Azuriks tab n / 80mg film about 30 pc

Description

Composition
Active substance:
Febuxostat 80 mg.
Excipients:
Mannitol, croscarmellose sodium, sodium hydrogencarbonate, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate, talc, colloidal silicon dioxide (Aerosil);
Coating: Hypromellose (gidroksipropilmetiltsellyulo-in), macrogol 6000 (polyethylene glycol 6000), titanium dioxide, talc, iron oxide yellow dye.
Description:
Biconvex oblong shape with rounded ends, film-coated yellow. The cross-sectional core of a white or nearly white.
Product form:
Azuriks® available in tablets, film-coated in dosages 80 mg and 120 mg; 30 tablets per pack.
Contraindications
– hypersensitivity to febuxostat and / or any of the excipients; – Children up to age 18; – Pregnancy and lactation;
Precautions – Renal failure-severe (creatinine clearance
Dosage
80 mg
Indications
Treatment of chronic hyperuricemia in patients with diseases accompanied by deposition of urate crystals, including the presence of tophi and / or gouty arthritis currently or history.
Azuriks 120 mg
Treatment and prevention of hyperuricemia in adult patients undergoing chemotherapy for hematological malignancies with a moderate or high risk of the Arctic Ocean.
Azuriks indicated for adult patients.
Gout.
Azuriksa recommended dose is 80 mg 1 time per day orally, regardless of the meal. If the concentration of uric acid in the blood serum over 6 mg / dL (357 pmol / l) after 2-4 weeks of treatment, Azuriksa dose can be increased up to 1 120 mg once a day.
drug effect occurs fairly rapidly, making it possible to re-determination of the concentration of uric acid after 2 weeks. The goal of treatment – reducing the uric acid concentration and maintain it at the level
The duration of prevention of gout attacks is at least 6 months.
In human liver mild recommended dose is 80 mg. Experience of a medicament for liver dysfunction moderately limited.
SLO.
Azuriksa recommended dose is 120 mg 1 time per day orally, regardless of the meal. Application Azuriksa should start 2 days prior to the start of cytotoxic therapy and continued for at least 7 days; however therapy can extend up to 9 days in accordance with the duration of chemotherapy and clinical evaluation.
From the reference phase of the study III (FLORENCE) were excluded only subjects with hepatic impairment, severe. For patients who were included in the study, the dose correction due to the state of the liver function is not required.
Renal insufficiency.
Patients with impaired renal function, mild or moderate dose adjustment is required. In patients with severe renal impairment (creatinine clearance
Abnormal liver function. Study of the efficacy and safety of febuxostat in patients with severe hepatic impairment (class C on a scale Child – Pugh) was conducted.
Elderly patients. For this category of patients dose adjustment is required.
Patients who have undergone organ transplantation. Experience with the febuxostat in this category of patients is not, therefore, use of the drug is not shown.
Interaction with other drugs
Mercaptopurine / azathioprine.
In accordance with febuxostat mechanism of action, consisting in the ability to inhibit xanthine oxidase, its concurrent use with mercaptopurine / azathioprine not recommended. Inhibition of xanthine oxidase can lead to increased concentrations of both drugs in plasma, which may cause a toxic reaction. Studies febuxostat interaction with drugs that are metabolized by xanthine oxidase, have been conducted.
Safety data of their simultaneous application with no cytotoxic therapy.
In a study in patients with SLO multiple chemotherapy regimens febuxostat was administered in a dose of 120 mg, including monoclonal antibodies. However, during this study the interaction of “drug – drug” and “drug – disease” have not been studied. Therefore, the opportunity to interact with all cytotoxic agents, when combined their purpose, can not be excluded.
Rosiglitazone / substrates of CYP 2C8.
Febuxostat is a weak inhibitor of CYP 2C8 in vitro. In a study involving healthy volunteers parallel introduction febuxostat 120 mg 1 time per day and 4 mg of rosiglitazone in a single dose did not affect the pharmacokinetics of rosiglitazone and its metabolite N-dezmetilroziglitazona that demonstrates that no febuxostat inhibits enzyme CYP 2C8 in vivo. Thus, simultaneous administration of febuxostat and rosiglitazone or other substrates CYP 2C8 does not require correction doses for these drugs.
Theophylline.
A study of the interaction of febuxostat in healthy volunteers to assess the effect of xanthine oxidase inhibition to increase theophylline levels in the circulation, have been reported with other xanthine oxidase inhibitors. The results showed that the simultaneous use of febuxostat 80 mg of theophylline and 400 mg showed no pharmacokinetic interaction or influence on the safety of theophylline. Febuxostat 80 mg can be used simultaneously with theophylline without any reservations. Data on the use febuxostat 120 mg absent.
Naproxen and other inhibitors of glucuronidation.
Febuxostat metabolism depends on the activity of UDP-glucuronyl. Drugs that inhibit the process of glucuronidation, such as NSAIDs and probenecid, could in theory change the elimination of febuxostat. In healthy volunteers, while the application febuxostat and naproxen 250 mg 2 times a day marked potentiation of febuxostat (Cmax is 28%, AUC – 41% T1 / 2 – 26%). In clinical studies the use of naproxen and other NSAID / COX-2 is not accompanied by a clinically significant increase in the severity and increased frequency of adverse reactions. Therefore, febuxostat may be used simultaneously with naproxen without changing their dose.
Inhibitors of glucuronidation.
Strong inducers of UDP-glucuronyl can enhance metabolism and reduce the effectiveness of febuxostat. Patients who use potent inducers of glucuronidation, it is recommended to control the level of uric acid in blood plasma after 1-2 weeks of therapy simultaneously. If you cancel the glucuronidation inducer may increase the level of febuxostat in blood plasma.
Colchicine / indometacin / hydrochlorothiazide / warfarin.
Febuxostat can be used simultaneously with colchicine or indomethacin unchanged drug dose. Also, it does not need to correct dose of febuxostat with concomitant use of hydrochlorothiazide. Concomitant use of warfarin with febuxostat does not require changing the dose of the latter. Application of febuxostat (80 or 120 mg 1 time per day) with warfarin did not affect the pharmacokinetics of the latter. The simultaneous use of febuxostat also had no effect on international normalized ratio and activity of Factor VII.
Desipramine / substrates of CYP 2D6.
According to data obtained in vitro, febuxostat is a weak inhibitor of CYP 2D6. Studies in healthy volunteers who received 120 mg febuxostat, an increase AUC desipramine (substrate CYP 2D6) by 22%, which indicates a weak inhibitory action febuxostat in vivo. Thus, while the application of febuxostat and CYP 2D6 substrates need not change their dose.
Antacids.
While the use of antacids include magnesium hydroxide and aluminum hydroxide, marked inhibition suction febuxostat (approximately 1 hour) and decrease Cmax by 32%, but the AUC febuxostat does not change significantly, however febuxostat can be combined with the use of antacids.
Overdose
In case of overdose is a symptomatic and supportive therapy.
pharmachologic effect
Pharmacodynamics:
Uric acid is the end product of purine metabolism in man and is formed by this reaction: hypoxanthine> xanthine> uric acid. Xanthine oxidase as a catalyst for both steps of the reaction. Febuxostat – 2-ariltiazola derivative. Its therapeutic effect is associated with decreased serum levels of uric acid by xanthine oxidase selective suppression. Febuxostat – is a powerful and selective inhibitor of xanthine oxidase nepurinovy ​​(NP-SIXO), its inhibition constant (Ki) in vitro is
Gout
Efficacy febuxostat preparation is confirmed in three major phase III studies (2 basic APEX and FACT study and additional study CONFIRMS, described below) involving 4101 patients with hyperuricemia and gout. Each of these basic studies III febuxostat phase more effectively reduced plasma uric acid concentration and maintain it at the appropriate level as compared with allopurinol. The primary efficacy endpoint was the proportion of patients in both studies, in which during the last 3 months the concentration of uric acid in the serum did not exceed 6.0 mg / dL (357 pmol / l). In a further study CONFIRMS III phase, the results of which become available after the first registration of the drug, the primary efficacy endpoint was the proportion of patients with uric acid concentration in blood plasma did not exceed 6.0 mg / dl at the time of the last visit. In these studies did not include patients who have undergone organ transplantation.
Investigation of APEX. Randomized, double-blind, multicenter study of the effectiveness of febuxostat with allopurinol and placebo-controlled phase III (Allopurinol and Placebo-Controlled Efficacy Study of Febuxostat – APEX) lasted 28 weeks. Total randomized 1072 patients: placebo (n = 134) febuxostat 80 mg 1 time per day (n = 267) febuxostat 120 mg 1 time per day (n = 269), febursostat 240 mg 1 time day (n = 134) and allopurinol (300 mg 1 time per day (n = 258) in patients with baseline serum creatinine concentration> 1.5 mg / dL or 100 mg 1 time per day (n = 10) patients with an initial serum creatinine concentration> 1.5 and
Study APEX showed a statistically significant advantage both treatment regimens febuxostat 80 mg 1 time per day and febuxostat 120 mg 1 time per day as compared with allopurinol in the usual dose of 300 mg (n = 258) / 100 mg (n = 10) in lowering plasma uric acid concentration
FACT study showed a statistically significant advantage of both modes (febuxostat 80 mg 1 time per day and febuxostat 120 mg 1 time per day) compared with allopurinol in the usual dose of 300 mg relative to reduce and maintain the serum concentration of uric acid
The evaluation results of the primary efficacy endpoint.
The proportion of patients with uric acid concentration in blood serum
Febuxostat 80 mg 1 time per day: 51% * (n = 517)
Febuxostat 120 mg 1 time per day: 51% * (n = 517)
Allopurinol 1 300/100 mg once a sutki1: 22% (n = 519)
1 Results in patients receiving 100 mg 1 time per day (n = 10: patients with baseline serum creatinine concentration> 1.5 and
Febuxostat rapidly reduced serum concentrations of uric acid, and this effect was maintained for a long time. Reducing the concentration of uric acid in plasma
Investigation CONFIRMS. Randomized phase III controlled study CONFIRMS duration of 26 weeks was carried out to assess the safety and efficacy of febuxostat at doses 40 and 80 mg compared with allopurinol in doses of 300 and 200 mg for patients with hyperuricemia and gout. Total 2,269 randomized patients: febuxostat 40 mg 1 time per day (n = 757) febuxostat 80 mg 1 time per day (n = 756) and 1 allopurinol 300/200 mg once daily (n = 756). Not less than 65% of patients had disorders mild and moderate renal impairment (creatinine clearance 30-89 ml / min). Prevention of gout attacks was mandatory for 26 weeks.
The proportion of patients with uric acid concentration in blood serum
The primary endpoint in the subgroup of patients with impaired renal function
The APEX study evaluated the efficacy of the drug involving 40 patients with impaired renal function (with an initial serum creatinine concentration> 1.5 and
In this case a clinically significant difference in reducing the serum concentration of uric acid in percentage of healthy volunteers were observed, regardless of renal function (58% in the group with normal renal function and 55% in the group with severe renal impairment).
Prospective analysis conducted in patients with gout and renal impairment using the CONFIRMS study showed that febuxostat was significantly more effective: the level of uric acid in serum decreased
The primary endpoint in the subgroup with serum uric acid concentration> 10 mg / dl
The initial concentration of uric acid> 10 mg / dl in serum observed in approximately 40% of patients (combined study APEX and FACT). Among these patients, the primary efficacy endpoint (a serum uric acid concentration
According CONFIRMS study, the proportion of patients achieving the primary efficacy endpoint (a serum uric acid concentration
Pregnancy and breast-feeding
Limited experience with febuxostat during pregnancy indicates no adverse effects on pregnancy and the fetus / newborn health. Studies in animals have not observed its direct or indirect adverse effect on the course of pregnancy, the developing embryo / fetus and during childbirth. The potential risk for humans is unknown. In connection with the above, the use of febuxostat is contraindicated during pregnancy.
It is unknown whether febuxostat passes into breast milk human. Animal studies have shown that febuxostat passes into breast milk and has a negative impact on the development of newborns are breastfed. In connection with the above, the use of febuxostat during lactation is contraindicated.
Conditions of supply of pharmacies
On prescription.
side effects
The most common adverse reactions in clinical studies (4072 patients treated with a dose of 10 to 300 mg), and during post-marketing surveillance in patients with gout were exacerbation (seizures), gout, liver function abnormalities, diarrhea, nausea, headache, rash and swelling. These reactions were mostly mild to moderate severity. During post-marketing surveillance have been reports of serious hypersensitivity reactions to febuxostat, some of them accompanied by systemic reactions.
The following are adverse reactions on frequency of occurrence and severity (in that order) that occurred during the clinical studies and in post-marketing period, and classified as follows: frequently (by> 1/100 to
special instructions
Cardiovascular diseases
Treatment of chronic hyperuricaemia. Febuxostat is not recommended for use in patients with ischemic heart disease or congestive heart failure.
In studies APEX and FACT with the group febuxostat compared with the group of allopurinol reported an increase in the number of violations with the cardiovascular system (Anti-Platelet Trialists’ Collaboration – APTC) (definition of endpoints in the group of combined analysis antiplatelet therapy (APTC), in including deaths due to cardiovascular disease, myocardial infarction, non-fatal, non-fatal stroke, 1.3 compared with 0.3 per 100 patient-years), unlike the CONFIRMS study. Frequency disturbances with the cardiovascular system (APTC), which have been reported in studies of combined phase III studies (Study APEX, FACT and CONFIRMS) was 0.7 compared to 0.6 per 100 patient-years for febuxostat and allopurinol, respectively. Within the framework of long-term large-scale studies the frequency of cardiovascular events reported, amounted to 1.2 and 0.6 cases per 100 patient-years for febuxostat and allopurinol, respectively. The differences were not statistically significant, and the causal relationship between these disorders and the use of febuxostat was absent. The risk factors in these patients were disease caused by atherosclerosis and / or myocardial infarction, or congestive heart failure history.
Prevention and treatment of hyperuricemia in patients at risk of developing the Arctic
Patients undergoing chemotherapy for hematological malignancies with moderate or high risk layer and applying febuxostat, if clinically indicated are supervised cardiology.
Allergy to drugs / hypersensitivity. Within the framework of post-marketing surveillance have been rare reports of serious allergic reaction / hypersensitivity reactions, including life-threatening syndrome of Stevens – Johnson syndrome, toxic epidermal necrolysis, and an acute anaphylactic reaction / shock. In most cases, they occur within 1 month of use of febuxostat. Several patients were impaired renal function and / or hypersensitivity to allopurinol in history. Тяжелые реакции гиперчувствительности, в том числе реакции, сопровождающиеся эозинофилией и системными симптомами (DRESS-синдром), в некоторых случаях были связаны с лихорадкой, гематологической, почечной или печеночной недостаточностью. Пациенты должны быть проинформированы о симптомах гиперчувствительности/аллергии, а также им требуется наблюдение относительно развития таких реакций. При появлении серьезных аллергических реакций/реакций гиперчувствительности применение фебуксостата следует немедленно прекратить, поскольку раннее прекращение применения улучшает прогноз. Если у больного возникли аллергическая реакция/реакция гиперчувствительности, в том числе синдром Стивенса — Джонсона, и острые анафилактические реакции/шок, то повторное назначение фебуксостата противопоказано.
Обострение (приступ) подагры. Лечение фебуксостатом следует начинать только в период после обострения болезни. Фебуксостат может спровоцировать приступ подагры в начале лечения за счет изменения уровня мочевой кислоты через выход уратов из депо. В начале лечения фебуксостатом рекомендуется назначить НПВП или колхицин на период не менее 6 мес для профилактики приступов подагры. При развитии приступа на фоне применения фебуксостата лечение продолжают. Одновременно проводят соответствующую индивидуальную терапию обострения подагры. При длительном применении фебуксостата частота и тяжесть приступов подагры снижаются.
Отложения ксантинов. У пациентов с ускоренным образованием уратов (например на фоне злокачественных новообразований и их лечения или при синдроме Леша — Нихана) возможно существенное увеличение абсолютной концентрации ксантинов в моче, сопровождающееся их отложением в мочевыводящих путях. Этого не наблюдалось в опорном клиническом исследовании фебуксостат при СЛО. Из-за ограниченности опыта применения фебуксостата при таком состоянии препарат не показан пациентам.
Меркаптопурин/азатиоприн. Фебуксостат не рекомендуется применять у пациентов, получающих меркаптопурин/азатиоприн.
Если одновременного применения нельзя избежать, состояние пациентов следует тщательно контролировать. Рекомендуется снижение дозы меркаптопурина/азатиоприна для избежания возможных гематологических эффектов.
Пациенты, перенесшие трансплантацию органов. Опыта применения фебуксостата у этой категории пациентов нет, поэтому применение препарата не показано.
Теофиллин. Однократное одновременное применение фебуксостата в дозе 80 мг и теофиллина в дозе 400 мг не продемонстрировало никаких фармакокинетических взаимодействий. Фебуксостат в дозе 80 мг можно применять одновременно с теофиллином без риска повышения концентрации теофиллина в плазме крови. Данные о применении фебуксостата в дозе120 мг отсутствуют.
Заболевания печени. В ходе комбинированной III фазы клинических исследований, у 5,0% пациентов, применявших фебуксостат, отмечены незначительные изменения печеночных показателей, поэтому рекомендуется проверять функциональные печеночные показатели до назначения фебуксостата и во время лечения при наличии показаний.
thyroid disease. У 5,5% больных, получавших фебуксостат в течение длительного времени, наблюдалось повышение ТТГ (>5,5 мкМЕ/мл), поэтому препарат следует с осторожностью назначать лицам с нарушением функции щитовидной железы.
Лактоза. Лекарственное средство содержит лактозу, поэтому пациентам с редкими наследственными заболеваниями, связанными с непереносимостью галактозы, недостаточностью лактазы или нарушением всасывания глюкозы/галактозы, препарат противопоказан.
Fertility. Исследования фертильности на животных в дозе 48 мг/кг/сут не выявили зависимости побочных реакций от дозы. Действие фебуксостата на репродуктивную функцию человека неизвестна.
Children. Применение фебуксостата у детей (в возрасте до 18 лет) не показано из-за отсутствия опыта его применения в педиатрии.
Способность влиять на скорость реакции при управлении транспортными средствами или работе с другими механизмами.
Были сообщения о развитии сонливости, головокружения, парестезии и нарушении четкости зрения на фоне применения фебуксостата, поэтому больным, применяющим фебуксостат, рекомендуется соблюдать осторожность при управлении транспортными средствами и работе с другими механизмами до тех пор, пока они не будут уверены в отсутствии вышеуказанных явлений.
Storage conditions
Store at room temperature of 15-25 degrees.
Dosing and Administration
Для перорального применения.
Азурикс применяется перорально независимо от приема пищи – 1 раз в сутки.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist