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

1 tablet, film-coated, contains: tablet core: active ingredient - zolpidem tartrate 5 mg; auxiliary components: lactose monohydrate 55,000 mg, microcrystalline cellulose 42,400 mg, sodium carboxymethyl starch 4,800 mg, povidone 1,800 mg, silicon dioxide colloid 0.400 mg, magnesium stearate 0.600 mg; tablet shell: hypromellose 1,280 mg, giprolose 1,280 mg, macrogol-400 0,400 mg, talc 0,200 mg, ferric oxide red oxide 0.008 mg, titanium dioxide 0.832 mg, carnauba wax 0.090 mg.

For a dosage of 10 mg

1 tablet, film-coated, contains: tablet core: active ingredient: zolpidem tartrate 10 mg; auxiliary Components: lactose monohydrate 60,000 mg, microcrystalline cellulose 42,400 mg, sodium carboxymethyl starch 4,800 mg, povidone 1,800 mg, silicon dioxide colloid 0,400 mg, magnesium stearate 0,600 mg; tablet shell: hypromellose 1,280 mg, giprolose 1,280 mg, macrogol-400 0,400 mg, talc 0,200 mg, titanium dioxide 0,840 mg, carnauba wax 0.090 mg.

Description:

Tablets 5 mg: round biconvex tablets, covered with a film coating of light pink color;

Tablets 10 mg: round biconvex tablets coated with a white or almost white film membrane, with a risk on one side.

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.

According to the classification, the allosteric sections of the gamma-aminobutyric acid complex (GABA) to which benzodiazepines bind, are called ω-modulating sites or receptors. To date, three subtypes have been identified: 1, 2 and 3. Unlike benzodiazepines, which unselectively bind and activate all three subtypes of ω-receptors, zolpidem selectively binds to ω₁receptor, so 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-receptor (lumbar spine, hippocampus) and ω₃receptor (certain peripheral regions). Modern experience shows that the pharmacological action of zolpidem differs from that of benzodiazepines.

Interaction with ω-receptors leads to the discovery of neuronal ionoform channels for chloride ions.

The effect comes quickly. 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:

Zolpidem is rapidly absorbed from the gastrointestinal tract (GIT). After taking a dose of 5 mg and 10 mg the maximum concentration in the blood plasma (C_max) is 59 ng / ml and 121 ng / ml, respectively, the time to reach the maximum concentration (TC_max) from 0.5 to 3 hours (mean time 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 with food or immediately after eating.

The pharmacokinetics of zolpidem remains unchanged for several weeks of use.

Bioavailability of zolpidem reaches 70 %, association with blood plasma proteins - 92%. There is a linear relationship between the dose of the drug and the concentration of zolpidem in the blood 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 (T1) of zolpidem is from 0.7 to 3.5 hours (an average of about 2.4 hours).

The total clearance of zolpidem is 0.26 l / h / kg, the volume of distribution is 0.54 l / kg.

Does not induce liver enzymes. Do not cumulate.

In elderly people, clearance in the blood plasma can decrease without a significant increase in T1 (an average of 3 hours), while C_max increases by 50%.

In patients with severe renal dysfunction, the clearance does not increase significantly. In patients with impaired liver function, bioavailability increases, T1 increases to 10 hours.

Indications:

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

Contraindications:

Hypersensitivity to zolpidem or other components of the drug;
severe, acute or chronic liver failure;
sleep apnea syndrome;
acute and / or severe respiratory failure;
pregnancy (I trimester) and the period of breastfeeding;
age under 18 years (effectiveness and safety not established);
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome;
severe myasthenia gravis.

Carefully:

Lung insufficiency of mild and moderate severity, depression, alcoholism, drug addiction and other addictions, pregnancy II and III trimester, respiratory failure of mild and moderate severity, patients with mental illness.

Pregnancy and lactation:

The drug SANVAL is contraindicated for use in the first trimester of pregnancy. If it is necessary to prescribe Sanval® 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.In studies on animals, the teratogenic and embryotoxic effect of the drug was not detected.

Women of reproductive age, patients receiving 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 SANVAL, patients should use reliable contraceptive methods.

In the case of zolpidem at the end of pregnancy or during labor (even at low doses), it is possible to develop a hypothermia in the newborn, transient respiratory depression or apnea, axial hypotension, arterial hypotension, and sucking disorders.

In addition, children born to mothers 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.

Zolpidem is excreted in breast milk, therefore it is contraindicated for use during breastfeeding, if it is necessary to use the drug Sangval® during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug is intended for oral administration, immediately before going to bed, after washing with liquid, after a short time after eating.

Patients with the use of the drug Sunval® should assume that they can afford a continuous sleep within 7-8 hours.

Doses and duration of treatment are determined by the attending physician. It is necessary to strictly adhere to the doctor's instructions and do not exceed the prescribed dose of Sanval®.

The maximum daily intake for adults is 10 mg at bedtime.

For elderly patients (over 65 years), weakened patients, as well as for patients with hepatic insufficiency, the initial dose is 5 mg; if necessary (insufficient clinical effect) and good tolerability of the drug, the dose may be increased to 10 mg.

The course of treatment should not exceed 4 weeks.

With transient insomnia, the recommended course of treatment is 2 to 5 days, with a situational one - 2 to 3 weeks.

Short periods of treatment do not require a gradual discontinuation of the drug.

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).

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: often (> 1/100 to <1/10), infrequently (> 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.

Adverse effects, especially from the 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.

Infectious and parasitic diseases

often: infections of the upper and lower respiratory tract.

Immune system disorders

frequency unknown: angioedema.

Disorders from the psyche

often: hallucinations, agitation, nightmares; infrequently: confusion, irritability; frequency unknown: anxiety, psychosis, dysphoria, aggression, delirium, anger, behavioral disorders, somnambulism,drug dependence (can develop, including when using therapeutic doses), with the withdrawal of the drug - the syndrome of "withdrawal" or "ricochet" insomnia, decreased libido, depression.

Most side effects from the psyche are paradoxical reactions.

Disturbances from the nervous system

often: drowsiness, headache, dizziness, increased insomnia, anterograde amnesia (effects of amnesia can be associated with behavioral reactions), the risk of developing which increases in proportion to the dose; frequency unknown: impaired consciousness.

Disturbances on the part of the organ of sight

infrequently: diplopia.

Disturbances from the respiratory system, chest and mediastinal organs

frequency unknown: respiratory depression.

Disorders from the gastrointestinal tract

often: diarrhea, nausea, vomiting, abdominal pain.

Disturbances from the liver and bile ducts

frequency is unknown: increased activity of "hepatic" enzymes in the blood.

Disturbances from the skin and subcutaneous tissues

frequency unknown: rash, itching, urticaria, increased sweating.

Disorders from the musculoskeletal system

often: back pain; frequency unknown: muscle weakness.

Other

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

If any undesirable phenomena not listed in this manual appear, you should consult your doctor.

Overdose:

If an accidental overdose with Sanval® occurs, seek medical advice immediately.

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, it took more than 1 hour, the patient should be allowed to take inside 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 overdose of zolpidem, even if there is excitement.

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 (seizures), 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 those purchased without a doctor's prescription.

Simultaneous application with ethanol It is not recommended because of the possible increase in the sedative effect of zolpidem.

With the simultaneous use of zolpidem with drugs (LS), depressing the central nervous system (neuroleptics, barbiturates,sleeping pills, anxiolytics / sedatives, antidepressants with sedative action, narcotic analgesics, antitussive central action), antiepileptic drugs, drugs for general anesthesia, blockers H₁histamine receptors with sedative effect, antihypertensive agents of central action; baclofen; thalidomide; Pisotifenum there is an increase in the oppressive effect on the central nervous system and the risk of respiratory depression, drowsiness, impaired psychomotor functions, incl. reduced ability to drive. Also, individual cases of visual hallucinations were reported when used simultaneously with antidepressants (bupropion, desipramine, fluoxetine, sertraline, venlafaxine).

Simultaneous application with fluvoxamine, ciprofloxacin is not recommended because of a possible increase in the concentration of zolpidem in the blood plasma.

When used simultaneously with narcotic analgesics Perhaps an increase in euphoria, leading to an increase in psychological dependence.

When used simultaneously with buprenorphine there is an increased risk of respiratory depression, up to a lethal outcome.It is necessary to warn the patient about strict observance of the doctor's recommendations on the dosage regimen.

Inhibitors and inducers CYP 450 Since the metabolism of zolpidem tartrate occurs in the liver with the participation of several enzymes of the cytochrome P450 family, the main one being the CYP3A4 isozyme with the participation of the CYP1A2 isoenzyme, possible interactions of zolpidem with drugs that are substrates or inductors of the CYP3A4 isoenzyme should be taken into account:

ketoconazole (a potent inhibitor of the isoenzyme CYP3A4) at a dose of 200 mg twice a day, and ritonavir increase T1, AUC and reduce the clearance of zolpidem. Correction of the dosing regimen is not required, but patients should be warned about the possible increase in sedative effect of zolpidem;
Itraconazole (inhibitor of the isoenzyme CYP3A4) is a minor, clinically insignificant change in the pharmacokinetics and pharmacodynamics of zolpidem.
rifampicin (inducer of the isoenzyme CYP3A4) accelerates metabolism, reduces the concentration and, as a consequence, the effectiveness of zolpidem.

Flumazenil eliminates the hypnotic effect of the drug Sanvall.

Interaction with selective serotonin reuptake inhibitors (SSRIs), warfarin, digoxin, ranitidine, cimetidine is not clinically significant.

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 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 continuation 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 carried out 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 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, the following conditions may occur: increased insomnia, nightmares, agitation, nervousness, delirium, hallucinations, confusion and onyricism, psychotic symptoms, disinhibition with impulsivity, 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; automaticbehavior 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 the dream 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 this behavior, the Sanval® drug 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 drug 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 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 with the use of therapeutic doses and / or in patients without individual risk factors.

When using Sanval® in therapeutic doses, the state of dependence on the drug is extremely rare.

In case of dependence on the drug SANVAL, upon termination of its admission, the development of withdrawal syndrome is possible, with common symptoms being: insomnia, headache and myalgia, dysphoria, anxiety, muscle tension and irritability. Less often (in more severe cases of withdrawal syndrome) there are 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 withdrawal syndrome can be observed for several days after discontinuation of treatment with the drug Sanvall®. 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

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 T_1/2, 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.

Using the 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.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused Sanval® preparation.

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

During the period of treatment with the drug SANVAL, care must be taken when driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

If the sleep duration was not sufficient after taking Sanval, the risk of psychomotor reactions is increased, which may pose an additional risk when driving transport and other potentially hazardous activities.

Form release / dosage:

Tablets, film-coated 5 mg or 10 mg.

Packaging:

Primary packaging:

10 tablets per blister of A1 / PVC

Secondary packaging:

Tablets 5 mg: 2 blisters together with instructions for use are placed in a cardboard box. Tablets 10 mg: 1 or 2 blisters together with instructions for use are placed in a cardboard box.

A transparent film of polyolefin with a printed logo is glued onto a cardboard bundle on both sides. , clearly visible in UV light, in order to ensure control of the first autopsy.

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.

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016194 / 01

Date of registration:06.05.2010

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp18.10.2015

Illustrated instructions

Instructions

Sanvall® (Sanval®)