Instructions for Feblorik film-coated tablets 40 mg blister No. 30
Composition
active ingredient: febuxostat;
1 film-coated tablet contains 40 mg or 80 mg of febuxostat;
excipients: lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate;
shell: Opadry white YS-1-7040.
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, round, biconvex, white to almost white in color, with a smooth surface.
Pharmacotherapeutic group
Medicines for the treatment of gout. Medicines that inhibit the formation of uric acid. Febuxostat. ATC code M04A A03.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Uric acid is the end product of purine metabolism in humans and is formed in the hypoxanthine → xanthine → uric acid cascade. Both steps of the above transformations are catalyzed by xanthine oxidase (XO). Febuxostat is a 2-arylthiazole derivative that achieves its therapeutic effect of lowering serum uric acid levels by selective inhibition of XO with in vitro Ki values in the range of 0.6–10 nM. Febuxostat is a nonpurine selective XO inhibitor (NP-SIXO) that potently inhibits both oxidized and reduced forms of XO.
Effect on uric acid and xanthine concentrations
In healthy volunteers, febuxostat resulted in a dose-dependent decrease in 24-hour mean serum uric acid concentrations and an increase in 24-hour mean serum xanthine concentrations. In addition, a decrease in total daily urinary uric acid excretion and an increase in total daily urinary xanthine excretion were observed. The percentage decrease in mean 24-hour serum uric acid concentration was approximately 55% after a daily dose of 80 mg.
Effect on cardiac repolarization
The effect of febuxostat on cardiac repolarization, as assessed by the QTc interval, was evaluated in healthy volunteers and patients with gout. Febuxostat at doses up to 300 mg/day (3.75 times the maximum recommended daily dose) at steady state showed no effect on the QTc interval.
Pharmacokinetics
In healthy volunteers, the maximum plasma concentration (Cmax) and the area under the pharmacokinetic concentration-time curve (AUC) increased in a dose-proportional manner after single and multiple doses of febuxostat in doses from 10 to 120 mg. There was no accumulation of febuxostat after doses of 10 to 240 mg every 24 hours. The estimated mean terminal elimination half-life (t1/2) of febuxostat was approximately 5 to 8 hours.
Absorption. Absorption of radiolabeled febuxostat after oral administration of a dose of the drug was at least 49% (based on total radioactivity recovered in urine). Cmax of febuxostat was observed between 1 and 1.5 hours after dosing. After multiple oral doses of 40 mg and 80 mg once daily, Cmax is approximately 1.6 ± 0.6 μg/mL (N=30) and 2.6 ± 1.7 μg/mL (N=227), respectively. The absolute bioavailability of febuxostat has not been studied. After multiple doses of 80 mg once daily in combination with a fatty meal, Cmax was reduced by 49% and AUC by 18%. However, this was not accompanied by clinically significant changes in the degree of reduction in plasma uric acid levels (in the case of multiple doses of 80 mg). Therefore, the drug can be used regardless of food intake.
Distribution: The estimated steady-state volume of distribution (Vss/F) for febuxostat was approximately 50 L (CV40%). The extent of binding of febuxostat to plasma proteins (primarily albumin) is 99.2% and does not change with increasing dose from 40 mg to 80 mg.
Metabolism: Febuxostat is extensively metabolized by conjugation involving uridine phosphate gluconyl transferase (UPG-gluconyl transferase) enzymes, including UGT1A1, UGT1A3, UGT1A9, and UGT2B7, and oxidation involving cytochrome P450 (CYP) enzymes, including CYP1A2, 2C8, and 2C9, and non-P450 enzymes. The relative contribution of each enzyme isoform to the metabolism of febuxostat is unknown. Oxidation of the isobutyl side chain results in the formation of four pharmacologically active hydroxy metabolites, all of which are present in human plasma at much lower levels than febuxostat.
The major metabolites of febuxostat in vivo in urine and feces are the acylglucuronide metabolites of febuxostat (35% of the dose) and the oxidative metabolites: 67M-1 (10% of the dose), 67M-2 (11% of the dose) and 67M-4 and a secondary metabolite from 67M-1 (14% of the dose).
Elimination. Febuxostat is eliminated from the body via the liver and kidneys. Following oral administration of 14C-febuxostat at a dose of 80 mg, approximately 49% was excreted in the urine as unchanged febuxostat (3%), acylglucuronide of the active substance (30%), known oxidized metabolites and their conjugates (13%), and other unknown metabolites (3%). In addition to renal excretion, approximately 45% of the drug was excreted in the feces as unchanged febuxostat (12%), acylglucuronide of the active substance (1%), known oxidized metabolites and their conjugates (25%), and other unknown metabolites (7%).
The CARES study was a non-inferiority study comparing cardiovascular outcomes with febuxostat and allopurinol in patients with gout and a history of major cardiovascular disease, including myocardial infarction, hospitalization for unstable angina, coronary or cerebral revascularization procedure, stroke, hospitalization for transient ischemic attack, peripheral vascular disease, or diabetes mellitus with evidence of microangiopathy or macroangiopathy.
The primary endpoint in the CARES study was the time to first occurrence of serious adverse cardiovascular events (SACEs), which included non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, and unstable angina with urgent coronary revascularization.
Endpoints (primary and secondary) were analyzed according to the intention-to-treat (ITT) analysis, including all subjects who were randomized and received at least one dose of the drug in the double-blind study.
When analyzing the individual components of the NMSC, the incidence of cardiovascular mortality was higher in the febuxostat group than in the allopurinol group (4.3% vs. 3.2% of patients). The incidence of other NMSCs was similar in the febuxostat and allopurinol groups, namely: non-fatal myocardial infarction (3.6% vs. 3.8% of patients), non-fatal stroke (2.3% vs. 2.3% of patients), and urgent revascularization for unstable angina (1.6% vs. 1.8% of patients).
All-cause mortality was also higher in the febuxostat group than in the allopurinol group (7.8% vs. 6.4% of patients), mainly due to the higher cardiovascular mortality rate in this group (see section 4.4).
Rates of accepted hospitalization for heart failure, hospitalization for arrhythmias not related to ischemia, venous thromboembolic events, and hospitalization for transient ischemic attacks were comparable for febuxostat and allopurinol.
Special patient groups
Kidney failure
During multiple dosing of febuxostat at a dose of 80 mg, there was no change in febuxostat Cmax in patients with mild and moderate renal impairment compared to patients with normal renal function. The mean total AUC of febuxostat increased approximately 1.8-fold compared to patients with normal renal function. The Cmax and AUC of the active metabolites increased 2- and 4-fold, respectively. However, the percentage reduction in serum uric acid concentration in patients with renal impairment was comparable to that in patients with normal renal function (58% in the normal renal function group and 55% in the severe renal impairment group).
Based on a population pharmacokinetic analysis, after multiple doses of febuxostat 40 mg or 80 mg, the mean CL/F of febuxostat in patients with gout and mild (n=334), moderate (n=232), or severe (n=34) renal impairment was decreased by 14%, 34%, and 48%, respectively, compared to patients with normal (n=89) renal function. The corresponding mean AUC of febuxostat in patients with renal impairment was increased by 18%, 49%, and 96% after the 40 mg dose and by 7%, 45%, and 98% after the 80 mg dose, respectively, compared to patients with normal renal function.
The use of febuxostat in patients with end-stage renal disease undergoing dialysis has not been studied.
Liver failure
Multiple dosing of febuxostat at a dose of 80 mg did not reveal significant changes in Cmax and AUC of febuxostat and its metabolites in patients with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment compared to patients with normal hepatic function. The drug has not been studied in patients with severe hepatic impairment (Child-Pugh Class C).
Age: After multiple oral doses of febuxostat, there were no significant changes in AUC of febuxostat and its metabolites in elderly patients compared to young healthy volunteers.
Gender: During multiple oral doses of febuxostat, febuxostat Cmax and AUC were 30% and 14% higher in females than in males, respectively. However, weight-adjusted Cmax and AUC were similar in both groups, and no dose adjustment for febuxostat is necessary based on gender.
Indication
For 40 mg and 80 mg dosages
Treatment of chronic hyperuricemia in patients with gout who have little response to allopurinol or are intolerant to allopurinol.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Contraindicated in patients receiving treatment with azathioprine or mercaptopurine.
Interaction with other medicinal products and other types of interactions
Due to its mechanism of action, febuxostat inhibits xanthine oxidase, therefore its concomitant use with mercaptopurine and azathioprine is not recommended. Inhibition of xanthine oxidase may lead to increased plasma concentrations of both drugs, which may cause toxic reactions. Interaction studies of febuxostat with drugs metabolized by xanthine oxidase have not been conducted.
Interaction studies of febuxostat during cytotoxic chemotherapy have not been conducted.
Rosiglitazone/CYP2C8 substrates
Febuxostat is a weak inhibitor of CYP2C8 in vitro. In a study in healthy volunteers, co-administration of febuxostat once daily with a single dose of rosiglitazone 4 mg did not affect the pharmacokinetics of rosiglitazone and its metabolite N-desmethyl rosiglitazone, demonstrating that febuxostat does not inhibit the CYP2C8 enzyme in vivo. Therefore, no dose adjustment of these medicinal products is required when febuxostat is co-administered with rosiglitazone or other CYP2C8 substrates.
Theophylline
An interaction study of febuxostat was conducted in healthy volunteers to evaluate the effect of xanthine oxidase inhibition on the increase in circulating theophylline levels observed with other xanthine oxidase inhibitors. The results showed that no pharmacokinetic interactions or effects on the safety of theophylline were observed when febuxostat 80 mg was co-administered with theophylline 400 mg. Therefore, febuxostat 80 mg can be co-administered with theophylline without any special precautions.
Naproxen and other glucuronidation inhibitors
Febuxostat metabolism is dependent on the activity of the enzyme UDP-glucuronyltransferase. Drugs that inhibit glucuronidation, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and probenecid, could theoretically alter the elimination of febuxostat. In healthy volunteers, co-administration of febuxostat with naproxen 250 mg twice daily resulted in an increase in febuxostat exposure (Cmax 28%, AUC 41%, t1/2 26%). In clinical studies, the use of naproxen and other NSAIDs/cyclooxygenase-2 (COX-2) inhibitors was not associated with a clinically significant increase in adverse reactions.
Febuxostat can be used concomitantly with naproxen without changing the dose of these drugs.
Glucuronidation inducers
Strong inducers of UDP-glucuronyltransferase may increase the metabolism and reduce the efficacy of febuxostat. In patients receiving strong inducers of glucuronidation, it is recommended to monitor plasma uric acid levels after 1–2 weeks of concomitant therapy. When the inducer of glucuronidation is discontinued, febuxostat plasma levels may increase.
Colchicine/indomethacin/hydrochlorothiazide/warfarin
Febuxostat can be used concomitantly with colchicine or indomethacin without changing the dose of the drugs.
There is also no need to change the dose of febuxostat when used simultaneously with hydrochlorothiazide.
Concomitant use of febuxostat with warfarin does not require a change in the dose of the latter. The use of febuxostat with warfarin does not affect the pharmacokinetics of the latter. Concomitant use with febuxostat also does not affect the international normalized ratio (INR) and factor VII activity.
Desipramine/CYP2D6 substrates
In vitro data indicate that febuxostat is a weak inhibitor of CYP2D6. In a study in healthy volunteers receiving febuxostat once daily, a 22% increase in the AUC of desipramine (a CYP2D6 substrate) was observed, indicating that febuxostat is a weak inhibitor of the CYP2D6 enzyme in vivo.
Therefore, there is no need to adjust the doses of febuxostat and CYP2D6 substrates when co-administered.
Antacids
When used simultaneously with antacids containing magnesium hydroxide and aluminum hydroxide, a delay in the absorption of febuxostat (approximately 1 hour) and a decrease in Cmax by 32% are observed, however, the AUC of febuxostat does not change significantly, therefore febuxostat can be combined with the use of antacids.
Application features
Gout attacks
At the beginning of treatment with febuxostat, an increase in gout attacks is often observed due to changes in serum uric acid levels.
To prevent gout attacks, concomitant prophylactic treatment with NSAIDs or colchicine is recommended when using febuxostat (see section 4.5).
Prophylactic therapy for flares may be continued for 6 months. If a gout flare occurs during treatment with febuxostat, febuxostat should not be discontinued.
In the post-marketing CARES study, which enrolled patients with gout who had a history of major cardiovascular disease, cerebrovascular disease, or diabetes with micro- and/or macrovascular disease, there was a higher rate (134 [1.5 per 100 patient-years]) of cardiovascular death in patients receiving febuxostat compared with patients receiving allopurinol (100 [1.1 per 100 patient-years]) [hazard ratio: 1.34, 95% CI: 1.03, 1.73]. The primary endpoint of major adverse cardiovascular events (MACE) [composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina with urgent coronary revascularization] was similar for febuxostat and allopurinol [hazard ratio: 1.03, 9]. % CI: 0.89, 1.21]. Febuxostat was similar to allopurinol for the treatment of nonfatal myocardial infarction, nonfatal stroke, and unstable angina with urgent coronary revascularization.
In the initial phase 3 randomized controlled trials in patients with gout, a higher rate of cardiovascular thromboembolic events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) was observed in patients receiving febuxostat [1.09 per 100 PY (95% CI 0.44-2.24)] than allopurinol [0.60 per 100 PY (95% CI 0.16-1.53)].
A potential increased risk of heart failure has also been reported in patients with pre-existing cardiovascular disease and/or cardiovascular risk factors. Febuxostat treatment is not recommended in patients with coronary artery disease or congestive heart failure. Signs and symptoms of myocardial infarction, stroke, and heart failure should be monitored.
The risks and benefits of febuxostat should be considered when deciding whether to initiate or continue treatment with febuxostat in patients. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.
Febuxostat should only be used in patients who have an inadequate response to or intolerance to allopurinol, or for whom treatment with allopurinol is not recommended.
Drug allergy/hypersensitivity
Serious skin and hypersensitivity reactions, including Stevens-Johnson syndrome, DRESS syndrome and toxic epidermal necrolysis, and acute anaphylactic reactions/shock have been reported in patients taking febuxostat.
In most cases, these reactions occurred within the first month of febuxostat use. Several patients had a history of renal impairment and/or hypersensitivity to allopurinol. Severe hypersensitivity reactions, including those with eosinophilia and systemic symptoms, were associated with fever, haematological, renal or hepatic failure in some cases.
Patients should be informed of the signs and symptoms of hypersensitivity/allergy and monitored for the development of such reactions. Febuxostat should be discontinued immediately if serious allergic/hypersensitivity reactions, including Stevens-Johnson syndrome, occur, as early discontinuation improves the prognosis. If a patient has experienced an allergic/hypersensitivity reaction, including Stevens-Johnson syndrome, and acute anaphylactic reactions/shock, then re-administration of febuxostat is contraindicated.
Xanthine deposition
In patients with accelerated urate formation (for example, against the background of malignant neoplasms and their treatment or in Lesch-Nyhan syndrome), a significant increase in the absolute concentration of xanthines in the urine is possible, accompanied by their deposition in the urinary tract. Due to limited experience with the use of febuxostat in such conditions, the drug is not indicated in such patients.
Patients who have undergone organ transplantation
There is no experience with the use of febuxostat in this category of patients, therefore the use of the drug is not indicated for them.
Patients with thyroid disease
Elevated TSH (> 5.5 μIU/mL) was observed in 5.5% of patients treated with febuxostat for long-term use in long-term open-label extension studies. Therefore, the drug should be used with caution in patients with thyroid dysfunction.
Liver reactions
During the post-marketing period, fatal and non-fatal cases of hepatic failure have been reported in patients taking febuxostat, although the reports do not contain sufficient information to establish a probable cause. Transaminase elevations greater than three times the upper limit of normal (ULN) have been observed in randomized controlled trials (aspartate aminotransferase (AST): 2%, 2%, alanine aminotransferase (ALT): 3%, 2% with febuxostat and allopurinol, respectively). No dose-response relationship was observed for these transaminases.
Liver function should be evaluated promptly in patients who develop symptoms suggestive of liver injury. These symptoms include fatigue, anorexia, upper abdominal discomfort, dark urine, or jaundice. In this clinical context, if a patient develops abnormal liver function tests (ALT >3 times the ULN), febuxostat should be discontinued, investigated, and the likely cause of the reaction should be determined. Febuxostat should not be restarted in these patients unless an explanation for the liver function test abnormalities is found.
Patients with serum ALT >3 times the upper limit of normal and serum total bilirubin >2 times the upper limit of normal without an alternative cause are at risk for severe drug-induced liver injury. Therefore, febuxostat should not be restarted in these patients. Patients with less severe elevations of ALT or serum bilirubin and an alternative probable cause for the reaction should be treated with caution when receiving febuxostat.
Lactose
The medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium compounds
The medicinal product contains croscarmellose sodium. Caution should be exercised when administering the medicinal product to patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
Pregnancy
Limited experience with the use of febuxostat during pregnancy indicates no adverse effects on the course of pregnancy and the health of the fetus/newborn. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development or parturition. The potential risk to humans is unknown. Therefore, febuxostat is contraindicated during pregnancy.
Breastfeeding period
It is not known whether febuxostat is excreted in human milk. Animal studies have shown that febuxostat is excreted in breast milk and has adverse effects on the development of breastfed infants. The risk of the drug passing into breast milk cannot be excluded. Therefore, the use of febuxostat during breastfeeding is contraindicated.
Fertility
Animal fertility studies at a dose of 48 mg/kg/day did not reveal any dose-related adverse reactions. The effect of febuxostat on human reproductive function is unknown.
Ability to influence reaction speed when driving vehicles or other mechanisms
There have been reports of drowsiness, dizziness, paresthesia, and blurred vision with the use of febuxostat, therefore patients using febuxostat are advised to be cautious when driving or operating machinery until they are certain that the above-mentioned adverse reactions have not occurred.
Method of administration and doses
Dosage
Gout
The recommended dose is 40 mg or 80 mg once daily, taken orally, with or without food. The recommended starting dose is 40 mg once daily.
If serum uric acid concentration exceeds 6 mg/dL (357 μmol/L) after 2 weeks of treatment, an increase in the dose of febuxostat to 80 mg once daily should be considered.
The duration of prevention of gout attacks is at least 6 months.
Kidney failure
No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment, the recommended dose is 40 mg.
Liver failure
The efficacy and safety of febuxostat in patients with severe hepatic impairment (Child-Pugh Class C) have not been studied.
No dose adjustment is required in mild hepatic impairment. Experience in moderate hepatic impairment is limited.
Elderly patients
No dose adjustment is required for this category of patients.
Method of administration and doses
It is administered orally, regardless of food intake.
Children.
The use of febuxostat in patients under 18 years of age is not indicated due to the lack of experience with its use in pediatrics.
Overdose
In case of overdose, symptomatic and supportive therapy is indicated.
Adverse reactions
Summary of safety profile
The table below lists the adverse reactions that patients have experienced when taking febuxostat and is classified as follows: common (≥ 1/100 to < 1/100)
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions observed in phase 3 combined long-term extension studies and post-marketing surveillance in patients with gout
| Infections and infestations | Rarely Herpes zoster, cellulitis, sinusitis, athlete's foot |
| Blood and lymphatic system disorders | Rarely Pancytopenia, thrombocytopenia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, splenomegaly, agranulocytosis*, eosinophilia* |
| On the part of the immune system | Rarely Anaphylactic reactions*, drug hypersensitivity* |
| From the endocrine system | Infrequently Increased thyroid-stimulating hormone levels |
| From the organs of vision | Rarely Blurred vision |
| Metabolic | Often*** Gout flare-ups (attacks) Infrequently decreased/increased appetite, cow's milk intolerance, dehydration, diabetes mellitus, dyslipidemia, gout, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia, weight loss/gain Rarely Weight loss, increased appetite, anorexia |
| From the psyche | Infrequently Decreased libido, insomnia Rarely Agitation, anxiety, depression, irritability, nervousness, panic attacks, personality change, psychotic behavior including aggression* |
| From the nervous system | Often Headache Infrequently Dizziness, paresthesia, hemiparesis, drowsiness, altered taste perception, hypoesthesia, decreased sense of smell Rarely Balance disorders, cerebrovascular disorders, acute polyradiculitis, hemiparesis, lacunar infarction, lethargy, migraine, transient ischemic attack, tremor |
| From the side of the organ of hearing and labyrinth | Rarely Tinnitus |
| From the side of the cardiovascular system | Infrequently Angina pectoris, atrial fibrillation/flutter, cardiac murmur, ECG abnormality, tachycardia, sinus bradycardia, tachycardia Rarely Myocardial infarction (some fatal)*, heart failure* |
| From the vascular system | Infrequently Arterial hypertension/hypotension, hot flashes, hot flashes with a feeling of heat |
| Respiratory system | Uncommon: shortness of breath, bronchitis, respiratory congestion, sneezing, throat irritation, upper respiratory tract infection, cough, dry nose. Rare: epistaxis, paranasal sinus hypersecretion, laryngeal edema, wheezing |
| Gastrointestinal tract | Often Diarrhea**, nausea Infrequently Abdominal pain, bloating, gastroesophageal reflux disease, vomiting, dry mouth, dyspepsia, constipation, frequent bowel movements, flatulence, stomach or intestinal discomfort, stomach ulcer, gastritis Rarely Pancreatitis, mouth ulcers |
| Liver and biliary tract disorders | Often Liver dysfunction** Infrequently Gallstone disease, cholecystitis, stenosis Rarely Hepatitis, jaundice*, liver failure (sometimes fatal)* |
| Skin and subcutaneous tissue disorders | Often Rash (including rashes with a lower incidence, see below) Infrequently Dermatitis, urticaria, pruritus, skin discolouration, skin lesion, petechiae, macular rash, maculopapular rash, papular rash Rarely Stevens-Johnson syndrome*, DRESS and toxic epidermal necrolysis*, angioedema*, drug reactions with eosinophilia and systemic symptoms*, generalised rash (serious)*, erythema*, exfoliative rash, follicular rash, vesicular rash, pustular rash, pruritic rash*, erythematous rash, choroid plexiform rash, alopecia, increased sweating, hair colour change, abnormal hair growth |
| Musculoskeletal and connective tissue disorders | Infrequently Joint pain, arthritis, muscle pain, musculoskeletal pain, muscle weakness, muscle cramps, muscle stiffness, bursitis, gouty tophus Rarely Rhabdomyolysis*, joint stiffness, musculoskeletal stiffness |
| Renal and urinary disorders | Infrequently Renal failure*, urolithiasis, hematuria, pollakiuria, proteinuria*, kidney and urinary tract infection Rarely Tubulointerstitial nephritis*, urinary urgency |
| Reproductive system and breast disorders | Infrequently Erectile dysfunction, breast pain, gynecomastia, mastitis |
| On the part of the body as a whole | Often Swelling Infrequently Fatigue, chest pain/discomfort, feeling sick, gait disturbance, flu-like symptoms, neoplasm (tumor), pain Rarely Thirst |
Laboratory indicators | Infrequently Increased creatinine, decreased bicarbonate, increased sodium, abnormal EEG, increased cholesterol, increased triglycerides, increased amylase, increased potassium, increased TSH, increased platelet count, decreased hematocrit, decreased hemoglobin, decreased red blood cell count, increased blood urea, increased blood urea nitrogen/creatinine ratio, increased LDH, increased PSA Rarely Increased glucose level, prolonged activated partial thromboplastin time, increased mean red blood cell volume, increased alkaline phosphatase, increased blood creatine phosphokinase, increased/decreased diuresis, decreased lymphocyte count, decreased neutrophil count, increased/decreased white blood cell count, abnormal coagulation test, increased low-density lipoprotein (LDL) level, prolonged prothrombin time, casts in urine, positive urine test for white blood cells and protein |
* Adverse reactions observed during post-marketing surveillance.
** Diarrhea and liver function test abnormalities requiring therapy observed in phase 3 studies occurred more frequently in patients receiving concomitant colchicine therapy.
*** See Pharmacodynamics section for the frequency of gout flares observed in phase 3 individual randomized controlled trials.
Gout flares (attacks) were usually observed shortly after initiation of treatment and during the first months of treatment. The frequency of gout attacks decreased over time. Prophylaxis of acute gout attacks is recommended when using febuxostat.
Expiration date
2 years.
Storage conditions
Store in original packaging at a temperature not exceeding 30°C. Keep out of the reach of children.
Incompatibility
Unknown.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Mankind Pharma Limited, Unit-II.
Location of the manufacturer and address of its place of business
Village Kishanpura, P.O. Jamniwala, Tehsil Paonta Sahib, District Sirmour 173025, Himachal Pradesh, India.
