Adenurik tab n / 120mg film about 28 pc

Description

Composition
Active substance:
1 tablet contains 80 mg: 80.0 mg-febuxostat. 1 tablet of 120 mg contains: febukostat-120 mg.
Excipients:
Lactose monohydrate 76.50 mg, 12.00 mg giproloza, microcrystalline cellulose (Avicel PH101), microcrystalline cellulose (Avicel PH102), croscarmellose sodium, magnesium stearate, aqueous colloidal silica. film coating: opadray® II Yellow 85F42129, consisting of: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, iron oxide yellow dye (E 172).
Description:
Film-coated tablets 80 mg
Oblong film-coated tablets from light-yellow to yellow color, embossed “80” on one side.
Film-coated Tablets, 120 mg
Oblong film-coated tablets from light-yellow to yellow color, embossed “120” on one side.
Product form:
Tablets, film-coated, 80 mg, 120 mg.
14 tablets in blisters (blister) made of PVC / Aclar / aluminum foil.
2, 4 or 6 blisters with instructions for use in a cardboard package.
Contraindications
Hypersensitivity to febuxostat and / or any of the excipients; Children up to age 18; pregnancy and lactation; hereditary galactose intolerance, lactase deficiency and malabsorption syndrome, glucose and galactose.
Precautions: renal failure, severe gravity (creatinine clearance
Dosage
120 mg
Indications
Chronic hyperuricemia for conditions involving deposition of urate crystals (tophi the presence and / or gouty arthritis, including, history).
Treatment and prevention of hyperuricemia in adult patients during cytostatic therapy of hematological malignancies with decay syndrome risk of developing tumors of moderate to high (only for dosing 120 mg).
Adenurik® drug intended for use in adults.
Interaction with other drugs
Mercaptopurine / azathioprine
The simultaneous use of mercaptopurine, azathioprine not Refer a, as inhibition of xanthine oxidase febuxostat may lead to increased concentrations mercaptopurine, azathioprine in plasma and enhance their toxic action. Studies on the interaction of febuxostat and substances metabolized with xanthine oxidase, have been conducted.
cytostatics
Studies of drug interactions febuxostat and cytostatic drugs have been conducted. In FLORENCE febuxostat study at a dose of 120 mg was used for tumor decay syndrome in patients undergoing cytotoxic therapy of various kinds (including monoclonal antibody therapy). However, as the studies of drug interactions febuxostat with cytotoxic drugs has been conducted, the potential interaction of febuxostat with cytotoxic chemotherapy applied simultaneously can not be excluded.
Rosiglitazone / substrates CYP2C8 isozyme
According to in vitro febuxostat it is a weak inhibitor of isozyme CYP2C8. In healthy volunteers, while the application febuxostat 120 mg 1 time per day and a single dose of 4 mg rosiglitazone changes pharmacokinetic parameters rosiglitazone and its metabolite N-dismetil rosiglitazone has been noted that the absence of svidelstvo febuxostat properties isoenzyme CYP2C8 in vivo inhibitor. With simultaneous use of febuxostat and rosiglitazone (or other substrates isoenzyme CYP2C8) correction dose is not required.
theophylline
When using other ksantioksidazy inhibitors simultaneously with theophylline was an increase in the concentration of theophylline in blood plasma. With simultaneous application of healthy volunteers at a dose of febuxostat 80 mg 1 time per day in a single dose of theophylline and 400 mg of changes tolerability or pharmacokinetic parameters of theophylline was not observed, thus while applying febuxostat 80 mg of theophylline and special precautionary measures are required. Studying the simultaneous application of febuxostat 120 mg and theophylline was conducted.
Naproxen and other inhibitors of glucuronidation
Metabolism febuxostat depends on the activity of the enzyme uridine diphosphate glucuronyl (UDFGT). Drugs that inhibit glucuronidation process, e.g., non-steroidal anti-inflammatory drugs (NSAIDs) and probenicid can theoretically affect the excretion of febuxostat. In healthy volunteers, while the application febuxostat and naproxen 250 mg 2-fold increase in performance was observed Cmax febuxostat 28%, AUC per day – 41%, and T1 / 2 – 26%. In clinical studies, the simultaneous use of febuxostat and naproxen or other NSAIDs / COX-2 is not accompanied by a clinically significant increase in the incidence of side effects. Dose adjustment while applying febuxostat and naproxen is not necessary.
inductors glucuronidation
When applied simultaneously with febuxostat potent inducers glucuronidation may increase its metabolism and decrease in efficiency. With simultaneous use requires monitoring of the concentration of uric acid in blood serum after 1-2 weeks after initiation of therapy. If you cancel the glucuronidation inducer may increase Cmax febuxostat.
Colchicine / indometacin / hydrochlorothiazide / warfarin
Febuxostat can be used simultaneously with colchicine or indomethacin without dose adjustment.
Also not required febuxostat dose correction while the use of hydrochlorothiazide.
The simultaneous use of febuxostat (80 mg or 120 mg once a day) with warfarin did not affect the pharmacokinetics of warfarin, INR (international normalized ratio), and Factor VII activity in healthy volunteers. With simultaneous application of febuxostat with warfarin dose warfarin correction is required.
Desipramine / isozyme CYP2D6 substrates
According to data obtained in vitro, febuxostat is a weak inhibitor of isozyme CYP2D6. A study in healthy volunteers during treatment with febuxostat 120 mg 1 time per day was an increase in AUC of desipramine (substrate isozyme CYP2D6) is 22%, which indicates a weak inhibitory effect of febuxostat on isozyme CYP2D6 in vivo. Thus, while the application of febuxostat isozyme CYP2D6 substrates and correction dose is not required.
antacids
While the use of antacids containing magnesium hydroxide or aluminum hydroxide, there is a decrease suction febuxostat (approximately 1 hour) and decrease Cmax by 32%, but febuxostat AUC were not significantly changed. Therefore, febuxostat may be taken concurrently with antacids.
Overdose
If overdose is a symptomatic and supportive therapy.
Symptoms: increased side effects.
pharmachologic effect
Pharmacological group:
Arthrifuge – xanthine oxidase inhibitor.
Pharmacodynamics:
Uric acid is the end product of purine metabolism in the human body, formed as a result of the cascade of hypoxanthine-xanthine uric acid reactions. Febuxostat derivative is 2-ariltiazola and is a potent selective inhibitor of xanthine oxidase nepurinovy ​​(the constant of inhibition in vitro of less than 1 nM). The enzyme xanthine oxidase catalyzes purine metabolism two steps: the oxidation of hypoxanthine to xanthine and then oxidation of xanthine to uric acid.
As a result, selective inhibition of xanthine oxidase febuxostat (oxidized and reduced forms) a reduction in the concentration of uric acid in serum.
At therapeutic concentrations febuxostat does not inhibit other enzymes involved in the metabolism of purines or pyrimidines such as guanindezaminaza, hypoxanthine, orotate phosphoribosyl, tidinmonofosfatdekarboksilaza or oro-purin-nucleoside.
Clinical efficacy and safety profile.
Gout.
Efficacy and safety of febuxostat was confirmed in three basic phase III clinical trials involving 4101 patients with hyperuricemia and gout (APEX, FACT and CONFIRMS).
In each of these studies led to the use of febuxostat more effective in reducing the concentration of uric acid and maintain its level in the serum as compared with allopurinol.
The primary endpoint in the APEX and FACT studies was the proportion of patients over the past three months, the concentration of uric acid in the serum did not exceed 6.0 mg / dL (357 pmol / l). In a further study CONFIRMS primary endpoint was the proportion of patients with uric acid concentration in blood serum was less than 6.0 mg / dl on the last visit. In these studies did not include patients who have had an organ transplant.
In a double-blind, randomized, multicenter, 28-week study APEX (the study of the effectiveness of febuxostat compared to allopurinol and placebo) included 1072 patients. Febuxostat was used in doses of 80 mg, 120 mg or 240 mg once a day; allopurinol – 300 mg once daily in patients with baseline plasma creatinine content
Pregnancy and breast-feeding
Due to insufficient data, the potential risk for humans febuxostat is not known, so the use of febuxostat during pregnancy is contraindicated. There is limited experience with febuxostat during pregnancy, in which the adverse effects on pregnancy and the fetus / neonate was noted. The animal was not observed direct and indirect adverse effects of study drug on the course of pregnancy, the developing embryo / fetus and the birth process.
No information on whether febuxostat passes into breast milk. The animal studies indicated that febuxostat passes into breast milk and has an adverse effect on the development of breast-fed babies. Thus, we can not exclude the risk to infants. In this regard, the use of febuxostat contraindicated during breastfeeding.
Conditions of supply of pharmacies
On prescription.
side effects
Taking into account the different nature of gout and decay syndrome of tumor, side effects associated with the use of febuxostat in data nosology actions are presented separately.
Gout
The most common adverse events in patients with gout when applying febuxostat on the results of clinical studies (4072 patients taking febuxostat at a dose of 10 mg to 300 mg), and according to the post-marketing surveillance were: gout, abnormal liver function, diarrhea, headache, nausea , skin rash and swelling. In most cases these phenomena characterized by mild or moderate severity. During post-marketing surveillance have been reported rare cases of hypersensitivity reactions to febuxostat, accompanied in some cases, systemic symptoms.
Possible side effects are listed below in accordance with the classification the World Health Organization in descending frequency of occurrence: very often (> 1/10); common (> 1/100,
special instructions
Acute gout attack
Application Adenurik® drug should be started only after the acute attack of gout. Starting time of the drug Adenurik® can trigger the development of an acute attack of gout due to the release of urate tissue depots and the subsequent increase in the concentration of uric acid in serum. For the prevention of gout attacks in the absence of contraindications to the simultaneous use of NSAIDs or colchicine for at least 6 months.
With the development of attack on the background of the drug Adenurik® drug application should proceed simultaneously conduct appropriate treatment of acute attacks of gout. With long-term use of the drug Adenurik® incidence and severity of gout attacks are decreased.
The deposition of xanthine
In rare cases, patients with the accelerated formation of urate (for example, against malignant tumors or Lesch-Nyhan syndrome) may be a significant increase in the absolute concentration of xanthine in urine, which may be accompanied by their deposition in the urinary tract. In the application of febuxostat within FLORENCE study in patients with the syndrome of the collapse of the tumor of this phenomenon was not observed. Due to limited data, the use of the drug Adenurik® in patients with Lesch-Nyhan syndrome is not Refer a.
Mercaptopurine / azathioprine
The simultaneous use of mercaptopurine, azathioprine Refer a no. If necessary, the simultaneous use, to reduce the effects on hematopoiesis toksichekogo system Refer a dose reduction mercaptopurine / azathioprine and careful medical supervision.
theophylline
With simultaneous application of healthy volunteers at a dose of febuxostat 80 mg 1 time per day and a single dose of 400 mg theophylline were observed changes of pharmacokinetic parameters. Thus, the simultaneous use of febuxostat 80 mg of theophylline and no risk of increasing the concentration of theophylline in blood plasma. Studying the simultaneous application of febuxostat 120 mg and theophylline was conducted.
Patients who have undergone organ transplants
Application Adenurik® drug in patients who have undergone organ transplants, is not recommended due to the lack of application experience.
Allergic reactions and hypersensitivity reactions
During post-marketing applications were rare reports of occurrence of severe allergic reactions (hypersensitivity reactions), including Stevens-Johnson syndrome, toksikodermalny necrolysis, anafilaktiches Kie response and shock.
In most cases these reactions developed within the first month of use Adenurik® preparation. Some patients had a history of renal insufficiency and / or hypersensitivity reactions against application of allopurinol.
In some cases severe hypersensitivity reactions, including drug reaction with eosinophilia syndrome and systemic symptoms (DRESS), accompanied by fever, changing blood parameters, impaired hepatic or renal function.
Patients should be informed about the possible signs and symptoms of allergic reactions (hypersensitivity reactions), and should be monitored carefully for the development of symptoms of allergic reaction / hypersensitivity reactions.
In case of severe allergic reactions / hypersensitivity reactions including Stevens-Johnson syndrome, should immediately discontinue use Adenurik® drug (earlier cancellation associated with a better prognosis). Repeated use of the drug is not recommended.
Cardiovascular diseases
Application Adenurik® drug is not recommended in patients with ischemic heart disease or congestive heart failure.
In studies APEX and FACT (unlike CONFIRMS studies) in the total group febuxostat compared with the group of allopurinol, an increase in the number of violations to the cardiovascular system, as defined in accordance with the system developed by a group of joint analysis of antiplatelet therapy (GSAAT) and comprising a death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke) – 1.3 compared to 0.3 cases per 100 patient-years. According to the combined data phase III clinical trials (APEX study, FACT and CONFIRMS) frequency disturbances with the cardiovascular system it was 0.7 in comparison with a frequency of 0.6 per 100 patient years.
Within the framework of long-term large-scale studies the frequency of cardiovascular disorders GSAAT were 1.2 and 0.6 cases per 100 patient-years for febuxostat and allopurinol, respectively. The differences were not statistically significant, a causal relationship between these disorders and the reception of febuxostat has not been established. The factors mentioned event risk in patients was found a history of the following conditions: atherosclerosis and / or myocardial infarction, or congestive heart failure.
Prevention and treatment of hyperuricemia in patients at risk of tumor lysis syndrome
In patients receiving cytotoxic therapy with Leukemia syndrome risk for collapse of the tumor from mild to vyrazhennnogo, Adenurik® use of the drug in the presence of indications dozhno carried out under the supervision of a cardiologist.
liver disease
According to the combined data phase III clinical trials at application febuxostat 5% of patients had abnormal liver functions mild.
Before the appointment Adenurik® drug is recommended to evaluate the function of the liver, and if there are indications – also during use.
Thyroid disease
Enhanced long-term open-label studies with prolonged use febuxostat in 5.5% of patients had increased concentration of thyroid stimulating hormone (> 5.5 mkIE / ml), in connection with which patients with thyroid dysfunction Adenurik® drug should be used with caution.
Препарат Аденурик® содержит лактозу, поэтому его применение у пациентов с дефицитом лактазы, наследственной непереносимостью лактозы, синдромом глюкозо-галактозной мальабсорбции противопоказано.
Влияние на способность к управлению автотранспортными средствами и управлению механизмами
При приеме препарата Аденурик® возможно появление сонливости, головокружения, парестезии и нечеткости зрения, и, как следствие, снижение реакции и способности к концентрации внимания, поэтому во время применения препарата Аденурик® необходимо соблюдать осторожность при управлении транспортными средствами и занятиями другими потенциально опасными видами деятельности, требующими концентрации внимания и быстроты психомоторных реакций.
Storage conditions
Store at a temperature not higher than 25 C.
Drug store out of reach of children !.
Dosing and Administration
Inside. Препарат Аденурик® принимают один раз в сутки, независимо от приема пищи.
Gout
Рекомендованная начальная доза составляет 80 мг фебуксостата один раз в сутки.
Через 2-4 недели рекомендуется контроль концентрации мочевой кислоты в сыворотке крови; если показатель превышает 6 мг/дл (357 мкмоль/л), доза препарата может быть увеличена до 120 мг 1 раз в сутки.
Снижение концентрации мочевой кислоты в сыворотке крови на фоне применения препарата Аденурик® происходит достаточно быстро, в связи с чем контроль концентрации мочевой кислоты можно проводить через две недели от начала приема препарата. Целью лечения является снижение и поддержание концентрации мочевой кислоты в сыворотке крови менее 6 мг/дл (357 мкмоль/л).
Профилактика развития острых приступов подагры рекомендуется в течение не менее 6 месяцев.
Синдром распада опухоли
Рекомендованная доза составляет 120 мг фебуксостата один раз в сутки независимо от приема пищи. Препарат Аденурик® следует начинать принимать за два дня до начала цитостатической терапии. Длительность применения препарата Аденурик® должна составлять не менее 7 дней. В зависимости от длительности курса химиотерапии продолжительность применения препарата Аденурик® может быть увеличена до 9 дней.
elderly patients
Коррекции дозы препарата не требуется.
Patients with hepatic insufficiency
Gout
У пациентов с печеночной недостаточностью легкой степени тяжести (класс А по шкале Чайлд-Пью: 5-6 баллов) рекомендованная доза препарата составляет 80 мг 1 раз в сутки. Опыт применения препарата при печеночной недостаточности средней степени тяжести ограничен.
Синдром распада опухоли
В исследовании FLORENCE коррекции дозы фебуксостата в зависимости от функции печени не требовалось (в исследование не включались пациенты с печеночной недостаточностью тяжелой степени тяжести).
Исследования эффективности и безопасности применения фебуксостата у пациентов с печеночной недостаточностью тяжелой степени тяжести (класс С по шкале Чайлд-Пью: 10-15 баллов) не проводились.
Patients with renal insufficiency
У пациентов с почечной недостаточностью легкой и средней степени тяжести коррекции дозы не требуется.
У пациентов с почечной недостаточностью тяжелой степени тяжести (клиренс креатинина
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist