ULORICrx

FAQs

Frequently asked questions about ULORIC

Head-to-head comparison: ULORIC and allopurinol

What clinical data are available about the efficacy of ULORIC vs allopurinol in patients with hyperuricemia and gout?

The efficacy of ULORIC has been demonstrated in 3 large phase 3, randomized, double-blind, controlled, head-to-head clinical trials with allopurinol.⁵

For a summary of the results, see ULORIC Efficacy and safety profile.

All 3 trials—APEX, FACT, and CONFIRMS—demonstrated the superiority of ULORIC 80 mg over allopurinol 300 mg in lowering serum uric acid to <6 mg/dL at final visit.⁵ Patients with mild to moderate renal impairment* or high baseline serum uric acid levels also benefited from ULORIC.⁵

ULORIC 80 mg was proven superior to allopurinol at lowering serum uric acid levels in 3 head-to-head studies.
ULORIC 40 mg, the recommended starting dose, was as effective as allopurinol at lowering serum uric acid levels.

*Mild to moderate renal impairment is defined as serum creatinine >1.5 mg/dL and ≤2 mg/dL or estimated creatinine clearance ≥30 mL/min and ≤89 mL/min.⁵

Important Safety Information

Phase 3 clinical trials: Combined study population

The participants in the ULORIC phase 3 clinical trials had a mean baseline serum uric acid level of 9.7 mg/dL and were reflective of the chronic gout population^18,19:

Male		95%
Race:	Caucasian	80%
	African American	10%
Ethnicity:	Hispanic or Latino	7%
Alcohol user		67%
Mild to moderate renal impairment (serum creatinine levels of > 1.5 mg/dL and ≤ 2 mg/dL or estimated creatinine clearance ≥ 30 mL/min and ≤ 89 mL/min)		59%
History of hypertension		49%
History of hyperlipidemia		38%
BMI ≥ 30 kg/m²		63%
Mean BMI		33 kg/m²
Baseline sUA ≥ 10 mg/dL		36%
Experienced a gout flare in previous year		85%

Clinical study details

APEX: Allopurinol and Placebo-Controlled Efficacy Study of Febuxostat

Design: A 6-month, multicenter, double-blind trial comparing the efficacy of ULORIC vs placebo and allopurinol in achieving a target serum uric acid level of <6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level of ≥8 mg/dL.¹⁸
Study arms: There were 5 study arms: placebo (n=134), allopurinol 300 mg/100 mg* (n=268), ULORIC 80 mg (n=267), ULORIC 120 mg (n=269), and ULORIC 240 mg (n=134, for safety assessment only). Patients received anti-inflammatory prophylaxis for 8 or 10 weeks (naproxen 250 mg twice daily or colchicine 0.6 mg once daily), with length and start date dependent on previous use of urate-lowering therapy.¹⁸ 
*Allopurinol-treated patients (n=10) with serum creatinine >1.5 mg/dL and ≤2 mg/dL received a dose of 100 mg daily. All other patients received 300 mg daily.
Results: A significantly higher proportion of patients achieved a serum uric acid level of <6 mg/dL on ULORIC 80 mg (72%, n=253)* than on allopurinol^† (39%, n=263) at the final visit.¹⁸
*p<0.001 vs allopurinol.

†Allopurinol patients (n=10) with serum creatinine >1.5 mg/dL and ≤2 mg/dL were dosed at 100 mg daily.

  FACT: Febuxostat and Allopurinol Controlled Trial

Design: A 12-month, multicenter, double-blind trial comparing the efficacy of ULORIC vs allopurinol in achieving a target serum uric acid level of <6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level of ≥8 mg/dL.¹⁹
Study arms: There were 3 study arms: allopurinol 300 mg (n=253), ULORIC 80 mg (n=256), and ULORIC 120 mg (n=251). Patients received anti-inflammatory prophylaxis for 8 or 10 weeks (naproxen 250 mg twice daily or colchicine 0.6 mg once daily), with length and start date dependent on previous use of urate-lowering therapy.¹⁹
Results: A significantly higher proportion of patients achieved a serum uric acid level of <6 mg/dL on ULORIC 80 mg (74%, n=249)* than on allopurinol (36%, n=242) at the final visit. 
*p<0.001 vs allopurinol.¹⁹

CONFIRMS: CONfirmation of Febuxostat in Reducing and Maintaining Serum Urate

Design: A 6-month, multicenter, double-blind trial comparing the efficacy of ULORIC vs allopurinol in achieving a target serum uric acid level of <6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level ≥8 mg/dL.²⁰
Study arms: There were 3 study arms: allopurinol 300 mg/200 mg* (n=756), ULORIC 40 mg (n=757), and ULORIC 80 mg (n=756). Patients received anti-inflammatory prophylaxis for 6 months (colchicine 0.6 mg once daily or naproxen 250 mg twice daily); subjects on previous urate-lowering therapy received prophylaxis for an additional month before the study began.²⁰ 
*Allopurinol-treated patients (n=145) with estimated Cl_Cr ≥30 mL/min and Cl_Cr ≤59 mL/min received 200 mg daily. All other patients received 300 mg daily.
Results:
- All study participants. ULORIC 40 mg (n=757) was as effective as allopurinol in lowering serum uric acid levels to <6 mg/dL at the final visit. ULORIC 80 mg (n=756) was superior to allopurinol (n=755) at lowering serum uric acid level to <6 mg/dL at the final visit (67% vs 42%) with p<0.001 vs allopurinol and p<0.001 vs ULORIC 40 mg.²⁰
- Patients with mild to moderate renal impairment.* ULORIC was superior to allopurinol in patients with mild to moderate renal impairment.* A significantly higher proportion of patients achieved a serum uric acid level of <6 mg/dL on ULORIC 80 mg (72%, n=503)^† and ULORIC 40 mg (50%, n=479)^‡ than on allopurinol^§ (42%, n=501) at the final visit.²⁰ 
    *Mild to moderate renal impairment is defined as serum creatinine levels of >1.5 mg/dL and ≤2 mg/dL or estimated creatinine clearance ≥30 mL/min and ≤89 mL/min.  
  
    ^†p<0.05 vs allopurinol and ULORIC 40 mg. 
  
    ^‡p<0.05 vs allopurinol. 
  
  ^§Allopurinol patients (n=145) with estimated Cl_Cr ≥30 mL/min and Cl_Cr ≤59 mL/min were dosed at 200 mg daily. All other patients received 300 mg daily.

Did patients with mild to moderate renal impairment* also benefit from ULORIC?

CONFIRMS included a group of patients with renal impairment as part of its trial design. Among patients in CONFIRMS with mild to moderate renal impairment,* ULORIC was superior to allopurinol in gout patients with mild to moderate renal impairment.²⁰

A significantly higher proportion of gout patients with mild to moderate renal impairment achieved a serum uric acid level of <6 mg/dL at the final visit with ULORIC 40 mg (50%, n=479)^† and ULORIC 80 mg (72%, n=503)^‡ than with allopurinol (42%, n=501).²⁰

*Mild to moderate renal impairment is defined as serum creatinine levels of >1.5 mg/dL and ≤2 mg/dL or estimated creatinine clearance ≥30 mL/min and ≤89 mL/min.

^†p<0.05 vs allopurinol.

^‡p<0.05 vs allopurinol and ULORIC 40 mg.²⁰

What impact does renal function have on elimination of allopurinol and ULORIC?

Allopurinol is eliminated primarily via renal excretion.¹⁷ Dose reductions of allopurinol are required in patients with renal impairment.¹⁷ ULORIC is eliminated by both hepatic and renal pathways.⁵ No dose adjustment is required in patients with mild or moderate renal or hepatic impairment who take ULORIC.*⁵ The correlation of this information to clinical outcomes has not been established.

There are insufficient data about ULORIC in patients with severe renal impairment and no data in patients with severe hepatic impairment. Caution should be exercised in these patients.⁵

*Mild to moderate renal impairment is defined as serum creatinine levels of >1.5 mg/dL and ≤2 mg/dL or estimated creatinine clearance ≥30 mL/min and ≤89 mL/min.⁵

Compare other aspects of allopurinol and ULORIC

How are allopurinol and ULORIC structurally different?

Allopurinol has a purine structure.¹⁷ ULORIC has a non–purine-based structure. Uloric is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.⁵ The correlation of this information to clinical outcomes has not been established.

View the structures of ULORIC and allopurinol

ULORIC dosage and administration

What is the recommended dose of ULORIC?

For treatment of hyperuricemia in patients with gout, ULORIC is recommended at a 40 mg or 80 mg once-daily dose. The recommended starting dose of ULORIC is 40 mg once daily. For patients who do not achieve serum uric acid levels <6 mg/dL after 2 weeks with 40 mg, ULORIC 80 mg is recommended.⁵ ULORIC can be administered without regard to food or antacid use.⁵

Find out more about ULORIC dosing

Which anti-inflammatory prophylaxis regimen was used in ULORIC clinical trials?

After initiation of any urate-lowering therapy, including ULORIC, an increase in gout flares may be observed as the reduction in serum uric acid can cause mobilization of urate from tissue deposits.⁵ Patients received anti-inflammatory prophylaxis (colchicine 0.6 mg once daily or naproxen 250 mg twice daily) in ULORIC clinical trials. Subjects on previous urate-lowering therapy received prophylaxis for an additional month before the study began.²⁰

If a gout flare occurs during treatment, ULORIC need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient.⁵

Are dose adjustments required for patients with renal or hepatic impairment?

No dose adjustment is necessary when administering ULORIC in patients with mild to moderate renal or hepatic impairment.*

*Mild to moderate renal impairment is defined as serum creatinine levels >1.5 mg/dL and ≤2 mg/dL or estimated creatinine clearance ≥30 mL/min and ≤89 mL/min. There are insufficient data in patients with severe renal impairment and no data in patients with severe hepatic impairment. Caution should be exercised in these patients.⁵

Are dose adjustments needed for concomitant medications?

No dose adjustments are needed for patients receiving certain common concomitant medications, including⁵:

Colchicine
Naproxen
Indomethacin
Hydrochlorothiazide
Warfarin
Desipramine*

ULORIC is contraindicated in patients being treated with azathioprine or mercaptopurine.⁵

*Co-administration of drugs that are CYP2D6 substrates (such as desipramine) with ULORIC is not expected to require dose adjustment.

Important Safety Information

ULORIC safety profile

What are the most common adverse events with ULORIC?

The following adverse reactions occurred in ≥1% of ULORIC-treated patients with a rate of at least 0.5% greater than seen in patients receiving placebo in phase 3 controlled studies.*

Adverse reaction	ULORIC 40 mg daily	ULORIC 80 mg daily	Allopurinol^†	Placebo
Liver function abnormalities	6.6%	4.6%	4.2%	0.7%
Nausea	1.1%	1.3%	0.8%	0.7%
Arthralgia	1.1%	0.7%	0.7%	0%
Rash	0.5%	1.6%	1.6%	0.7%
	N=757	N=1279	N=1277	N=134

*ULORIC 80 mg and allopurinol were included in CONFIRMS, APEX, and FACT studies. Placebo was included only in APEX, and ULORIC 40 mg was included only in CONFIRMS.

^†Of the subjects who received allopurinol, 10 received 100 mg, 145 received 200 mg, and 1122 received 300 mg, based on level of renal impairment.

Learn more about the safety profile data for ULORIC

Are there cardiovascular safety concerns associated with ULORIC?

A higher rate of cardiovascular thromboembolic events was observed in patients treated with ULORIC than those treated with allopurinol in clinical trials. Monitor patients on ULORIC for signs and symptoms of myocardial infarction and stroke.⁵

Gout patients frequently have associated comorbidities, such as renal impairment, hypertension, hyperlipidemia, and obesity, putting them at a higher risk of cardiovascular events. The patients included in ULORIC clinical trials were reflective of the chronic gout population with many of these comorbidities.⁵

Cardiovascular thromboembolic events were adjudicated in the 3 phase 3 randomized controlled studies and the long-term extension studies. These events were adjudicated to one of the pre-defined endpoints from the Antiplatelet Trialists' Collaboration (APTC) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). The incidences of adjudicated Anti-Platelet Trialists’ Collaboration (APTC) events per 100 patient-years of exposure were⁵:

Incidence rate of adjudicated APTC* events per 100 patient-years of exposure

Phase 3 Randomized controlled studies	Rate	95% Cl
Placebo	0.00	0.00, 6.16
ULORIC 40 mg	0.00	0.00, 1.08
ULORIC 80 mg	1.09	0.44, 2.24
Allopurinol	0.60	0.16, 1.53

Long-term extension studies	Rate	95% Cl
ULORIC 80 mg	0.97	0.57, 1.56
Allopurinol	0.58	0.02, 3.24

*Antiplatelet Trialists’ Collaboration

Overall, a higher rate of APTC events was observed in patients treated with ULORIC [0.74 per 100 patient-years (95% confidence interval [CI] 0.36–1.37)] than allopurinol [0.60 per 100 patient-years (95% CI 0.16–1.53)].⁵

APTC end points were defined as non-fatal myocardial infarctions, non-fatal strokes, or cardiovascular deaths
The rate of these events was calculated according to patient-years of exposure (number of patients multiplied by number of years patients were observed on the study drugs)
The overall event rates indicate that less than 1 cardiovascular thromboembolic event (0.74 for ULORIC and 0.60 for allopurinol) occurred for every 100 patient-years of exposure
A causal relationship with ULORIC has not been established. Monitor for signs and symptoms of myocardial infarction and stroke

Which liver function abnormalities were observed, and how were they reported?

Liver function abnormalities data were collected in 2 different ways:

As elevations reported by the investigator as adverse events, regardless of the degree of elevation of the liver function test results⁵

	Placebo	ULORIC 40 mg daily	ULORIC 80 mg daily	Allopurinol 300/200/100 mg daily
Adverse reaction	N=134	N=757	N=1279	N=1277
Liver function abnormalities	0.7%	6.6%	4.6%	4.2%

As actual lab values of transaminase elevations greater than 3 times upper limit of normal (ULN) during phase 3 trials⁵

ALT and/or AST ≥3 x ULN	ULORIC	Allopurinol
AST	2%	2%
ALT	3%	2%

Monitor liver function tests periodically.

View the safety profile data for ULORIC

ULORIC accessibility and affordability

Will my patients’ insurance pay for ULORIC?

Takeda works with managed care organizations to ensure ULORIC is accessible across a range of formulary plans. Talk to a Takeda Sales Representative for the current formulary status of ULORIC in your area.

How can I make ULORIC more affordable for my patients?

Give your patients the ULORIC Savings Card. Eligible patients will pay no more than $35 on each prescription.*

Ask your Sales Representative for ULORIC Savings Cards that you can distribute to patients, or direct patients to access ULORIC Savings Cards at www.ULORIC.com/savings.

*Offer expires March 31, 2012.

What help does Takeda offer for indigent patients?

Takeda believes all patients should have access to the medication prescribed by their healthcare providers. Help At Hand offers patients several program options for receiving free or low-cost prescription assistance so they can get the medication they need.

Find out more at the Takeda website

What other support is available for my gout patients with hyperuricemia?

You may offer patients more support by directing them to the ULORIC patients’ website and more.

Learn about these ULORIC patient support tools

Questions about ULORICrx?

Find answers to questions you have about ULORICrx.

Visit ULORICrx help

Patient profiles

Learn more about gout patients with hyperuricemia.

Review patient profiles

Watch as rheumatologist Dr. Chad Boomershine and family practitioner Dr. Gary Ruoff discuss the treatment of hyperuricemia in patients with gout.

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Indication

ULORIC is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout. ULORIC is not recommended for the treatment of asymptomatic hyperuricemia.

Important Safety Information

ULORIC is contraindicated in patients being treated with azathioprine or mercaptopurine.
An increase in gout flares is frequently observed during initiation of anti-hyperuricemic agents, including ULORIC. If a gout flare occurs during treatment, ULORIC need not be discontinued. Prophylactic therapy (i.e. – NSAIDs or colchicine) upon initiation of treatment may be beneficial for up to six months.
Cardiovascular Events: In randomized controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions, and non-fatal strokes) in patients treated with ULORIC [0.74 per 100 P-Y (95% CI 0.36-1.37)] than allopurinol [0.60 per 100 P-Y (95% CI 0.16-1.53)]. A causal relationship with ULORIC has not been established. Monitor for signs and symptoms of MI and stroke.
Liver Enzyme Elevations: In randomized controlled studies, transaminase elevations greater than 3 times the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% in ULORIC and allopurinol-treated patients, respectively). No dose-effect relationship for these transaminase elevations was noted. Laboratory assessment of liver function is recommended at, for example, 2 and 4 months following initiation of ULORIC and periodically thereafter.
Adverse reactions occurring in at least 1% of ULORIC-treated patients, and, at least 0.5% greater than placebo, are liver function abnormalities, nausea, arthralgia, and rash.

Please click here for complete Prescribing Information.

Show references

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