Febuxostat 80 mg Tablet, Coated, 30-count
Other active recalls for Febuxostat (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Xanthine Oxidase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Febuxostat is used to treat gout in adults who were not treated successfully with or who are not able to take allopurinol (Aloprim, Zyloprim). Gout is a type of arthritis in which uric acid, a naturally occurring substance in the body, builds up in the joints and causes sudden attacks of redness, swelling, pain, and heat in one or more joints. 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.
Read the full MedlinePlus article ↗- You're right that allopurinol is typically tried first for gout. Febuxostat is specifically approved for people who haven't responded well enough to allopurinol at the highest tole...
- Why am I on febuxostat instead of allopurinol — isn't allopurinol the usual gout medicine?
- This is actually very common and completely expected in the early weeks. When febuxostat starts lowering your uric acid, it stirs up deposits that have built up in your joints, whi...
- My gout attacks are actually getting worse since I started this medicine. Is something wrong?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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UNII UKE75GEA7F
Hydroxypropyl cellulose is a plant-based polymer used as a binder and thickener. It helps hold tablet ingredients together, controls how fast the medicine dissolves, and improves the texture of liquid formulations.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII SA1B764746
A synthetic polymer commonly used as a solvent and binder in medicines. It helps dissolve active ingredients, improve texture, and ensure consistent tablet or capsule formation.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
13 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.7479 | $22.44 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Febuxostat 80 mg 00054-0414-13 | Hikma | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 00527-2248-32 | Lannett | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 00904-7396-46 | MAJOR | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 00904-7485-03 | Major | 30 tablets | $0.281 | AB | Discontinued | — |
| Febuxostat 80 mg 16714-0060-01 | NorthStar | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 27808-0207-01 | Tris | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 33342-0275-07 | Macleods | 30 films | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 43547-0296-03 | Solco | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mg 72205-0029-30 | Novadoz | 30 tablets | $0.281 | AB | Availability likely | — |
| Febuxostat 80 mgthis 46708-0191-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 47335-0722-18 | Sun | 1000 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 51407-0294-30 | Golden | 30 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 55111-0797-01 | DR | 100 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 59651-0114-01 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 62332-0191-06 | Alembic | 60 tablets | — | AB | FDA listed | — |
| Uloric 80 mg 64764-0677-11 | Takeda | 100 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 67877-0669-01 | Ascend | 100 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 68071-3761-09 | NuCare | 90 tablets | — | AB | FDA listed | — |
| febuxostat 80 mg 70771-1553-00 | Zydus | 1000 tablets | — | AB | FDA listed | — |
| Febuxostat 80 mg 72303-0856-01 | HEC | 30 tablets | — | AB | FDA listed | — |
| febuxostat 80 mg 72578-0137-01 | Viona | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 46708-0191-06 | 60 TABLET, COATED in 1 CARTON (46708-191-06) | 2019-07-01 | Active |
| 46708-0191-10 | 100 TABLET, COATED in 1 CARTON (46708-191-10) | 2019-07-01 | Active |
| 46708-0191-30 You're viewing this | 30 TABLET, COATED in 1 BOTTLE (46708-191-30) | 2019-07-01 | Active |
| 46708-0191-31 | 100 TABLET, COATED in 1 BOTTLE (46708-191-31) | 2019-07-01 | Active |
| 46708-0191-91 | 1000 TABLET, COATED in 1 BOTTLE (46708-191-91) | 2019-07-01 | Active |
Pack size FAQ
What quantity is in NDC 46708-0191-30?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CARDIOVASCULAR DEATH Gout patients with established cardiovascular (CV) disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study [see Warnings and Precautions (5.1)]. Consider the risks and benefits of febuxostat tablets when deciding to prescribe or continue patients on febuxostat tablets. Febuxostat tablets should only be used in patients 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 [see Indications and Usage (1)].
WARNING: CARDIOVASCULAR DEATH See full prescribing information for complete boxed warning. Gout patients with established cardiovascular (CV) disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study. (5.1) Consider the risks and benefits of febuxostat tablets when deciding to prescribe or continue patients on febuxostat tablets.
Febuxostat tablets should only be used in patients 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. (1)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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. For the safe and effective use of allopurinol, see allopurinol prescribing information. Limitations of Use : Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricemia.
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. (1) For the safe and effective use of allopurinol, see allopurinol prescribing information. Limitations of Use: Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricemia.
(1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended febuxostat tablet dosage is 40 mg or 80 mg once daily. The recommended starting dose is 40 mg once daily. For patients who do not achieve a serum uric acid (sUA) less than 6 mg/dL after 2 weeks, the recommended dosage is 80 mg once daily. (2.1) Can be administered without regard to food or antacid use. (2.1) Limit the dosage of febuxostat tablet to 40 mg once daily in patients with severe renal impairment. (2.2, 8.6)
2.1Recommended Dose The recommended febuxostat tablet dosage is 40 mg or 80 mg once daily. The recommended starting dosage of febuxostat tablet is 40 mg once daily. For patients who do not achieve a serum uric acid (sUA) less than 6 mg/dL after two weeks, the recommended febuxostat tablet dosage is 80 mg once daily. Febuxostat tablets can be taken without regard to food or antacid use [see Clinical Pharmacology (12.3)].
2.2Dosage Recommendations in Patients with Renal Impairment and Hepatic Impairment No dose adjustment is necessary when administering febuxostat tablets in patients with mild or moderate renal impairment. The recommended dosage of febuxostat tablet is limited to 40 mg once daily in patients with severe renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] . No dose adjustment is necessary in patients with mild to moderate hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)] .
2.3Uric Acid Level 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.
2.4Recommended Prophylaxis for Gout Flares Gout flares may occur after initiation of febuxostat tablets due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of febuxostat tablets. Prophylactic therapy may be beneficial for up to six months [see Clinical Studies ( 14.1)] .
If a gout flare occurs during febuxostat tablets treatment, febuxostat tablets need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient [see Warnings and Precautions ( 5.2)] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 40 mg tablets, light green to green, round, biconvex, film-coated tablets debossed with L440 on one side and plain on other side 80 mg tablets, light green to green, tear drop shaped, biconvex film-coated tablets debossed with L441 on one side and plain on other side. Tablet: 40 mg, 80 mg. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine [see Drug Interactions ( 7)] . Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine. (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cardiovascular Death : In a CV outcomes study, there was a higher rate of CV death in patients treated with febuxostat tablets compared to allopurinol; in the same study febuxostat tablets was non-inferior to allopurinol for the primary endpoint of major adverse cardiovascular events (MACE). Consider the risks and benefits of febuxostat tablets when deciding to prescribe or continue patients on febuxostat tablets. (1, 5.1) Gout Flares : An increase in gout flares is frequently observed during initiation of anti-hyperuricemic agents, including febuxostat tablets.
If a gout flare occurs during treatment, febuxostat tablets need not be discontinued. Prophylactic therapy (i.e., non-steroidal anti-inflammatory drug [NSAID] or colchicine upon initiation of treatment) may be beneficial for up to six months. (2.4, 5.2) Hepatic Effects: Postmarketing reports of hepatic failure, sometimes fatal.
Causality cannot be excluded. If liver injury is detected, promptly interrupt febuxostat tablets and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart febuxostat tablets if liver injury is confirmed and no alternate etiology can be found.
(5.3) Serious Skin Reactions : Postmarketing reports of serious skin and hypersensitivity reactions, including Stevens-Johnson Syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN) have been reported in patients taking febuxostat tablets. Discontinue febuxostat tablets if serious skin reactions are suspected. (5.4)
5.1Cardiovascular Death In a cardiovascular (CV) outcome study (ClinicalTrials.gov identifier NCT01101035), gout patients with established CV disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol. The CV outcomes study in patients with gout (CARES) was a randomized, double-blinded, allopurinol-controlled, non-inferiority study conducted to evaluate the risk of major adverse cardiovascular events (MACE) in patients with gout who were treated with febuxostat tablets.
The study enrolled patients who had a history of major CV disease, cerebrovascular disease or diabetes mellitus with micro-and/or macrovascular disease. The primary endpoint was the time to first occurrence of MACE defined as the composite of CV death, nonfatal MI, nonfatal stroke, or unstable angina with urgent coronary revascularization. The study was designed to exclude a prespecified risk margin of 1.3 for the hazard ratio of MACE.
Results showed that febuxostat tablets was non-inferior to allopurinol for the primary endpoint of MACE [Hazard Ratio: 1.03, 95% Confidence Interval (CI): 0.89, 1.21]. However, there was a significant increase in CV deaths in patients treated with febuxostat tablets (134 [1.5 per 100 patient-years]) compared to patients treated with allopurinol (100 [1.1 per 100 patient-years]) [Hazard Ratio: 1.34, 95% CI: 1.03, 1.73]. Sudden cardiac death was the most common cause of adjudicated CV deaths in the febuxostat tablets group (83 of 3,098; 2.7%) as compared to the allopurinol group (56 of 3,092; 1.8%).
Febuxostat tablets were similar to allopurinol for nonfatal MI, nonfatal stroke and unstable angina with urgent coronary revascularization [see Clinical Studies (14.2)] . Because of the increased risk of CV death, febuxostat tablets should only be used in patients 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 [see Indications and Usage(1)] . Consider the risks and benefits of febuxostat tablets when deciding to prescribe or continue patients on febuxostat tablets [see Indications and Usage (1)] .
Consider use of prophylactic low-dose aspirin therapy in patients with a history of CV disease. Physicians and patients should remain alert for the development of adverse CV event signs and symptoms. Pa…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the prescribing information: Cardiovascular Death [see Warnings and Precautions (5.1)] Hepatic Effects [see Warnings and Precautions (5.3)] Serious Skin Reactions [see Warnings and Precautions (5.4)] Adverse reactions occurring in at least 1% of patients treated with febuxostat tablets, and at least 0.5% greater than placebo, are liver function abnormalities, nausea, arthralgia, and rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In Phase 2 and 3 clinical studies, a total of 2757 patients with hyperuricemia and gout were treated with febuxostat tablets 40 mg or 80 mg daily. For febuxostat tablets 40 mg, 559 patients were treated for ≥6 months.
For febuxostat tablets 80 mg, 1377 patients were treated for ≥6 months, 674 patients were treated for ≥1 year and 515 patients were treated for ≥2 years. In the CARES study, a total of 3098 patients were treated with febuxostat tablets 40 mg or 80 mg daily; of these, 2155 patients were treated for ≥1 year and 1539 were treated for ≥2 years [see Clinical Studies (14.2)] . Most Common Adverse Reactions In three randomized, controlled clinical studies (Studies 1, 2 and 3), which were six to 12 months in duration, the following adverse reactions were reported by the treating physician as related to study drug.
Table 1 summarizes adverse reactions reported at a rate of at least 1% in febuxostat tablets treatment groups and at least 0.5% greater than placebo. Table 1: Adverse Reactions Occurring in ≥ 1% of Patients Treated with Febuxostat Tablets and at Least 0.5% Greater than Seen in Patients Receiving Placebo in Controlled Studies Adverse Reactions Placebo Febuxostat Tablets allopurinol* (N=134) 40 mg daily (N=757) 80 mg daily (N=1279) N=1277 Liver Function Abnormalities 0.7% 6.6% 4.6% 4.2% Nausea 0.7% 1.1% 1.3% 0.8% Arthralgia 0% 1.1% 0.7% 0.7% Rash 0.7% 0.5% 1.6% 1.6% * Of the patients who received allopurinol, 10 received 100 mg, 145 received 200 mg, and 1122 received 300 mg, based on level of renal impairment.
The most common adverse reaction leading to discontinuation from therapy was liver function abnormalities in 1.8% of febuxostat tablets 40 mg, 1.2% of febuxostat tablets 80 mg, and in 0.9% of patients treated with allopurinol. In addition to the adverse reactions presented in Table 1, dizziness was reported in more than 1% of patients treated with febuxostat tablets although not at a rate more than 0.5% greater than placebo. In the CARES study, liver function abnormalities and diarrhea were reported in more than 1% of patients treated with febuxostat tablets, although not at a rate more than 0.5% greater than allopurinol.
Less Common Adverse Reactions In clinical studies the following adverse reactions occurred in less than 1% of patients and in more than one subject treated with doses ranging from 40 mg to 240 mg of febuxostat tablets. This list also includes adverse reactions (less than 1% of patients) associated with organ systems from Warnings and Precautions. Blood and Lymphatic System Disorders : anemia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia.
Cardiac Disorders : angina pectoris, atrial fibrillation/flutter, cardiac murmur, ECG abnormal, palpitations, sinus bradycardia, tachycardia. Ear and Labyrinth Disorders : deafness, tinnitus, vertigo. Eye Disorders : vision blurred.
Gastrointestinal Disorders : abdominal distention, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, gastroesophageal reflux disease, gastrointestinal dis…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Concomitant administration of febuxostat tablets with XO substrate drugs, azathioprine or mercaptopurine could increase plasma concentrations of these drugs resulting in severe toxicity. (7)
7.1Xanthine Oxidase Substrate Drugs Febuxostat 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 with theophylline.
Drug interaction studies of febuxostat tablets with other drugs that are metabolized by XO (e.g., mercaptopurine and azathioprine) have not been conducted. Inhibition of XO by febuxostat tablets may cause increased plasma concentrations of these drugs leading to toxicity [see Clinical Pharmacology (12.3)] . Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine [see Contraindications (4)].
7.2Cytotoxic 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.
7.3In Vivo Drug Interaction Studies Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine [see Clinical Pharmacology (12.3)]. Therefore, febuxostat tablets may be used concomitantly with these medications.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS No studies have been conducted in patients with severe hepatic impairment. Caution should be exercised in these patients. (8.7) No studies have been conducted in patients with secondary hyperuricemia(including patients being treated for Lesch-Nyhan syndrome or malignant disease, or in organ transplant recipients); therefore, febuxostat tablets are not recommended for use in these patients. (8.8)
8.1Pregnancy Risk Summary Limited available data with febuxostat tablets use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. No adverse developmental effects were observed in embryo-fetal development studies with oral administration of febuxostat to pregnant rats and rabbits during organogenesis at doses that produced maternal exposures up to 40 and 51 times, respectively, the exposure at the maximum recommended human dose (MRHD). No adverse developmental effects were observed in a pre-and postnatal development study with administration of febuxostat to pregnant rats from organogenesis through lactation at an exposure approximately 11 times the MRHD (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation Days 7 to 17, febuxostat was not teratogenic and did not affect fetal development or survival at exposures up to approximately 40 times the MRHD (on an AUC basis at maternal oral doses up to 48 mg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation Days 6 to 18, febuxostat was not teratogenic and did not affect fetal development at exposures up to approximately 51 times the MRHD (on an AUC basis at maternal oral doses up to 48 mg/kg/day).
In a pre-and postnatal development study in pregnant female rats dosed orally from gestation Day 7 through lactation Day 20, febuxostat had no effects on delivery or growth and development of offspring at a dose approximately 11 times the MRHD (on an AUC basis at a maternal oral dose of 12 mg/kg/day). However, increased neonatal mortality and a reduction in neonatal body weight gain were observed in the presence of maternal toxicity at a dose approximately 40 times the MRHD (on an AUC basis at a maternal oral dose of 48 mg/kg/day).
Febuxostat crossed the placental barrier following oral administration to pregnant rats and was detected in fetal tissues.
8.2Lactation Risk Summary There are no data on the presence of febuxostat in human milk, the effects on the breastfed infant, or the effects on milk production. Febuxostat is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for febuxostat and any potential adverse effects on the breastfed child from febuxostat or from the underlying maternal condition.
Data Animal Data Orally administered febuxostat was detected in the milk of lactating rats at up to approximately 7 times the plasma concentration.
8.4Pediatric Use Safety and effectiveness of febuxostat tablets in pediatric patients have not been established.
8.5Geriatric Use No dose adjustment is necessary in elderly patients. Of the total number of patients in Studies 1, 2, and 3 (clinical studies of febuxostat tablets in the treatment of gout) [see Clinical Studies (14.1)] , 16% were 65 and over, while 4% were 75 and over. Comparing patients in different age groups, no clinically significant differences in safety or effectiveness were observed but greater sensitivity of some older individuals cannot be ruled ou…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Limited available data with febuxostat tablets use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. No adverse developmental effects were observed in embryo-fetal development studies with oral administration of febuxostat to pregnant rats and rabbits during organogenesis at doses that produced maternal exposures up to 40 and 51 times, respectively, the exposure at the maximum recommended human dose (MRHD). No adverse developmental effects were observed in a pre-and postnatal development study with administration of febuxostat to pregnant rats from organogenesis through lactation at an exposure approximately 11 times the MRHD (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation Days 7 to 17, febuxostat was not teratogenic and did not affect fetal development or survival at exposures up to approximately 40 times the MRHD (on an AUC basis at maternal oral doses up to 48 mg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation Days 6 to 18, febuxostat was not teratogenic and did not affect fetal development at exposures up to approximately 51 times the MRHD (on an AUC basis at maternal oral doses up to 48 mg/kg/day).
In a pre-and postnatal development study in pregnant female rats dosed orally from gestation Day 7 through lactation Day 20, febuxostat had no effects on delivery or growth and development of offspring at a dose approximately 11 times the MRHD (on an AUC basis at a maternal oral dose of 12 mg/kg/day). However, increased neonatal mortality and a reduction in neonatal body weight gain were observed in the presence of maternal toxicity at a dose approximately 40 times the MRHD (on an AUC basis at a maternal oral dose of 48 mg/kg/day).
Febuxostat crossed the placental barrier following oral administration to pregnant rats and was detected in fetal tissues.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of febuxostat tablets in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use No dose adjustment is necessary in elderly patients. Of the total number of patients in Studies 1, 2, and 3 (clinical studies of febuxostat tablets in the treatment of gout) [see Clinical Studies (14.1)] , 16% were 65 and over, while 4% were 75 and over. Comparing patients in different age groups, no clinically significant differences in safety or effectiveness were observed but greater sensitivity of some older individuals cannot be ruled out.
The C max and AUC 24 of febuxostat following multiple oral doses of febuxostat tablets in geriatric patients (≥65 years) were similar to those in younger patients (18 to 40 years) [see Clinical Pharmacology (12.3)].
🆘 Overdosage ▾
10 OVERDOSAGE Febuxostat tablets were studied in healthy patients in doses up to 300 mg daily for seven days without evidence of dose-limiting toxicities. No overdose of febuxostat tablets were reported in clinical studies. Patients should be managed by symptomatic and supportive care should there be an overdose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Febuxostat tablet, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. Febuxostat tablet is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.
12.2Pharmacodynamics Effect on Uric Acid and Xanthine Concentrations In healthy patients, febuxostat tablets 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, there was a decrease in the total daily urinary uric acid excretion. Also, there was an increase in total daily urinary xanthine excretion.
Percent reduction in 24 hour mean serum uric acid concentrations was between 40% and 55% at the exposure levels of 40 mg and 80 mg daily doses. Effect on Cardiac Repolarization The effect of febuxostat tablets on cardiac repolarization as assessed by the QTc interval was evaluated in normal healthy patients and in patients with gout. Febuxostat tablets in doses up to 300 mg daily (3.75 times the maximum recommended daily dosage), at steady-state, did not demonstrate an effect on the QTc interval.
12.3Pharmacokinetics In healthy patients, maximum plasma concentrations (C max ) and AUC of febuxostat increased in a dose proportional manner following single and multiple doses of 10 mg (0.25 times the lowest recommended dosage) to 120 mg (1.5 times the maximum recommended dosage). There is no accumulation when therapeutic doses are administered every 24 hours. Febuxostat has an apparent mean terminal elimination half-life ( t1/2 ) of approximately 5 to 8 hours.
Febuxostat pharmacokinetic parameters for patients with hyperuricemia and gout estimated by population pharmacokinetic analyses were similar to those estimated in healthy patients. Absorption The absorption of radiolabeled febuxostat following oral dose administration was estimated to be at least 49% (based on total radioactivity recovered in urine). Maximum plasma concentrations of febuxostat occurred between 1 and 1.5 hours postdose.
After multiple oral 40 mg and 80 mg once daily doses, C max is approximately 1.6 ± 0.6 mcg/mL (N=30), and 2.6 ± 1.7 mcg/mL (N=227), respectively. Absolute bioavailability of the febuxostat tablet has not been studied. Following multiple 80 mg once daily doses with a high fat meal, there was a 49% decrease in C max and an 18% decrease in AUC, respectively.
However, no clinically significant change in the percent decrease in serum uric acid concentration was observed (58% fed vs 51% fasting). Thus, febuxostat may be taken without regard to food. Concomitant ingestion of an antacid containing magnesium hydroxide and aluminum hydroxide with an 80 mg single dose of febuxostat tablet has been shown to delay absorption of febuxostat (approximately one hour) and to cause a 31% decrease in C max and a 15% decrease in AUC ∞ .
As AUC rather than C max was related to drug effect, change observed in AUC was not considered clinically significant. Therefore, febuxostat tablets may be taken without regard to antacid use. Distribution 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. Metabolism 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…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Febuxostat tablet, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. Febuxostat tablet is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Febuxostat tablets are available in two strengths as 40 mg and 80 mg. 40 mg: Light green to green, round, biconvex, film-coated tablets debossed with L440 on one side and plain on other side. They are supplied as: NDC 46708-190-30 bottle of 30 units NDC 46708-190-31 bottle of 100 units NDC 46708-190-91 bottle of 1000 units NDC 46708-190-08 80 Tablets Carton of 80 (10 x 8) Unit-Dose Tablets NDC 46708-190-10 100 Tablets Carton of 100 (10 x 10) Unit-Dose Tablets 80 mg: Light green to green, tear drop shaped, biconvex film coated tablets debossed with L441 on one side and plain on other side and supplied as: NDC 46708-191-30 bottle of 30 units NDC 46708-191-31 bottle of 100 units NDC 46708-191-91 bottle of 1000 units NDC 46708-191-06 60 Tablets Carton of 60 (10 x 6) Unit-Dose Tablets NDC 46708-191-10 100 Tablets Carton of 100 (10 x 10) Unit-Dose Tablets Protect from light.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Febuxostat is a xanthine oxidase inhibitor. The active ingredient in febuxostat tablet is 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid, with a molecular weight of 316.38. The empirical formula is C 16 H 16 N 2 O 3 S.
The chemical structure is: Febuxostat is a non-hygroscopic, white to off white powder that is freely soluble in N,N-dimethylformamide; soluble in dimethyl sulfoxide; sparingly soluble in ethanol; slightly soluble in methanol and acetonitrile; and practically insoluble in water. The melting range is 201°C to 208°C. Febuxostat tablets for oral use contain the active ingredient, febuxostat, and are available in two dosage strengths, 40 mg and 80 mg.
Inactive ingredients include: lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and polyvinyl alcohol, talc, polyethylene glycol 3000, titanium dioxide, D&C yellow No. 10 aluminum Lake, FD&C blue No. 1 aluminum lake and FD&C blue No.
2 aluminum lake. Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) CV Death Inform patients that gout patients with established CV disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study. Inform all patients of the higher rate of CV death with febuxostat tablets compared to allopurinol. Instruct all patients (those with and without CV disease) to be alert for the development of signs and symptoms of CV events [see Warnings and Precautions (5.1)] .
Gout Flares Inform patients that after initiation of febuxostat tablets there was an increased frequency of gout flares. Instruct patients that it is recommended to initiate and continue gout prophylaxis therapy for six months while taking febuxostat tablets [see Warnings and Precautions (5.2)] . Hepatic Effects Inform patients that hepatic effects have occurred in patients treated with febuxostat tablets and instruct them to inform their healthcare provider if they experience liver injury symptoms [see Warnings and Precautions (5.3)] .
Serious Skin Reactions Inform patients that serious skin and hypersensitivity reactions have occurred in patients treated with febuxostat tablets. Instruct patients to discontinue febuxostat tablets if they develop symptoms of these reactions [see Warnings and Precautions (5.4)] .