Azurix tablets 80mg, No. 30

• Chronic hyperuricemia in conditions accompanied by the deposition of urate crystals (in the presence of tophus and / or gouty arthritis, including a history);

• treatment and prevention of hyperuricemia in adult patients during cytostatic therapy of hemoblastoses with a moderate to high risk of tumor disintegration syndrome (only for a dosage of 120 mg).

The drug is taken orally, 1 time / day, regardless of food intake.

Gout

The recommended initial dose is 80 mg of AzurixЃ 1 time / day.

After 2-4 weeks, it is recommended to control the concentration of uric acid in the blood serum; if the indicator exceeds 6 mg / dl (357 ?mol / l), the dose of the drug can be increased to 120 mg 1 time / day.

The decrease in the concentration of uric acid in the blood serum against the background of the use of the drug occurs rather quickly, in connection with which the control of the concentration of uric acid can be carried out 2 weeks after the start of the drug intake. The goal of treatment is to reduce and maintain serum uric acid concentrations below 6 mg / dL (357 ?mol / L).

Prevention of the development of acute gout attacks is recommended for at least 6 months.

Tumor disintegration syndrome

The recommended dose is 120 mg of AzurixЃ 1 time / day, regardless of food intake. The drug should be taken 2 days before the start of cytostatic therapy. The duration of the drug should be at least 7 days. Depending on the duration of the course of chemotherapy, the duration of the drug may be increased to 9 days.

No dose adjustment is required in elderly patients.

In patients with mild hepatic impairment (class A on the Child-Pugh scale: 5-6 points), the recommended dose of AzurixЃ is 80 mg 1 time / day. Experience with febuxostat in moderate hepatic failure is limited.

In patients with mild to moderate renal insufficiency, dose adjustment is not required. In patients with severe renal insufficiency (CC <30 ml / min), the efficacy and safety of febuxostat has not been adequately studied.

Film-coated tablets

1 tab. febuxostat

Excipients: mannitol, sodium croscarmellose, sodium bicarbonate, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate, talc, colloidal silicon dioxide (aerosil).

• Hypersensitivity to febuxostat and / or to any of the excipients;

• age under 18;

• pregnancy;

• period of breastfeeding.

Carefully:

• renal failure of severe severity (CC <30 ml / min) (efficacy and safety have not been studied enough);

• liver failure;

• history of allergic reactions;

• Ischemic heart disease;

• congestive heart failure;

• diseases of the thyroid gland;

• simultaneous use with mercaptopurine / azathioprine (it is possible to increase the concentration of these substances in the blood plasma and increase their toxicity);

• conditions after organ transplantation (experience with febuxostat is limited);

• Lesch-Nyhan syndrome (experience with febuxostat is limited).

pharmachologic effect

Uric acid is the end product of purine metabolism in the human body, formed as a result of the hypoxanthine - xanthine - uric acid cascade. Febuxostat is a 2-arylthiazole derivative and is a potent selective non-purine xanthine oxidase inhibitor (in vitro inhibition constant less than 1 nM). The xanthine oxidase enzyme catalyzes two stages of purine metabolism: the oxidation of hypoxanthine to xanthine, and then the oxidation of xanthine to uric acid.

As a result of the selective inhibition of xanthine oxidase (oxidized and reduced form) by febuxostat, the concentration of uric acid in the blood serum decreases.

At therapeutic concentrations, febuxostat does not inhibit other enzymes involved in the metabolism of purines or pyrimidines, such as guanine deaminase, hypoxanthine guanine phosphoribosyltransferase, orotate phosphoribosyltransferase, orothi-dinmonophosphate decarboxylase or purine-nucleosylase phosphorylase phosphorylphosphoric acid phosphoribosyltransferase.

Pharmacokinetics

Suction

After oral administration, febuxostat is rapidly and almost completely (at least 84% of the dose taken) absorbed from the gastrointestinal tract. With repeated administration of febuxostat at a dose of 80 mg or a single dose of 120 mg simultaneously with the intake of fatty foods, the Cmax of febuxostat in blood plasma decreased by 49% and 38%, respectively, and the AUC - by 18% and 16%, respectively. However, this did not affect the clinical efficacy of reducing the concentration of uric acid in the blood serum (with repeated administration of febuxostat at a dose of 80 mg), in this regard, febuxostat can be taken regardless of food intake.

Cmax is achieved within 1-1.5 hours after oral administration and is 2.8-3.2 ?g / ml with a single oral administration at a dose of 80 mg and 5.0-5.3 ?g / ml with a single dose of 120 mg. The absolute bioavailability of febuxostat in tablet form has not been studied.

With repeated oral administration of febuxostat at doses of 10-240 mg 1 time / day, no cumulation was observed.

Distribution

The apparent Vd at steady state varies from 29 L to 75 L after oral administration of febuxostat in doses of 10-300 mg. The degree of binding to plasma proteins (mainly albumin) reaches 99.2% and does not change when the dose is increased from 80 mg to 120 mg. For active metabolites, the degree of binding to plasma proteins varies from 82% to 91%.

Metabolism

Febuxostat is metabolized by conjugation with the participation of uridine diphosphate glucuronyl transferase (UDPGT) and oxidation with the participation of enzymes of the cytochrome P450 system (CYP). Four pharmacologically active hydroxyl metabolites have been isolated, of which three are found in human blood plasma. In vitro studies on human liver microsomes have shown that oxidized metabolites are formed mainly under the influence of isoenzymes CYP1A1, CYP1A2, CYP2C8 or CYP2C9, while febuxostat glucuronide is formed mainly under the influence of isoenzymes UGT1A1, UGT1A8 and UGT1A9.

Withdrawal

Febuxostat and its metabolites are excreted from the body through the intestines and by the kidneys.

After oral administration of febuxostat labeled with a radioisotope 14C at a dose of 80 mg, approximately 49% is excreted by the kidneys: unchanged - about 3%, in the form of acylglucuronide - 30%, in the form of oxidized metabolites and their conjugates - 13%, in the form of other metabolites - 3%.

Approximately 45% of febuxostat is excreted through the intestine: as unchanged febuxostat - 12%, acylglucuronide - 1%, oxidized metabolites and their conjugates - 25%, other metabolites - 7%.

The apparent T1 / 2 of febuxostat is 5-8 hours.

Pharmacokinetics in special patient groups

In patients with mild or moderate renal insufficiency, dose adjustment is not required.

With repeated oral administration 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 hepatic insufficiency (class A on the Child-Pugh scale: 5-6 points) and average (class B on the Child-Pugh scale). Pugh: 7-9 points) of severity compared to healthy volunteers. Pharmacokinetic studies of febuxostat in patients with severe hepatic impairment (Child-Pugh class C: 10-15 points) have not been conducted.

With repeated oral administration of febuxostat, there were no significant changes in the AUC of febuxostat and its metabolites in elderly patients compared with young healthy volunteers.

With repeated oral administration of febuxostat, the Cmax and AUC of febuxostat were 24% and 12% higher in women than in men, respectively. However, the Cmax and AUC values ??corrected for the patient's body weight were similar for both groups. Thus, there is no need to adjust the dose of the drug depending on the gender of the patient.

Side effect

From the hematopoietic system: rarely - pancytopenia, thrombocytopenia.

From the immune system: rarely - anaphylactic reactions , hypersensitivity reactions .

From the nervous system: often - headache; infrequently - dizziness, paresthesia, hemiparesis, drowsiness, change in taste, hypesthesia, hyposmia (weakening of the sense of smell).

From the side of the psyche: infrequently - decreased libido, insomnia; rarely - nervousness.

From the endocrine system: infrequently - an increase in the concentration of TSH in the blood plasma.

From the side of metabolism: often - attacks of gout ***; infrequently - diabetes mellitus, hyperlipidemia, decreased appetite, weight gain; rarely - weight loss, increased appetite, anorexia.

From the side of the organ of vision: rarely - blurred vision.

On the part of the organ of hearing and labyrinth disorders: rarely - tinnitus.

From the side of the cardiovascular system: infrequently - atrial fibrillation, palpitations, ECG changes, left bundle branch block (see section 'Tumor collapse syndrome'), sinus tachycardia (see section 'Tumor collapse syndrome'), increased blood pressure , 'hot flushes' of blood to the face, a feeling of heat, hemorrhages (see the section 'Tumor disintegration syndrome').

From the respiratory system: infrequently - dyspnea, bronchitis, upper respiratory tract infections, cough, chest pain, chest discomfort.

From the digestive system: often - diarrhea **, nausea; infrequently - abdominal pain, bloating, gastroesophageal reflux disease, vomiting, dryness of the oral mucosa, dyspeptic symptoms, constipation, frequent stools, flatulence, abdominal discomfort; rarely - pancreatitis, ulcerative stomatitis.

From the liver and biliary tract: often - liver dysfunction * ; infrequently - cholelithiasis; rarely - hepatitis, jaundice , liver damage *.

On the part of the skin and subcutaneous tissues: often - a rash (including the various types of rashes mentioned below with a lower frequency); infrequently - dermatitis, urticaria, pruritus, skin discoloration, skin lesions, petechiae, macular rash, maculopapular rash, papular rash; rarely - toxic epidermal necrolysis , Stevens-Johnson syndrome , angioedema , drug reaction with eosinophilia and systemic symptoms (see section 'Special instructions'), severe forms of generalized rash , erythema, exfoliative rash, follicular rash, vesicular rash, pustular rash, pustular rash itchy rash , erythematous rash, measles-like rash, alopecia, hyperhidrosis.

From the musculoskeletal system: infrequently - arthralgia, arthritis, myalgia, musculoskeletal pain, muscle weakness, muscle spasm, muscle tension, bursitis; rarely - rhabdomyolysis *, joint stiffness, muscle stiffness.

From the urinary system: infrequently - renal failure, nephrolithiasis, hematuria, pollakiuria, proteinuria; rarely - tubulointerstitial nephritis *, urge to urinate.

Reproductive system disorders: infrequently - erectile dysfunction.

Others: often - edema; infrequently - increased fatigue; rarely, thirst.

Influence on the results of laboratory and instrumental studies: infrequently - an increase in the activity of amylase in the blood plasma, a decrease in the number of platelets, a decrease in the number of leukocytes, a decrease in the number of lymphocytes, an increase in the content of creatine and creatinine in the blood plasma, a decrease in hemoglobin, an increase in the concentration of urea in the blood plasma, an increase in the concentration triglycerides in the blood plasma, an increase in the concentration of cholesterol in the blood plasma, a decrease in hematocrit, an increase in the activity of LDH in the blood plasma, an increase in the content of potassium in the blood plasma; rarely - an increase in the concentration of glucose in the blood plasma, lengthening of APTT, a decrease in the number of erythrocytes, an increase in the activity of alkaline phosphatase in the blood plasma.

* HP observed during the post-marketing observation period.

** Non-infectious diarrhea and liver disorders observed in phase III studies were more common with concomitant use of colchicine.

*** Additional information regarding the development of acute attacks of gout in the section 'Special instructions'.

Description of individual IOs

In the period of post-marketing use, there have been rare reports of severe allergic reactions (hypersensitivity reactions), including Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic reactions and shock.

Stevens-Johnson syndrome and toxic epidermal necrolysis are characterized by a progressive skin rash associated with bullous skin or mucous membranes, and eye irritation. Hypersensitivity reactions to febuxostat can also manifest with the following symptoms: skin reactions characterized by infiltrative maculopapular rashes; generalized or exfoliative rash, as well as skin lesions, facial edema, fever, hematopoietic disorders such as thrombocytopenia and eosinophilia, and involvement of one or more organs (liver and kidney, including tubulointerstitial nephritis).

Gout attacks usually occur shortly after starting the drug and during the first months of therapy. Subsequently, the frequency of attacks decreases. It is recommended to prevent the development of acute gout attacks.

Tumor disintegration syndrome

In the FLORENCE study comparing the effects of febcostat and allopurinol (346 patients receiving chemotherapy for hematological malignancies and at moderate to high risk of developing tumor breakdown syndrome), side effects were noted in 22 patients (6.4%). In both groups (febuxostat group and allopurinol group), the incidence of side effects was the same (11 patients each, 6.4%). Most of the HP cases were mild to moderate. Overall, with the exception of the three HPs listed below, the FLORENCE study found no other safety profile for febuxostat in addition to that for gout.

From the side of the cardiovascular system: infrequently - left bundle branch block, sinus tachycardia, hemorrhages.

Application during pregnancy and lactation

Due to insufficient data, the potential human risk of febuxostat is not known, therefore, the use of febuxostat during pregnancy is contraindicated. There is limited experience with febuxostat during pregnancy with no adverse effects on pregnancy and fetal / newborn health. In animal studies, no direct or indirect adverse effects of the drug on the course of pregnancy, the development of the embryo / fetus and the process of childbirth were noted.

There is no evidence of whether febuxostat passes into breast milk. In animal studies, it has been noted that febuxostat passes into breast milk and has an adverse effect on the development of nursing infants. Thus, the risk to infants cannot be excluded. Therefore, the use of febuxostat is contraindicated during breastfeeding.

Application for violations of liver function

The drug should be prescribed with caution in liver failure.

Application for impaired renal function

The drug should be prescribed with caution in severe renal failure (CC <30 ml / min).

Application in children

The use of the drug under the age of 18 is contraindicated.

Use in elderly patients

No dose adjustment is required in elderly patients.

special instructions

Acute gout attack

The use of the drug should be started only after the relief of an acute attack of gout. The beginning of the use of the drug can provoke the development of an acute attack of gout due to the release of urates from tissue depots and a subsequent increase in the concentration of uric acid in the blood serum. For the prevention of gout attacks in the absence of contraindications, the simultaneous use of NSAIDs or colchicine is recommended for at least 6 months.

With the development of an attack against the background of the use of the drug, the reception should be continued and at the same time the appropriate treatment of an acute attack of gout should be carried out. With prolonged use of the drug, the frequency and severity of gout attacks decrease.

Deposition of xanthines

In rare cases, in patients with accelerated urate formation (for example, against the background of malignant neoplasms or Lesch-Nychen syndrome), a significant increase in the absolute concentration of xanthines in the urine is possible, which may be accompanied by their deposition in the urinary tract. This phenomenon was not observed with febuxostat in the FLORENCE study in patients with tumor disintegration syndrome. Due to limited data, the use of the drug in patients with Lesch-Nychen syndrome is not recommended.

Mercaptopurine / Azathioprine

Concomitant use with mercaptopurine, azathioprine is not recommended. If necessary, simultaneous use, to reduce the toxic effect on the hematopoietic system, it is recommended to reduce the dose of mercaptopurine / azathioprine and close medical supervision.

Theophylline

ѕри одновременном применении у здоровых добровольцев фебуксостата в дозе 80 мг 1 раз/сут и разовой дозы теофиллина 400 мг не отмечалось изменений фармакокинетических показателей. “аким образом, одновременное применение фебуксостата в дозе 80 мг и теофиллина не несет риска увеличени¤ концентрации теофиллина в плазме крови. »зучение одновременного применени¤ фебуксостата в дозе 120 мг и теофиллина не проводилось.

ѕациенты, перенесшие трансплантацию органов

ѕрименение препарата у пациентов, перенесших трансплантацию органов, не рекомендуетс¤ в св¤зи с отсутствием опыта применени¤.

јллергические реакции и реакции гиперчувствительности

¬ период постмаркетингового применени¤ имели место редкие сообщени¤ о возникновении т¤желых аллергических реакций (реакций гиперчувствительности), включа¤ синдром —тивенса-?жонсона, токсический эпидермальный некролиз, анафилактические реакции и шок.

¬ большинстве случаев данные реакции развивались в течение первого мес¤ца применени¤ препарата. ” части пациентов в анамнезе имелась почечна¤ недостаточность и/или реакции гиперчувствительности на фоне применени¤ аллопуринола.

¬ отдельных случа¤х т¤желые реакции гиперчувствительности, в т.ч. синдром лекарственной реакции с эозинофилией и системными симптомами (DRESS), сопровождались лихорадкой, изменением показателей крови, нарушением функции печени или почек.

ѕациенты должны быть проинформированы о возможных признаках и симптомах аллергических реакций (реакций гиперчувствительности), и должны находитьс¤ под тщательным наблюдением на предмет развити¤ симптомов аллергических реакций/реакций гиперчувствительности.

¬ случае возникновени¤ т¤желых аллергических реакций/реакций гиперчувствительности, включа¤ синдром —тивенса-?жонсона, необходимо немедленно прекратить применение препарата (более ранн¤¤ отмена ассоциирована с лучшим прогнозом). ѕовторное применение препарата не рекомендуетс¤.

—ердечно-сосудистые заболевани¤

ѕрименение препарата не рекомендуетс¤ у пациентов с »Ѕ— или застойной сердечной недостаточностью.

¬ исследовани¤х APEX и FACT (в отличие от исследовани¤ CONFIRMS) в общей группе фебуксостата по сравнению с группой аллопуринола отмечалось увеличение количества нарушений со стороны сердечно-сосудистой системы, определенных в соответствии с системой, разработанной группой по совместному анализу антитромбоцитарной терапии (v—јј“) и включающих в себ¤ смерть от сердечно-сосудистых причин, нелетальный инфаркт миокарда, инсульт без летального исхода) - 1.3 по сравнению с 0.3 случаев на 100 пациенто-лет. —огласно объединенным данным клинических исследовани¤х III фазы (исследовани¤ APEX, FACT и CONFIRMS) частота нарушений со стороны сердечно-сосудистой системы составила 0.7 в сравнении с частотой 0.6 случаев на 100 пациенто-лет.

¬ рамках долгосрочных широкомасштабных исследований частота сердечно-сосудистых нарушений v—јј“ составила 1.2 и 0.6 случаев на 100 пациенто-лет дл¤ фебуксостата и аллопуринола, соответственно. –азличи¤ не были статистически достоверны, причинно-следственна¤ св¤зь между указанными нарушени¤ми и приемом фебуксостата не была установлена. ¬ качестве факторов риска развити¤ указанных событий у пациентов было установлено наличие в анамнезе следующих состо¤ний: атеросклероз и/или инфаркт миокарда, или застойна¤ сердечна¤ недостаточность.

ѕрофилактика и лечение гиперурикемии у пациентов с риском развити¤ синдрома распада опухоли

” пациентов, получающих цитостатическую терапию гемобластозов с риском развити¤ синдрома распада опухоли от умеренного до выраженного, применение препарата при наличии показаний должно проводитьс¤ под наблюдением кардиолога.

«аболевани¤ печени

—огласно объединенным данным клинических исследований III фазы при применении фебуксостата у 5% пациентов отмечались нарушени¤ функции печени легкой степени т¤жести.

ѕеред назначением препарата рекомендуетс¤ провести оценку функции печени, а при наличии показаний - также во врем¤ применени¤.

«аболевани¤ щитовидной железы

¬ расширенных долгосрочных открытых исследовани¤х при длительном применении фебуксостата у 5.5% пациентов отмечалось повышение концентрации тиреотропного гормона (>5.5 мкћ?/мл), в св¤зи с чем пациентам с нарушением функции щитовидной железы препарат следует назначать с осторожностью.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

ѕри приеме препарата возможно по¤вление сонливости, головокружени¤, парестезии и нечеткости зрени¤ и, как следствие, снижение реакции и способности к концентрации внимани¤, поэтому во врем¤ применени¤ препарата необходимо соблюдать осторожность при управлении транспортными средствами и зан¤ти¤ми другими потенциально опасными видами де¤тельности, требующими концентрации внимани¤ и быстроты психомоторных реакций.

ѕередозировка

—имптомы: усиление побочных эффектов.

Ћечение: при передозировке препарата показана симптоматическа¤ и поддерживающа¤ терапи¤.

Ћекарственное взаимодействие

ћеркаптопурин/азатиоприн

ќдновременное применение с меркаптопурином, азатиоприном не рекомендуетс¤, т.к. ингибирование ксантиноксидазы фебуксостатом может приводить к повышению концентрации меркаптопурина, азатиоприна в плазме крови и усилению их токсического действи¤. »сследований по изучению взаимодействи¤ фебуксостата и веществ, метаболизирующихс¤ с участием ксантиноксидазы, не проводилось.

?итостатики

»сследований по изучению лекарственного взаимодействи¤ фебуксостата и цитостатических препаратов не проводилось. ¬ исследовании FLORENCE фебуксостат в дозе 120 мг примен¤лс¤ при синдроме распада опухоли у пациентов, подвергавшихс¤ цитостатической терапии различного вида (в т.ч. терапии моноклональными антителами). “ем не менее, т.к. исследований по изучению лекарственного взаимодействи¤ фебуксостата с цитотоксическими препаратами не проводилось, потенциального взаимодействи¤ фебуксостата с одновременно примен¤емыми цитотоксическими химиопрепаратами нельз¤ исключить.

–осиглитазон/субстраты изофермента CYP2C8

ѕо данным in vitro фебуксостат ¤вл¤етс¤ слабым ингибитором изофермента CYP2C8. ” здоровых добровольцев при одновременном применении 120 мг фебуксостата 1 раз/сут и разовой дозы 4 мг росиглитазона изменений фармакокинетических показателей росиглитазона и его метаболита N-дисметил росиглитазона отмечено не было, что свидетельствует об отсутствии у фебуксостата свойств ингибитора изофермента CYP2C8 in vivo. ѕри одновременном применении фебуксостата и росиглитазона (или других субстратов изофермента CYP2C8) коррекции дозы не требуетс¤.

“еофиллин

ѕри применении других ингибиторов ксантиоксидазы одновременно с теофиллином было отмечено увеличение концентрации теофиллина в плазме крови. ѕри одновременном применении у здоровых добровольцев фебуксостата в дозе 80 мг 1 раз/сут и разовой дозы теофиллина 400 мг изменений фармакокинетических показателей или переносимости теофиллина не наблюдалось, таким образом, при одновременном применении фебуксостата в дозе 80 мг и теофиллина особых мер осторожности не требуетс¤. »зучение одновременного применени¤ фебуксостата в дозе 120 мг и теофиллина не проводилось.

Ќапроксен и другие ингибиторы глюкуронизации

ћетаболизм фебуксостата зависит от активности фермента уридиндифосфатглюкуронилтрансферазы (”?‘v“). Ћекарственные препараты, угнетающие процесс глюкуронизации, например, Ќѕ¬ѕ и пробеницид, теоретически могут оказывать вли¤ние на выведение фебуксостата. ” здоровых добровольцев при одновременном применении фебуксостата и напроксена в дозе 250 мг 2 раза/сут наблюдалось увеличение показателей —mах фебуксостата на 28%, AUC - на 41% и “1/2 - на 26%. ¬ клинических исследовани¤х одновременное применение фебуксостата и напроксена или других Ќѕ¬ѕ/ингибиторов ?ќv-2 не сопровождалось клинически значимым повышением частоты возникновени¤ побочных ¤влений.  оррекции дозы при одновременном применении фебуксостата и напроксена не требуетс¤.

»ндукторы глюкуронизации

ѕри одновременном применении фебуксостата с сильными индукторами глюкуронизации возможно усиление его метаболизма и снижение эффективности. ѕри одновременном применении необходим контроль концентрации мочевой кислоты в сыворотке крови через 1-2 недели после начала терапии. ѕри отмене индуктора глюкуронизации возможно повышение —mах фебуксостата.

 олхицин/индометацин/гидрохлоротиазид/варфарин

‘ебуксостат можно примен¤ть одновременно с колхицином или индометацином без коррекции дозы.

“акже не требуетс¤ коррекции дозы фебуксостата при одновременном применении с гидрохлоротиазидом.

ќдновременное применение фебуксостата (80 мг или 120 мг 1 раз/сут) с варфарином не вли¤ет на фармакокинетику варфарина, ћЌќ и активность фактора VII у здоровых добровольцев. ѕри одновременном применении фебуксостата с варфарином коррекции дозы варфарина не требуетс¤.

Desipramine / CYP2D6 isoenzyme substrates

According to in vitro data, febuxostat is a weak inhibitor of the isoenzyme CYP2D6. In a study in healthy volunteers, while using febuxostat at a dose of 120 mg 1 time / day, there was an increase in the AUC of desipramine (a substrate of the CYP2D6 isoenzyme) by 22%, which indicates a weak inhibitory effect of febuxostat on the CYP2D6 isoenzyme in vivo. Thus, with the simultaneous use of febuxostat and substrates of the isoenzyme CYP2D6, dose adjustment is not required.

Antacids

With simultaneous use with antacids containing magnesium hydroxide or aluminum hydroxide, there is a decrease in absorption of febuxostat (approximately 1 hour) and a decrease in Cmax by 32%, however, the AUC of febuxostat did not change significantly. Therefore, febuxostat can be taken concurrently with antacids.