Azurix pills 80mg, 30pcs

Pharmacological action

Uric acid is the end product of human purine metabolism and is formed by the following reaction: hypoxanthine → xanthine → uric acid. Xanthine oxidase is a catalyst for both stages of this reaction. Febuxostat is a derivative of 2-arylthiazole. Its therapeutic effect is associated with a decrease in the concentration of uric acid in the blood serum by selective suppression of xanthine oxidase. Febuxostat is a powerful and selective non-purine xanthine oxidase inhibitor (NP-SIXO), its inhibition constant (Ki) in vitro is Febuxostat has been shown to significantly inhibit the activity of both the oxidized and reduced forms of xanthine oxidase. At therapeutic concentrations, febuxostat does not affect other enzymes involved in purine or pyrimidine metabolism, such as guanindesaminase, hypoxanthinguanine phosphoribosyltransferase, orotidine monophosphate decarboxylase, or purine nucleoside phosphorylase. Clinical efficacy and safety: The sub-efficacy of febuxostat was confirmed in phase III of three main studies (2 main APEX and FACT studies and an additional CONFIRMS study, described below), including 4101 patients with hyperuricemia and gout. In each of these major phase III trials, febuxostat was more effective in reducing and maintaining plasma uric acid concentrations than allopurinol. The primary efficacy endpoint in both studies was the proportion of patients whose serum uric acid concentrations did not exceed 6.0 mg/dl (357 mmol/L) within the last 3 months. In the additional phase III CONFIRMS study, the results of which became available after the first registration of the drug, the primary endpoint of effectiveness was the proportion of patients whose uric acid concentration in blood plasma did not exceed 6.0 mg/dl at the time of the last visit. These studies did not include patients who had undergone organ transplants. APEX research. A randomized, double-blind, multicenter efficacy trial of febuxostat with placebo and allopurinol phase III (Allopurinoland Placebo — Controlled Efficacy Studyof Febuxostat-APEX) lasted 28 weeks. A total of 1072 patients were randomized: placebo (n=134), febuxostat 80 mg once daily (n=267), febuxostat 120 mg once daily (n=269), febursostat 240 mg once daily (n=134), and allopurinol (300 mg once daily (n=258) in patients with baseline serum creatinine >1.5 mg/day or 100 mg once daily (n=10) in patients with baseline serum creatinine concentrations >>1.5 and ≤2.0 mg/dl). To assess safety, febuxostat was administered at a dose of 240 mg (2 times higher than the maximum recommended dose). The APEX study showed a statistically significant advantage of both treatment regimens febuxostat 80 mg once daily and febuxostat 120 mg once daily over allopurinol 300 mg (n=258)/100 mg (n=10) in reducing plasma uric acid concentrations Research FACT. Efficacy study of febuxostat with allopurinol control (TheFebuxostat Allopurinol Controlled Trial, FACT) Phase III — a randomized, double-blind, multicenter study lasting 52 weeks. A total of 760 patients were randomly assigned to febuxostat 80 mg once daily (n=256), febuxostat 120 mg once daily (n=251), and allopurinol 300 mg once daily (n=253). The FACT study showed a statistically significant advantage of both regimens (febuxostat at a dose of 80 mg once a day and febuxostat at a dose of 120 mg once a day) compared to allopurinol at a normal dose of 300 mg in terms of reducing and maintaining the serum uric acid concentration Table 1 shows the results of evaluating the primary performance endpoint. Table 1 Proportion of patients with serum uric acid concentrations <6.0 mg / dl (357 mmol / L) at the last three monthly visits

1 Results among patients who received 100 mg 1 time per day (n=10 patients with initial serum creatinine concentration >1.5 and ≤2.0 mg/DL) or 300 mg 1 time a day (n=509), in the analysis were combined. *p<0.001 compared to allopurinol; #pFebuxostat rapidly reduced the serum uric acid concentration, and this effect persisted for a long time. Reduction of uric acid concentration in plasma The CONFIRMS study. A 26-week randomized controlled trial, CONFIRMS3, was conducted to evaluate the safety and efficacy of febuxostat 40 and 80 mg versus allopurinol 300 and 200 mg in patients with gout and hyperuricemia. A total of 2269 patients were randomized: febuxostat 40 mg once daily (n=757), febuxostat 80 mg once daily (n=756), and allopurinol 300/200 mg once daily (n=756). At least 65% of patients had mild to moderate renal impairment (with a creatinine clearance of 30-89 ml / min). Prevention of gout attacks was mandatory for 26 weeks. Percentage of patients with serum uric acid concentrations Primary endpoint in a subgroup of patients with impaired renal function, the APEX study evaluated the efficacy of the drug in 40 patients with impaired renal function (with baseline serum creatinine concentrations >1.5 and ≤2.0 mg / dl). In these patients randomized to the allopurinol group, the dose of the drug was reduced to 100 mg once a day. The primary efficacy endpoint was achieved in the febuxostat group in 44% (80 mg once daily),45% (120 mg once daily), and 60% (240 mg once daily) patients, compared to 0% in the allopurinol 100 mg once daily and placebo groups. At the same time, there were no clinically significant differences in the decrease in serum uric acid concentration as a percentage in healthy volunteers, regardless of the functional state of the kidneys (58% in the group with normal renal function and 55% in the group with severe renal impairment). A prospective analysis conducted in patients with gout and impaired renal function using the CONFIRMS study showed that febuxostat was significantly more effective: serum uric acid levels were reduced Primary endpoint in the subgroup of patients with a serum uric acid concentration ≥10 mg/dl, an initial uric acid concentration ≥10 mg/dl in the blood serum was observed in approximately 40% of patients (combined APEX and FACT studies). Among these patients, the primary endpoint of efficacy (serum uric acid concentration According to the CONFIRMS study, the proportion of patients who achieved the primary efficacy endpoint (with serum uric acid concentration Clinical results: Percentage of patients requiring therapy for gout attacks APEX study. During the 8-week follow-up period, data from patients in the febuxostat 120 mg treatment group (36%) who required therapy for gout attacks were compared with those in the febuxostat 80 mg treatment group (28%), allopurinol 300 mg treatment group (23%), or placebo treatment group (20%). The frequency of seizures was higher after the preventive period and gradually decreased over time. In 46-55% of patients, gout attacks were treated from the 8th and 28th weeks. Gout attacks that occurred during the last 4 weeks of the trial (24-28 weeks) were reported in 15% (febuxostat 80 and 120 mg),14% (allopurinol 300 mg) and 20% (placebo) of patients.Research FACT. During the 8-week prevention period, data from patients in the febuxostat 120 mg treatment group (36%) who required therapy for gout attacks were compared with those in the two treatment groups who used febuxostat 80 mg (22%) or allopurinol 300 mg (21%). After the 8-week prevention period, the frequency of seizures increased and gradually decreased over time (64 and 70% of patients treated for gout attacks from week 8 to 52). Gout attacks during the last 4 weeks of the trial (49-52 weeks) were reported in 6-8% (febuxostat 80 and 120 mg) and 11% (allopurinol 300 mg) of patients. The proportion of patients who required treatment for gout exacerbations (APEX and FACT study) was lower in the groups where the average serum uric acid concentration after treatment decreased to <6.0; <5.0 orDuring the CONFIRMS study, the proportion of patients who needed treatment for gout attacks (1 day every 6 months) was 31% and 25% in the groups receiving febuxostat 80 mg and allopurinol, respectively. There were no differences in the ratio of patients who required treatment for gout attacks between the groups treated with febuxostat 80 and 40 mg. Long-term advanced open RESEARCHEXAMPLE Research (C 02-021). The EXCEL trial is a 3-year open-label, multicenter, randomized, extended allopurinol-controlled phase III safety trial that was conducted to evaluate safety in patients who completed the main Phase III trials (APEX or FACT). A total of 1086 patients were included in the study: febuxostat 80 mg once daily (n=649), febuxostat 120 mg once daily (n=292), or allopurinol 300/100 mg once daily (n=145). For approximately 69% of patients, no adjustment of therapy was required to achieve a final stable result. Patients whose plasma uric acid concentration was >6.0 mg/dl when measured three times consecutively were excluded from the study. The level of uric acid concentration in the blood serum did not change over time (for example, in 91 and 93% of patients who first used febuxostat at doses of 80 and 120 mg, respectively, the level of uric acid concentration in the blood serum wasAccording to a 3-year follow-up, less than 4% of patients who needed treatment for gout attacks showed a decrease in the frequency of gout attacks at the 16th-24th and 30th-36th months (i. e., more than 96% of patients did not need treatment for gout attacks). In 46 and 38% of patients who received final stable treatment with febuxostat at a dose of 80 or 120 mg, respectively, once a day, complete disappearance of the primary palpable topus was noted. The FOCUS Study (TMX-01-005) is a 5 — year, open-label, multicenter, extended-release, phase II safety study that was conducted in patients who completed 4 weeks of double-dose febuxostat in the TMX-01-004 blind trial. The study included 116 patients who first received febuxostat 80 mg once a day. In 62% of patients, to maintain the serum uric acid concentration at the level ofThe proportion of patients with a plasma uric acid concentration <6.0 mg / dl (357 mmol / L) at the last visit was >80% (81-100%) for each of the febuxostat dose groups. In phase III clinical trials in patients treated with febuxostat, minor changes in hepatic parameters were recorded (5.0%). The frequency of these changes is similar to that of allopurinol (4.2%). In long-term open-label extended-release studies, patients treated with febuxostat (5.5%) or allopurinol (5.8%) for a long time showed an increase in TSH levels (>5.5 MIU/ml). Tumor Lysis syndrome (SLO)The efficacy and safety of febuxostat for the prevention and treatment of CF was evaluated in the FLORENCE study (FLO-01). febuxostat showed a better and faster effect on reducing urate levels compared to allopurinol. FLORENCE was a randomized (1:1) double-blind phase III reference study comparing febuxostat 120 mg once daily and allopurinol 200-300 mg / day (mean daily dose of allopurinol ± standard deviation: 349.7±112.90 mg) under the control of uric acid concentration in blood serum. The selected patients had to be candidates for allopurinol treatment or not have access to rasburicase. The primary endpoints were serum uric acid AUC (AUC sUA1-8) and change in serum creatinine (sC) levels from day 1 to day 8 each. The study included 346 patients with hematological malignancies receiving chemotherapy with a moderate/high risk of developing CF. The mean AUC of sUA1-8 mg * h / dl was significantly lower with febuxostat (514.0±225.71 compared to 708.0±234.42; mean of least squares for difference: -196.794 [95% confidence interval (CI) -238.600… -154.988]; p=0.0001). In addition, the mean serum uric acid level was significantly lower when febuxostat was used, starting from the first 24 hours of treatment and at any subsequent time. There were no statistically significant differences in mean serum creatinine (%) between febuxostat and allopurinol (-0.83±26.98 vs. -4.92±16.70, respectively; mean of least squares for the difference: 4.0970 [95% CI -0.6467; 8.8406]; p=0.0903). Taking into account the secondary endpoints, there were no statistically significant differences in the incidence of laboratory–confirmed AF (8.1 and 9.2% for febuxostat and allopurinol, respectively; relative risk (RR) 0.875 [95% CI 0.4408-1.7369]; p=0.8488) and the clinical picture of tumor collapse syndrome (1.7 and 1.2% for febuxostat and allopurinol, respectively; RR 0.994 [95% CI 0.9691; 1.0199]; p=1.0000). The frequency of all signs and symptoms that occurred during treatment, as well as adverse reactions, was 67.6% compared to 64.7% and 6.4% compared to 6.4% for febuxostat and allopurinol, respectively. In the FLORENCE study, febuxostat showed a better and faster effect on reducing serum uric acid levels compared to allopurinol. Data for comparison of febuxostat and rasburicase are currently unavailable. The efficacy and safety of febuxostat have not been established for patients with acute severe CF, such as patients in whom other urate-lowering therapies do not work. Preclinical safety data The described effects of the drug, observed in clinical studies at exposure, are many times higher than the maximum exposure in humans. Carcinogenesis, mutagenesis, impaired fertility Statistically significant increase in the incidence of bladder tumors (transitional cell papilloma and carcinoma) was observed only in male rats in the maximum dose group (approximately 11 times higher than human exposure) and was associated with the deposition of xanthine crystals. Studies on male and female mice and rats did not reveal a likely increase in the incidence of other tumors. These changes were considered as a manifestation of the peculiarities of purine metabolism and urine composition and had no clinical significance. In standard genotoxicity studies, no biologically significant genotoxic effects of febuxostat were observed. Febuxostat in doses up to 48 mg / kg / day orally did not affect fertility and reproductive function in male and female rats. Data on fertility disorders, teratogenic effects or harmful effects on the fetus have not been obtained. When the exposure was 4.3 times higher than recommended for humans, rats showed increased toxicity to the female, followed by a decrease in the rate of weaning from breastfeeding and a slowdown in the development of offspring. Teratogenic effects of the drug were not observed in studies on pregnant rats with an exposure 4.3 times higher than recommended for humans, and on pregnant rabbits with an exposure 13 times higher than recommended for humans. Pharmacokinetics. In healthy volunteers, Cmax and AUC increased in proportion to the dose after single and multiple use of febuxostat in doses of 10-120 mg. At doses of 120-300 mg, the increase in AUC was greater than proportional to the dose. No accumulation of febuxostat was observed at doses of 10-240 mg every 24 hours. The estimated mean terminal half-life of febuxostat was approximately 5-8 hours. A population-based pharmacokinetic/pharmacodynamic analysis was performed based on data obtained from 211 patients with hyperuricemia and gout who used febuxostat at doses of 40-240 mg once a day. In general, the obtained values of pharmacokinetic parameters were similar to those in healthy volunteers, which, therefore, are a good model for evaluating the pharmacokinetics/pharmacodynamics of the drug in patients with gout. Suction. Febuxostat is rapidly absorbed (tmax [time to reach Cmax] — 1.0–1.5 h) and is well absorbed (84%). With single and multiple oral use of febuxostat at doses of 80 mg or 120 mg once a day, the Cmax is respectively 2.8–3.2 and 5.0–5.3 mcg / ml. The absolute bioavailability of febuxostat was not analyzed. With repeated use at a dose of 80 mg once a day or with a single use at a dose of 120 mg in combination with fatty foods, Cmax decreased by 49 and 38%, and AUC-by 18 and 16%, respectively.However, this was not accompanied by clinically significant changes in the degree of decrease in the level of uric acid in blood plasma (with repeated use at a dose of 80 mg). Thus, the drug can be used regardless of food intake. Distribution. The estimated volume of distribution at steady state (Vss/F) for febuxostat varies from 29 to 75 liters after oral use at a dose of 10-300 mg. The degree of binding to plasma proteins (mainly albumin) is 99.2% and does not change when the dose is increased from 80 to 120 mg. For the active metabolites of febuxostat, the degree of binding to plasma proteins ranges from 82 to 91%. Metabolism. Febuxostat is actively metabolized by conjugation with the participation of uridine phosphate gluconyltransferase (UDP-gluconyltransferase) and oxidation with the participation of cytochrome P450 (CYP) enzymes. A total of 4 pharmacologically active hydroxyl metabolites of febuxostat were described; 3 of them were detected in human blood plasma. In vitro studies on human liver microsomes have shown that these oxidized metabolites are formed mainly by the action of CYP A1, CYP A2, CYP 2C8 and CYP 2C9, while febuxostataglucuronide is formed mainly by the action of UDP-gluconyltransferase 1A1,1A8,1A9. Output. Febuxostat is excreted by the liver and kidneys. After oral use of 14C-febuxostat at a dose of 80 mg, approximately 49% was excreted unchanged in the urine as febuxostat (3%), acylglucuronide (30%), known oxidized metabolites and their conjugates (13%) and other unknown metabolites (3%). In addition to renal excretion, approximately 45% was excreted in the faeces as unchanged febuxostat (12%), acylglucuronide (1%), known oxidized metabolites and their conjugates (25%), and other unknown metabolites (7%). Special groups of patients. Kidney failure. With repeated use of febuxostat at a dose of 80 mg, there were no changes in the Cmax of Febuxostat in patients with mild, moderate or severe renal insufficiency compared with patients with normal renal function. The mean total AUC of febuxostat increased approximately 1.8-fold from 7.5 mcg / h / ml in patients with normal renal function to 13.2 mcg/h / ml in those with severe renal insufficiency. Cmax and AUC of active metabolites were increased 2 and 4 times, respectively. However, patients with mild, moderate or severe renal insufficiency do not need to adjust the dose of the drug. Impaired liver function. With repeated use of febuxostat at a dose of 80 mg, there were no significant changes in the Cmax and AUC of febuxostat and its metabolites in patients with mild to moderate (class A and B on the Child — Pugh scale) degree of hepatic insufficiency compared with patients with normal liver function. Studies of the drug in patients with severe hepatic insufficiency (Child — Pugh class C) have not been conducted. Age. With repeated oral use of febuxostat, there were no significant changes in the AUC of febuxostat and its metabolites in elderly patients compared with young healthy volunteers. Paul. With repeated oral use of febuxostat, the max and AUC of febuxostat in women were 24 and 12% higher, respectively, than in men. However, Cmax and AUC adjusted by body weight were similar for both groups, so changes in the dose of febuxostat depending on gender are not required.

Indications

Treatment of chronic hyperuricemia in patients with diseases associated with the deposition of urate crystals, including in the presence of tophi and/or gouty arthritis at present or in the anamnesis. Azurix 120 mg treatment and prevention of hyperuricemia in adult patients undergoing chemotherapy for hematological malignancies with a moderate or high risk of CF. Azurix is indicated for adult patients.

Contraindications

Hypersensitivity to the Active ingredient or any other auxiliary component of the drug.

Side effects

The most frequent adverse reactions in clinical trials (4072 patients treated with a dose of 10 to 300 mg) and in the course of post-marketing surveillance in patients with gout were exacerbations (attacks) of gout, liver function disorders, diarrhea, nausea, headache, rashes and edema. These reactions were mostly mild to moderate in severity. Serious hypersensitivity reactions to febuxostat were reported during post-marketing surveillance, some of them accompanied by systemic reactions. Table 2 lists adverse reactions by frequency and severity (in descending order) that occurred during clinical trials and in the post-marketing period, and is classified as follows: common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), and rare (≥1/10,000 toTable 2 Adverse reactions that occurred in phase III combined randomized extended-term studies and post-marketing follow-up in patients with gout

*Adverse reactions were noted within the post-marketing analysis. ** Diarrhoea and abnormal liver function tests that required therapy were reported during clinical trials and developed more frequently in patients receiving concomitant colchicine therapy. *** See the section PHARMACOLOGICAL PROPERTIES for the frequency of gout attacks that occurred in phase III individual randomized controlled trials. Description of selected adverse reactsi N the context of post-marketing surveillance, rare cases of serious hypersensitivity reactions to febuxostat have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylactic reactions/shock. Stevens-Johnson syndrome and toxic epidermal necrolysis are characterized by progressive skin rashes with bullous lesions of the skin or mucous membrane and irritation of the mucous membrane of the eye. Hypersensitivity reactions to febuxostat can be manifested by the following symptoms: skin reaction in the form of infiltrated maculopapular rash, generalized or exfoliative rash, thrombocytopenia and damage to individual organs or several organs (liver and kidneys, including tubulointerstitial nephritis). Exacerbation (attacks) of gout is usually noted shortly after the start of treatment and during the first months of therapy. The frequency of gout attacks decreased over time. When using febuxostat, prevention of acute attacks of gout is recommended. In the FLORENCE Phase III randomized double-blind reference trial (FLO-01), which compared febuxostat and allopurinol (346 patients receiving chemotherapy for hematological malignancies with a moderate or high risk of SLO), only 22 (6.4%) patients developed adverse reactions, namely 11 (6.4%) patients in each treatment group. Most of the adverse reactions were mild to moderate. Overall, the FLORENCE trial did not raise any additional concerns about the safety of febuxostat in patients with gout, with the exception of the three adverse reactions listed below (see Table 2). From the cardiovascular system: infrequently-blockage of the left bundle branch, ventricular tachycardia; sometimes-bleeding. Reports of possible adverse reactions. Reports of possible adverse reactions after drug registration play an important role. This allows you to continue monitoring the benefit / risk ratio for this drug.

Interaction

Mercaptopurine/azathioprine. In accordance with the mechanism of action of febuxostat, which consists in the ability to suppress xanthine oxidase, its simultaneous use with mercaptopurine/azathioprine is not recommended. Inhibition of xanthine oxidase can lead to an increase in the concentration of both drugs in the blood plasma, which can cause a toxic reaction. Studies of the interaction of febuxostat with drugs that are metabolized by xanthine oxidase have not been conducted. There are no data on the safety of their simultaneous use in cytotoxic therapy. During the study, patients with CF with multiple chemotherapy regimens were prescribed febuxostat at a dose of 120 mg, including monoclonal antibodies. However, drug — drug and drug — disease interactions were not investigated during this study. Therefore, the possibility of interaction with any cytotoxic drugs, with their combined appointment, cannot be excluded. Rosiglitazone / CYP 2C8 substrates. Febuxostat is a weak inhibitor of CYP 2C8 in vitro. In a study in healthy volunteers, concurrent use of 120 mg of febuxostat once daily and 4 mg of rosiglitazone in a single dose did not affect the pharmacokinetics of rosiglitazone and its metabolite N-desmethylrosiglitazone, which demonstrates that febuxostat does not inhibit the CYP 2C8 invivo enzyme. Thus, concomitant use of febuxostat and rosiglitazone or other CYP 2C8 substrates does not require dose adjustment for these drugs. Theophylline. A study of the interaction of febuxostat with healthy volunteers was conducted to assess the effect of xanthine oxidase inhibition on the increase in theophylline levels in the circulating blood observed with other xanthine oxidase inhibitors. The results showed that concomitant use of febuxostat 80 mg and theophylline 400 mg showed no pharmacokinetic interactions or effects on the safety of theophylline. Febuxostat at a dose of 80 mg can be used simultaneously with theophylline without special reservations. There are no data on the use of febuxostat at a dose of 120 mg. Naproxen and other glucuronidation inhibitors. The metabolism of febuxostat depends on the activity of UDP-glucuronyltransferase. Drugs that inhibit the glucuronidation process, such as NSAIDs and probenecid, can theoretically alter the excretion of febuxostat. In healthy volunteers, the simultaneous use of febuxostat and naproxen 250 mg 2 times a day increased the effect of febuxostat (Cmax is 28%, AUC is 41%, Half-life is 26%). In clinical trials, the use of naproxen and other NSAIDs/COX-2 inhibitors was not accompanied by a clinically significant increase in the severity and frequency of adverse reactions. Thus, febuxostat can be used simultaneously with naproxen without changing their dose. Glucuronidation inhibitors. Powerful inducers of UDP-glucuronyltransferase can increase metabolism and reduce the effectiveness of febuxostat. In patients who use powerful inducers of glucuronidation, it is recommended to monitor the level of uric acid in blood plasma after 1-2 weeks of simultaneous therapy. If the glucuronidation inducer is discontinued, the level of febuxostat in the blood plasma may increase. Colchicine / Indometacin / hydrochlorothiazide/warfarin. Febuxostat can be used simultaneously with colchicine or Indometacin without changing the dose of drugs. It is also not necessary to correct the dose of febuxostat when used in combination with hydrochlorothiazide. Concomitant use of febuxostat with warfarin does not require a change in the dose of the latter. The use of febuxostat (80 or 120 mg once a day) with warfarin does not affect the pharmacokinetics of the latter. Concomitant use with febuxostat also did not affect the international normalized ratio and factor VII activity. Desipramine/CYP 2D6 substrates. According to initro data, febuxostat is a weak inhibitor of CYP 2D6. In studies involving healthy volunteers receiving 120 mg of febuxostat, an increase in the AUC of desipramine (a CYP 2D6 substrate) by 22% was noted, indicating a weak inhibitory effect of febuxostat invivo. Thus, when using febuxostat and CYP 2D6 substrates simultaneously, there is no need to change their doses. Antacids. When used concomitantly with antacids containing magnesium hydroxide and aluminum hydroxide, the absorption of febuxostat is inhibited (approximately for 1 h) and Cmax decreases by 32%, but the AUC of febuxostat does not change significantly, so febuxostat can be combined with the use of antacids.

How to take, course of use and dosage

Gout. The recommended dose of Azurixac is 80 mg once a day orally, regardless of food intake. If the concentration of uric acid in the blood serum exceeds 6 mg / dl (357 mmol/l) after 2-4 weeks of treatment, the dose of Azurix can be increased to 120 mg once a day. The effect of the drug occurs quite quickly, which makes it possible to re-determine the concentration of uric acid after 2 weeks. The goal of treatment is to reduce the concentration of uric acid and maintain it at the level ofThe duration of prevention of gout attacks is at least 6 months. SLO. The recommended dose of Azurixac is 120 mg once daily orally, regardless of food intake. Azurix should be started 2 days before the start of cytotoxic therapy and continued for at least 7 days; however, therapy can be extended to 9 days according to the duration of chemotherapy and clinical evaluation. Kidney failure. In patients with mild or moderate renal impairment, no dose adjustment is required. In patients with severe renal impairment (creatinine clearance Impaired liver function. The efficacy and safety of febuxostat in patients with severe hepatic impairment (Child — Pugh class C) have not been studied. Gout: For mild hepatic impairment, the recommended dose is 80 mg. The experience of using the drug in patients with moderate hepatic impairment is limited. SLO. Only subjects with severe hepatic impairment were excluded from the Phase III reference study (FLORENCE). For patients who were included in the study, no dose adjustment is required due to the state of liver function. Elderly patients. No dose adjustment is required for this category of patients. Patients who have undergone organ transplantation. There is no experience of using febuxostat in this category of patients, so the use of the drug is not indicated. Method of applicationfor oral use. Azurix is used orally regardless of food intake.

Overdose

In case of overdose, symptomatic and supportive therapy is indicated.

Special instructions

Cardiovascular diseasestreatment of chronic hyperuricemia. Febuxostat is not recommended for use in patients with CHD or congestive heart failure. In the APEX and FACT studies in the general febuxostat group compared to the allopurinol group, an increase in the number of cardiovascular disorders (Anti-Platelet Trialists’ Collaboration-APTC) was reported (determination of endpoints in the group of combined antiplatelet therapy analysis (APTC), including fatal outcomes due to cardiovascular disease, myocardial infarction without a fatal outcome, stroke without a fatal outcome; 1.3 compared to 0.3 cases per 100 patient — years), as opposed to the CONFIRMS study. The reported incidence of cardiovascular events (APTC) in the combined phase III trials (APEX, FACT, and CONFIRMS) was 0.7 compared to 0.6 cases per 100 patient-years for febuxostat and allopurinol, respectively. In long-term, large-scale studies, the reported incidence of cardiovascular events was 1.2 and 0.6 cases per 100 patient-years for febuxostat and allopurinol, respectively. The differences were not statistically significant, and there was no causal relationship between these disorders and the use of febuxostat. Risk factors for these patients were diseases that occurred as a result of atherosclerosis and / or myocardial infarction, or a history of congestive heart failure. Prevention and treatment of hyperuricemia in patients at risk of developing CP Patients undergoing chemotherapy for hematological malignancies with a moderate or high risk of CP and using febuxostat, if clinically indicated, are under the supervision of a cardiologist. Drug allergy/hypersensitivity. In post-marketing surveillance, there were rare reports of severe allergic/hypersensitivity reactions, including life-threatening Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute anaphylactic reactions/shock. In most cases, they occurred during the 1st month of febuxostat use. Several patients had a history of renal impairment and / or hypersensitivity to allopurinol. Severe hypersensitivity reactions, including reactions associated with eosinophilia and systemic symptoms (DRESS syndrome), have in some cases been associated with fever, hematological, renal or hepatic insufficiency. Patients should be informed about the symptoms of hypersensitivity/allergy, and they should be monitored for the development of such reactions. If serious allergic reactions/hypersensitivity reactions occur, the use of febuxostat should be stopped immediately, as early discontinuation of use improves the prognosis. If the patient has an allergic/hypersensitivity reaction, including Stevens — Johnson syndrome, and acute anaphylactic reactions/shock, then repeated use of febuxostat is contraindicated. Exacerbation (attack) of gout. Treatment with febuxostat should be started only in the period after an exacerbation of the disease. Febuxostat can trigger an attack of gout at the beginning of treatment by changing the level of uric acid through the exit of urates from the depot. At the beginning of treatment with febuxostat, it is recommended to prescribe NSAIDs or colchicine for a period of at least 6 months to prevent gout attacks. With the development of an attack against the background of the use of febuxostat, treatment is continued. At the same time, appropriate individual therapy for exacerbation of gout is carried out. With prolonged use of febuxostat, the frequency and severity of gout attacks are reduced. Xanthine deposits. In patients with accelerated urate formation (for example, on the background of malignant neoplasms and their treatment, or with Lesch-Nihan syndrome), a significant increase in the absolute concentration of xanthines in the urine may occur, accompanied by their deposition in the urinary tract. This was not observed in the febuxostat reference clinical trial for CF. Due to the limited experience of using febuxostat in this condition, the drug is not indicated for patients. Mercaptopurine/azathioprine. Febuxostat is not recommended for use in patients receiving mercaptopurine/azathioprine. If concomitant use cannot be avoided, patients should be carefully monitored. It is recommended to reduce the dose of mercaptopurine/azathioprine to avoid possible hematological effects. Patients who have undergone organ transplantation. There is no experience of using febuxostat in this category of patients, so the use of the drug is not indicated. Theophylline. A single concomitant use of febuxostat at a dose of 80 mg and theophylline at a dose of 400 mg did not demonstrate any pharmacokinetic interactions. Febuxostat at a dose of 80 mg can be used simultaneously with theophylline without the risk of increasing the concentration of theophylline in blood plasma. There are no data on the use of febuxostat at a dose of 120 mg. Liver diseases. During the combined phase III clinical trials,5.0% of patients treated with febuxostat showed minor changes in liver parameters, so it is recommended to check liver function indicators before prescribing febuxostat and during treatment, if indicated. Diseases of the thyroid gland. In 5.5% of patients treated with febuxostat for a long time, an increase in TSH (>5.5 MIU/ml) was observed, so the drug should be prescribed with caution to people with impaired thyroid function. Lactose. The drug contains lactose, so the drug is contraindicated in patients with rare hereditary diseases associated with galactose intolerance, lactase deficiency or glucose/galactose malabsorption. Use during pregnancy and lactation. Limited experience with the use of febuxostat during pregnancy indicates that there is no adverse effect on the course of pregnancy and the health of the fetus / newborn. In animal studies, no direct or indirect side effects on pregnancy, embryo/fetal development, or delivery were observed. The potential risk to humans is unknown. In connection with the above, the use of febuxostat is contraindicated during pregnancy. It is not known whether febuxostat penetrates into human breast milk. Animal studies have shown that febuxostat penetrates into breast milk and has a negative effect on the development of newborns who are breastfed. In connection with the above, the use of febuxostat during breast-feeding is contraindicated. Fertility. Animal fertility studies at a dose of 48 mg / kg / day showed no dose-dependent adverse reactions. The effect of febuxostat on human reproductive function is unknown. Children. The use of febuxostat in children (under 18 years of age) is not indicated due to the lack of experience in its use in pediatrics. Ability to influence the reaction rate when driving vehicles or working with other mechanisms. There have been reports of drowsiness, dizziness, paresthesia, and visual impairment associated with the use of febuxostat, so patients using febuxostat are advised to use caution when driving vehicles and working with other mechanisms until they are sure that the above phenomena are absent.

Storage conditions

It does not require special storage conditions.

Active ingredient

Febuxostat

Conditions of release from pharmacies

Prescription