INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SONNAT® (SONNAT®)

Composition:

Active substance: zopiclone;

One tablet contains 7.5 mg of zopiclone, calculated as 100 % substance;

Excipients: povidone; talc; lactose monohydrate (Tablita-80); microcrystalline cellulose; calcium stearate; coating mixture "Opadry II Yellow" 33G22507 (triethyl citrate; hypromellose; lactose monohydrate; titanium dioxide (E 171); polyethylene glycol; yellow iron oxide (E 172)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of creamy-yellow color, round-shaped, biconvex surface, with the imprint "KMP" on one side of the tablet. A white core is visible in cross-section.

Pharmacotherapeutic group. Hypnotics and sedatives. Zopiclone.

ATC code N05CF01.

Pharmacological Properties.

Pharmacodynamics.

Zopiclone belongs to the cyclopyrrolone group and is 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 chloride ion channel opening).

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 distinctive 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 stages of deep sleep (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%.

The time of administration, multiple dosing, and patient gender do not influence absorption.

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 at 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 breastfeeding, 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 N-oxide (pharmacologically active in animals) and N-desmethylated derivative (pharmacologically inactive in animals). Apparent elimination half-lives, determined in 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-dose administration.

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 by the kidneys as free metabolites (N-oxide and N-desmethylated derivative), and about 16% via feces.

Special patient populations.

Elderly patients. Although hepatic metabolism is somewhat reduced and the mean elimination half-life is 7 hours, no accumulation of zopiclone in plasma has been observed after repeated administration in numerous studies.

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 due to the large volume of distribution of zopiclone.

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

Clinical characteristics.

Indications.

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

Contraindications.

The drug must never be used in patients with:

hypersensitivity to zopiclone or to any of the excipients of the drug;
severe respiratory insufficiency;
sleep apnea syndrome;
severe, acute or chronic hepatic insufficiency (due to the risk of encephalopathy);
myasthenia gravis;
parasomnia previously observed after taking zopiclone (see section "Special precautions");
congenital galactosemia; glucose/galactose malabsorption syndrome or lactase deficiency (due to the presence of lactose in the drug).

Interaction with other medicinal products and other forms of interactions.

Sedative drugs. It should be taken into account 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 be hazardous 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.

Hypnotics. Currently prescribed hypnotics are either benzodiazepines and their derivatives (zolpidem, zopiclone), or H1-antihistamines. In addition to enhancing sedative effects, when used concomitantly with other CNS depressants or when alcohol is consumed, the possible potentiation of respiratory depression caused by benzodiazepines should be considered, particularly in elderly patients, especially when co-administered with opioids, 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 should be limited when used concomitantly (see section "Special precautions").

Undesirable combinations.

Alcohol (as beverage or excipient) potentiates the sedative effect of benzodiazepines and related substances. 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 (sodium oxybutyrate). Enhanced central nervous system depression. Impaired concentration ability may be hazardous 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 hypnotics. Enhanced central nervous system depression.

Other sedative agents. Enhanced central nervous system depression.

Combinations to be considered.

Other central nervous system depressants: morphine derivatives (analgesics, antitussives and drugs used in opioid substitution therapy for treatment of opioid dependence, except buprenorphine), neuroleptics, barbiturates, anxiolytics, other hypnotics, sedative antidepressants, antiepileptic drugs, anaesthetics, sedative H1-antihistamines, centrally-acting antihypertensives, baclofen, thalidomide, pizotifen. Enhanced CNS depression. 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 used in 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 decrease when co-administered with CYP3A4 inducers.

Buprenorphine. When buprenorphine is used as substitution therapy for treatment of opioid dependence, the risk of respiratory depression increases, which may potentially be fatal. The risk/benefit ratio of using this combination should 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 for use.

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

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 duration with SonnatÒ did not exceed 4 weeks, no significant tolerance to the drug was observed.

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

The risk of developing dependence increases with higher doses and prolonged duration of treatment with this medicinal product. 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 in patients without specific risk factors.

In rare cases, dependence on zopiclone has been observed during the use of 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 symptoms occur less frequently: agitation 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, irritability, hyperacusis, numbness, and tingling in the limbs.

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

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

Isolated cases of drug abuse have also been reported.

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

Psychomotor disturbances. Like any other sedative/hypnotic substances, zopiclone causes central nervous system depression. 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 activities requiring concentration (see section "Ability to affect reaction speed when driving or operating machinery");
use of doses higher than recommended;
concomitant use with other agents that depress central nervous system function, alcohol, illicit substances, or other medicinal products that increase zopiclone blood concentrations (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, after taking zopiclone, especially within 12 hours after taking this drug.

Amnesia. Anterograde amnesia may occur several hours after taking the tablet. To reduce the risk of developing these symptoms, patients 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 a syndrome of altered consciousness (varying degrees) with memory and behavioral disturbances.

The following symptoms may develop:

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

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

abnormal behavior;
autoaggression 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 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 more pronounced in patients with cerebral disorders.

Some patients may experience restlessness and daytime anxiety.

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

Concomitant alcohol consumption and use of other central nervous system depressants increase the risk of such behaviors, as does the use of 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 "Interaction with other medicinal products and other types of interactions" and "Side effects").

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

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

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

The efficacy and safety of the drug can only be evaluated once equilibrium state is achieved.

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

During clinical trials, 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 result in sedation, respiratory depression, coma, and death.

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

When zopiclone and opioids are prescribed concomitantly, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients should be closely monitored for any signs of respiratory depression and sedative effects (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 related drugs due to the increased risk of behavioral disorders and the risk of developing sedative and/or myorelaxant effects, which may lead to falls, often with serious consequences for this patient group.

Precautionary measures in use. Particular 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 patient's type of insomnia (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.

In patients with a major depressive episode, benzodiazepines and related drugs should not be prescribed as monotherapy, 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 made available 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, their depressant effect on the respiratory center should be considered (especially since anxiety and restlessness may be warning signs of respiratory decompensation requiring transfer to intensive care) (see section "Side effects").

Elderly patients with renal insufficiency. Although no accumulation of zopiclone was observed after long-term 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 for use").

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 substantial amount of data collected from cohort studies has not revealed any evidence that the use of benzodiazepines during the first trimester of pregnancy leads to fetal 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 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 near 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. Although these signs are reversible, they may persist for 1–3 weeks depending on the half-life of the prescribed benzodiazepine. With high-dose use, respiratory depression or apnea and hypothermia may occur in the newborn. Furthermore, the newborn may develop a withdrawal syndrome, even in the absence of signs of drug exposure. Characteristic signs of this condition include, in particular, excessive excitability, psychomotor agitation, and tremor in the newborn, occurring some time after delivery. The time to onset of these symptoms depends on the drug's half-life and may be prolonged in case of a long half-life.

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

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 and operate machinery.

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

Impairment of driving ability and behavioral changes such as falling asleep at the wheel may occur with monotherapy of zopiclone at therapeutic doses.

Moreover, these effects are potentiated by concomitant alcohol consumption or use of other central nervous system depressants (see sections "Special precautions for use" and "Interaction with other medicinal products and other types of interactions"). Patients must be warned about the necessity of avoiding alcohol or other psychoactive substances during zopiclone treatment.

Method of Administration and Dosage

For oral use.

Dosing. Treatment should always be initiated at the lowest effective dose; the maximum dose must not be exceeded. The medication should be taken in bed immediately before going to sleep, as a single dose. Do not take an additional dose of the medication during the same night!

The 3.75 mg dose is specifically intended for elderly patients over 65 years of age and individuals belonging to high-risk groups.

Standard doses:

Adults under 65 years of age: 7.5 mg once daily.
Patients over 65 years of age: 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 be initiated at a dose of 3.75 mg once daily (see section "Pharmacokinetics").

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

Treatment Duration

Treatment with this medicinal product should be as short as possible and must not exceed four weeks, including the period of gradual dose reduction (see section "Special Warnings and Precautions for Use").

Patients should be advised to take the medication for:

In cases of situational insomnia – 2–5 days (e.g., during travel);
In cases of transient insomnia – 2–3 weeks (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 should 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 medicinal product.

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 population.

Overdose

Overdose can be life-threatening, particularly when multiple central nervous system depressants (including alcohol) are taken concomitantly.

Following ingestion of a large amount of zopiclone, overdose primarily manifests as central nervous system depression, ranging from drowsiness to coma, depending on the dose ingested. Mild overdose may present with symptoms of confusion or lethargy.

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

If oral overdose occurred within the last hour, emesis may be induced; otherwise, gastric lavage should be performed with protection of the airway. Administration of activated charcoal may then be beneficial to reduce drug absorption.

Close monitoring of cardiac and respiratory function in a specialized unit is recommended.

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

For diagnosis and/or treatment of accidental or intentional benzodiazepine overdose, administration of flumazenil may be helpful. Flumazenil has an antagonistic effect on benzodiazepines and may therefore induce neurological disturbances (agitation, restlessness, seizures, and emotional lability), particularly in patients with epilepsy.

Side effects

Adverse reactions are categorized by frequency using the following classification: 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).

Side effects depend on dosage and individual patient sensitivity.

Psychiatric disorders

Uncommon: excitement, nightmares.

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

Frequency not known: behavioral disturbances, delirium, 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.

Patients more prone to developing these symptoms include elderly patients and children.

Depression. Latent depression may become manifest during treatment with benzodiazepines and their derivatives.

Disorders of the nervous system

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 impairment.

Disorders of the respiratory system, thoracic and mediastinal organs

Rare: dyspnea.

Frequency not known: respiratory depression.

Disorders of the skin and subcutaneous tissue

Rare: skin rash, itching, urticaria.

Disorders of the musculoskeletal and connective tissue system

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 blood levels of transaminases and/or alkaline phosphatase, 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 suspected adverse reactions. Reporting of suspected adverse reactions after drug registration is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 5 years.

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

Keep out of reach of children.

Packaging. 10 tablets per blister, 1 or 3 blisters per pack.

Prescription category. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.

Sonat®