Usual Adult Dose for Gout

Initial dose: 40 mg orally once a day

• If serum uric acid level is greater than 6 mg/dL after 2 weeks, increase the dose to 80 mg orally once a day

Maintenance dose: 40 to 80 mg orally once a day
Maximum dose: 80 mg/day

Comments:

• Use of this drug should occur after an acute gout flare subsides.
• Gout flares may occur due to increased urate mobilization from tissue deposits, especially during initiation; gout flare prophylaxis with a NSAID or colchicine is recommended and may be beneficial for up to 6 months.
• Uric acid levels may be checked as soon as 2 weeks after beginning this drug.

Use: For the chronic management of hyperuricemia in patients with gout who have an inadequate experience to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable.

Renal Dose Adjustments

Mild to Moderate Renal Dysfunction: No adjustment recommended
Severe Renal Dysfunction (CrCl 15 to less than 30 mL/min): Maximum daily dose should be limited to 40 mg/day
ESRD (CrCl less than 15 mL/min): Data not available

Liver Dose Adjustments

Mild to Moderate Liver Dysfunction (Child-Pugh Class A and B): No adjustment recommended
Severe Liver Dysfunction (Child-Pugh Class C): Use with caution

• For patients who develop ALT levels greater than 3 times the upper limit of normal (3 x ULN): Interrupt treatment; do not restart without another explanation for ALT abnormalities.
• For patients who develop ALT levels greater than 3 x ULN AND bilirubin greater than 2 x ULN: Therapy should be discontinued and not restarted in patients without alternative etiologies.
• For patients with lesser ALT or bilirubin elevations AND with an alternate probable cause: Use with caution.

Dose Adjustments

Therapeutic target is to decrease and maintain serum uric acid levels below 6 mg/dL

Concomitant use with mercaptopurine/azathioprine is contraindicated

Precautions

WARNING: CARDIOVASCULAR DEATH

• Gout patients with established cardiovascular (CV) disease treated with this drug had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study.
• Consider the risks and benefits when deciding to prescribe or continue patients on this drug; therapy 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.

CONTRAINDICATIONS:

• Concomitant use of azathioprine or mercaptopurine

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• May be taken with or without food
• This drug may be taken without regard to antacid use

Storage requirements:

• Protect from light

General:

• This drug is not recommended for use in patients for whom the rate of urate formation is greatly increased (e.g., malignant disease and its treatment, Lesch-Nyhan syndrome); in rare cases, the concentration of xanthine in urine could rise and deposit in the urinary tract.
• This drug should not be used to treat asymptomatic hyperuricemia.
• This drug should not be started until an acute gout flare has subsided; if gout flares occur during treatment, manage concurrently; discontinuation of this drug should not be necessary.

Monitoring:

• Obtain liver function tests at baseline and periodically thereafter; liver tests should be conducted in patients reporting signs/symptoms of liver injury (e.g., fatigue, anemia, upper right abdominal discomfort, dark urine, jaundice).
• Monitor for signs and symptoms of myocardial infarction and stroke
• Serum uric acid may be measured as soon as 2 weeks after starting this drug

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide).
• Patients should be informed that a higher risk of cardiovascular death with this drug compared to allopurinol has been observed; they should be alert for the development of signs and symptoms of cardiovascular events and instructed on steps to take if they occur.
• Patients should speak with a healthcare provider before starting any new medications, including over the counter medications.
• Patients should be instructed to report skin or hypersensitivity reactions including rash, blistering, chest pain, shortness of breath, or neurological symptoms suggesting a stroke.
• Instruct patients to report signs/symptoms of liver injury to the health care provider.
• Inform patients that gout flares may occur, and they should not stop taking this drug if a gout flare occurs.
• Patients should be advised to speak to their healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.