The instruction for medical use of FLUKONAZOL-TK medicine the Trade name of Flukonazol-shopping Mall Mezhdunarodnoye the unlicensed name Flukonazol Lekarstvennaya a form mg Capsules 100.00 and 150.00 Structure One capsule contains active agent – flukonazol 100.00 and 150.00 mg excipients: lactoses monohydrate, potato starch, polyvinylpirrolidone low-molecular medical, kaltsiyastearat. structure of a cover of the capsule: lid: 100.00 mg — the titan dioxide (E 171), gelatin, a lid: 150.00 mg of iron black oxide (E 172), titan dioxide (E 171), gelatin. body: 100.00 mg — gland black oxide (E 172), the titan dioxide (E 171), gelatin. body: 150.00 mg — red crimson (E 124), the titan dioxide (E 171), gelatin. The description Solid gelatin capsules 3 of No. in size, with the body gray and a lid of white color (for a dosage of 100.00 mg). Solid gelatin capsules 2 of No. in size, with the body pink and a lid of black color (for a dosage of 150.00 mg). Contents of capsules – powder of color, white or white with a creamy shade. Pharmacotherapeutic group Antifungal means for system use. Triazole derivatives. Flukonazol the ATX J02AC01 Code the Pharmacological Pharmacokinetics Drug properties is well absorbed, its bioavailability exceeds 90%. 11–12% of Flukonazol contact proteins of blood plasma. Flukonazol well gets into all liquids of an organism, including liquor. In a corneal layer of skin, epidermis, a derma and stalemate liquid the concentration exceeding serumal are reached. Flukonazol collects in a corneal layer of skin, in 6 months after completion of therapy drug is defined in nails. The maximum level in blood plasma is reached during 0.5-1.5 h. Elimination half-life makes about 30 h that allows to use drug of 1 times a day or once. It is allocated generally with kidneys, 80% reveal in urine in not changed look. The clearance of drug is proportional to clearance of creatinine. A pharmacodynamics of Flukonazol-shopping mall — synthetic antifungal drug, groups of triazoles. It is applied to treatment of superficial and system mycoses. Flukonazol – shopping mall is selection inhibitor of enzyme 14α-demetilazy of a fungal cell, slows down synthesis of ergosterol, the main component of cell membranes of fungi and a mold. Possesses fungistasis and it is active concerning many pathogenic fungi, such as Candidaspp. (C. albicans, S. tropicalis), Cryptococcusneoformans, Coccidioidesimmitis, Histoplasmacapsulatum, Blastomycesdermatitidis, Sporothrixschenkii, Paracoccidioidesbrasiliensis and also concerning the majority of dermatophytes. Is less active concerning Aspergillusspp. And Penicilliummarneffei. S. are resistant to drug krusei, S. of glabrato, Fusariumspp. and Zygomycetes Indications – a cryptococcosis, including cryptococcal meningitis and infections of other localization (for example, lungs, skin), including. at patients with the normal immune response and patients with AIDS, recipients of transplanted organs and patients with other forms of an immunodeficiency, maintenance therapy for the purpose of prevention of a recurrence of a cryptococcosis at patients with AIDS – generalized candidiasis, including a kandidemiya, disseminate candidiasis and other forms of an invasive candidosis infection, such as infections of a peritoneum, endocardium, an eye, respiratory and uric ways, including at the patients with malignant tumors who are in intensive care units and receiving cytotoxic or immunosuppressive therapy and also at patients with other factors contributing ment of candidiasis – candidiasis of mucous membranes, including mucous oral cavities, drinks, a gullet, noninvasive bronchopulmonary infections, a kandiduriya, the skin and mucous and chronic atrophic candidiasis of an oral cavity (connected with carrying dentures) at patients with normal and suppressed immune function, prevention of a recurrence of oropharyngeal candidiasis at patients about AIDS – genital candidiasis, acute or recurrent vaginal candidiasis, prevention for the purpose of reduction of frequency of a recurrence of vaginal candidiasis (3 and more episodes a year), kandidoznyybalanit – prevention of fungal infections at the patients with malignant new growths predisposed ment of such infections as a result of cytotoxic chemotherapy or radiation therapy – a dermatomycosis, including mycoses of feet, smooth skin of a trunk, extremities, a chromophytosis, an onychomycosis and skin candidosis infections – deep endemic mycoses at patients with normal immunity, a coccidioidomycosis, a paracoccidioidomycosis, a sporotrichosis and histoplasmosis. The route of administration and doses Accept inside, daily, 1 time a day. The daily dose depends by nature and weights of a fungal infection and is defined individually. Duration of treatment depends on clinical and mycologic effect. Adults in cryptococcal infections in the first day, as a rule, appoint 400 mg, and then continue treatment in a dose of 200-400 mg once a day. Treatment duration, as a rule, is 6-8 weeks. For prevention of a recurrence of cryptococcal meningitis at patients with AIDS (after end of a full course of primary treatment) therapy of Flukonazolom-shopping mall in a dose of 200 mg can be continued during very long time, in candidosis infections the dose makes 400 mg in the first day, then on 200 mg a day, if necessary the dose can be increased up to 400 mg a day. Duration of therapy depends on clinical performance in oropharyngeal candidiasis – on 100 – 150 mg within 7-14 days or if necessary once a day – longer time. In atrophic candidiasis of a mucous membrane of an oral cavity usually appoint in a dose 100 mg within 14 days, in other candidosis infections of mucous membranes once a day (except for vaginal candidiasis) the effective dose usually makes 100 mg lasting treatment of 14-30 days, in vaginal candidiasis and a balanitis of Flukonazol-of shopping mall accept once in a dose 150 mg for prevention of fungal infections at patients with reduced function of immunity a dose makes 100 mg once a day while the patient treats risk group in a skin infection, including mycoses of feet, skins of inguinal area and candidosis infections the recommended dose makes 150 mg once a week or 100 mg once a day. Therapy duration usually is 2-4 weeks, however in mycoses of feet longer therapy can be required (up to 6 weeks). In a chromophytosis the recommended dose makes 100 mg within 2-4 weeks once a day. In an onychomycosis the recommended dose makes 150 mg once a week. Treatment should be continued before substitution of the infected nail (growth of not infected nail). Patients of advanced age: In the absence of symptoms of a renal failure, drug is used in a usual dose. For elderly patients with a renal failure at single dose the change of a dose is not required. At repeated reception drug appoint from 100 to 400 mg in an initial dose. After that the daily dose (depending on indicators of clearance of creatinine) is determined by the table: Clearance of creatinine, ml/min. Percent of the recommended dose & gt, 50,100% of 11-50 50% Sick, regularly being on dialysis One dose after each dialysis Treatment have to proceed not less than 2 weeks after receiving a negative hemoculture or disappearance of manifestations of a disease. At the first episodes of a disease the treatment continues within 7–14 days, and patients with an immunodeficiency have 3 weeks. In case of very serious condition performing 30-day therapy is necessary. Duration of therapy of cryptococcal meningitis — 6–8 weeks, dermatomycoses — 2–4 weeks, dermatofitiya of feet — within 6 weeks. Side effects Flukonazol is usually well had Often (from ≥1/100 to & lt, 1/10) – a headache – nausea, vomiting, an abdominal pain, diarrhea – increase in level of alkaline phosphatase, serumal level of aminotransferases (ALT and nuclear heating plant) – rash Infrequently (from ≥1/1.000 to ≤1/100) – insomnia, drowsiness – spasms, dizziness, paresthesia, change of taste – vertigo – dyspepsia, a meteorism, dryness in a mouth – a cholestasia, jaundice, increase in level of bilirubin – an itching, medicinal rash (including persistent medicamentous rash), a small tortoiseshell, the increased sweating, – myalgia, – fatigue, an indisposition, weakness, fever Seldom (from ≥1/10.000 to ≤1/1.000) – an agranulocytosis, a leukopenia, a neutropenia, thrombocytopenia – an anaphylaxis, a Quincke’s disease – a gipertriglitseridemiya, a hypercholesterolemia, a hypopotassemia – a tremor – tachycardia, blinking/trembling of ventricles, increase in an interval of QT – dyspepsia, a meteorism, dryness in a mouth – hepatotoxicity, including exceptional cases with a lethal outcome, a liver failure, hepatocellular necrosis, hepatitis, hepatocellular damages – a toxic epidermal necrolysis, Stephens-Johnson’s syndrome, sharp generalized exanthematous pustulez, exfoliative dermatitis, a face edema, an alopecia At patients about AIDS or cancer, at treatment of Flukonazolom-shopping mall and similar drugs observed changes of indicators of blood, function of kidneys and a liver, however the clinical value of these changes and their communication with treatment are not established. Contraindications – hypersensitivity to a flukonazol, other components of drug or azolny substances with similar to a flukonazol structure – a concomitant use of a terfenadin during repeated use of Flukonazol in a dose of 400 mg/days and more – a concomitant use of the medicines extending intervalQT and which are metabolized by means of CYP3A4 enzyme, such as tsizaprid, astemizol, Amiodaronum, erythromycin, Pimozidum and quinidine – patients with rare hereditary problems of intolerance of a galactose, a lactose intolerance or a glyukozo-galaktoznoymalyabsorbtion since capsules flukonazol contain lactose – pregnancy and the period of a lactation – children’s age up to 18 years Medicinal interactions Influence of other medicines on Flukonazol of shopping Mall Hydrokhlorotiazid: simultaneous use of a hydrochlorothiazide and Flukonazol Flukonazol in plasma increases concentration by 40%. The effect of this increase does not demand changes of a dosage of Flukonazol from the patients receiving the accompanying diuretics. Rifampicin: simultaneous use of Flukonazol and rifampicin leads to 25% to decrease in AUC (the area under a curve concentration time) and to 20% to decrease in elimination half-life of Flukonazol. At the patients receiving the accompanying therapy by rifampicin the increase in a dose of Flukonazol of shopping mall is necessary. Flukonazol’s influence on other Flukonazol medicines is powerful inhibitor of an isoenzyme tsitokhromar450 (CYP) 2C9 and moderate inhibitor of CYP3A4 enzyme. Except the interactions provided below there is a risk of increase in plasma concentration of other connections which are metabolized CYP2C9 and CYP3A4 enzymes at simultaneous use with Flukonazol. Therefore, it is necessary to show care when using these combinations, and for patients the careful control is necessary. Enzyme – inhibiting effect of Flukonazol remains 4-5 days after the termination of treatment by Flukonazol because of long elimination half-life. Alfentanil: at simultaneous therapy with Flukonazol the decrease in clearance and volume of distribution and also lengthening of T½ (elimination half-life) of an alfentanil is observed. The possible mechanism of action is the inhibition Flukonazol of CYP3A4 enzyme. Dose adjustment of an alfentanil can be required. Amitriptyline, nortriptilin: Flukonazol strengthens effect of amitriptyline and a nortriptilin. 5-nortriptilin and/or S-amitriptyline can be measured in the beginning of combination therapy and in a week. If it is necessary, amitriptyline doses / nortriptilina have to be corrected. Amphotericinum B: simultaneous use of Flukonazol and Amphotericinum B for the infected mice with the normal and weakened immunity, showed the following results: small additional antifungal action in the system infections caused by C. albicans, any interaction in the intracranial infection caused by Cryptococcusneoformans, antagonism of two drugs on the system infection caused by A. fumigatus. Clinically significant results received in this research are unknown. Anticoagulants: Flukonazol raises a prothrombin time (12%) at simultaneous use with warfarin. In a post-market research, as well as with other azolny antifungal drugs, it was reported about bleeding episodes (hematomas, bleedings from a nose, gastrointestinal bleedings, a hamaturia and a melena), connected with increase in a prothrombin time at the patients receiving Flukonazol along with warfarin twice, perhaps because of inhibition of metabolism of warfarin by means of CYP2C9 isoenzyme. At patients who accept coumarinic or indandionovy anticoagulants in combination with Flukonazolom-shopping mall it is necessary to control a prothrombin time. There can be a need for anticoagulant dose adjustment. Azithromycin: no significant pharmacokinetic interaction between Flukonazolomi azithromycin was revealed. Vorikonazol (CYP2C9, CYP2C19 and CYP3A4 inhibitor): simultaneous use of an oral vorikonazol (to 400 mg there are each 12 hours in 1 – y day, then to 200 mg there are each 12 hours within 2.5 days) and an oral flukonazol (400 mg in 1 – y day, then to 200 mg there are each 24 hours within 4 days) led to increase in concentration and AUCvorikonazola on average by 57% (90% of C1: 20%, 107%) and 79% (90% of CI: 40%, 128%), respectively. Co-administration of a vorikonazol and Flukonazola-shopping mall in any dose is not recommended. In case of use of a vorikonazol directly after Flukonazola-shopping mall it is recommended to carry out monitoring of the undesirable phenomena connected with use of a vorikonazol. Benzodiazepines (short action): at simultaneous use with midazolam, Flukonazol leads to significant increase in concentration of midazolam and psychomotor effects. This influence on midazolam is more significant after oral administration of Flukonazol, than after intravenous administration. If the patients receiving Flukonazol-shopping mall need the accompanying therapy by benzodiazepines, the dose decline of benzodiazepines is necessary, and patients need to be observed carefully. Flukonazol increases AUC of a triazolam (single dose) approximately by 50%, Cmax for 20-32% and t½ for 25-50%, because of inhibition of metabolism of a triazolam. Dose adjustment of a triazolam can be required. Carbamazepine: Flukonazol inhibits metabolism of carbamazepine and increases concentration of the last in serum by 30%. There is a risk of development of karbamazepinovy toxicity. Dose adjustment of carbamazepine depending on measurements of concentration / effect can be required. Blockers of calcium channels: some antagonists of calcium channels (nifedipine, isradipin, amlodipin, verapamil and felodipin) are metabolized by CYP3A4 enzyme. Flukonazol can increase considerably system influence of antagonists of calcium channels. Frequent monitoring on side effect of drugs is recommended. Flukonazol has the potential of increase in system influence of antagonists of the channel of calcium. Frequent monitoring of the undesirable phenomena is recommended. Tselekoksib: during the accompanying therapy by Flukonazol (200 mg a day) and tselekoksiby (200 mg), Cmax and AUCtselekoksiba increased by 68% and 134%, respectively. A half of a dose of a tselekoksib in combination with Flukonazol can be required. Cyclosporine: Flukonazol considerably increases concentration and AUCtsiklosporina. This combination can be used by a cyclosporine dose decline depending on its concentration. Cyclophosphamide: combination therapy of cyclophosphamide and Flukonazol leads to increase in levels of bilirubin and creatinine in blood serum. The combination can be used before the risk of increase in levels of bilirubin and creatinine in blood serum appears. Fentanyl: Flukonazol considerably delays fentanyl elimination. The increased concentration of fentanyl can result in respiratory insufficiency. Galofantrin: Flukonazol can increase concentration of a galofantrin in plasma because of the inhibiting effect on CYP3A4. Hydrochlorthiazidum: in a research of pharmacokinetic interaction the simultaneous use of several doses of Hydrochlorthiazidum for the healthy volunteers receiving flukonazol increased concentration of a flukonazol in blood plasma by 40%.
ri such impact of change of the mode of reception of a flukonazol it is not required from the patients who are at the same time receiving diuretics. Inhibitors A-reductases hydroxymethylglutaryl coenzyme (GMG-KoA-reduktazy): risk of development of a myopathy and acute necrosis of skeletal muscles increases (rhabdomyolysis) when Flukonazol appoint along with GMG-KoA-reduktazy inhibitors which are metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin. If the accompanying therapy is necessary, the patient has to be observed on emergence of symptoms of a myopathy and a rhabdomyolysis and also control of level of a creatine kinase has to be carried out. Intake of GMG-KoA-reduktazy inhibitors should be stopped if substantial increase of level of a creatine kinase is observed or if it is diagnosed or development of a myopathy / rhabdomyolysis is suspected. Lozartan Flukonazol inhibits metabolism of a losartan to its active metabolite (E-31 74) which is responsible for the most part of antagonism of receptors of angiotensin II which occurs during treatment by Lozartan. Patients have to control arterial blood pressure constantly. Methadone: Flukonazol can increase concentration of methadone in blood serum. Methadone dose adjustment can be required. Non-steroidal anti-inflammatory drugs (NPVP): Cmax and AUC of a flurbiprofen increase by 23% and 81%, respectively, at co-administration with Flukonazol in comparison with monotherapy flurbiprofeny. The same way, Cmax and AUC pharmacological of active isomer [S-(+) – an ibuprofen] were increased by 15% and 82%, respectively, when Flukonazol was appointed along with racemic mix of an ibuprofen (400 mg) in comparison with monotherapy of the last. Flukonazol can strengthen system influence of other NPVP which are metabolized by means of CYP2C9 (for example, Naproxenum, to lornoksika, meloksika, diclofenac). Frequent monitoring on side effect and the toxicity connected with NPVP is recommended. Dose adjustment of NPVP can be required. Oral contraceptives: no significant influence of a dose of Flukonazola50 of mg on the level of hormones was noted while at a daily dose of 200 mg, AUC (the areas under a curve concentration time) ethinylestradiol and levonorgestrel were increased by 40% and 24%, respectively. Thus, repeated use of Flukonazol in such doses can hardly influence efficiency of the combined oral contraceptive drugs. Ivakaftor: simultaneous use with an ivakaftor, a stimulator of a gene of the regulator of transmembrane conductivity in a mucoviscidosis (CFTR), increases the level of influence of an ivakaftor by 3 times, and influence level hydroxymethyl – an ivakaftor (M1) – by 1.9 times. The ivakaftor dose decline up to 150 mg is recommended to the patients who are at the same time accepting moderate CYP3A inhibitors, such as flukonazol and erythromycin once a day. Phenytoinum: Flukonazol inhibits hepatic metabolism of Phenytoinum. At a concomitant use, levels of concentration of Phenytoinum in blood serum have to be checked to avoid fenitoinovy toxicity. Prednisonum: the patients who are on long-term treatment by Flukonazol and Prednisonum have to be controlled on development of insufficiency of bark of adrenal glands after cancellation of reception of Flukonazol. Rifabutin: simultaneous use with Flukonazol leads to increase in levels of a rifabutin in blood serum up to 80%. It was reported about cases of development of a uveitis in patients which at the same time appointed Flukonazol and rifabutin. Careful control of a condition of the patients receiving rifabutin and Flukonazol-shopping mall at the same time is necessary. Sakvinavir: Flukonazol increases AUCsakvinavira approximately by 50%, Cmax approximately for 55% and reduces clearance of a sakvinavir approximately by 50% at the expense of inhibition of hepatic metabolism of a sakvinavir by means of CYP3A4 and inhibition of the R-glycoprotein. Dose adjustment of a sakvinavir can be required. Sirolimus: Flukonazol increases plasma concentration of a sirolimus, presumably, by inhibition of metabolism of a sirolimus by means of CYP3A4 and the R-glycoprotein. This combination can be used at dose adjustment of a sirolimus depending on effect/concentration measurements. Sulphonylurea: Flukonazol extends elimination half-life from serum at a concomitant use of oral drugs of sulphonylurea (for example, chlorpropamide, glibenclamide, glipizid, tolbutamide). Frequent control of glucose of blood and the corresponding reduction of a dose of sulphonylurea is recommended. Takrolimus: Flukonazol can increase serumal concentration of a takrolimus at oral administration up to 5 times at the expense of inhibition of metabolism of a takrolimus in intestines by means of CYP3A4. No significant pharmacokinetic changes at intravenous administration of a takrolimus were revealed. Increase in level of a takrolimus was connected with nephrotoxicity. The dosage of an oral takrolimus has to be reduced depending on concentration of drug. Theophylline: Flukonazol’s reception on 200 mg within 14 days leads to decrease in average speed of clearance of theophylline by 18%. It is necessary to observe carefully the patients accepting Flukonazol-shopping mall and theophylline in high doses, or patients with the increased risk of toxic effect of theophylline for the purpose of early detection of symptoms of overdose of theophylline, at their emergence the therapy should be changed as appropriate. Periwinkle alkaloid: Flukonazol can increase plasma levels of alkaloid of a periwinkle (for example, Vincristinum and vinblastine) and to result in neurotoxicity, because of inhibiting effect on CYP3A4. Vitamin A: This combination can be used, but patients should be observed for the purpose of identification of the side effects connected with central nervous system. Zidovudine: Flukonazol increases Cmax and AUCzidovudina by 84% and 74%, respectively, because of about 45% of decrease in clearance of a zidovudine at oral administration. Elimination half-life of a zidovudine is extended approximately for 128% after combination therapy with Flukonazol. The patients receiving this combination have to be observed for the purpose of identification of the side reactions connected with reception of a zidovudine. Reduction of a dose of a zidovudine can be required. Tofasitinib: influence increases at joint reception of a tofasitinib with drugs which lead as to average inhibition of CYP3A4 and strong inhibition of CYP2C9 (flukonazol). Researches of interaction of the oral Flukonazol forms at its concomitant use with food, Cimetidinum, antacids and also after total body irradiation for bone marrow transplantation showed that these factors have no clinically significant impact on Flukonazol’s absorption. Amiodaronum: simultaneous use of a flukonazol with Amiodaronum can lead to Amiodaronum metabolism inhibition. Use of Amiodaronum was followed by lengthening of an interval of QT. Simultaneous use of a flukonazol with Amiodaronum is contraindicated. Influence of a flukonazol on other medicines. Flukonazol is strong inhibitor of an isoenzyme CYP2C9 of cytochrome P – 450, and moderate CYP3A4 inhibitor. Flukonazol also inhibits CYP2C19 isoenzyme. Also there is a risk of increase in plasma concentration of other components, metaboliziruyemy CYP2C9, CYP2C19 and CYP3A4 enzymes and applied along with Flukonazolom-shopping mall. Therefore it is necessary to combine these drugs carefully, and patients have to be under careful observation of the doctor. Inhibiting effect of Flukonazola-shopping mall on enzymes continues within 4 – 5 days after the treatment termination by this drug because of the long period of its semi-removal. Researches about interaction of a flukonazol with other drugs were not conducted yet, but such interactions can arise. Special instructions In rare instances Flukonazol’s use was followed by toxic changes of a liver, including with a lethal outcome, mainly at patients with associated diseases. Hepatotoxic action of Flukonazol usually was reversible, his signs disappeared after the therapy termination. Patients at whom during treatment by Flukonazol indicators of function of a liver are broken need to be observed for the purpose of identification of signs of damage of a liver. At emergence of clinical signs or symptoms of damage of a liver which can be connected with use of Flukonazola-shopping mall, drug should be cancelled. The Flukonazol-shopping mall in rare instances can cause anaphylactic reactions. During treatment by Flukonazol at patients exfoliative skin reactions, such as Stephens-Johnson’s syndrome and toxic epidermal necrolysis in rare instances developed. Patients with AIDS are more inclined ment of heavy skin reactions at use of many drugs. At emergence in the patient during treatment of a superficial fungal infection of rash which can be connected with use of Flukonazola-shopping mall, drug should be cancelled. At appearance of rash in patients with their invasive/system fungal infections it is necessary to observe and cancel carefully Flukonazol-shopping mall at emergence of bullous defeats or a mnogoformny erythema. The Flukonazol-shopping mall can cause increase in an interval of QT at the ECG. At Flukonazol’s use the increase in an interval of QT and blinking/trembling of ventricles noted very seldom at patients with multiple factors of risk, such as organic heart diseases, disturbances of electrolytic balance and the accompanying therapy contributing to the development of similar disturbances. Therefore such patients with potentially pro-arrhythmic states should apply Flukonazola-shopping mall with care. At use of Flukonazola-shopping mall of 150 mg concerning vaginal candidiasis the patients have to be warned that improvement of symptoms is usually observed in 24 h, but their total disappearance sometimes requires several days. At preservation of symptoms within several days, it is necessary to see a doctor. Flukonazol is CYP2C9 inhibitor of strong action and CYP3A4 inhibitor of average action. The patients accepting treatment flukonazoly who accept the accompanying therapy by drugs with a narrow therapeutic window metabolized through CYP2C9 and CYP3A4 have to be examined. Patients with diseases of a liver, heart before use of Flukonazola-of shopping mall are recommended to consult with the doctor. Flukonazol-TKdolzhen to be taken with caution by patients with renal dysfunction. Adrenal insufficiency can be also observed, though is rare, at use of a flukonazol. The feature of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms Should be careful when driving or using of the equipment as there can be dizziness or spasms. Overdose Symptoms: nausea, vomiting, diarya, in more hard cases — spasms. Treatment: gastric lavage, symptomatic treatment. Flukonazol is brought, generally with urine therefore the artificial diuresis can accelerate drug removal. The session of a hemodialysis lasting 3 h reduces the Flukonazola level in plasma approximately by 50%. A form of release and packing For a dosage of 100.00 mg on 10 capsules in blister strip packaging. On one blister strip packaging together with the instruction for use in the state and Russian languages place in a pack from cardboard. For a dosage of 150.00 mg on 1 capsule in blister strip packaging. On one blister strip packaging together with the instruction for use in the state and Russian languages place in a pack from cardboard. To Store storage conditions in the dry, protected from light place, at a temperature not over 25 of 0C. To store out of children’s reach! 3 years not to apply a period of storage after the expiry date specified on packing. Prescription status According to the prescription the Name and the address of Shopping Mall Pharm Aktobe LLP producer, the Republic of Kazakhstan, Aktobe New of the village of the lake, uch. No. 467, phone number / fax 8 (7132) 21 72 15 The owner of the registration certificate of Shopping Mall Pharm Aktobe LLP, the Republic of Kazakhstan the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) of Shopping Mall Pharm Aktobe LLP, the Republic of Kazakhstan, Aktobe New of the village of the lake, uch. No. 467, phone number / fax 8 (7132) 21 72 15