INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ZOPICLONE (ZOPICLONE)

Composition:

Active ingredient: 1 tablet contains zopiclone (calculated as 100% zopiclone content) – 7.5 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; potato starch; povidone; colloidal anhydrous silicon dioxide; talc; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: intact, regular round cylinders with flat upper and lower surfaces, beveled edges, a dividing score line, white or white with a creamy shade.

Pharmacotherapeutic group.
Hypnotics and sedatives. ATC code N05CF01.

Pharmacological Properties.

Pharmacodynamics.

Zopiclone belongs to the cyclopyrrolone group and is structurally related to the pharmaceutical class of benzodiazepines. The pharmacodynamic effects of zopiclone are qualitatively similar to those of other compounds in this class: it acts as a myorelaxant, anxiolytic, sedative, hypnotic agent, anticonvulsant, and amnestic (causing memory impairment).

These effects are due to its action as a specific agonist at receptors belonging to the GABA-omega macromolecular receptor complex in the central nervous system (known as BZ1 and BZ2), which modulate the opening of chloride ion channels.

In humans, zopiclone has been shown to prolong sleep duration, improve sleep quality, and reduce the frequency of nocturnal and early morning awakenings.

This effect is associated with distinct electroencephalographic characteristics that differ from those typical of benzodiazepines. Polysomnographic studies show that zopiclone reduces the duration of stage I sleep, increases the duration of stage II sleep, maintains or prolongs deep sleep stages (III and IV), and preserves the paradoxical sleep stage or rapid eye movement (REM) sleep.

Pharmacokinetics.

Absorption. Zopiclone is rapidly absorbed: peak plasma concentrations are reached within 1.5–2 hours and are 30, 60, and 115 ng/mL after administration of 3.75 mg, 7.5 mg, and 15 mg, respectively. Bioavailability is approximately 80%.

Absorption is not affected by the time of administration, repeated dosing, or patient gender.

Distribution. Zopiclone is very rapidly distributed from the vascular compartment. Plasma protein binding is low (approximately 45%), and binding is non-saturable. The risk of drug interactions due to displacement from protein-binding sites is very low.

Plasma concentration decline over the dose range of 3.75 mg to 15 mg is dose-independent. The elimination half-life is approximately 5 hours.

Benzodiazepines and related compounds cross the blood-brain barrier and placenta and are excreted into breast milk. During lactation, the pharmacokinetic profiles of zopiclone in milk and maternal plasma are similar. The estimated percentage of the dose ingested by the infant does not exceed 0.2% of the dose received by the mother over 24 hours.

Metabolism. Zopiclone undergoes extensive hepatic metabolism. Two major metabolites are formed: N-oxide (pharmacologically active in animals) and N-desmethylated derivative (pharmacologically inactive in animals). Apparent elimination half-lives, determined from urinary excretion studies, are approximately 4.5 and 7.5 hours, respectively. This is consistent with the observation that no significant accumulation occurs after repeated dosing (15 mg) over 14 days. No increase in enzymatic activity was observed in animal studies, even with high doses.

Excretion. The low renal clearance of unchanged zopiclone (mean 8.4 mL/min) compared to plasma clearance (232 mL/min) indicates that zopiclone is primarily eliminated in metabolized form. Approximately 80% of the substance is excreted in urine as free metabolites (N-oxide and N-desmethylated derivative), and about 16% is excreted in feces.

Special patient groups.

Elderly patients: although hepatic metabolism is somewhat reduced and the mean elimination half-life is 7 hours, numerous studies have not shown accumulation of zopiclone in plasma after repeated administration.

Patients with renal impairment: no accumulation of zopiclone or its metabolites has been observed during long-term treatment. Zopiclone crosses dialysis membranes. Hemodialysis is not effective in treating overdose because zopiclone has a large volume of distribution.

Patients with liver cirrhosis: plasma clearance of zopiclone is significantly reduced due to slowed demethylation; therefore, dose adjustment is required for these patients.

Clinical characteristics.

Indications.

For short-term treatment of severe sleep disorders in adults: transient and temporary insomnia.

Contraindications.

The drug must never be administered to patients with:

hypersensitivity to zopiclone or to any of the excipients of the medicinal product;
severe respiratory insufficiency;
sleep apnea syndrome;
severe, acute or chronic hepatic insufficiency (due to the risk of encephalopathy);
myasthenia gravis;
parasomnia previously occurring after taking zopiclone (see section "Special precautions").

Interaction with other medicinal products and other forms of interaction.

Sedative agents. It should be considered that many medicinal products or substances may cause additive central nervous system (CNS) depressant effects and reduce the patient's concentration ability. Impaired concentration ability may pose a danger when driving vehicles or operating machinery. Such substances include morphine derivatives (analgesics, antitussives and opioid substitution therapy agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally acting antihypertensives, baclofen, and thalidomide.

Hypnotic agents. Currently, hypnotics include either benzodiazepines and their derivatives (zolpidem, zopiclone), or H1-antihistamines. In addition to enhancing sedative effects, when co-administered with other CNS depressants or when alcohol is consumed, possible potentiation of benzodiazepine-induced respiratory depression must be considered, particularly in elderly patients, especially when benzodiazepines are prescribed together with morphine-like substances, other benzodiazepines, or phenobarbital.

Opioids. Concomitant use of benzodiazepines and other sedative-hypnotic medicinal products, including zopiclone and opioids, increases the risk of sedation, respiratory depression, coma, and death due to additional CNS depressant effects. Dose and duration of treatment with benzodiazepines and opioids when used concomitantly should be limited (see section "Special precautions").

Undesirable combinations.

Alcohol (as a beverage or as an excipient in medicinal products) potentiates the sedative effect of benzodiazepines and their derivatives. Due to reduced concentration ability, driving vehicles and operating machinery may be hazardous.

Patients should avoid consuming alcoholic beverages or taking medications containing alcohol.

Sodium oxybate (gamma-hydroxybutyrate) enhances central nervous system depression. Impaired concentration ability may pose a danger when driving vehicles or operating machinery.

Combinations requiring precautions.

Rifampicin. Decreased plasma concentration and reduced efficacy of zopiclone due to enhanced hepatic metabolism; therefore, concomitant use of zopiclone and rifampicin requires careful clinical monitoring. If necessary, an alternative hypnotic may be prescribed.

Barbiturates. Increased risk of respiratory depression, which may be fatal in case of overdose.

Other hypnotic agents. Enhanced central nervous system depression.

Other sedative agents. Enhanced central nervous system depression.

Combinations with warnings.

Other agents that depress central nervous system activity: morphine derivatives (analgesics, antitussives and drugs for opioid substitution therapy in treatment of opioid dependence, except buprenorphine), neuroleptics, barbiturates, anxiolytics, other hypnotics, sedative antidepressants, antiepileptic drugs, anesthetics, sedative H1-antihistamines, centrally acting antihypertensives, baclofen, thalidomide, pizotifen. Enhanced depression of CNS activity. Due to reduced concentration ability, driving vehicles and operating machinery may be hazardous. Furthermore, concomitant use of zopiclone with morphine derivatives (analgesics, antitussives and drugs for opioid substitution therapy) and barbiturates increases the risk of respiratory depression, which may be fatal in case of overdose.

Narcotic analgesics enhance euphoria, which may lead to increased psychological dependence.

Zopiclone is metabolized via cytochrome P450 (CYP3A4 isoenzyme); therefore, plasma levels of zopiclone may increase when co-administered with CYP3A4 inhibitors, and may decrease when co-administered with CYP3A4 inducers.

Buprenorphine. When used as substitution therapy in treatment of opioid dependence, the risk of respiratory depression increases, potentially leading to fatal outcome. The risk/benefit ratio of using this combination must be carefully evaluated. Patients should be warned to strictly adhere to the doses prescribed by the physician.

Clozapine. Increased risk of collapse with respiratory arrest and/or cardiac arrest.

Clarithromycin, erythromycin, telithromycin. Slight enhancement of zopiclone's sedative effects.

Ketoconazole, itraconazole, voriconazole. Slight enhancement of zopiclone's sedative effects.

Nelfinavir, ritonavir-boosted protease inhibitor. Slight enhancement of zopiclone's sedative effects.

Special precautions.

Warnings. This medicinal product contains lactose and therefore should not be used in patients with such rare hereditary conditions as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Drug tolerance. When benzodiazepines or related substances are used for several weeks, their sedative and hypnotic effects may gradually decrease despite the dose remaining unchanged.

In patients whose treatment with Zopiclone did not exceed 4 weeks, no significant drug tolerance was observed.

Drug dependence. The use of zopiclone may lead to drug abuse and/or development of physical and psychological dependence.

The risk of dependence increases with higher doses and longer duration of treatment. The risk of abuse and dependence is higher in patients with a history of psychiatric disorders and/or alcohol, illicit substances, or drug abuse. Zopiclone should be used with particular caution in patients with current or past history of alcohol, illicit substances, or drug abuse or dependence.

Dependence may develop even with therapeutic doses and/or in patients without specific risk factors.

In rare cases, dependence on zopiclone has been observed with therapeutic doses.

After discontinuation of treatment, dependence may lead to withdrawal symptoms.

Some of these symptoms occur frequently: insomnia, headache, excessive anxiety, myalgia, muscle tension, and irritability.

Other less common symptoms: excited state or even confusion, limb paresthesia, increased sensitivity to light, noise, and physical contact, depersonalization, derealization, hallucinations, and seizures.

Withdrawal symptoms may also include tremor, palpitations, tachycardia, delirium, night terrors, agitation, hyperacusis, numbness, and tingling in the limbs.

Withdrawal symptoms may develop several days after treatment discontinuation. When using short-acting benzodiazepines, especially at high doses, withdrawal symptoms may even occur between two doses.

The risk of drug dependence may increase when multiple benzodiazepines are used simultaneously in the treatment of anxiety disorders or sleep disturbances.

Isolated cases of drug abuse are also known.

Rebound insomnia. This transient rebound effect may manifest as a worsening of the insomnia for which benzodiazepines or their derivatives were initially prescribed.

Psychomotor disturbances. Like any other sedative/hypnotic agents, zopiclone exerts a depressant effect on the central nervous system. Psychomotor disturbances may occur several hours after taking the drug.

The risk of psychomotor disturbances, including impaired ability to drive, increases in the following situations:

administration of this medicinal product less than 12 hours before performing tasks requiring concentration (see section "Ability to affect reaction speed when driving or operating machinery");
use of a dose higher than recommended;
concomitant use with other agents that depress central nervous system function, alcohol, illicit substances, or other medicinal products that increase zopiclone concentrations in blood (see section "Interaction with other medicinal products and other types of interactions").

Patients should be advised to avoid hazardous activities requiring full attention or motor coordination, such as operating machinery or driving, for at least 12 hours after taking zopiclone.

Amnesia. Anterograde amnesia and psychomotor impairment may occur several hours after taking the tablet. To reduce the risk of these effects, the patient should take the tablet immediately before bedtime, i.e., while already in bed (see section "Method of administration and dosage"), and ensure conditions are optimal for several hours of uninterrupted sleep (7–8 hours).

Behavioral disorders. In some patients, benzodiazepines and related substances may cause altered states of consciousness (varying in severity) with memory and behavioral disturbances.

Symptoms may include:

worsening of insomnia, night terrors, agitation, nervousness;
delirium, delusions, hallucinations, oneirophrenic state, confusion, psychosis-like symptoms;
mental inhibition, mild excitability;
euphoria, irritability;
anterograde amnesia;
suggestibility (susceptibility to suggestion).

These symptoms may be accompanied by potentially harmful disorders for the patient or others:

abnormal behavior;
self-aggression or aggression toward others, especially if family members or friends try to prevent the patient from doing what they wish;
automatic behavior with subsequent amnesia.

The appearance of these symptoms requires immediate discontinuation of treatment.

Psychotic behavioral changes occur more frequently in patients with aggressive behavior and unusual reactions to sedatives, benzodiazepines, or alcohol consumption, and may also include depersonalization, restlessness, and anger.

The drug affects cognitive functions, specifically mental performance and attention concentration. The risk of these complications is higher in patients with cerebral disorders.

Some patients may experience daytime restlessness and anxiety.

Sleepwalking and related behaviors. In patients receiving zopiclone treatment, episodes of complex behaviors (when the patient takes a hypnotic-sedative drug and does not fully awaken) have been observed, such as sleepwalking and other related episodes, including sleep-driving, preparing and eating food, making phone calls, and sexual activity, all accompanied by amnesia upon awakening.

Concomitant alcohol consumption and use of other central nervous system depressants increase the risk of such behaviors, as does using zopiclone at doses exceeding the maximum recommended dose.

Such episodes may occur after the first or any subsequent dose of zopiclone. Patients who develop sleepwalking-related behavioral disturbances should discontinue zopiclone, as this may be dangerous for both the patients and their surroundings (see sections "Contraindications," "Interaction with other medicinal products and other types of interactions," "Adverse reactions").

Risk of drug accumulation. Benzodiazepines and related substances (as well as any other medicinal product) remain in the body for a time approximately equal to 5 half-lives (see section "Pharmacokinetics").

In elderly patients and patients with impaired liver function, the elimination half-life may be significantly prolonged.

After repeated dosing, zopiclone or its metabolites reach steady-state levels much later and at higher concentrations.

The efficacy and safety of the drug can only be assessed once steady-state levels are achieved.

Dose adjustment may be necessary (see section "Method of administration and dosage").

During clinical studies, no accumulation of zopiclone was observed in patients with renal insufficiency (see section "Pharmacokinetics").

Risk of concomitant use with opioids. Concomitant use of benzodiazepines and other sedative hypnotics, including zopiclone, with opioids may cause sedation, respiratory depression, coma, and death.

Due to these risks, concomitant prescription of opioids and benzodiazepines should be limited only to cases where alternative treatment options are insufficient.

When zopiclone and opioids are prescribed together, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients require close monitoring for any signs of respiratory depression and sedation (see section "Interaction with other medicinal products and other types of interactions").

Elderly patients. Caution should be exercised when treating elderly patients with benzodiazepines or their derivatives due to the increased risk of behavioral disturbances and the risk of sedative and/or myorelaxant effects, which may lead to falls, often with serious consequences in this patient group.

Precautions for use. Special caution is recommended when prescribing to patients with a history of alcoholism or other types of dependence on medicinal products or other substances (see section "Interaction with other medicinal products and other types of interactions").

Before prescribing a hypnotic, comprehensive evaluation and identification of the underlying causes of insomnia should be performed in all cases.

Insomnia may be a symptom of a physical or mental disorder. If insomnia persists or worsens after a short treatment period, the clinical diagnosis should be re-evaluated.

Duration of treatment. The duration of treatment should be clearly defined based on the type of insomnia present (see section "Method of administration and dosage").

Suicide, depression, major depressive episode. Data from some epidemiological studies indicate an increased frequency of suicidal ideation, suicide attempts, and suicide cases in patients with or without depression who received benzodiazepines and other hypnotics, including zopiclone. However, a causal relationship has not been established.

Since insomnia may be a symptom of depression, depression should be treated. If insomnia persists, the clinical diagnosis should be re-evaluated.

Benzodiazepines and related drugs should not be prescribed as monotherapy in patients with major depressive episodes, as they do not treat depression, which may continue to progress, accompanied by unchanged or increased suicide risk.

Since suicide risk may exist in such patients, the smallest possible number of zopiclone tablets should be available to them to minimize the risk of intentional overdose.

Gradual dose reduction. Patients should be clearly instructed on how to gradually discontinue treatment.

In addition to the necessity of gradual dose reduction, patients should also be warned about the risk of rebound insomnia to minimize the development of any insomnia that may arise due to withdrawal symptoms, even with gradual discontinuation.

Patients should be informed about possible discomfort during the period of gradual treatment discontinuation.

Respiratory insufficiency. When prescribing benzodiazepines and related drugs to patients with respiratory insufficiency, one should remember their depressant effect on the respiratory center (especially since anxiety and restlessness may be warning signs of respiratory decompensation requiring transfer of the patient to intensive care) (see section "Adverse reactions").

Elderly patients with renal insufficiency. Although no accumulation of zopiclone was detected after prolonged use, this patient group should be prescribed half the usual recommended dose as a precautionary measure (see section "Method of administration and dosage" and section "Special precautions").

Caution should be exercised when prescribing to patients with depression.

It is not recommended to prescribe the drug to patients with severe hepatic insufficiency and encephalopathy.

The drug should not be prescribed at the initial stage of psychosis treatment.

Use during pregnancy or breastfeeding.

Pregnancy. A large body of data collected from cohort studies has not shown any evidence that the use of benzodiazepines during the first trimester of pregnancy leads to congenital malformations. However, in some case-control epidemiological studies, an increased frequency of cleft lip and palate was observed with benzodiazepine use. According to these data, the frequency of cleft lip and palate was less than 2 cases per 1000 newborns exposed to benzodiazepines during intrauterine development, compared to an expected frequency of 1 per 1000 in the general population.

Reduced fetal movements and changes in fetal heart rate have been described with high-dose benzodiazepine use during the second and/or third trimesters of pregnancy. The use of benzodiazepines at the end of pregnancy, even at low doses, may cause signs of drug effects in the newborn, such as axial hypotonia and difficulty sucking, leading to poor weight gain. These signs are reversible but may persist from 1 to 3 weeks, depending on the half-life of the prescribed benzodiazepine. With high-dose use, respiratory depression or apnea and hypothermia may be observed in newborns. In addition, newborns may develop withdrawal syndrome, even in the absence of signs of drug absorption. It is characterized, in particular, by symptoms such as excessive excitability, psychomotor agitation, and tremor, appearing some time after delivery. The time of onset depends on the drug's half-life and may be significant in case of long half-life.

Given these data, as a precautionary measure, the use of zopiclone during pregnancy, regardless of the trimester, is not recommended.

Women of reproductive age receiving zopiclone treatment should be instructed to contact their physician if they plan pregnancy or if they become pregnant in early stages, so that their need for treatment can be reassessed.

If zopiclone treatment is absolutely necessary during pregnancy, high doses should be avoided shortly before the expected delivery date, and the above-described effects should be considered when monitoring the newborn.

Lactation period. Zopiclone is not recommended during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Zopiclone may have a pronounced effect on the ability to drive vehicles and operate machinery.

Patients who drive vehicles or operate machinery should be warned that, as with any other hypnotic drugs, somnolence, slowed reaction time, dizziness, lethargy, blurred vision or double vision, and reduced attention concentration may occur, along with impaired ability to drive, especially within the first 12 hours after taking zopiclone (see section "Adverse reactions"). To minimize this risk, an interval of at least 12 hours between taking zopiclone and driving, operating machinery, or working at heights is recommended.

Impaired ability to drive and behavioral changes such as falling asleep at the wheel may occur during monotherapy with zopiclone at therapeutic doses.

Furthermore, these effects are intensified by concomitant alcohol consumption or use of other central nervous system depressants (see sections "Special precautions" and "Interaction with other medicinal products and other types of interactions").

Patients should be warned not to consume alcohol or other psychoactive substances during zopiclone treatment.

Dosage and Administration

For oral use.

Dosing. Treatment should always begin with the lowest effective dose; the maximum dose must not be exceeded.

The medicine should be taken in bed immediately before going to sleep, as a single dose. An additional dose of the medicine must not be taken during the same night!

The 3.75 mg dose is specifically intended for elderly patients aged 65 years and older and for patients belonging to high-risk groups.

Recommended doses:

Adults under 65 years of age: 7.5 mg once daily.
Patients aged 65 years and older: 3.75 mg once daily; the 7.5 mg dose may be used only in exceptional cases.
Patients with hepatic impairment or chronic respiratory insufficiency: the recommended dose is 3.75 mg once daily (see section "Pharmacokinetics").
Patients with renal insufficiency: treatment should start with a dose of 3.75 mg once daily (see section "Pharmacokinetics").

In all cases, the daily dose must not exceed 7.5 mg.

Treatment duration. Treatment should be as short as possible. The treatment course should not exceed 4 weeks, including the period of gradual dose reduction (see section "Special precautions for use").

Patients should be advised to take the medicine for:

2–5 days — in case of transient insomnia (e.g., during travel);
2–3 weeks — in case of short-term insomnia (e.g., caused by a significant life event).

In some cases, it may be necessary to extend treatment beyond the recommended period. However, treatment duration must not be extended beyond the maximum period without re-evaluation of the patient's condition, as the risk of abuse and dependence increases with prolonged use of this medicine.

Children.

The safety and efficacy of zopiclone in children and adolescents (under 18 years of age) have not been established. Therefore, zopiclone is not recommended for use in this patient group.

Overdose.

Overdose may be life-threatening, especially in cases of concomitant overdose with other central nervous system depressants (including alcohol).

Symptoms. Ingestion of a large amount of zopiclone leads primarily to central nervous system depression, ranging from drowsiness to coma, depending on the ingested dose. Mild overdose may present with confusion or lethargy.

In more severe cases, ataxia, muscle hypotonia, arterial hypotension, methemoglobinemia, respiratory depression, and occasionally fatal outcomes may occur. Other risk factors that may exacerbate overdose symptoms include concomitant medical conditions.

Treatment. If oral overdose occurred less than one hour ago, vomiting may be induced in a conscious patient; otherwise, gastric lavage should be performed with airway protection. Administration of activated charcoal afterward may help reduce drug absorption.

Careful monitoring of cardiac and respiratory functions in a specialized unit is recommended.

Hemodialysis is not considered appropriate for treating overdose, as zopiclone has a large volume of distribution.

For diagnosis and/or treatment of accidental or intentional benzodiazepine overdose, administration of intravenous flumazenil may be beneficial.

Flumazenil has effects opposite to those of benzodiazepines and may therefore provoke neurological disturbances (agitation, restlessness, seizures, and emotional lability), particularly in patients with epilepsy.

Adverse reactions.

Adverse effects depend on the dose and individual patient sensitivity.

The following classification is used to determine the frequency of adverse reactions: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Psychiatric disorders.

Uncommon: excitement, nightmares.

Rare: impaired consciousness, changes in libido, irritability, aggression, aggressive behavior, hallucinations.

Frequency not known: behavioral disturbances, delirium, delusions, rage attacks, nervousness, parasomnia including sleepwalking (see section "Special precautions"), physical and psychological dependence on the drug, even at therapeutic doses, with withdrawal syndrome or rebound symptoms after discontinuation of the drug (see section "Special precautions"), confusion, insomnia, tension.

During treatment with benzodiazepines and their derivatives, psychotic-like symptoms, inappropriate behavior, and other behavioral disturbances may occur. In rare cases, these symptoms may be severe. Elderly patients and children are more prone to developing these symptoms.

During treatment with benzodiazepines and their derivatives, latent depression may become manifest.

Nervous system disorders.

Common: reduced reaction speed or even drowsiness (especially in elderly patients), dysgeusia.

Uncommon: feeling of faintness, headache.

Rare: anterograde amnesia, which may occur with therapeutic doses (risk increases proportionally with dose).

Frequency not known: ataxia, paresthesia, cognitive disorders such as memory, attention, and speech disturbances.

Respiratory, thoracic and mediastinal disorders.

Rare: dyspnea.

Frequency not known: respiratory depression.

Skin and subcutaneous tissue disorders.

Rare: skin rash, pruritus, urticaria.

Musculoskeletal and connective tissue disorders.

Frequency not known: muscle hypotonia.

General disorders.

Uncommon: asthenia.

Immune system disorders.

Very rare: angioedema, anaphylactic reactions.

Eye disorders.

Frequency not known: diplopia.

Gastrointestinal disorders.

Common: dry mouth.

Uncommon: nausea.

Frequency not known: dyspepsia, vomiting.

Hepatobiliary disorders.

Very rare: increased levels of transaminases and/or alkaline phosphatase in blood, which in exceptional cases may lead to clinical signs of impaired liver function.

Injury, poisoning and procedural complications.

Rare: falls (especially in elderly patients) (see section "Special precautions").

Reporting of adverse reactions.

Reporting of adverse reactions after drug registration is highly important. It allows continuous monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1, 2, or 3 blisters in a carton.

Prescription status.

Prescription only.

Manufacturer.

JSC "Lubnipharm".

Manufacturer's address and location of its business activities.

16 Barvinkova Street, Lubny, Poltava region, 37500, Ukraine.