Usual Adult Dose for Gout

Dose will vary with the severity of the disease:

Initial dose: 100 mg orally once a day

• Increase in increments of 100 mg weekly until a serum uric level of 6 mg/dL or less is attained

Mild Gout:

• Average maintenance dose: 200 to 300 mg orally once a day

Moderately Severe Tophaceous Gout:

• Average maintenance dose: 400 to 600 mg orally/day in divided doses

Minimal Effective Dose: 100 to 200 mg per day
Maximum Dose: 800 mg per day

Comments:

• Oral doses in excess of 300 mg/day should be given in divided doses, preferably after meals to minimize gastric irritation.
• A gradual dose titration is recommended to reduce the possibility of acute gouty attacks.
• Normal serum urate levels are usually achieved in 1 to 3 weeks.

Use: For the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy).

Usual Adult Dose for Hyperuricemia Secondary to Chemotherapy

Parenteral:
200 to 400 mg/m2/day IV as a single infusion or in equally divided infusions at 6, 8, or 12 hour intervals
Maximum dose: 600 mg/day

Oral:
Initial dose: 600 to 800 mg orally in divided doses
Maintenance: Adjust dose as needed based on serum uric acid levels
Maximum dose: 800 mg per day

Comments:

• When possible, therapy should be initiated 24 to 48 hours before the start of chemotherapy; treatment should be discontinued when the potential for overproduction of uric acid is no longer present.
• Oral doses in excess of 300 mg/day should be given in divided doses, preferably after meals to minimize gastric irritation.
• The dose to lower serum uric acid to normal or near-normal varies with the severity of the disease; the above dosing represents suggested doses; serum uric acid levels should serve as an index.
• Fluid intake should be sufficient to maintain a daily urinary output of at least 2 L; neutral or preferably slightly alkaline urine is desirable.

Use: For the management of patients with leukemia, lymphoma, and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels; IV therapy is available for patients who cannot tolerate oral therapy.

Usual Adult Dose for Calcium Oxalate Calculi with Hyperuricosuria

200 to 300 mg orally once a day or in divided doses

Comments:

• Carefully assess risk versus benefit when initiating therapy and periodically thereafter.
• Dose adjustments should be based on control of hyperuricosuria based on 24-hour urinary urate determinations.
• Clinical experience suggests these patients may benefit dietary changes in addition to drug therapy.

Use: For the management recurrent calcium oxalate calculi in patients whose daily uric acid excretion exceeds 800 mg/day in males or 750 mg/day in females.

Usual Pediatric Dose for Hyperuricemia Secondary to Chemotherapy

Parenteral:
Initial dose: 200 mg/m2/day IV as a single infusion or in equally divided infusions at 6, 8, or 12 hour intervals
Maximum dose: 600 mg/day

Oral:
Age: Less than 6 years: 150 mg orally once a day or in divided doses
Age: 6 to 10 years: 300 mg orally once a day or in divided doses
Age: Greater than 10 years: 600 to 800 mg orally per day in divided doses

• After 48 hours, evaluate and adjust dose as needed

Comments:

• Oral doses in excess of 300 mg should be administered in divided doses.
• When possible, therapy should be initiated 24 to 48 hours before the start of chemotherapy; treatment should be discontinued when the potential for overproduction of uric acid is no longer present.
• The dose to lower serum uric acid to normal or near-normal varies with the severity of the disease; the above dosing represents suggested doses in children; serum uric acid levels should serve as an index.
• Fluid intake should be sufficient to maintain a daily urinary output of at least 2 L; neutral or preferably slightly alkaline urine is desirable.

Use: For the management of patients with leukemia, lymphoma, and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels.

Renal Dose Adjustments

CrCl 10 to 20 mL/min: 200 mg IV/orally once a day
CrCl less than 10 mL/min: 100 mg IV/orally once a day
CrCl less than 3 mL/min: 100 mg IV/orally at extended intervals

Liver Dose Adjustments

Use with caution.

If anorexia, weight loss, or pruritus develops, an evaluation of liver function tests should be part of diagnostic workup.

Dose Adjustments

Patients receiving Concomitant Colchicine and/or NSAIDs:

• Continue colchicine and/or NSAID therapy until serum uric acid level has been normalized and patient has been free from acute gouty attacks for several months.

Switching from a Uricosuric Agent:

• Gradually reduce the dose of the uricosuric agent while increasing the allopurinol dose to a dose that maintains a normal serum uric acid level; this may take several weeks.

• Concomitant administration of allopurinol 300 to 600 mg per day with mercaptopurine or azathioprine will require dose reduction of mercaptopurine or azathioprine to one-third or one-fourth of the usual dose.

Therapeutic drug monitoring:

• Dose adjustments should be based on serum uric acid concentrations and urinary uric acid levels.
• Because estimation of uric acid can be difficult, reliance on single serum uric acid determinations is not recommended.

Serum Uric Acid Levels (upper limit of normal):

• Men and premenopausal women: 7 mg/dL
• Postmenopausal women: 6 mg/dL

Precautions

CONTRAINDICATIONS:

• Patients who have developed a severe reaction to this drug should not be restarted on this drug

Consult WARNINGS section for additional precautions.

Dialysis

This drug is dialyzable; consider dosing after each dialysis session

Other Comments

Administration advice:

• Maintain fluid intake sufficient to yield a daily urinary output of at least 2 L; neutral or slightly alkaline urine is desirable.

Oral:

• Take orally after meals to minimize gastric irritation
• Oral doses in excess of 300 mg should be administered in divided doses
• Missed dose: Do not double dose at next scheduled time

Parenteral:

• Administer as a single IV infusion or in equally divided infusions at 6, 8, or 12 hour intervals.
• Final concentration should not exceed 6 mg/mL; rate of infusion depends on the volume of infusate.

Reconstitution/preparation techniques:

• Reconstitute 500 mg vial with 25 mL of sterile water for injection
• Prior to administration, dilute to a final concentration of no greater than 6 mg/mL with 0.9% Sodium Chloride or 5% Dextrose; sodium bicarbonate-containing solutions should not be used
• IV administration should begin within 10 hours of reconstitution

Storage requirements:

• Reconstituted solution and diluted solution should be stored at 20C to 25C (68F to 77F); do not refrigerate

IV compatibility:

• The following drugs are physically incompatible in solution with allopurinol sodium: amikacin sulfate, amphotericin B, carmustine, cefotaxime sodium, chlorpromazine hydrochloride, cimetidine hydrochloride, clindamycin phosphate, cytarabine, dacarbazine, daunorubicin hydrochloride, diphenhydramine hydrochloride, doxorubicin hydrochloride, doxycycline hyclate, droperidol, floxuridine, gentamicin sulfate, haloperidol lactate, hydroxyzine hydrochloride, idarubicin hydrochloride, imipenem-cilastatin sodium, mechlorethamine hydrochloride, meperidine hydrochloride, metoclopramide hydrochloride, methylprednisolone sodium succinate, minocycline hydrochloride, nalbuphine hydrochloride, netilmicin sulfate, ondansetron hydrochloride, prochlorperazine edisylate, promethazine hydrochloride, sodium bicarbonate, streptozocin, tobramycin sulfate, vinorelbine tartrate

General:

• As this is not an innocuous drug, use is not recommended for the treatment of asymptomatic hyperuricemia.
• Dosage for maintaining serum uric acid within the normal range is best determined by using the serum uric acid level as an index.
• Except for use for hyperuricemia secondary to malignancy or for certain rare inborn errors of purine metabolism, this drug is rarely indicated in children.

Monitoring:

• Monitor serum uric acid levels.
• Monitor renal function in patients with renal impairment, those with concurrent conditions that may affect renal function such as hypertension, diabetes, and those concomitantly receiving thiazide diuretics.
• Monitor liver function during the early stages of therapy in patients with preexisting liver disease.

Patient advice:

• Instruct patients to immediately stop this drug and consult their healthcare provider at first sign of a skin rash or any sign of an allergic reaction.
• Encourage patients to increase fluid intake to prevent renal stones.
• Inform patients that optimal benefit may not occur for 2 to 6 weeks.
• Patients should be advised that drowsiness may occur and they should use caution when engaging in hazardous activities until the full effect of this drug is known.