Febuxostat 40, 80 mg

• purine nucleotides catabolism leads to uric acid production.

• Hypoxanthine and xanthine are the intermediate products
of this catabolism.
• Xanthine oxidase catalyzes the oxidation of xanthine to uric
acid.
• Uric acid is the final oxidation product of purine catabolism,
which means that it cannot be further metabolized.
• The kidneys excrete two-thirds of the total uric acid amount
that is produced daily, while the remaining one-third is
broken down by intestinal flora and excreted in the stool
• Hyperuricemia is defined as a plasma uric acid level greater
than 7.0 mg/dL at physiological temperature (37°C) and
neutral pH
• High uric acid blood levels can involve uric acid crystals
articular and extra-articular deposition
• This process is often silent, although it favors progressive
joint destruction, renal failure and cardiovascular risk.

That is the reason why the Guidelines suggest serum uric

acid levels ≤ 6 mg/dL in people having chronic hyperuricemia
with urate deposition.
• Hyperuricemia is recognized as the main risk factor for
gout

• Management of gout requires long-term treatment aimed

at lowering sUA levels to a subsaturating range (usually ≤
6.0 mg/dl) at which urate crystal formation and
deposition are prevented or reversed.
Optimal treatment of gout is based on two principles:

adequate chronic use of urate-lowering therapies (ULT)

1. Xanthine oxidase (XO) inhibitor (ADENOXAT)
2. Uricosurics

Aiming to achieve target serum urate (sUA) levels

 ADENOXAT

In 2009, a nonpurine selective XO inhibitor, febuxostat,

was approved by the U.S. Food and Drug Administration
FDA for the treatment of gout
 Mechanism of Action
• Adenoxat is a potent ligand for, and inhibitor of, both the
oxidized and reduced forms of XO
• In contrast, allopurinol, a purine analog, weakly inhibits
only the oxidized form of XO, and its oxidized derivative,
oxypurinol, binds only to the reduced form of XO.
• Adenoxat has shown more potent and longer-lasting
hypouricemic activity than allopurinol.
• Adenoxat produces significant dose-dependent decreases
in sUA levels as a result of inhibition of uric acid
production
• Adenoxat has minimal effects on other enzymes of purine
and pyrimidine metabolism
How are The changes in sUA with Adenoxat
VS allopurinol?
• This retrospective study included 16040 patients with sUA > 8 mg/dl
• patients were treated with either Febuxostat or allopurinol
• The most common doses were 40 mg/day for Febuxostat and 300
mg/day for allopurinol

A significantly higher proportion of Febuxostat users attained sUA

goals of <6.0 mg/dl (p<0.001) and <5.0 mg/dl (p <0.001)
Adenoxat users also has a shorter average length of time to
target sUA goal attainment than allopurinol users

Adenoxat is an effective option for treatment of hyperuricemia in patients with gout

 Adenoxat is more potent than Allopurinol
The FACT study

• 762 patients with gout and serum uric acid ≥ 8 mg/dl received either
Febuxostat (80, 120 mg) or Allopurinol (300 mg) once daily for 52
weeks
• The endpoint was the achievement of a serum uric acid level < 6
mg/dl
Adenoxat reduced serum uric acid levels more than allopurinol in gouty
patients with elevated serum uric acid levels
Adenoxat is more potent than Allopurinol
The APEX trials

• This study included 1072 subjects with hyperuricemia (sUA > 8 mg/dl)
and gout with normal or impaired renal function
• Patients received once daily febuxostat ( 80, 120 mg) or Allopurinol (300,
100 mg based on renal function) for 28 weeks
• The primary endpoint was the proportion of subjects with sUA < 6 mg/dl
Adenoxat has no active metabolites with a high lipid solubility and biliary excretion occurs
in addition to renal excretion
Adenoxat can be given to patients with renal disease

Adenoxat is a better choice for mild/moderate renal failure patients.

 Adenoxat is effective in lowering urinary
UA excretion
• Higher urinary uric acid excretion is a suspected risk factor for calcium
oxalate stone formation.
• This study included 99 participants with higher uUA excretion (>700
mg/24 h) and a recent (≤ 5 years) history of kidney stones
• They received daily Febuxostat at 80 mg, Allopurinol at 300 mg or
placebo for 6 months
Adenoxat leads to significantly greater reduction in 24 – hours urinary UA than
Allopurinol
Adenoxat is non-purine selective XO inhibitor.
Adenoxat Reduces uric acid levels significantly within 2 weeks after
initiation of therapy more than Allopurinol.
Adenoxat lowers 24 hours urinary uric acid in stone formers.
Adenoxat prevents of gout flares.
Adenoxat No dose adjustment is necessary in renal impairment.
Adenoxat can be taken with colchicine and NSAIDs.