Adenuric tablets are coated. 80 mg 28 pcs. 28 pcs. (Febuksostat)

Release form

Film-coated tablets

Indications

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

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

Adenuric® is intended for use in adults.

Contraindications

- hypersensitivity to febuxostat and / or any of the excipients

- children under 18 years of age

- pregnancy and lactation

- hereditary galactose intolerance, lactase deficiency and malabsorption syndrome of glucose and galactose.

Precautions

- severe renal failure (creatinine clearance, liver failure

- history of allergic reactions

- coronary heart disease

- congestive heart failure

- thyroid disease / smerlkp - simultaneous use in plasma and increased toxicity)

- conditions after organ transplantation (experience with febuxostat is limited)

- Lesch-Nihan syndrome (experience USAGE febuxostat limited)

Use during pregnancy and lactation

Due to insufficient data, the potential risk of febuxostat to humans is not known, therefore the use of febuxostat during pregnancy is contraindicated. There is limited experience with the use of febuxostat during pregnancy, during which there was no adverse effect on the course of pregnancy and the condition of the fetus / newborn.

In animal studies, there was no direct or indirect adverse effect of the drug on pregnancy, the development of the embryo / fetus, and the birth process.

There is no data on whether febuxostat passes into breast milk. In animal studies, febuxostat passes into breast milk and has an adverse effect on the development of fed babies. Thus, risk to infants cannot be ruled out. In this regard, the use of febuxostat is contraindicated in the period of breastfeeding.

Special instructions

Acute gout attack

Use of the drug Adenurik® should only be started after the relief of an acute attack of gout. The beginning of the use of the drug Adenurik® can provoke the development of an acute attack of gout due to the release of urates from tissue depots and the 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 for at least 6 months is recommended.

When an attack develops with the use of Adenuric®, the use of the drug should be continued and at the same time appropriate treatment for an acute attack of gout.

With prolonged use of the drug Adenurik®, the frequency and severity of gout attacks are reduced.

Xanthine deposition

In rare cases in patients with accelerated urate formation (e.g. against the background of malignant neoplasms or with Lesch-Nihan 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. When using febuxostat in the FLORENCE study in patients with tumor decay syndrome, this phenomenon was not observed. Due to limited data, the use of the drug Adenurik® in patients with Lesch-Nihan syndrome is not recommended.

Mercaptopurin / 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 careful medical supervision.

Theophylline

With the simultaneous use of febuxostat in a dose of 80 mg once a day in healthy volunteers and a single dose of theophylline 400 mg, there were no changes in pharmacokinetic parameters. Thus, the simultaneous use of febuxostat in a dose of 80 mg and theophylline does not bear the risk of increasing theophylline concentration in blood plasma.

The study of the simultaneous use of febuxostat in a dose of 120 mg and theophylline was not conducted.

patients, undergoing organ transplantation

The use of Adenuric® in patients undergoing organ transplantation is not recommended due to the lack of experience in use.

Allergic and hypersensitivity reactions

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

In most cases, these reactions developed during the first month of using Adenurik®. Some patients had a history of renal failure and / or hypersensitivity reactions during the use of allopurinol.

In some cases, severe hypersensitivity reactions, including, drug reaction syndrome with eosinophilia and systemic symptoms (DRESS), accompanied by fever, changes in blood counts, impaired liver or kidney function.

Patients should be informed of the possible signs and symptoms of allergic reactions (hypersensitivity reactions), and should be closely monitored for the development of symptoms of allergic reactions / hypersensitivity reactions.

In case of severe allergic / hypersensitivity reactions, including Stevens-Johnson syndrome, the use of Adenuric® should be stopped immediately (earlier withdrawal is associated with a better prognosis). Repeated use of the drug is not recommended.

Cardiovascular disease

Adenuric® is not recommended for patients with coronary heart disease or congestive heart failure.

In the APEX and FACT studies (as opposed to the CONFIRMS study), the total febuxostat group compared with the allopurinol group showed an increase in the number of disorders of the cardiovascular system, determined in accordance with the system developed by the group for the joint analysis of antiplatelet therapy (GSAAT) and including death from cardiovascular causes, non-lethal myocardial infarction, non-fatal stroke) - 1.3 compared with 0.3 cases per 100 patient-years. According to the combined data from phase III clinical trials (APEX studies, FACT and CONFIRMS), the frequency of disorders of the cardiovascular system was 0.7 compared with a frequency of 0.6 cases per 100 patient-years.

Within the framework of long-term large-scale studies, the frequency of cardiovascular disorders of the GSAAT was 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 taking febuxostat has not been established. As a risk factor for the development of these events in patients, a history of the following conditions was found: atherosclerosis and / or myocardial infarction, or congestive heart failure.

Prevention and treatment of hyperuricemia in patients at risk of developing tumor decomposition syndrome

In patients receiving cytostatic therapy of hemoblastoses with a risk of developing a moderate to severe tumor decay syndrome, the use of the drug Adenurik®, if indicated, should be carried out under the supervision of a cardiologist.

Liver diseases

According to the combined data of phase III clinical trials using febuxostat in 5% of patients, mild liver function disorders were noted.

Before prescribing Adenuric®, it is recommended to evaluate liver function, and if indicated, also during use.

Thyroid diseases

In an extended, long-term open-label study with prolonged use of febuxostat, 5.5% of patients showed an increase in thyroid-stimulating hormone concentration (> 5.5 μIU / ml), due to with which patients with impaired thyroid function Adenuric® should be prescribed with caution.

Adenuric® contains lactose, therefore its use in patients with lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome is contraindicated.

Effect on the ability to drive vehicles and control mechanisms

When taking Adenurik®, drowsiness, dizziness, paresthesia and blurred vision may occur, and as a result, a decrease in reaction and ability to concentrate, therefore, during the use of Adenurik®, it is necessary to observe caution when driving vehicles and engaging in other potentially hazardous activities that require concentration and speed of psychomotor reactions.

Composition

Core:

Active ingredient:

febuxostat - 80.0 mg.

Excipients:

lactose monohydrate - 76.50 mg,

hyprolose - 12.00 mg,

microcrystalline cellulose (Avicel PH 101) - 129.00 mg,

microcrystalline cellulose (Avicel PH 102) - 172.50 mg,

croscarmellose sodium - 25.00 mg,

magnesium stearate - 2.50 mg,

silicon dioxide colloidal aqueous - 2.50 mg.

Film coating:

opadrayВ®II yellow 85 F 42129, consisting of: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide dye (E 172) - 20.84 mg.

Dosage and Administration

Inside. The drug Adenurik® is taken once a day, regardless of food intake.

Gout

The recommended starting dose is 80 mg of febuxostat once a 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 once a day.

The decrease in the concentration of uric acid in the blood serum during the use of the drug Adenurik® occurs quite quickly, and therefore the control of the concentration of uric acid can be carried out two weeks after the start of the drug. The aim of the treatment is to reduce and maintain a serum uric acid concentration of less than 6 mg / dl (357 ?mol / L).

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

Tumor decay syndrome

The recommended dose is 120 mg of febuxostat once a day, regardless of food intake. Adenuric® should be taken two days before the start of cytostatic therapy. The duration of use of the drug Adenuric® should be at least 7 days. Depending on the duration of the chemotherapy course, the duration of the use of Adenuric® can be increased to 9 days.

Elderly patients

Dosage adjustment of the drug is not required.

Patients with hepatic insufficiency

Gout

In patients with mild hepatic insufficiency (class A on the Child-Pugh scale: 5-6 points), the recommended dose of the drug is 80 mg once a day. The experience of using the drug with moderate liver failure is limited.

Tumor decay syndrome

In the FLORENCE study, dose adjustment of febuxostat depending on liver function was not required (the study did not include patients with severe liver failure).

Studies on the efficacy and safety of using febuxostat in patients with severe hepatic insufficiency (class C on the Child-Pugh scale: 10-15 points) have not been conducted.

Patients with renal failure

Dose adjustment is not required in patients with mild or moderate renal failure.

In patients with severe renal failure (creatinine clearance <30 ml / min), the efficacy and safety of the drug have not been adequately studied.

Side effects

Taking into account the different nature of the course of gout and tumor decay syndrome, side effects when using febuxostat for these nosologies of action are presented separately.

Gout

The most common side effects in patients with gout when using febuxostat according to the results of clinical trials (4072 patients taking febuxostat in a dose of 10 mg to 300 mg) and according to post-marketing observation were: gout attack, impaired liver function, diarrhea, headache pain, nausea, skin rash, and swelling. In most cases, these phenomena were characterized by mild or moderate severity. In the period of post-marketing observation, rare cases of the development of hypersensitivity reactions to febuxostat were observed, accompanied in some cases by systemic symptoms.

Possible side effects are listed below according to the World Health Organization's classification for descending incidence: very often (? 1/10) often (? 1/100,

The incidence of side effects is based on clinical studies and post-marketing experience with febuxostat.

On the part of the blood and lymphatic 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 perception, hyposthesia, hyposmia (weakening sense of smell).

From the endocrine system

Infrequently: an increase in the concentration of thyroid-stimulating hormone (TSH) in the blood plasma.

Metabolism and nutrition

Often: gout attacks ***

Infrequently: diabetes, hyperlipidemia, loss of appetite, weight gain

Rarely: weight loss, increased appetite, anorexia.

Psyche

Infrequently: decreased libido, insomnia

Rarely: nervousness.

From the organ of vision

Rarely: blurred vision.

From the side of the swearing hearing and labyrinthine disorders

Rarely: tinnitus.

From the side of the heart

Infrequently: atrial fibrillation, palpitations, ECG changes, left bundle branch block (see the section “Tumor decay syndrome”), sinus tachycardia (see the section “Tumor decay syndrome”).

From the side of the vessels

Infrequently: increased blood pressure, flushing of the face, sensation of heat, hemorrhage (see the section "Tumor decomposition syndrome").

From the respiratory system, chest and mediastinal organs

Uncommon: dyspnea, bronchitis, upper respiratory tract infection, cough, chest pain, discomfort in the chest area.

From the digestive tract

Often: diarrhea **, nausea

Infrequently: abdominal pain, bloating, gastroesophageal reflux disease, vomiting, dry mucous membranes of the mouth, dyspeptic symptoms, constipation, rapid stool, flatulence, discomfort : pancreatitis, ulcerative stomatitis.

From the liver and biliary tract

Often: liver dysfunction **

Infrequently: cholelithiasis

Rarely: hepatitis, jaundice *, liver damage *.

From the skin and subcutaneous tissue

Often: skin rash (including various types of rashes, mentioned below with a lower frequency)

Infrequently: dermatitis, urticaria, skin itching, discoloration of the skin, skin lesions, petechiae, macular rash, maculopapular rash, papular rash

Rarely: toxic dermal 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, 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 *, stiffness of joints, stiffness of muscles.

Disorders of the kidneys and urinary tract

Infrequently: renal failure, nephrolithiasis, hematuria, pollakiuria, proteinuria

Rarely: tubulointerstitial nephritis *, peremptory urination.

From the reproductive system

Infrequently: erectile dysfunction.

General disorders:

Often: swelling

Infrequently: fatigue

Rarely: thirst.

Influence on the results of laboratory and instrumental studies

Infrequently: increased plasma amylase activity, decreased platelet count, decreased white blood cell count, decreased lymphocyte count, increased plasma creatine and creatinine, decreased hemoglobin, increased plasma urea concentration, increased plasma triglycerides, increased plasma cholesterol, decreased hematocrit, increased plasma lactate dehydrogenase activity , Increased potassium in the blood plasma.

Rarely: increased plasma glucose concentration, prolonged activated partial thromboplastin time, decreased red blood cell count, increased plasma alkaline phosphatase activity.

* Side effects observed during post-marketing surveillance.

** Non-infectious diarrhea and liver disorders observed in phase III trials were more common with colchicine.

*** Additional information on the development of acute gout attacks in the Special Instructions section.

Description of individual side effects of

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

Stevens-Johnson syndrome and toxicodermal necrolysis are characterized by the occurrence of progressive skin rash in combination with bullous skin or mucous membranes, as well as eye irritation. Hypersensitivity reactions to febuxostat can also be manifested by the following symptoms: skin reactions characterized by infiltrative maculopapular rashes, generalized or exfoliative rash, as well as skin lesions, facial swelling, fever, disorders of the blood forming organs, such as thrombocytopenia and eosinophilia, or several organs (liver and kidneys, including tubulointerstitial nephritis).

Gout attacks are usually observed shortly after the start of Adenuric® and during the first months of therapy. Subsequently, the frequency of seizures decreases. It is recommended to prevent the development of acute attacks of gout.



tumor decay syndrome In the FLORENCE study, side effects were observed in 22 patients (6.4%). In both groups (febuxostat group and allopurinol group), the incidence of side effects was the same (11 patients, 6.4%). In most cases, adverse events were characterized by mild or moderate severity. In general, with the exception of the three side effects indicated below by the FLORENCE study, no specific features of the febuxostat safety profile in addition to that of gout were noted.

From the side of the heart

Infrequently: blockade of the left bundle branch, sinus tachycardia.

From the side of the vessels

Infrequently: hemorrhages (see section "Tumor Decay Syndrome").

Drug Interactions

Mercaptopurin / azathioprine

Concomitant use with mercaptopurine, azathioprine is not recommended, because inhibition of xanthine oxidase by febuxostat can lead to an increase in the concentration of mercaptopurine, azathioprine in the blood plasma and an increase in their toxic effect. Studies to study the interaction of febuxostat and substances metabolized by xanthine oxidase have not been conducted.

Cytostatics

No studies have been conducted on the drug interaction of febuxostat and cytostatic drugs. In the FLORENCE study, febuxostat in a dose of 120 mg was used for tumor decay syndrome in patients undergoing various types of cytostatic therapy (including monoclonal antibody therapy). Nonetheless, since studies on the drug interaction of febuxostat with cytotoxic drugs have not been conducted, the potential interaction of febuxostat with the simultaneously used cytotoxic chemotherapy cannot be ruled out.

Rosiglitazone / substrates of the isoenzyme CYP 2 C 8

According to in vitro febuxostat is a weak inhibitor of the isoenzyme CYP 2 C 8. In healthy volunteers, 120 mg of febuxostat is used once a day and a single dose of 4 mg of rosiglitazone changes its pharmacokinetic metabolism and its pharmacokinetic parameters No N-dismethyl rosiglitazone was noted, which indicates the absence of the inhibitor of the isoenzyme CYP 2 C 8 in febuxostat in vivo. With the simultaneous use of febuxostat and rosiglitazone (or other substrates of the CYP 2 C 8 isoenzyme), dose adjustment is not required.

Theophylline

With the use of other xanthioxidase inhibitors, an increase in theophylline concentration in blood plasma was observed simultaneously with theophylline. With the simultaneous use of febuxostat in healthy volunteers at a dose of 80 mg once a day and a single dose of theophylline 400 mg, there were no changes in the pharmacokinetic parameters or tolerance of theophylline, thus, with the simultaneous use of febuxostat at a dose of 80 mg and theophylline, special precautions are not required. A study of the simultaneous use of febuxostat at a dose of 120 mg and theophylline was not conducted.

Naproxen and other glucuronidation inhibitors

The metabolism of febuxostat depends on the activity of the enzyme uridine diphosphate-glucuronyl transferase (UDFGT). Medicines that inhibit the glucuronidation process, for example, non-steroidal anti-inflammatory drugs (NSAIDs) and probenicide can theoretically affect the excretion of febuxostat. In healthy volunteers with the simultaneous use of febuxostat and naproxen at a dose of 250 mg 2 times a day, an increase in Cmax of febuxostat by 28%, AUC by 41% and T? - by 26%.

In clinical studies, the simultaneous use of febuxostat and naproxen or other NSAIDs / COX-2 inhibitors was not accompanied by a clinically significant increase in the incidence of adverse events. Dose adjustment with the simultaneous use of febuxostat and naproxen is not required.

Inducers of glucuronidation

With the simultaneous use of febuxostat with strong inducers of glucuronidation, it is possible to increase its metabolism and decrease its effectiveness. With simultaneous use, it is necessary to control the concentration of uric acid in the blood serum 1-2 weeks after the start of therapy. With the abolition of the glucuronidation inducer, an increase in Cmax of febuxostat is possible.

Colchicine / indomethacin / hydrochlorothiazide / warfarin

Febuxostat can be used simultaneously with colchicine or indomethacin without dose adjustment.

Also, no dose adjustment of febuxostat is required when used with hydrochlorothiazide.

The simultaneous use of febuxostat (80 mg or 120 mg once a day) with warfarin does not affect the pharmacokinetics of warfarin, INR (international normalized ratio) and factor VII activity in healthy volunteers. With the simultaneous use of febuxostat with warfarin, a dose adjustment of warfarin is not required.

Desipramine / substrates of the isoenzyme CYP 2 D 6

According to obtained in vitro, febuxostat is a weak inhibitor of the isoenzyme CYP 2 D 6. In a study in healthy volunteers, the use of febuxostat at a dose of 120 mg once a day showed an increase in AUC of desipramine (substrate of the isoenzyme CYP 2 D 6) by 22%, which indicates the weak inhibitory effect of febuxostat on the CYP 2 D 6 isoenzyme in vivo. Thus, with the simultaneous use of febuxostat and substrates of the CYP 2 D 6 isoenzyme, dose adjustment is not required.

Antacids

When used simultaneously with antacids containing magnesium hydroxide or aluminum hydroxide, there is a decrease in the absorption of febuxostat (by about 1 hour) and a decrease in Cmax by 32%, however, the AUC of febuxostat did not change significantly. Thus, febuxostat can be taken simultaneously with antacids.

Overdose of

In case of an overdose of the drug, symptomatic and supportive therapy is indicated. Symptoms: increased side effects.

Storage conditions

Do not store above 25 ° C.

Keep out of the reach and sight of children!

Expiration

3 years.

active substance

febuxostat

Terms leave through pharmacies

In retseptu

Lekarstvennaja form

tablets

Appointment

Adults doctor's prescription

Indications

Indications

Gout

Menarini-von Heyden GmbH, Germany



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