What is febuxostat used to treat?
Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion.
What does febuxostat do to uric acid?
Febuxostat reduces the production of uric acid in your body. A build-up of uric acid can cause gout symptoms. Febuxostat is used to keep uric acid levels from getting to high in people with gout. Febuxostat is for use only in people who cannot take another medicine called allopurinol, or when allopurinol has stopped working.
How is febuxostat metabolized and oxidized?
Febuxostat is metabolized primarily by uridine diphosphate glucuronosyl-transferase (UGT) enzymes by means of conjugation. A small portion also undergoes oxidation via cytochrome P (CYP) 450 isoenzymes. However, oxidation via CYP 450 is clinically insignificant in terms of the drug’s pharmacokinetics.
How long does febuxostat take to take effect?
PHARMACOKINETICS AND PHARMACODYNAMICS12,14,18,19 Febuxostat is administered orally and is quickly absorbed; it reaches its maximum plasma concentration in 1 to 1.5 hours after the dose is taken. Following oral absorption, approximately 85% of the drug is absorbed.
What is the mechanism of action of febuxostat and how will this drug help ar?
Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels.
How does febuxostat reduce uric acid?
Febuxostat works by blocking the production of urate. This brings down the urate levels enough to allow the crystals to begin dissolving and prevent attacks of gout in the long term. Before starting febuxostat most people will have tried another drug called allopurinol.
What class of drug is febuxostat?
Febuxostat is in a class of medications called xanthine oxidase inhibitors. It works by decreasing the amount of uric acid that is made in the body. Febuxostat is used to prevent gout attacks but not to treat them once they occur.
What type of inhibitor is febuxostat?
Febuxostat is a medication used in the management and treatment of hyperuricemia and gout. It is in a class of medications known as xanthine oxidase inhibitors.
Which is best tablet for uric acid?
Allopurinol is a medicine used to lower levels of uric acid in your blood. If you produce too much uric acid or your kidneys do not filter enough out, it can build up and cause tiny, sharp crystals to form in and around your joints. Allopurinol is used to treat gout and kidney stones.
Which one is better allopurinol or febuxostat?
Experts usually recommend allopurinol as the first choice medication for gout — especially in people with heart concerns. Compared to febuxostat, allopurinol is also typically less expensive and has more possible uses.
Does febuxostat reduce creatinine?
When analyzing the changes in serum creatinine, no significant difference was seen. However, after sub-group analysis of studies with treatment duration greater or equal to 6 months, a significantly lower serum creatinine in the patients with febuxostat treatment compared with those in the control group were observed.
What is the best time to take febuxostat?
It is best taken in the morning. If you do shift work or want to take your medicine at night, talk to your doctor, nurse or pharmacist. You can take febuxostat with or without food. Keep taking febuxostat every day, to prevent gout attacks.
Who should not take febuxostat?
Febuxostat has not been studied in children. It should not be used in children younger than 18 years.
Does febuxostat increase potassium?
Contraindicated (1)febuxostat increases levels of azathioprine by decreasing metabolism. Contraindicated. Monitor Closely (1)dichlorphenamide and febuxostat both decrease serum potassium.
Is febuxostat safe for liver?
Febuxostat is a newly introduced nonpurine xanthine oxidase inhibitor used for the treatment of gout. Chronic febuxostat therapy has been associated with minor serum aminotransferase elevations, but has yet to be linked to cases of clinically apparent acute liver injury.
Does febuxostat increase blood pressure?
Furthermore, the safety and efficacy of febuxostat have been proved without doses adjustment in patients with mild-to-moderate renal impairment. Numbers of studies suggested that allopurinol and febuxostat may be effective in decreasing blood pressure (BP) and retarding the progression of CKD.
How long does it take for febuxostat to lower uric acid levels?
It can take six months to become fully effective. It does not have any effect during a gout attack, although you should continue to take it regularly every day even if this happens. During the first few months of taking febuxostat, your blood levels of uric acid may rise for a short while before they fall.
How long does it take to lower uric acid with febuxostat?
Over a 24-hour period, febuxostat results in a dose-dependent decrease in serum uric acid concentrations. As a result, total daily urinary uric acid excretions are reduced with an increase in total daily urinary xanthine excretion.
What is the best time to take febuxostat?
It is best taken in the morning. If you do shift work or want to take your medicine at night, talk to your doctor, nurse or pharmacist. You can take febuxostat with or without food. Keep taking febuxostat every day, to prevent gout attacks.
Can febuxostat be used for long term?
Febuxostat oral tablet is used for long-term treatment. It comes with serious risks if you don't take it as prescribed. If you stop taking the drug suddenly or don't take it at all: Your uric acid levels will likely remain high and continue to cause gout symptoms.
What is febuxostat used for?
4 In early 2008, febuxostat was granted marketing authorization by the European Commission for the treatment of chronic hyperuricemia and gout. 5 In the following year, the FDA for approved febuxostat for use in the chronic management of hyperuricemia in adult patients with gout who have an inadequate response or intolerance to allopurinol. 10 Gout is a form of arthritis that is caused by the accumulation of uric acid crystal in or around a joint, leading to inflammation and further deposition of uric acid crystal deposition in bones, joints, tissues, and other organs in the long term. Gout is closely associated with hyperuricemia. Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels. 5#N#In February 2019, a black box warning for febuxostat was added, based on the findings of a post-market clinical study (the CARES trial) where there was an increased risk of cardiovascular (CV) fatal outcomes in patients with gout and known cardiovascular disease treated with febuxostat, when compared to those treated with allopurinol. The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases. 1, 9
What is the binding rate of Febuxostat?
Febuxostat is approximately 99.2% bound to plasma proteins, primarily to albumin. Plasma protein binding is constant over the concentration range achieved with 40 mg and 80 mg doses. 10
How long does febuxostat last?
No dose-limiting toxicities were observed with febuxostat administered at doses up to 300 mg daily for seven days in healthy subjects. There are no reports of overdose of febuxostat in clinical studies and there is no known antidote. Overdose should be managed by symptomatic and supportive care. 10. Pathways.
What is the mechanism of action of gout?
Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time.
What is thiazolecarboxylic acid?
This compound belongs to the class of organic compounds known as thiazolecarboxylic acids and derivatives. These are heterocyclic compounds containing a thiazole ring which bears a carboxylic acid group (or a derivative thereof).
Does Febuxostat work?
Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion.
Is febuxostat a second line drug?
The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases. 1, 9. Type. Small Molecule.
How is Febuxostat metabolized?
Febuxostat is metabolized by conjugation and oxidation via multiple metabolizing enzymes. The relative contribution of each enzyme isoform is not clear. Drug interactions between Febuxostat Tablets and a drug that inhibits or induces one particular enzyme isoform is in general not expected.
What is a Febuxostat?
Febuxostat Tablets are xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable.
How soon after Febuxostat can you test for uric acid?
Testing for the target serum uric acid level of less than 6 mg/dL may be performed as early as two weeks after initiating Febuxostat Tablets therapy.
What is the active ingredient in Febuxostat?
The active ingredient in Febuxostat Tablets is 2- [3-cyano-4- (2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid, with a molecular weight of 316.38.
What enzymes are used to metabolize febuxostat?
Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes including UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and oxidation via cytochrome P450 (CYP) enzymes including CYP1A2, 2C8 and 2C9 and non-P450 enzymes. The relative contribution of each enzyme isoform in the metabolism of febuxostat is not clear. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxy metabolites, all of which occur in plasma of humans at a much lower extent than febuxostat.
What is the mean steady state volume of febuxostat?
The mean apparent steady state volume of distribution (V ss /F) of febuxostat was approximately 50 L (CV ~40%). The plasma protein binding of febuxostat is approximately 99.2% (primarily to albumin), and is constant over the concentration range achieved with 40 mg and 80 mg doses.
Is Febuxostat a fatal drug?
There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking Febuxostat Tablets, although the reports contain insufficient information necessary to establish the probable cause. During randomized controlled studies, transaminase elevations greater than three times the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% in Febuxostat Tablets and allopurinol-treated patients, respectively). No dose-effect relationship for these transaminase elevations was noted [see Clinical Pharmacology (12.3)] .
What is the purpose of Febuxostat?
Febuxostat is used to keep uric acid levels from getting to high in people with gout. Febuxostat is for use only in people who cannot take another medicine called allopurinol, or when allopurinol has stopped working. Febuxostat may also be used for purposes not listed in this medication guide.
How should I take febuxostat?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.
What should I avoid while taking febuxostat?
Follow your doctor's instructions about any restrictions on food, beverages, or activity.
How long does it take for liver to improve after taking a med?
For best results, keep using your medications as directed. Call your doctor if your symptoms do not improve after 6 months, or if they get worse. You will need frequent blood tests to check your liver function. Store at room temperature away from moisture, heat, and light.
What other medications can affect Febuxostat?
Tell your doctor about all your other medicines, especially: theophylline. This list is not complete. Other drugs may affect febuxostat, including prescription and over-the-counter medicines, vitamins, and herbal products.
Can you take Febuxostat if you are allergic to it?
You should not use febuxostat if you are allergic to it, or if you also use:
Does febuxostat cause heart problems?
Taking febuxostat may increase your risk of serious or fatal heart problems. Seek medical attention if you have chest pain, trouble breathing, fast heartbeats, sudden severe headache, numbness or weakness on one side of your body, or problems with vision or speech.
Does xanthine oxidase inhibit purine?
At therapeutic concentration does not inhibit other enzymes involved in purine and pyrimidine synthesis.
Can febuxostat be used for gout?
Consider the risks and benefits of febuxostat when deciding to prescribe or continue patients on febuxostat. Febuxostat should only be used in patients who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopuri nol, or for whom treatment with allopuri nol is not advisable.
What is Febuxostat used for?
Febuxostat is a medication used in the management and treatment of hyperuricemia and gout. It is in a class of medications known as xanthine oxidase inhibitors. This activity describes the indications, mechanism of action, administration, adverse effects, contraindications, monitoring, and toxicity of febuxostat.
How is Febuxostat administered?
Febuxostat is administered orally with an initial dose of 40 mg per day. [9] Its administration can be without regard to food or antacid use. The clinician can increase the dose of febuxostat 80 mg per day in patients that do not achieve a serum uric acid level of less than 6 mg/dL after two weeks of treatment with 40 mg so long as the patient does not have severe renal impairment (defined as clearance of 15 to 29 mL/min). Febuxostat is available in both 40 mg and 80 mg tablet formulations, and estimates are that greater than 49% of the dose is absorbed when taken orally. [9] Upon initiating treatment with febuxostat, gout flares may occur. [10] Therefore, flare prophylaxis with either a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended concurrently with febuxostat treatment and may continue for up to six months. [11] [12]
What is needed for the administration and monitoring of febuxostat?
As with many medications, interprofessional communication and teamwork are necessary for the administration and monitoring of febuxostat. With the recent revisions of the FDA guidelines, physicians, nurses and pharmacists need to be particularly aware of current prescribing information. [3]
Is febuxostat an enzyme?
Febuxostat is an inhibitor of the enzyme xanthine oxidase and is FDA-approved for the chronic management of hyperuricemia in patients diagnosed with gout. [1] [2] Due to the finding of an increased risk of death with febuxostat versus allopurinol, the FDA recently recommended limiting the use of febuxostat to patients for which allopurinol is not efficacious or patients who experience severe side effects with allopurinol. [3]
Does febuxostat cause gout?
An increase in gout flares frequently occurs after the initiation of febuxostat. [10] This increase is likely due to reduced serum uric acid levels, which mobilizes the urate crystals in tissue deposits. Therefore, flare prophylaxis with either a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended concurrently with febuxostat treatment and may continue for up to six months. Febuxostat should not be used to treat secondary hyperuricemia or asymptomatic hyperuricemia.
How long does it take for febuxostat to be absorbed?
Febuxostat is administered orally and is quickly absorbed; it reaches its maximum plasma concentration in 1 to 1.5 hours after the dose is taken. Following oral absorption, approximately 85% of the drug is absorbed. Although the rate and extent of absorption may decrease with food intake and antacid use, no clinically significant change in the effect of febuxostat has been reported; therefore, it may be taken without regard to food or antacid consumption. There is no accumulation when it is given in therapeutic doses in daily intervals (once every 24 hours). It is approximately 99.2% protein-bound, primarily to albumin.
When does febuxostat decrease urate?
All febuxostat groups also experienced significantly greater decreases in serum urate levels from baseline at week 28 ( or at the final visit) compared with patients receiving allopurinol or placebo. However, no significant differences among the groups were seen in the proportion of patients requiring treatment for gout flares between weeks 8 and 28, in the number of tophi, or in the percentage of reduction in tophus area.
How long is the phase 3 trial of Febuxostat?
A study called The Efficacy and Safety of Oral Febuxostat in Subjects with Gout (CONFIRMS) was the largest phase 3, 28-week , multicenter trial to compare daily febuxostat with allopurinol. A total of 2,269 patients received febuxostat 40 mg, febuxostat 80 mg, or allopurinol 300 mg. Patients with an estimated creatinine clearance [CrCl] of 30 to 59 mL/minute received 200 mg. Prophylaxis of gout flares was provided at the investigators’ discretion throughout the study.
Does febuxostat interact with cyp 450?
There are no interactions between febuxostat and CYP 450 enzymes or CYP 1A2, 2C9, 2C19, 2D6, or 3A4. There appear to be no clinically significant effects of febuxostat on colchicine, indomethacin, or naproxen, medications that are commonly used to treat gout. Because hydrochlorothiazide (HCT) can cause an increase in uric acid levels, it was studied with febuxostat. When the two agents are used together, the increase in uric acid levels has been determined to be insignificant. No dose adjustment is necessary when febuxostat is used with HCT, warfarin (Coumadin, Bristol-Myers Squibb), or desipramine (Norpramin, Sanofi-Aventis).
Is allopurinol a purine XO inhibitor?
Allopurinol (Zyloprim, Prometheus), a potent purine xanthine oxidase (XO) inhibitor, is the most commonly used drug in the treatment of hyperuricemia. Until recently, it was the only available inhibitor of uric acid synthesis. In February 2009, the FDA approved febuxostat (Uloric, Takeda Pharmaceutics America), a structurally unrelated non-purine XO inhibitor, for the chronic management of hyperuricemia in patients with gout.12,13
Does Febuxostat inhibit XO?
As a non-puri ne selective XO inhibitor, febuxostat inhibits both oxidized and reduced types of XO. It does not inhibit enzymes involved in purine or pyrimidine metabolism, as does allopurinol. Febuxostat is also structurally unrelated to allopurinol; its structure does not resemble a pyrimidine or a purine. The drug’s active ingredient is 2-(3-cyano-4[2-methylpropoxy] phenyl)-4-methylthiazole-5-carboxylic acid. The empirical formula is C16H16N2O3S, with a molecular weight of 316.38. As a result of its selectivity and structural differences, febuxostat tends to cause fewer adverse events when compared with allopurinol.
Does febuxostat cause gout?
Patients should be informed that an increase in gout flares is common after the commencement of febuxostat therapy. This is the result of the shift in urate from tissue deposits caused by the reduction in serum uric acid levels. To help avoid such flares, prophylactic treatment with an NSAID or colchicine is recommended when febuxostat is initiated. It may be beneficial to continue prophylactic therapy for up to six months. Febuxostat does not need to be discontinued if a flare occurs.
Identification
Pharmacology
- Indication
1. Febuxostat is indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. It is not recom…
Interactions
- Drug Interactions information
1. This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Categories
- ATC Codes
1. M04AA03 — Febuxostat
Chemical Identifiers
- UNII
1. 101V0R1N2E - CAS number
1. 144060-53-7
References
- Synthesis Reference
1. EPO Patent Report
Pharmacoeconomics
- Manufacturers
1. Not Available - Packagers
1. Not Available
Properties
- State
1. Solid
Spectra
- Mass Spec (NIST)
1. Download (42.2 KB)
Indications and Usage For Febuxostat Tablets
Febuxostat Tablets Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
- Xanthine Oxidase Substrate Drugs
Febuxostat tablet is an XO inhibitor. Based on a drug interaction study in healthy patients, febuxostat altered the metabolism of theophylline (a substrate of XO) in humans [see Clinical Pharmacology (12.3)].Therefore, use with caution when coadministering Febuxostat Tablets wit… - Cytotoxic Chemotherapy Drugs
Drug interaction studies of Febuxostat Tablets with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of Febuxostat Tablets during cytotoxic chemotherapy.
Use in Specific Populations
Overdosage
Febuxostat Tablets Description