Fokusin® Combi (Fokusin® Combi)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Similar drugsTo uncover
Dosage form: & nbspa set of modified release capsules and film-coated tablets
Composition:

Composition per one capsule: active substance: tamsulosin hydrochloride 0.4 mg; Excipients: methacrylic acid and ethyl acrylate copolymer [1: 1] [30% dispersion] - 74.9 mg (in the form of a solid); cellulose microcrystalline - 257.1 mg; dibutyl sebacate 8.4 mg; polysorbate 80 - 0.5 mg; silicon dioxide colloid - 3,7 mg; talc - 0.3 mg; shell capsules: dye azorubin - 0,2%; dye blue patented - 0.12%; gelatin - up to 100%.

Composition per one tablet: active substance: finasteride 5 mg; auxiliary substances: core: lactose monohydrate - 77.45 mg; corn starch - 40.0 mg; Povidone K30 - 3.25 mg; sodium carboxymethyl starch (type A) 2.6 mg; docusate sodium 0.4 mg; magnesium stearate - 1.3 mg; film sheath: hypromellose 2910/5 - 3,15 mg; macrogol 6000 - 0.3 mg; talc - 0.3 mg; titanium dioxide - 0.2 mg; simethicone emulsion SE4 - 0.03 mg; iron oxide oxide yellow - 0.02 mg.

Description:

Tamsulosin

Hard gelatin capsules number 1. Body and lid: dark blue, transparent. Contents of capsules: white or almost white pellets.

Finasteride

Round, biconvex tablets of light yellow color, film-coated

Pharmacotherapeutic group:Tamsulosin: α1-adrenoblocker; finasteride: 5α-reductase inhibitor
ATX: & nbsp
  • Tamsulosin
  • Finasteride
    • Pharmacodynamics:

    The pharmacological action is α-adrenoblocking, antiandrogenic.

    The drug Fokusin® Combi is designed to treat and control the symptoms of benign prostatic hyperplasia (BPH), if necessary combined treatment with tamsulosin and finasteride.

    Focussin® Combi can only be used with an enlarged prostate (volume of the prostate more than 40 cm3). With this increase in the prostate, the combination treatment alleviates the symptoms of BPH and slows the clinical progression of the disease more effectively than monotherapy with finasteride or the α 1 -adrenoreceptor blocker.

    Pharmacodynamics of tamsulosin

    Tamsulosin selectively and competitively blocks postsynaptic α1A-adrenoceptors of smooth muscles of the prostate, bladder neck and prostatic part of the urethra, as well as α1D-adrenoreceptors of the bladder. This effect leads to a decrease in the tone of the smooth muscles of the prostate gland, the neck of the bladder and the prostatic part of the urethra, improve detrusor function and reduce the symptoms of obstruction and irritation associated with benign prostatic hyperplasia.

    Typically, the therapeutic effect develops 2 weeks after the start of the drug, although some patients report a decrease in the severity of symptoms after the first dose.

    The ability of tamsulosin to affect α1A -adrenoceptors 20 times greater than its ability to affect α1B-adrenoceptors of smooth muscles of blood vessels. Due to this high selectivity, the drug does not cause any clinically significant decrease in systemic blood pressure (BP) in both patients with arterial hypertension and in patients with normal BP.

    Pharmacodynamics of finasteride

    Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of 5α-reductase II type - an intracellular enzyme that converts testosterone in a more active androgen - dihydrotestosterone (DHT). In BPH, its increase depends on the conversion of testosterone to DHT in the prostate gland.

    Finasteride is highly effective in reducing the concentration of DHT in both blood and prostate tissue. Suppression of DHT formation is accompanied by a decrease in the size of the prostate gland,an increase in the maximum rate of urination and a decrease in the severity of symptoms associated with prostatic hyperplasia. Finasteride does not have an affinity for androgen receptors.

    In patients with BPH, which finasteride in a dose of 5 mg per day was administered for 4 years (study MTOPS), There was a decrease in the concentration of DHT in the blood by about 70%, which was associated with a decrease in the volume of the prostate gland by approximately 20%. In addition, approximately 50% decreased the concentration of prostate-specific antigen (PSA) compared to its initial concentration, which suggests a decrease in the growth of prostatic epithelial cells. Reduction in the concentration of DHT and a decrease in the severity of prostatic hyperplasia, accompanied by a decrease in the concentration of PSA, persisted for up to 4 years. In these studies, the content of testosterone in the blood plasma increased by approximately 10-20%, remaining within physiological values. It has been established that long-term use (more than 4 years) of finasteride in patients with BPH with mild or significant symptoms of the disease reduced the risk of urological complications (acute urinary retention,(transurethral resection (TUR) of the prostate or prostatectomy) by 51%, and was accompanied by a pronounced and persistent decrease in the volume of the prostate gland, as well as a persistent increase in the maximum rate of urination and improvement in symptoms (study PLESS).

    Pharmacokinetics:

    Pharmacokinetics of tamsulosin

    Suction

    After oral administration tamsulosin quickly and almost completely absorbed in the small intestine, its bioavailability is almost 100%. Eating food reduces the absorption of the drug. Therefore, to achieve the proper level of absorption, the drug should be taken daily at the dose specified in the medical instructions, after breakfast.

    The pharmacokinetics of tamsulosin is linear.

    After a single dose of tamsulosin inside at a dose of 0.4 mg, the maximum concentration (CmOh) in the blood plasma occurs after 6 hours. Against the background of multiple reception, the equilibrium state appears by the 5th day, while Cmax the drug is approximately 2-3 times higher, than on a background of a single reception.Although these indicators were obtained in elderly patients, it is assumed that they are similar in young patients. At a single and multiple admission there can be expressed individual fluctuations in the concentration of the drug in the blood plasma.

    Distribution

    Binding to plasma proteins is 99%. The volume of tamsulosin distribution is insignificant and is approximately 0.2 l / kg.

    Metabolism

    Tamsulosin does not undergo pre-systemic metabolism and is slowly biotransformed in the liver to form pharmacologically active metabolites that retain high selectivity to α1A adrenoreceptors. Most of the active substance is present in the blood in unchanged form. In rats, insignificant induction of microsomal liver enzymes caused by tamsulosin was detected. None of the metabolites is more effective or toxic than the basic substance.

    Excretion

    Tamsulosin and its metabolites are mainly excreted by the kidneys, approximately 9% of the accepted dose of the drug is excreted unchanged. The half-life (T1/2) of the drug from the blood plasma is 10 hours after a single capsule intake of 0.4 mg, after repeated administration -13h. With kidney disease, dose adjustment is not required.

    Pharmacokinetics of finasteride

    Suction

    finasteride in the blood plasma is reached approximately 2 hours after ingestion and within 6-8 hours the absorption is completely completed. The bioavailability of finasteride for oral administration is approximately 80% of the intravenous reference dose and is not dependent on food intake.

    Distribution

    The association with plasma proteins is approximately 93%. Plasma clearance is about 165 ml / min, the volume of distribution - 76 liters.

    With prolonged therapy, slow accumulation of finasteride is observed. With a daily intake of finasteride inside at a dose of 5 mg, its minimum equilibrium concentration in the blood plasma reaches 8-10 ng / ml and over time remains stable.

    In patients who received finasteride for 7-10 days, the drug was detected in the cerebrospinal fluid. When taking finasteride at a dose of 5 mg per day, the drug is also found in seminal fluid. The concentration of finasteride in the seminal fluid ranges from undetectable (<1 ng / ml) to 21 ng / ml, which did not affect the concentration of circulating DHT in adult men.

    Metabolism

    Finasteride is actively metabolized in the liver by oxidative biotransformation. Two of the five metabolites of finasteride have a weak activity and account for 20% of the total inhibition of 5α-reductase.

    Excretion

    T1/2 finasteride average is 6 hours (4-12 hours). In men after a single oral dose of finasteride, labeled 14C, 39% of the accepted dose is excreted by the kidneys in the form of metabolites (unchanged finasteride practically not excreted by the kidneys), 57% through the intestine.

    Pharmacokinetics in selected patient groups

    Elderly patients

    In the elderly, the rate of excretion of finasteride somewhat decreases. With age T1/2 increases: in men 18-60 years, the average T1/2 is 6 hours, and in men over 70 years-8 hours. These changes are not of clinical significance, a decrease in the dose of the drug in elderly men is not required.

    Patients with impaired renal function

    In patients with chronic renal failure (creatinine clearance (CK) from 9 to 55 ml / min), the distribution of the labeled 14With finasteride at a single admission did not differ from that of healthy volunteers. The connection of finasteride with plasma proteins was also not different in patients with impaired renal function.

    With renal insufficiency, a part of the finasteride metabolites, which is normally excreted by the kidneys, is excreted through the intestine. This is manifested by an increase in the amount of finasteride metabolites in the feces with an appropriate decrease in their concentration in the urine. In patients with renal failure who are on dialysis, correction of the dose of finasteride is not required.

    Patients with impaired hepatic function

    The pharmacokinetics in patients with impaired liver function have not been adequately studied. Because the finasteride actively metabolized in the liver, such patients should be used with caution.

    Indications:

    - Treatment and reduction of the risk of progression of symptoms associated with BPH.

    - Prevention of urological complications in patients with BPH:

    - acute urinary retention;

    - the need for surgical interventions (prostate TUR and prostatectomy).

    Contraindications:

    - Hypersensitivity to the active ingredients or excipients of the drug.

    - Orthostatic hypotension (including anamnesis).

    - Hepatic insufficiency of severe severity.

    - Hereditary lactose intolerance, lactase insufficiency or impaired glucose / galactose absorption.

    - Women.

    - Age to 18 years (effectiveness and safety not established).

    Carefully:

    The preparation of Fokusin® Combi should be administered with caution in the following cases:

    - liver disease;

    - the presence of a risk of obstructive uropathy;

    - chronic renal failure (CC <10 ml / min);

    - planning of operative treatment of cataract;

    - simultaneous application with potent or moderately active inhibitors of isoenzyme CYP3A4 (e.g., ketoconazole, voriconazole).

    Pregnancy and lactation:

    Focussin® Combi should not be taken by women.

    During preclinical studies of the intrauterine development of rats, the ability of 5α-reductase inhibitors II type (including finasteride) cause anomalies in the development of external genital organs in the male fetus. Many of these disorders, such as hypospadias observed in male rats that have been exposed to fetal steroid, are similar to those observed in male infants with a genetically determined 5α-reductase deficiency II type.In this regard, pregnant women and women of reproductive age should avoid contact with crushed or lost integrity tablets containing finasteride. To avoid contact with semen, the male receiving finasteride, it is recommended to use a condom, since the drug penetrates into the sperm (see the section "Pharmacokinetics").

    Dosing and Administration:

    The preparation Fokusin® Kombi contains tamsulosin 0.4 mg in modified release capsules and finasteride 5 mg in film-coated tablets. The drug is intended for daily oral administration. The daily dose of the preparation Fokusin® Combi includes 1 capsule with a modified release of tamsulosin 0.4 mg and 1 film-coated tablet finasteride 5 mg.

    Tamsulosin 0.4 mg capsules with modified release should be taken at the same time of day after meals. Capsules should be swallowed whole, do not break and do not chew, as this can disrupt the sustained release of the active substance.

    Finasteride 5 mg tablets, film-coated,should be taken regardless of food at the same time.

    For a full therapeutic effect, a long-term use of the preparation Fokusin® Combi is necessary. If unwanted reactions appear, you can transfer the patient to monotherapy with finasteride, but with an increase in the severity of BPH symptoms it is recommended to return to the combined regimen.

    Side effects:

    The frequency of adverse reactions is presented in accordance with the classification of the Medical Dictionary of Regulatory Activities (MedDRA): very often (≥ 10%); often (≥ 1% and <10%); infrequently (≥ 0.1% and <1%); rarely (≥ 0.01% and <0.1%); very rarely (<0.01%); the frequency is unknown (it is not possible to determine the frequency of occurrence according to the available data).

    Undesirable reactions against tamsulosin monotherapy

    Disturbances from the nervous system

    Often: dizziness.

    Infrequently: headache.

    Rarely: fainting.

    Disturbances on the part of the organ of sight

    Frequency unknown: blurred vision, visual impairment.

    Heart Disease

    Infrequently: sensation of "palpitation".

    Vascular disorders

    Infrequently: orthostatic hypotension.

    Disturbances from the respiratory system of the chest and mediastinal organs Infrequently: rhinitis.

    Frequency unknown: nose bleed.

    Disorders from the gastrointestinal tract

    Infrequently: nausea, vomiting, constipation, or diarrhea.

    Frequency unknown: dry mouth.

    Disturbances from the skin and subcutaneous tissues

    Infrequently: skin rash, itching, hives.

    Rarely: angioedema.

    Rarely: Stevens-Johnson syndrome.

    Frequency unknown: erythema multiforme, exfoliative dermatitis.

    Violations of the genitals and mammary gland

    Rarely: priapism.

    Frequency unknown: ejaculation disorders, including retrograde ejaculation, lack of ejaculation.

    General disorders and disorders at the site of administration

    Infrequently: asthenic syndrome.

    In the course of post-marketing application of tamsulosin, in addition to the listed undesirable reactions, atrial fibrillation, arrhythmia, tachycardia and dyspnea (frequency of occurrence is unknown) were noted.

    In the post-registration period, cases of intraoperative irrosis syndrome (a variant of the "narrow pupil" syndrome) were also revealed,which developed during surgical operations for cataracts and was associated with the administration of tamsulosin (see section "Special instructions").

    Undesirable reactions against monotherapy with finasteride

    Immune system disorders

    Frequency unknown: hypersensitivity reactions, including swelling of the lips, tongue, pharynx and face.

    Disorders of the psyche

    Often: decreased libido.

    Frequency unknown: depression.

    Heart Disease

    Frequency unknown: sensation of "palpitation".

    Disturbances from the liver and bile ducts

    Frequency unknown: increased activity of "liver" enzymes.

    Disturbances from the skin and subcutaneous tissues

    Infrequently: a rash.

    Frequency unknown: urticaria, itching.

    Violations of the genitals and mammary glands

    Often: erectile disfunction.

    Infrequently: violation of ejaculation, increase and soreness of the mammary glands.

    Frequency unknown: soreness of the testicles, sexual dysfunction (impaired ejaculation and erectile dysfunction), which can continue after the end of treatment. Male infertility and / or decreased quality of seminal fluid,which is restored after the cessation of treatment.

    Impact on the results of laboratory and instrumental research

    In patients receiving finasteride, a decrease in the concentration of prostate-specific antigen (PSA) in the blood plasma is possible. Often there was a decrease in ejaculate volume.

    In addition, in the course of clinical trials and post-registration use, cases of breast cancer in men have been reported (see section "Special instructions").

    Undesirable reactions against combined treatment

    In patients receiving combined treatment (finasteride and α1-adrenoblocker), the same undesirable reactions appear with the same frequency as with monotherapy with finasteride and α1-adrenoblocker. The results obtained showed that erectile dysfunction and ejaculation disorder appeared more often with combined treatment, whereas progression of the disease (including increased manifestation of BPH symptoms or the need for surgical treatment) occurred more often with monotherapy.

    Overdose:

    There are no cases of simultaneous overdose of finasteride and tamsulosin.

    Tamsulosin

    There is no clinical evidence of an overdose of tamsulosin.

    Symptoms: a theoretically acute overdose of tamsulosin can cause severe arterial hypotension, which can lead to cardiovascular disorders.

    Treatment: to restore blood pressure and heart rhythm of the patient must be laid on the back, legs lifted. If necessary, plasma-substituting drugs should be used and, depending on the patient's condition, vasoconstrictors. It is recommended to monitor kidney function and conduct general activities aimed at maintaining vital functions. Dialysis is not indicated because of significant binding of tamsulosin to plasma proteins. If the drug was taken recently, it is advisable to induce vomiting. After taking a large amount of the drug should be washed stomach and appoint Activated carbon and osmotic laxative (for example, sodium sulfate).

    Finasteride

    A single application of finasteride 400 mg and repeated administration in a dose up to 80 mg / day for 3 months were not associated with undesirable reactions. In case of an overdose, no specific treatment is required.

    Interaction:

    In studies in vitro hepatic microsomal fractions (model of the metabolism of the preparation by the enzymatic system of cytochrome P450) determined that tamsulosin does not enter into pharmacokinetic interaction with finasteride during metabolism in the liver.

    Interaction of tamsulosin with other drugs

    No drug interaction was found with simultaneous application tamsulosin with atenolol, enalapril or theophylline.

    Co-administration with cimetidine may cause an increase in tamsulosin concentration in the blood plasma, while furosemide causes it to decline. Nevertheless, a dose change is not required, since the concentration of tamsulosin remains within the normal range.

    In vitro diazepam, propranolol, trichloromethiazide, chloromadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not change the content of free tamsulosin fraction in human blood plasma. Also tamsulosin does not change the plasma content of the free fraction of diazepam, trichloromethiazide, propranolol and chloromadinone.

    Diclofenac and warfarin can increase the rate of excretion of tamsulosin.

    Joint use of tamsulosin and potent inhibitors of isoenzyme CYP3A4 can cause an increase in the systemic exposure of tamsulosin. Simultaneous administration of tamsulosin with ketoconazole (a potent inhibitor of isoenzyme CYP3A4) led to an increase in the area under the "concentration-time" curve (AUC) and FROMmax tamsulosin in 2.8 and 2.2 times, respectively.

    Tamsulosin should not be used in combination with potent inhibitors of isoenzyme CYP3A4 in patients with a "slow metabolism" of the isoenzyme CYP2D6.

    Caution should be exercised when tamsulosin is combined with potent or moderately active isoenzyme inhibitors CYP3A4.

    The combined use of tamsulosin hydrochloride with paroxetine, a potent inhibitor CYP2D6, led to an increase in CmOh and AUC tamsulosin in 1,3 and 1,6 times, respectively, but this increase is not clinically significant.

    There is a possibility that the joint use of other α1-adrenoblockers with tamsulosin can enhance the hypotensive effect.

    The interaction of finasteride with other drugs

    Clinically significant interaction of finasteride with other drugs was not revealed. Finasteride metabolized mainly with the participation of isoenzyme CYP3A4 system of cytochrome P450, without exerting a significant influence on the function of this system. Although the risk of the influence of finasteride on the pharmacokinetics of other drugs is assessed as not high, there is a possibility that inhibitors or inducers of isoenzyme CYP3A4 will have an effect on the concentration of finasteride in blood plasma. Nevertheless, given the established safety intervals, it seems unlikely that an increase in the concentration of finasteride in the blood plasma associated with the concomitant use of such inhibitors will be of clinical importance. In clinical trials, the following drugs were tested: propranolol, digoxin, glibenclamide, warfarin. theophylline, phenazone, while there was no clinically significant interaction with finasteride.

    Special instructions:

    Before starting treatment with the drug Fokusin® Combi, the patient should be excluded from other diseases that manifest the same symptoms as BPH. Before the treatment and regularly during treatment, it is necessary to perform digital rectal examination of the prostate and, if necessary, to determine the content of PSA in the blood plasma.

    Patients with a large volume of residual urine and / or severe difficulty urinating should be examined for obstructive uropathy.

    Precautions for the use of tamsulosin

    As with other blockers α1-adrenoceptors, during treatment with tamsulosin, a decrease in blood pressure can occur, which in rare cases can lead to fainting. Tamsulosin should be used with caution in patients predisposed to orthostatic hypotension. At the first signs of orthostatic hypotension (eg, dizziness, weakness), you should sit or lay the patient until the symptoms disappear completely.

    Care should be taken when treating patients with severe renal insufficiency (CC less than 10 ml / min), since the effect of the drug in this population has not been studied.

    With the development of angioedema, as well as other immunological reactions, such as Stevens-Johnson syndrome, the drug should be discontinued immediately. The patient should be under the supervision of a doctor before the elimination of this pathological condition. Re-administration of tamsulosin is not allowed.

    The intraoperative iris of the iris (a variant of the "narrow pupil" syndrome) syndrome was observed during surgery for cataracts in some patients taking tamsulosin. The syndrome of intraoperative instability of the iris can increase the incidence of complications during or after surgery. It is not recommended to begin treatment with tamsulosin in patients who are scheduled for surgical cataract treatment. Discontinuing tamsulosin for 1-2 weeks before surgery usually reduces the risk of complications, but the benefits of discontinuing treatment to date remain unknown. For the prevention of the development of intraoperative irrosis syndrome, the surgeon and ophthalmologist in the preoperative period should find out whether the patient has taken tamsulosin earlier or continues to receive it. This will allow to take appropriate measures during the planning and during the surgical intervention.

    Tamsulosin should not be used in combination with potent inhibitors of isoenzyme CYP3A4 In patients with the phenotype of "slow metabolism" by isoenzyme CYP2D6.

    Caution should be exercised when taking tamsulosin with potent and moderate isoenzyme inhibitors CYP3A4.

    Precautions when applying finasteride

    Influence on the content of PSA and diagnosis of prostate cancer

    To date, the clinical advantages of using finasteride in patients with prostate cancer have not been proven. In controlled clinical trials in patients with BPH and an elevated PSA concentration based on plasma PSA and prostate biopsy results, the use of finasteride does not change the incidence of prostate cancer and does not affect the incidence of prostate cancer in patients who took finasteride or placebo.

    Before the start of treatment and periodically during the treatment with finasteride, it is recommended to perform digital rectal examination and to apply other methods of diagnosis of prostate cancer. To detect prostate cancer, the level of PSA in the blood plasma is determined. In general, the initial concentration of PSA above 10 ng / ml indicates the need for further examination of the patient and biopsy.At a PSA concentration within 4-10 ng / ml, a patient examination is recommended. The concentration of PSA in men with prostate cancer and without it can significantly coincide, therefore in men with BPH normal values ​​of PSA do not allow to exclude prostate cancer, regardless of the drug treatment finasteride. The initial concentration of PSA below 4 ng / ml also does not exclude prostate cancer.

    Finasteride at a dose of 5 mg per day causes a decrease in plasma PSA concentration by approximately 50% in patients with BPH even in the presence of prostate cancer. This fact should be taken into account when assessing the PSA index in patients with BPH receiving finasteride treatment, as a decrease in the PSA concentration does not exclude the presence of concomitant prostate cancer. This decrease can be expected at any PSA concentration, although it may vary among patients. Analysis of PSA values ​​in more than 3,000 patients in the study PLESS confirmed that in patients who took finasteride for 6 months or more, the values ​​of PSA should be doubled to be compared with the normal values ​​of this parameter in patients not receiving treatment.This correction preserves the sensitivity and specificity of the PSA analysis and the possibility of detecting prostate cancer.

    Any persistent increase in plasma PSA in patients treated with finasteride requires a thorough examination to determine the cause, which may be the failure to adhere to the regimen. The concentration of PSA in the blood plasma correlates with the age of patients and the volume of the prostate gland, and the volume of the prostate correlates with the age of the patient. When evaluating the results of laboratory studies, it should be borne in mind that in patients receiving finasteride treatment, 5 mg, the PSA content in the blood plasma is reduced. The majority of patients during the first months of therapy experienced a rapid decline in the PSA index with its subsequent stabilization at a new baseline level.

    Finasteride does not significantly reduce the percentage of free PSA (ratio of free PSA to total PSA). This indicator remains even on the background of treatment. If the percentage of free PSA is used to diagnose prostate cancer, correction of the values ​​of this indicator is not necessary.

    Breast cancer in men

    In clinical trials and post-registration studies of the use of finasteride, cases of breast cancer were noted. The patient should be informed that with any changes in the breast tissue (for example, compaction, pain, gynecomastia, discharge from the nipple) should consult a doctor without delay.

    Children

    The use of the drug Fokusin® Combi in children is contraindicated.

    The safety and efficacy of tamsulosin and finasteride in children younger than 18 years of age have not been established.

    Lactose

    The finasteride tablets contain lactose monohydrate. Patients with rare hereditary lactose intolerance, lactase deficiency, or glucose / galactose absorption impairment should not take this drug.

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

    The unfavorable influence of finasteride on the ability to manage vehicles and mechanisms was not reported. Similar action of tamsulosin was not studied. However, the possibility of dizziness, fainting, and visual impairment should be considered. They should temporarily refrain from driving vehicles and working with mechanisms with an increased risk of injury.

    Form release / dosage:

    A set of modified release capsules of 0.4 mg and tablets coated film coating, 5 mg.

    Packaging:

    For 10 capsules in a blister of PVC / PVDC / A1.

    For 10 or 15 tablets in a blister of PVC / PVDC / A1. For 3 blisters (10 capsules) and 3 blisters (10 tablets) or 2 blisters (15 tablets), together with instructions for use, put in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004088
    Date of registration:23.01.2017
    Expiration Date:23.01.2022
    The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic
    Manufacturer: & nbsp
    ZENTIVA, k.s. Czech Republic
    Saneca Pharmaceuticals a.s. The Slovak Republic
    Representation: & nbspSanofi Aventis GroupSanofi Aventis Group
    Information update date: & nbsp06.02.2017
    Illustrated instructions
      Instructions
      Up