- Febuxostat belongs to class of drug called xanthine oxidase inhibitors which are used in treatment of hyperuricemia and gout. It is non- purine xanthine oxidase inhibitor.
- Febuxostat got its FDA approval for medical in 2009.
Indications of febuxostat
- It is FDA approved for chronic management of hyperuricemia in patients with gout. Preferred in patients who doesn’t show response to allopurinol, who are intolerant to allopurinol in whom allopurinol is contraindicated.
- It is not preferred for treating secondary or asymptomatic hyperuricemia.
Mechanism of action of febuxostat
- It is non-purine, potent, selective inhibitor of enzyme xanthine oxidase. Xanthine oxidase plays important role in purine metabolism and is responsible for generation of uric acid from xanthine and hypoxanthine. Gout is a disease characterized by deposition of monosodium urate crystals inn body tissues, especially around joints.
- It forms stable complex with both reduced and oxidized form of xanthine oxidase and hence inhibit formation of uric acid. The overall result is lowering of serum uric acid level.
Pharmacokinetics of febuxostat
- It is well absorbed after oral administration, binds to plasma proteins (around 99.2%), mainly albumin. It may reach peak plasma concentration in 1 hour of oral administration.
- Metabolism takes place in liver by cytochrome P450 enzymes and UDP- glucuronosyltransferase (UGT). It is excreted via urine and feces. Its elimination half-life is around 5-8 hours.
- The maximum daily dose allowed is 80 mg. It is not excreted via renal route in the same extent as allopurinol. Hence, its serum uric acid lowering capacity is not altered in patients with mild to moderate renal impairment and requires less adjustment compared to allopurinol.
Adverse effects
- Some common side effects include nausea, headache, diarrhea, liver function abnormalities and rashes.
- In February 2019, a black box warning for febuxostat was issued by FDA which states that there is increased risk of cardiovascular related fatality in patients with gout and known cardiovascular diseases when treated with this drug compared with these treated with allopurinol. Hence, FDA and manufacturer advise health professionals to limit it’s use as second line therapy in those patients who cannot tolerate allopurinol.
- Some less common adverse effects include anemia, neutropenia, splenomegaly, abdominal pain, dry mouth, joint stiffness, muscle spasm, weight decrease/ increase etc.
Drug Interactions
- It interferes with metabolism of drugs like 6-mercaptopurine, azathioprine and theophylline. It can increase their blood plasma concentration, Hence, when these drugs are co-administered with febuxostat, dosage of these drugs should be reduced.
Contraindication
- Contraindicated in patients with known hypersensitivity to febuxostat.
- It is pregnancy category C drug which mean that there are no sufficient studies in pregnant women.
Comparison with allopurinol
- Allopurinol is purine-based xanthine oxidase inhibitor. Febuxostat is non purine xanthine oxidase inhibitor.
- Allopurinol and its active metabolite oxypurinol bind to only one form (oxidized or reduced) of xanthine oxidase. Febuxostat binds to both oxidized and reduced forms of febuxostat.
- Renal clearance of febuxostat is less compared to allopurinol.
References
- https://go.drugbank.com/drugs/DB04854
- https://www.statpearls.com/ArticleLibrary/viewarticle/37707
- https://en.wikipedia.org/wiki/Febuxostat
- Hu M et al. Febuxostat in the management of hyperuricemia and chronic gout: a review. Ther Clin Risk Manag. 2008; 4(6): 1209–1220.
- Pandey A et al. Febuxostat – A New Treatment for Hyperuricemia in Gout – A Review Article. National Journal of Physiology, Pharmacy & Pharmacology. 2012; 2(1): 23-28.
- Pharmacology and Pharmacotherapeutics. 24th edition.
- Lippincott Illustrated Reviews Pharmacology, 6th edition