastfeeding should be discontinued.

Dosing and Administration:

The bottle is equipped with a dropper. 1 ml corresponds to 25 drops, which is equivalent to 10 mg of zolpidem.

Drops for ingestion should be taken with the liquid (water) just before bedtime.

The duration of treatment should be as short as possible. On average, it should be from a few days to two weeks and should not exceed 4 weeks, including the cancellation period. Cancellation should take place taking into account the individual characteristics of the patient.

In the case of prolonged use of the drug to reduce the possibility of developing "ricochet" insomnia, the cessation of zolpidem should be gradual (first a decrease in the daily dose and then the drug cancellation).

Adults

The recommended daily dose is 10 mg (25 drops).

The daily dose of zolpidem should not exceed 10 mg.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their rate of development as follows: common (> 1/100 to <1/10), uncommon (> 1/1000 to <1/100), rarely (> 1 / 10000 to <1/1000) and very rarely (<1/10000), including individual messages; the frequency is unknown - based on the available data, the frequency of occurrence can not be determined.

The frequency of most side effects depends on the dose. Side effects are more common in women than in men.

From the central and peripheral nervous system:

Often: drowsiness, sensation of intoxication, headache, dizziness, increased insomnia, anterograde amnesia (the effects of amnesia can be associated with behavioral reactions), the risk of developing it increases in proportion to the dose, hallucinations (including visual and auditory), increased excitability, "nightmarish" dreams, emotional lability, vertego, ataxia.

Infrequently: migraine, parasthesia, tremor, confusion, decreased concentration of attention (with insufficient sleep time), irritability, euphoria.

Rarely: aggressiveness, delirium, psychotic disorders, somnambulism, inadequate behavior and other behavioral disorders (these reactions occur more often in the elderly).

Rarely: anger.

Frequency unknown: dysphoria, behavioral disorders, drug dependence (can develop including when taking therapeutic doses), with the withdrawal of the drug - the syndrome of "withdrawal" or "ricochet" insomnia, decreased libido,addictive to the drug (reducing sedative and hypnotic effects when applied for several weeks). Most side effects from the psyche are paradoxical reactions.

From the digestive system:

Often: diarrhea.

Infrequently: nausea, vomiting, abdominal pain, dysphagia, flatulence, hiccough, gastroenteritis.

Rarely: increased activity of "liver" enzymes.

From the musculoskeletal system:

Not very often: muscle weakness, arthritis.

From the skin and subcutaneous fat:

Infrequently: rash, itching, urticaria, increased sweating.

Rarely: pallor, swelling of the Quincke.

From the side of the organs of sight

Infrequently: diplopia.

From the side of the cardiovascular system

Infrequently: tachycardia, cerebrovascular disorders, increase and decrease in blood pressure, orthostatic hypotension.

On the part of the respiratory system

Infrequently: bronchitis, cough, shortness of breath.

From the endocrine system:

Infrequently: hyperglycemia.

Other:

Often: feeling tired.

Infrequently: trauma, falls (mainly in elderly patients), peripheral edema, fever.

If any undesirable phenomena not listed in these instructions for use appear, you should consult your doctor.

Overdose:

In case of accidental drug overdose Onyria should immediately consult a doctor.

Symptoms mainly due to the depression of the central nervous system (CNS): there may be a loss of consciousness from mild forms (confusion, inhibition) to severe (up to coma), ataxia, lower blood pressure, respiratory depression, life-threatening patient.

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 intake of an excessive dose of the drug has passed more than 1 hour, the patient should be allowed to take in or enter through a probe (with unconsciousness) Activated carbon to reduce the absorption of zolpidem.

In case of overdose, symptomatic therapy is performed (in hospital settings) and treatment aimed at maintaining the basic functions of the body, in particular the functions of respiration and the cardiovascular system.

Sedatives should not be used after an overdosage with zolpidem, even if agitation occurs.

In case of severe overdose for differential diagnosis and / or treatment should consider the introduction of flumazenil in hospital (antagonist benzodiazepine receptors), but it should be remembered that suppression of benzodiazepine receptors can cause neurologic disorders (convulsions), especially in patients with epilepsy. Zolpidem is not excreted by hemodialysis.

Interaction:

Before taking the drug, the patient should inform the doctor about all medications that he takes, including over-the-counter medicines.

Not recommended combinations: ethanol enhances the sedative effect of zolpidem.

Combinations requiring caution when used: medicines (drugs), oppressive central nervous system (neuroleptics, barbiturates, other sleeping pills, anxiolytics / sedatives, antidepressants with sedative action, narcotic analgesics, central antitussives), antiepileptics, drugs for general anesthesia, H1-histamine receptor blockers with sedative effect, antihypertensive agents of central action; baclofen; thalidomide; pisotifen - increased oppressive effect on the central nervous system and the risk of respiratory depression.

Buprenorphine is a risk of respiratory depression.

Ketoconazole (a potent inhibitor of the isoenzyme CYP3A4) at a dose of 200 mg twice a day, and ritonavir increase T1, the area under the "concentration-time" curve and reduce the clearance of zolpidem (possibly strengthening the sedative effect of zolpidem).

Itraconazole (inhibitor of the isoenzyme CYP3A4) is a minor, clinically insignificant change in the pharmacokinetics and pharmacodynamics of zolpidem.

Interactions that should be taken into account:

Rifampicin (inducer of the isoenzyme CYP3A4) accelerates metabolism, reduces the concentration and, as a consequence, the effectiveness of zolpidem.

Flumazenil eliminates the sleeping pills of zolpidem

Special instructions:

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.

Mental diseases

Sleeping pills, such as zolpidem, are not recommended as the main treatment for mental illness.

Depression

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 do 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.

Amnesia

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 conditions for a continuous 8-hour sleep.

Mental and "paradoxical" reactions

As is known, with the use of sedatives / hypnotics, incl. and zolpidem, the following conditions can occur: increased insomnia, nightmares, agitation, nervousness, delirium, hallucinations, confusion and onyricism, psychotic symptoms, disinhibition with impulsivity, euphoria, increased excitability, anterograde amnesia, increased suggestibility, aggressiveness.

These reactions can be accompanied by the following potentially behavioral disorders that are potentially dangerous for the patient or others: unusual for the patient behavior with the phenomena of automatism, autoaggression or aggression towards others, followed by 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, behavior and memory of varying degrees of severity. In patients receiving zolpidem, there was walking in a dream and other related complex behavior: driving in a sleepy state,preparation and reception of food, phone calls, sexual intercourse with incomplete awakening with amnesia of these actions. Taking alcohol and other drugs with CNS depressant together with zolpidem, as well as taking zolpidem at doses exceeding the recommended dose, apparently increases the risk of such behavior. If the patient reports an episode (s) of this behavior, taking the drug Onyria should be discontinued.

Addiction

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

Formation of dependence

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 alcoholism or the abuse of other drugs and non-medicinal substances in the anamnesis. Such patients should be monitored carefully when receiving sleeping pills.

However, dependence can also occur with the use of therapeutic doses and / or in patients without individual risk factors.

When using the drug Onyria in therapeutic doses, dependence on the drug is extremely rare.

In case of dependence on the drug Onyria at the termination of his admission, the development of the "withdrawal" syndrome is possible, the common symptoms of which are: insomnia, headache and myalgia, dysphoria, anxiety, muscle tension and irritability. Less often (in more severe cases of the "cancellation" syndrome), there is agitation or even episodes of confusion, derealization, depersonalization, numbness and paresthesia of the extremities, excessive sensitivity to light, noise, physical contact, hallucinations and convulsions.

The "cancellation" syndrome can be observed for several days after discontinuation of drug treatment Onyrica. When taking zolpidem (as well as other short-acting benzodiazepines), there may be symptoms of the "cancellation" syndrome in the interval between two doses, especially in high doses.

Regardless of the indications for use, the combination of zolpidem with benzodiazepines increases the riskdevelopment of dependence.

There are reports of drug abuse cases.

"Ricochet" insomnia

Transient syndrome with the abolition of sleeping pills as a return to 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 T1 is possible, which may lead to cumulation of zolpidem in its repeated administration. Based on the features of pharmacokinetics of zolpidem, cumulation is not expected in renal failure.

Use in elderly patients

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.

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

During the period of drug treatment Onyria Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

If after taking the drug Onyria the duration of sleep was not sufficient, then the risk of disturbances in psychomotor reactions increases, which may pose an additional risk in the management of transport and other potentially hazardous activities.

Form release / dosage:

Drops for ingestion 10 mg / ml.

Packaging:

To 30 ml of the drug in a bottle of orange glass type III, equipped with a dropper of low-density polyethylene and a plastic lid with protection from opening by children. One bottle together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in a place protected from light.

Keep 60 days after first opening the vial.

Keep out of the reach of children.

The drug belongs to the list of psychotropic substances (list III).

Shelf life:

2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002277

Date of registration:15.10.2013

The owner of the registration certificate:Italfarmaco SpAItalfarmaco SpA Italy

Manufacturer: & nbsp

ITALFARMACO, S.p.A. Italy

Representation: & nbspITALFARMAKO SpA ITALFARMAKO SpA Italy

Information update date: & nbsp08.09.2015

Illustrated instructions

Instructions

Onyria (Oniria)