FEBUXOSTAT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FEBUXOSTAT (FEBUXOSTAT).

How it works

Febuxostat is a non-purine selective inhibitor of xanthine oxidase (XO). It inhibits both oxidized and reduced forms of XO, thereby reducing the conversion of hypoxanthine to xanthine and xanthine to uric acid, leading to decreased serum uric acid levels.

What the body does with it

Metabolism	Primarily metabolized by conjugation via UDP-glucuronosyltransferases (UGT1A1, UGT1A3, UGT1A9, and UGT2B7) and oxidation via cytochrome P450 (CYP) enzymes, including CYP1A2, CYP2C8, and CYP2C9, with minor contribution from CYP3A4/5.
Excretion	Renal: 1-3% unchanged; biliary/fecal: ~50% as metabolites (acyl glucuronides, oxidative metabolites); other: ~49% metabolized and eliminated via multiple pathways including biliary and direct intestinal excretion of unchanged drug.
Half-life	Terminal elimination half-life: 5-8 hours in healthy subjects; prolonged in renal impairment (e.g., up to 9.6 hours in moderate impairment). Clinical context: dosing interval is once daily, consistent with half-life.
Protein binding	99% (primarily to albumin; minor binding to alpha-1-acid glycoprotein).
Volume of Distribution	Approximately 0.7 L/kg (indicating distribution into total body water; not extensively tissue-bound).
Bioavailability	Oral: at least 49% (absolute bioavailability not established; estimated based on mass balance studies).
Onset of Action	Oral: Reduction in serum urate observed within 2 weeks; full effect by 4-6 weeks.
Duration of Action	Duration of action: 24 hours (once-daily dosing maintains urate reduction). Clinical note: steady-state achieved in ~5-7 days.

Classification & Brands

Dosing & administration

40 mg orally once daily; may increase to 80 mg orally once daily if serum urate goal not achieved after 2 weeks.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min). For severe renal impairment (eGFR <30 mL/min), limited data; use with caution, not recommended in dialysis.
Liver impairment	Child-Pugh Class A or B: no dose adjustment. Child-Pugh Class C: not recommended (no studies).
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	No specific dose adjustment required; use with caution due to potential for decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FEBUXOSTAT (FEBUXOSTAT).

Breastfeeding	Excretion in human milk unknown; M/P ratio not determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy.
Teratogenic Risk	Pregnancy Category C. No adequate studies in pregnant women. In animal studies, febuxostat caused developmental toxicity (reduced fetal weight, increased skeletal variations) at maternal toxic doses. First trimester: unknown risk; avoid unless benefits outweigh risks. Second/third trimester: limited data; potential for fetal harm based on animal findings.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent revascularization in patients with established cardiovascular disease (based on the CARES trial). Febuxostat should be avoided in patients with a history of myocardial infarction or stroke, unless no other therapy is appropriate.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use with azathioprine, 6-mercaptopurine, or theophylline (due to risk of toxicity); severe renal impairment (CrCl <30 mL/min) based on trial data; history of myocardial infarction or stroke (relative contraindication per FDA).

Clinical Precautions

Precautions

Cardiovascular events (see black box warning); hepatotoxicity (elevated liver enzymes, hepatic failure); gout flares upon initiation (prophylaxis recommended); renal impairment (dose adjustment for severe impairment); hypersensitivity reactions (including Stevens-Johnson syndrome); thyroid function abnormalities (elevated TSH).

Clinical Tips & Counseling

Drug interactions

Loading safety data…

FEBUXOSTAT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FEBUXOSTAT (FEBUXOSTAT).

How it works

What the body does with it

Metabolism	Primarily metabolized by conjugation via UDP-glucuronosyltransferases (UGT1A1, UGT1A3, UGT1A9, and UGT2B7) and oxidation via cytochrome P450 (CYP) enzymes, including CYP1A2, CYP2C8, and CYP2C9, with minor contribution from CYP3A4/5.
Excretion	Renal: 1-3% unchanged; biliary/fecal: ~50% as metabolites (acyl glucuronides, oxidative metabolites); other: ~49% metabolized and eliminated via multiple pathways including biliary and direct intestinal excretion of unchanged drug.
Half-life	Terminal elimination half-life: 5-8 hours in healthy subjects; prolonged in renal impairment (e.g., up to 9.6 hours in moderate impairment). Clinical context: dosing interval is once daily, consistent with half-life.
Protein binding	99% (primarily to albumin; minor binding to alpha-1-acid glycoprotein).
Volume of Distribution	Approximately 0.7 L/kg (indicating distribution into total body water; not extensively tissue-bound).
Bioavailability	Oral: at least 49% (absolute bioavailability not established; estimated based on mass balance studies).
Onset of Action	Oral: Reduction in serum urate observed within 2 weeks; full effect by 4-6 weeks.
Duration of Action	Duration of action: 24 hours (once-daily dosing maintains urate reduction). Clinical note: steady-state achieved in ~5-7 days.

Classification & Brands

Dosing & administration

40 mg orally once daily; may increase to 80 mg orally once daily if serum urate goal not achieved after 2 weeks.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min). For severe renal impairment (eGFR <30 mL/min), limited data; use with caution, not recommended in dialysis.
Liver impairment	Child-Pugh Class A or B: no dose adjustment. Child-Pugh Class C: not recommended (no studies).
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	No specific dose adjustment required; use with caution due to potential for decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FEBUXOSTAT (FEBUXOSTAT).

Breastfeeding	Excretion in human milk unknown; M/P ratio not determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy.
Teratogenic Risk	Pregnancy Category C. No adequate studies in pregnant women. In animal studies, febuxostat caused developmental toxicity (reduced fetal weight, increased skeletal variations) at maternal toxic doses. First trimester: unknown risk; avoid unless benefits outweigh risks. Second/third trimester: limited data; potential for fetal harm based on animal findings.