Acentra®

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

Composition:

Active substance: sertraline;

One film-coated tablet contains 50 mg or 100 mg of sertraline as sertraline hydrochloride;

Excipients: calcium hydrogen phosphate, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropylcellulose, talc, magnesium stearate;

Coating: Oparay 03H28758 white (hypromellose, titanium dioxide (E 171), talc, propylene glycol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, film-coated tablets with beveled edges and a division line on one side.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06AB06.

Pharmacological Properties.

Pharmacodynamics.

Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) reuptake in vitro, which in animals enhances the effects of 5-HT. Sertraline has only a very weak effect on neuronal reuptake of norepinephrine and dopamine. Due to its selective inhibition of 5-HT reuptake, sertraline does not stimulate catecholaminergic activity. The drug has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA, or benzodiazepine receptors. Chronic administration of sertraline in animals leads to a reduction in brain norepinephrine receptor activity, a phenomenon also observed with other clinically effective antidepressants and anti-obsessive agents.

Sertraline does not cause drug dependence. Sertraline does not produce the stimulant effects or anxiety typical of d-amphetamine, nor does it cause the sedative effects or psychomotor impairments typical of alprazolam. Sertraline does not act as a positive reinforcer in rhesus monkeys trained to self-administer cocaine, nor does it substitute as a discriminative stimulus for d-amphetamine or phenobarbital in this animal species.

Clinical Efficacy and Safety

Cardiac Electrophysiology

In a dedicated thorough QTc study conducted at steady state under supratherapeutic drug exposure in healthy volunteers (receiving sertraline 400 mg/day, twice the maximum recommended daily dose), the upper bound of the two-sided 90% confidence interval [CI] for the time-matched, least-squares mean difference in QTcF between sertraline and placebo (11.666 ms) exceeded the predefined threshold of 10 ms at 4 hours post-dose. An exposure–response analysis demonstrated a positive relationship between QTcF and plasma sertraline concentrations [0.036 ms/(ng/mL); p < 0.0001]. As shown by the exposure–response model, the threshold for clinically significant QTcF prolongation (i.e., predicted 90% CI exceeding 10 ms) is at least 2.6 times higher than the mean maximum analyte concentration (Cmax) (86 ng/mL) following administration of the maximum recommended dose of sertraline (200 mg/day) (see sections "Special Instructions", "Interaction with Other Medicinal Products and Other Forms of Interaction", "Adverse Reactions", and "Overdose").

Obsessive-Compulsive Disorder (OCD) in Pediatric Patients

The safety and efficacy of sertraline (50–200 mg/day) were evaluated in the treatment of children (6–12 years) and adolescents (13–17 years) without depression, who were treated as outpatients for obsessive-compulsive disorder (OCD). After a 1-week initial period of single-blind placebo administration, patients were randomized to receive either sertraline or placebo for 12 weeks with flexible dosing. Children (6–12 years) initiated treatment at a dose of 25 mg. Patients randomized to sertraline showed significantly greater improvement compared to those receiving placebo, as assessed by the Yale-Brown Children's Obsessive-Compulsive Scale (CY-BOCS) (p = 0.005), the National Institute of Mental Health (NIMH) Global Obsessive-Compulsive Scale (p = 0.019), and the Clinical Global Impression-Improvement scale (p = 0.002). Additionally, patients in the sertraline group showed a trend toward greater improvement on the Clinical Global Impression-Severity scale (p = 0.089). The mean baseline CY-BOCS score and mean change from baseline in the placebo group were 22.25 ± 6.15 and –3.4 ± 0.82, respectively, while in the sertraline group, the mean baseline score and mean change from baseline were 23.36 ± 4.56 and –6.8 ± 0.87, respectively. In a retrospective analysis, the percentage of patients who responded to therapy—defined as those with at least a 25% reduction in CY-BOCS score (primary efficacy parameter) from baseline to endpoint—was 53% in the sertraline group compared to 37% in the placebo group (p = 0.03).

Data on long-term safety and efficacy of sertraline in this pediatric patient population are lacking.

Children

Data on the use of sertraline in children under 6 years of age are lacking.

Post-marketing Safety Study SPRITES

An observational post-marketing study involving 941 patients aged 6–16 years was conducted to evaluate the long-term safety of sertraline treatment (with and without psychotherapy) compared to psychotherapy alone, with respect to cognitive, emotional, physical, and sexual maturation over up to 3 years. This study was conducted under real-world clinical practice conditions involving children and adolescents with a primary diagnosis of OCD, depression, or other anxiety disorders, and assessed cognitive functions (using the Trails B test and the Metacognition Index from the Behavior Rating Inventory of Executive Function (BRIEF)), behavioral/emotional regulation (assessed via the BRIEF Behavioral Regulation Index), and physical/sexual maturation (assessed via standardized height/weight, body mass index (BMI), and Tanner stage). Sertraline use in children is approved only for patients aged 6 years and older with OCD (see section "Indications").

Standardization of each primary outcome measure based on age- and sex-specific norms indicated that overall outcomes were consistent with normal development. No statistically significant differences in primary outcome measures were observed except for body weight. A statistically significant result for standardized body weight was observed in the comparative analysis; however, the magnitude of body weight change was small [mean (standard deviation/SD) change in standardized z-scores < 0.5 SD]. A dose–response relationship for weight gain was observed.

Pharmacokinetics.

Absorption

The pharmacokinetics of sertraline in the dose range of 50–200 mg is dose-dependent. After 14 days of once-daily oral administration of sertraline at doses of 50–200 mg, peak plasma concentrations of sertraline are reached within 4.5–8.4 hours after daily dosing. Food intake does not significantly alter the bioavailability of sertraline tablets.

Distribution

Approximately 98% of circulating sertraline is protein-bound.

Biotransformation

Sertraline undergoes extensive presystemic metabolism (first-pass effect) in the liver.

Elimination

The mean elimination half-life of sertraline is approximately 26 hours (ranging from 22 to 36 hours). Based on this terminal half-life, drug accumulation (approximately doubling of levels) occurs at steady state, which is achieved after one week of once-daily dosing. The elimination half-life of N-desmethylsertraline is 62–104 hours. Sertraline and N-desmethylsertraline are extensively metabolized in humans, with their final metabolites excreted in equal amounts in feces and urine. Only a very small fraction (<0.2%) of sertraline is excreted unchanged in urine.

Pharmacokinetics in Specific Patient Populations

Children with Obsessive-Compulsive Disorder (OCD)

A low initial dose is recommended for pediatric patients, especially those with low body weight, with dose titration in 25 mg increments. Adolescents may be given the same doses as adults.

Adolescents and Elderly Patients

The pharmacokinetic profile of sertraline in adolescents and elderly patients does not differ significantly from that in adults aged 18–65 years.

Hepatic Impairment

In patients with hepatic impairment, the elimination half-life of sertraline is prolonged and the area under the plasma concentration-time curve (AUC) is increased by threefold (see sections "Dosage and Administration" and "Special Instructions").

Renal Impairment

No significant accumulation of sertraline was observed in patients with moderate or severe renal impairment.

Clinical characteristics.

Indications.

Sertraline is indicated for the treatment of the following disorders:

• Major depressive episodes (MDE). Prevention of MDE recurrence.
• Panic disorder with or without agoraphobia.
• Obsessive-compulsive disorder (OCD) in adults and children aged 6–17 years.
• Social anxiety disorder.
• Post-traumatic stress disorder (PTSD).

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Concomitant use of sertraline with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome, manifested by symptoms such as agitation, tremor, and hyperthermia.

Sertraline therapy may be initiated no earlier than 14 days after discontinuation of treatment with irreversible MAOIs.

Sertraline administration must be discontinued at least 7 days before starting therapy with irreversible MAOIs (see section "Interaction with other medicinal products and other types of interactions").

Concomitant use of sertraline and pimozide is contraindicated (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Contraindicated

MAO inhibitors

Irreversible MAO inhibitors (e.g., selegiline)

Concomitant use of sertraline with irreversible MAO inhibitors such as selegiline is contraindicated. Sertraline must not be prescribed within at least 14 days after stopping treatment with irreversible MAO inhibitors. Sertraline treatment should be discontinued at least 7 days before initiating therapy with irreversible MAOIs (see section "Contraindications").

Reversible selective MAO-A inhibitor (moclobemide)

Due to the risk of serotonin syndrome, combination of sertraline with reversible MAO inhibitors such as moclobemide should not be used. After discontinuation of reversible MAO inhibitors, the interval before starting sertraline therapy may be shorter than 14 days; however, sertraline should be discontinued at least 7 days before initiating therapy with reversible MAO inhibitors (see section "Contraindications").

Reversible non-selective MAO inhibitors (linezolid)

The antibiotic linezolid is a weak reversible non-selective MAO inhibitor and should not be used in patients receiving sertraline (see section "Contraindications").

Severe adverse reactions have been reported in patients who recently discontinued MAO inhibitors (e.g., methylene blue) and started sertraline, or who discontinued sertraline shortly before initiating MAO inhibitors. These reactions included tremor, myoclonus, increased sweating, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and fatal outcomes.

Pimozide

In a single-dose study with a low dose of pimozide (2 mg), an increase in pimozide levels by approximately 35% was observed. This increase in levels was not associated with any changes in ECG parameters. Although the mechanism of this interaction is unknown, concomitant administration of sertraline and pimozide is contraindicated due to the narrow therapeutic index of pimozide (see section "Contraindications").

Not recommended for concomitant use with sertraline

Alcohol and CNS depressants

Concomitant administration of sertraline at a dose of 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor functions in healthy volunteers; however, concomitant use of sertraline with alcohol is not recommended.

Other serotonergic medicinal products

(see section "Special precautions for use").

Sertraline should be used with caution when co-administered with fentanyl, primarily used during general anesthesia and in chronic pain management, other serotonergic agents (including other serotonergic antidepressants, amphetamines, triptans), and other opioid agents (including buprenorphine).

Special precautions for use

QT-prolonging agents

The risk of QTc interval prolongation and/or ventricular arrhythmias (e.g., torsades de pointes) may be increased when sertraline is used concomitantly with other agents that prolong the QTc interval (e.g., certain antipsychotics and antibiotics) (see sections "Special precautions for use" and "Pharmacodynamics").

Lithium

In a placebo-controlled study involving healthy volunteers, concomitant administration of sertraline and lithium did not significantly alter lithium pharmacokinetics but resulted in increased tremor compared to placebo, suggesting a possible pharmacodynamic interaction. Appropriate patient monitoring is required when sertraline and lithium are used concomitantly.

Phenytoin

Results from a placebo-controlled study in healthy volunteers indicate that prolonged administration of sertraline at a dose of 200 mg daily does not result in clinically significant inhibition of phenytoin metabolism. However, there have been reports of elevated phenytoin exposure in patients taking sertraline; monitoring of plasma phenytoin concentrations is recommended during the initial phase of sertraline therapy, with appropriate adjustment of phenytoin dosage. Additionally, concomitant use of sertraline with phenytoin may lead to decreased plasma concentrations of sertraline. A reduction in sertraline plasma levels under the influence of other CYP3A4 enzyme inducers such as phenobarbital, carbamazepine, St. John’s wort, and rifampicin cannot be excluded.

Triptans

During the post-marketing surveillance period, isolated reports have been received of cases of weakness, hyperreflexia, incoordination, confusion, anxiety, and agitation with concomitant use of sertraline and sumatriptan. Serotonin syndrome symptoms may also develop with the use of other drugs in this class (triptans). If concomitant treatment with sertraline and triptans is clinically necessary, appropriate patient monitoring should be ensured (see section "Special precautions for use").

Warfarin

Concomitant use of sertraline at a dose of 200 mg daily and warfarin resulted in a small but statistically significant increase in prothrombin time, which may in rare cases lead to disturbances in the international normalized ratio (INR). Therefore, prothrombin time should be carefully monitored at the beginning of sertraline therapy and upon its discontinuation.

Interaction with other medicinal products, digoxin, atenolol, cimetidine

Concomitant use with cimetidine led to a significant reduction in sertraline clearance. The clinical significance of these changes is not established. Sertraline does not affect the beta-blocking properties of atenolol. No interaction was observed with concomitant administration of sertraline 200 mg/day and digoxin.

Medicinal products affecting platelet function

The risk of bleeding may be increased when selective serotonin reuptake inhibitors (SSRIs), including sertraline, are used concomitantly with medicinal products affecting platelet function (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and ticlopidine), or with other medicinal products that may increase the risk of bleeding (see section "Special precautions for use").

Neuromuscular blocking agents

SSRIs may reduce cholinesterase activity in plasma, leading to prolonged neuromuscular blockade with mivacurium or other neuromuscular blocking agents.

Drugs metabolized by cytochrome P450

Sertraline may act as a weak or moderate inhibitor of the CYP2D6 isoenzyme. Prolonged administration of sertraline at a dose of 50 mg daily resulted in a moderate increase (on average by 23–37%) in steady-state plasma concentrations of desipramine (a marker of CYP2D6 activity). Clinically significant interactions may occur with other CYP2D6 substrates that have narrow therapeutic ranges, such as class 1C antiarrhythmics (particularly propafenone and flecainide), tricyclic antidepressants, and typical antipsychotics, especially when sertraline is used at higher doses.

Sertraline is not a clinically significant inhibitor of the CYP3A4, CYP2C9, CYP2C19, or CYP1A2 isoenzymes. This is supported by results from in vivo drug interaction studies using substrates of CYP3A4 (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate (diazepam), and CYP2C9 substrates (tolbutamide, glyburide, and phenytoin). In vitro study results indicate that sertraline has very low or no potential to inhibit CYP1A2.

Concomitant use of sertraline with metamizole, an inducer of metabolic enzymes including CYP2B6 and CYP3A4, may lead to decreased plasma concentrations of sertraline with potential reduction in clinical efficacy. Therefore, caution is recommended when using metamizole and sertraline concomitantly; if necessary, clinical response and/or drug plasma levels should be monitored.

Special precautions for use.

Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS)

Cases of potentially life-threatening syndromes such as serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS) have been reported during treatment with SSRIs, including sertraline. The risk of developing SS or NMS increases when SSRIs are used concomitantly with other serotonergic agents (including other serotonergic antidepressants and triptans), drugs that impair serotonin metabolism (including monoamine oxidase inhibitors, such as methylene blue), antipsychotics and other dopamine antagonists, and opioids (including buprenorphine). Serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic nervous system disturbances (e.g., tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). Some manifestations of serotonin syndrome, including hyperthermia, muscle rigidity, autonomic instability, and mental status changes, resemble those of neuroleptic malignant syndrome. Patients should be monitored for signs and symptoms of SS or NMS (see section "Contraindications").

Switching from SSRIs, antidepressants, or anti-obsessive agents

There are limited data from controlled studies on the optimal timing for switching from SSRIs, antidepressants, or anti-obsessive agents to sertraline. Caution is advised when changing treatments, especially when switching to sertraline from long-acting agents such as fluoxetine.

Other serotonergic agents, e.g., tryptophan, fenfluramine, and 5-HT agonists

Concomitant use of sertraline with other agents that enhance serotonergic neurotransmission, including amphetamines, tryptophan, fenfluramine, 5-HT agonists, or herbal preparations containing St. John’s wort (Hypericum perforatum), should be undertaken with caution and, if possible, avoided due to potential pharmacodynamic interactions.

QTc interval prolongation / torsades de pointes ventricular tachycardia

Cases of QTc interval prolongation and torsades de point游戏副本

Dosage and Administration

Initiation of Treatment

Depression and OCD

Treatment with sertraline should be initiated at a dose of 50 mg once daily.

Panic Disorders, PTSD, and Social Anxiety Disorder

Treatment should be initiated at a dose of 25 mg once daily. After 1 week, the dose should be increased to 50 mg once daily. This dosing regimen has been shown to reduce the frequency of adverse effects typical of panic disorders in the early stages of treatment.

Dose Titration

Depression, OCD, Panic Disorders, Social Anxiety Disorder, and PTSD

For patients who do not respond to the 50 mg dose, dose escalation may be necessary. The dose should be gradually increased in 50 mg increments, with intervals of at least 1 week, up to a maximum dose not exceeding 200 mg once daily. Dose adjustments should not occur more frequently than once per week, considering the 24-hour half-life of sertraline.

Therapeutic effects may be observed within 7 days of treatment. However, a longer period is usually required to observe a therapeutic response, particularly in patients with OCD.

Maintenance Dose

Dosage during long-term therapy should be maintained at the lowest effective level, with appropriate adjustments based on therapeutic response.

Depression

Long-term therapy may also be used to prevent relapse of major depressive episodes. In most cases, the recommended dose for relapse prevention is the same as that used during treatment of the depressive episode. Patients with depression should be treated for a sufficient duration—typically at least 6 months—to ensure complete symptom remission.

Panic Disorders and OCD

During long-term therapy in patients with panic disorders and OCD, regular evaluation of treatment is recommended, as prevention of relapse has not been established for these disorders.

Use in Elderly Patients

Sertraline should be used with caution in elderly patients, as they may be at increased risk of developing hyponatremia (see section "Special Warnings and Precautions for Use").

Use in Hepatic Impairment

Sertraline should be used with caution in patients with hepatic disease. In cases of hepatic impairment, the dose or frequency of administration should be reduced (see section "Special Warnings and Precautions for Use"). Sertraline is not recommended for patients with severe hepatic impairment due to the lack of clinical data on its use in such patients (see section "Special Warnings and Precautions for Use").

Use in Renal Impairment

Dosage adjustment is not required in patients with renal impairment (see section "Special Warnings and Precautions for Use").

Use in Children

Children and Adolescents with OCD

Ages 13–17 years: initial dose is 50 mg once daily.

Ages 6–12 years: initial dose is 25 mg once daily. After 1 week, the dose may be increased to 50 mg once daily.

If necessary and no desired effect is observed at a dose of 50 mg daily, further dose increases may be considered, increasing by 50 mg at a time over several weeks. The maximum dose is up to 200 mg daily.

However, when increasing the dose beyond 50 mg in pediatric patients, the generally lower body weight of children compared to adults should be taken into account. Dose adjustments should not occur more frequently than once per week.

Efficacy of sertraline in children with major depressive disorder has not been demonstrated.

Data on the use of sertraline in children under 6 years of age are lacking (see section "Special Warnings and Precautions for Use").

Withdrawal Symptoms Observed upon Discontinuation of Sertraline

Abrupt discontinuation of the drug should be avoided. When stopping sertraline treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). If intolerable symptoms occur after dose reduction or discontinuation, consideration may be given to resuming the previously prescribed dose. The physician may then continue tapering the dose, but more gradually.

Children

Sertraline should not be used for the treatment of children, except for children aged 6 years and older with obsessive-compulsive disorder (see section "Dosage and Administration").

Overdose

Toxicity

Sertraline has a wide safety margin in overdose, which depends on the patient population and/or concomitant use of other drugs. Cases of overdose with sertraline as monotherapy up to 13.5 g have been reported. Fatalities have been reported following overdose of sertraline, both as monotherapy and in combination with other drugs and/or alcohol. Therefore, every case of overdose requires intensive management.

Symptoms

Symptoms of overdose include serotonin-mediated adverse effects such as somnolence, gastrointestinal disturbances (including nausea and vomiting), tachycardia, tremor, agitation, and dizziness. Rarely, cases of coma have been reported.

Prolongation of the QTc interval/ventricular tachycardia of the torsades de pointes type has been reported following sertraline overdose; therefore, ECG monitoring is recommended in all cases of overdose (see sections "Special Warnings and Precautions for Use," "Interaction with Other Medicinal Products and Other Forms of Interaction," and "Pharmacodynamics").

Treatment

There is no specific antidote for sertraline. Maintenance of a patent airway and adequate oxygenation and ventilation should be ensured and supported as needed. Administration of activated charcoal, which may be used with a laxative, may be as effective as gastric lavage and should be considered in overdose management. Induction of emesis is not recommended. Recommended monitoring includes cardiac monitoring (e.g., ECG) and vital signs, along with symptomatic and supportive therapy. Due to the large volume of distribution of sertraline, interventions such as forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be beneficial.

Adverse reactions.

The intensity and frequency of certain adverse reactions may decrease with continued use – in such cases, discontinuation of treatment is usually not required.

Withdrawal syndromes observed upon discontinuation of sertraline therapy

Discontinuation of sertraline therapy, particularly abrupt discontinuation, usually results in the development of withdrawal symptoms. The most commonly reported adverse events included dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, and headache. These symptoms were usually mild or moderate and resolved spontaneously; however, in some patients they may be severe and/or prolonged. Therefore, when sertraline therapy is no longer required, gradual discontinuation by dose tapering is recommended (see sections "Dosage and administration" and "Special precautions").

Elderly patients

The use of SSRIs or SNRIs, including sertraline, has been associated with clinically significant cases of hyponatraemia in elderly patients, in whom the risk of developing this adverse effect may be increased (see section "Special precautions").

Children

In over 600 children treated with sertraline, the overall adverse reaction profile was generally similar to that observed in studies involving adult patients. The following adverse reactions were reported in controlled trials (number of patients receiving sertraline was 281):

Very common (≥ 1/10): headache (22%), insomnia (21%), diarrhoea (11%) and nausea (15%).

Common (≥ 1/100 to < 1/10): chest pain, mania, pyrexia, vomiting, loss of appetite, affective lability, aggression, agitation, nervousness, attention disturbance, dizziness, hyperkinesia, migraine, somnolence, tremor, visual disturbance, dry mouth, dyspepsia, night terrors, increased fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.

Uncommon (≥ 1/1000 to < 1/100): QT interval prolongation on ECG (see sections "Special precautions", "Interaction with other medicinal products and other forms of interaction", and "Pharmacodynamics"), suicide attempt, seizures, extrapyramidal disorder, paraesthesia, depression, hallucinations, purpura, hyperventilation, anaemia, liver function abnormalities, increased alanine aminotransferase levels, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, haematuria, pustular rash, rhinitis, injury, weight decrease, muscle twitching, unusual dreams, apathy, albuminuria, pollakiuria, polyuria, breast pain, menstrual disorder, alopecia, dermatitis, skin lesions, unusual skin odour, urticaria, bruxism, hot flushes.

Class-specific effects

An increased risk of bone fractures has been observed in patients aged 50 years and older who were treated with SSRIs and tricyclic antidepressants. The mechanism underlying this increased risk is unknown.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorised is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

The medicinal product does not require special storage conditions.

Keep out of the reach of children.

Packaging

7 tablets in a blister, 4 blisters in a carton.

Prescription status

Prescription only.

Manufacturer

KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.