Urica

Febuxostat.

Febuxostat (Urica) 40 mg Tablet: Each Film-coated tablet contains: Febuxostat 40 mg.
Green colored, round shaped film-coated tablet. Both sides plain. They shall have no critical or minor defects in excess of AQL 4.0.
Febuxostat (Urica) 80 mg Tablet: Each Film-coated tablet contains Febuxostat 80 mg.
Green colored, round shaped film-coated tablet with a breakline on one side and other side plain. They shall have no critical or minor defects in excess of AQL 4.0.

Pharmacology: Pharmacodynamics: Febuxostat (Urica) is a xanthine oxidase inhibitor that achieve its therapeutic effect by decreasing serum uric acid Febuxostat (Urica) is not expected to inhibit other enzymes involved in purine pyrimidine synthesis and metabolism at therapeutic concentrations.
In healthy subjects Febuxostat (Urica) resulted in dose dependent decreased in 24-hrs mean serum uric acid concentrations and an increase in 24-hrs mean serum xanthine concentrations There was also decrease in total urinary uric acid excretion and an increase in total daily urinary xanthine excretion. Percent reduction in 24-hrs mean serum uric acid concentrations was between 40-55% at the exposure levels of 40 mg and 80 mg daily doses
Pharmacokinetics: Maximum plasma concentrations (Cmax) and area under the curve (AUC) of Febuxostat (Urica) increased in a dose proportional manner following single and multiple dose of 10-120 mg in healthy subjects. There is no accumulation when therapeutic doses are administered every 24 hrs. Febuxostat (Urica) has an apparent mean terminal elimination half-life (t1/2) of approximately 5-8 hrs. The pharmacokinetic parameters of Febuxostat (Urica) for patients with hyperuricemia and gout were similar to those estimated in healthy subjects.
The absorption radiolabeled Febuxostat (Urica) following oral dose administration was estimated to be at least 49% with maximum plasma concentration occurring between 1-1.5 hrs post-dose. After multiple oral 40 mg and 80 mg once daily doses. Cmax is approximately 1.6±0.6 mcg/mL, and 2.6±1.7 mcg/mL, respectively. The absolute bioavailability of Febuxostat (Urica) tablet has not been studied.
Following multiple 80 mg once daily doses with a high fat meal, there was a 49% decrease in Cmax and an 18% decrease in AUC, respectively. However, no clinically significant change in the percent decrease in serum uric acid concentration was observed.
Concomitant ingestion of an antacid-containing magnesium hydroxide and aluminum hydroxide with an 80-mg single dose of Febuxostat (Urica) has been shown to delay absorption of Febuxostat (Urica) (approximately 1 hr) and to cause a 31% decrease in Cmax and a 15% increase in AUC infinity. As AUC rather than Cmax was related to drug effect, change observed in AUC was not considered clinically significant.
The mean apparent steady state volume of distribution (Vss/F) of Febuxostat (Urica) was approximately 50 L. The plasma protein binding of Febuxostat (Urica) is approximately 99.2%, primarily to albumin and is constant over the concentration range achieved with 40-mg and 80-mg doses.
Febuxostat (Urica) is extensively metabolized by both conjugation via uridine diphosphate glucuronyl transferase (UGT) enzymes including UGT1A1, UGT1A3, UGT1A9 & UGT2B7 and oxidation via cytochrome P450 (CYP) enzymes including CYP1A2, 2C8 & 2C9 and non-P450 enzymes. The oxidation of the isobutyl side chain leads to the formation of 4 pharmacologically active hydroxy metabolites, all of which occur in human plasma at a much lower extent than Febuxostat (Urica).
The apparent mean terminal elimination (t1/2) of Febuxostat (Urica) is approximately 5-8 hrs.
In urine and faeces, acyl glucuronide metabolites of Febuxostat (Urica) and oxidative metabolites 67M-1, 67M-2, and 67M-4, a secondary metabolite from 67-M-1, appeared to be the major metabolites of Febuxostat (Urica) in vivo.
Febuxostat (Urica) is eliminated by both hepatic and renal pathways. Following an 80-mg oral dose of 14C-labeled Febuxostat (Urica), approximately 49% of the dose was recovered in the urine as unchanged Febuxostat (Urica) (3%), the acyl glucuronide of the drug (30%), its known oxidative metabolites and their conjugates (13%) and other known metabolites (3%). Also, approximately 45% of the dose was recovered in feces as unchanged Febuxostat (Urica) (12%). The acyl glucuronide (1%), its known oxidative metabolites and their conjugates (25%) and other known metabolites (7%).

Treatment of chronic hyperuricemia conditions where urate deposition has already occurred (including a history or presence of tophus and/or gouty arthritis).

Recommended Starting Dose: 40 mg once daily.
The dosage may be increased to 80 mg in patients who do not achieve a serum uric acid (sUA) of <6 mg/dL after 2 weeks of therapy with Febuxostat (Urica) 40 mg.
Usual Adult Dose: 40-80 mg once daily or as prescribed by a physician.
May be taken without regard to food or antacid use.

Febuxostat (Urica) was studied in healthy subjects in doses up to 300 mg daily for 7 days without evidence of dose-limiting toxicities. No overdose of Febuxostat was reported in clinical studies. Patients should be managed by symptomatic and supportive care when overdose occurs.

Hypersensitivity to Febuxostat (Urica) or to any excipients of the formulation.
Patients on treatment with Azathioprine. Mercaptopurine, or Theophylline.

Gout Flares: After irritation of Febuxostat (Urica), an increase in gout flares is frequently observed. This increase is due to reduction in serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of Febuxostat (Urica). Prophylactic therapy may be beneficial for up to 6 months. Febuxostat (Urica) treatment should not be discontinued when gout flares occur. The gout flare should be managed concurrently, as appropriate for individual patient.
Cardiovascular Events: In randomized controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions and non-fatal strokes) in patients treated with Febuxostat (Urica) than with Allopurinol. A causal relationship with Febuxostat (Urica) has not been established. Signs and symptoms of myocardial infarction and stroke should be monitored.
Liver Enzyme Elevations: In randomized controlled studies, transaminase elevations > 3 times the upper limit of normal were observed (AST: 2%, 2% and ALT: 3%, 2% in Febuxostat (Urica) and Allopurinol-treated patients, respectively). No dose-effect relationship for these transaminase elevations was noted.
Renal Impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment. There are insufficient data in patients with severe renal impairment; therefore, caution should be exercised in these patients.
Hepatic Impairment: No dose adjustment is necessary in patients with mild-moderate hepatic impairment. No studios have been conducted in patients with severe hepatic impairment, thus, caution should be exercised in these patients.
Secondary Hyperuricemia: No studies have been conducted in patients with secondary hyperuricemia (including organ transplant recipients) Febuxostat (Urica) is not recommended for use in patients whose rate of urate formation is greatly increased (eg. malignant disease and its treatment, Lesch-Nyhan syndrome). In rare cases, the concentration of xanthine in urine could rise sufficiently to allow deposition in urinary tract.
Use in Children: The safety and efficacy of Febuxostat (Urica) have not been established in patients <18 years.
Use in Elderly: No dose adjustment is necessary in elderly patients. The Cmax and AUC24 of Febuxostat (Urica) following multiple oral doses in geriatric subjects (≥65 years) were similar to those in younger subjects (18-40 years).

Use in Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Febuxostat (Urica) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: It is not known if Febuxostat (Urica) is excreted in human milk. Since many drugs are excreted in human milk, caution should be exercised when administering Febuxostat (Urica) to breastfeeding women.

Adverse effects reported in 1% or more of patients receiving Febuxostat (Urica) include dizziness, liver function abnormalities, nausea, arthralgia and rash.
Less common adverse effects (<1% of patients) include: General: Asthenia, chest pain/discomfort, edema, fatigue, abnormal feeling, gait abnormality, influenza-like symptoms, mass pain, thirst.
Gastrointestinal: Abdominal distention, abnormal pain, constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, gastroesophageal reflux disease, gastrointestinal discomfort, gingival pain, hematemesis, Hyperchlorhydria, hematochezia, mouth ulceration, pancreatitis, peptic ulcer, vomiting.
Cardiac: Angina pectoris, atrial fibrillation/flutter, cardiac murmur, abnormal electrocardiogram, palpitations, sinus bradycardia, tachycardia, hypertension, hypotension, flushing.
Nervous System: Altered taste, balance disorder, cerebrovascular accident, Guillain-Barre syndrome, headache, hemiparesis, hypoesthesia, hyposmia, lacunar infarction, lethargy, mental impairment, migraine, paresthesia, somnolence, transient ischemic attack, tremor.
Psychiatric: Agitation, anxiety, depression, insomnia, irritability, decreased libido, nervousness, panic attack, personality change, psychotic behavior including aggressive thoughts.
Respiratory: Bronchitis, cough, dyspnea, epistaxis, nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory tract congestion, sneezing, throat irritation, upper respiratory tract infection.
Hepatobiliary: Cholelithiasis/cholecystitis, hepatic steatosis, hepatitis, hepatomegaly.
Renal: Hematuria, nephrolithiasis, pollakiuria, proteinuria, renal failure, renal insufficiency, urgency, incontinence, tubulointerstitial nephritis.
Hematologic: Anemia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia.
Metabolic/Endocrine: Anorexia, decreased/increased appetite, decreased/increased weight, dehydration, diabetes mellitus, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia.
Musculoskeletal: Arthritis, Joint stiffness, joint swelling, muscle spasms/twitching/tightness/weakness, musculoskeletal pain/ stiffness, myalgia, rhabdomyolysis.
Dermatologic: Alopecia, angioedema, dermatitis, dermographism, ecchymosis, eczema, hair color changes, abnormal hair growth hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin discoloration/altered pigmentation, skin lesion, abnormal skin odor, urticaria, herpes zoster, generalized rash, Stevens-Johnson syndrome, skin hypersensitivity reactions.
Special senses: Deafness, tinnitus, vertigo, blurred vision.
Reproductive System and breast Changes: breast pain, erectile dysfunction, gynecomastia.
Immune System: Hypersensitivity, anaphylaxis, anaphylactic reaction.
Procedural Complications: Contusion.
Laboratory Parameters: Activated partial thromboplastin time prolonged, abnormal electroencephalopathy, abnormal coagulation lest, prolonged prothrombin time, urinary casts, urine positive for white blood cells and protein.
Increase in: Blood urea Nitrogen (BUN)/Creatinine ratio, Creatine phosphokinase, sodium, glucose, cholesterol, triglycerides, blood urea, amylase, potassium, thyroid-stimulating hormone, mean corpuscular volume, white blood cells, alkaline phosphatase, low-density lipoprotein, lactate dehydrogenase, prostate specific antigen, urine output.
Decrease in: Bicarbonate, platelet count, hematocrit, hemoglobin, red blood cells, white blood cells, urine output, lymphocyte count, neutrophil count.
Seek advice from a healthcare professional at the first sign of any adverse drug reaction.

Cytotoxic Chemotherapy Drugs: No data are available on the safety of Febuxostat (Urica) during cytotoxic chemotherapy.
In-vivo Drug Interactions: No clinically significant interactions with Colchicine, Naproxen, Indomethacin, Hydrochlorothiazide, Warfarin or Desipramine were seen with Febuxostat (Urica). Dose adjustment is not needed.
Mercapturine, Azathioprine: Febuxostat (Urica) may cause increased plasma concentrations of those drugs resulting in toxicity.
Xanthine Oxidase (XO) Substrate Drugs: Febuxostat (Urica) was shown to alter metabolism of XO substrate drugs (eg. Theophylline). A 400-fold increase in the amount of 1-methylxanthin, a major metabolite of Theophylline, was excreted in urine. Use with caution when co-administering Febuxostat and Theophylline.

Store at temperatures not exceeding 30°C.

Hyperuricemia & Gout Preparations

M04AA03 - febuxostat ; Belongs to the class of preparations inhibiting uric acid production. Used in the treatment of gout.

Rx