Zyloprim Dosage

Recommended Testing Prior to Treatment Initiation

Prior to initiating treatment with ZYLOPRIM in patients with gout, assess the following baseline tests: serum uric acid level, complete blood count, chemistry panel, liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin), kidney function tests (serum creatinine and eGFR).

Recommended Prophylaxis for Gout Flares

Gout flares may occur after initiation of ZYLOPRIM due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with colchicine or an anti-inflammatory agent according to practice guidelines is recommended upon initiation of ZYLOPRIM. While adjusting the dosage of ZYLOPRIM in patients who are being treated with colchicine and/or anti-inflammatory agents, continue flare prophylaxis drugs until serum uric acid has been normalized and the patient has been free of gout flares for several months. If a gout flare occurs during ZYLOPRIM treatment, ZYLOPRIM need not be discontinued. Manage the gout flare concurrently, as appropriate for the individual patient.

Recommended Dosage for Gout

The initial recommended dosage for the management of gout is 100 mg orally daily, with weekly increments of 100 mg, until a serum uric acid level of 6 mg/dL or less is reached. Initiating treatment with lower dosages of ZYLOPRIM and titrating slowly, decreases the risk of gout flares and drug induced serious adverse reactions.
In patients with renal impairment the initial dosage is 50 mg orally daily with lower dose increases until serum uric acid level of 6 mg/dL or less is reached. For complete dosage recommendations for patients with renal impairment see Table 1.
The minimal effective dosage is 100 mg to 200 mg daily and the maximal recommended dosage is 800 mg daily. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Doses in excess of 300 mg should be administered in divided doses. Monitor patient's kidney function during the early stages of administration of ZYLOPRIM and decrease the dosage or withdraw the drug if persistent abnormalities in kidney function occur.
The dosage of ZYLOPRIM to achieve control of gout varies with the severity of the disease. In general, gout control is achieved with 200 mg to 300 mg daily in patients with mild gout, and with 400 mg to 600 mg daily in patients with moderate to severe tophaceous gout. Gout attacks usually become shorter and less severe after several months of therapy.
If a dose of ZYLOPRIM is missed, there is no need to double the dose at the next scheduled time. ZYLOPRIM is generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or preferably, slightly alkaline urine are desirable.

Inform patients of the possibility of gout flares. Instruct them to remain on ZYLOPRIM if this occurs and to increase fluid intake during therapy to prevent kidney stones.

Concurrent Use of Uricosuric Agents

Some patients, may benefit using uricosuric agents concurrently, to reduce serum uric acid to target levels.
When transferring a patient from a uricosuric agent to ZYLOPRIM, reduce the dose of the uricosuric agent over a period of several weeks and increase the dose of ZYLOPRIM gradually to the required dose needed to maintain target serum uric acid level.

Recommended Dosage for Hyperuricemia Associated with Cancer Therapy

Initiate therapy with ZYLOPRIM 24 hours to 48 hours before the start of chemotherapy known to cause tumor cell lysis. Administer fluids sufficient to yield a daily urinary output of at least 2 liters in adults (at least 100 mL/m2/hour in pediatric patients) with a neutral or, preferably, slightly alkaline urine.
The recommended dosage of ZYLOPRIM is:

• Adult patients – 300 mg to 800 mg orally daily
• Pediatric patients - 100 mg/m2 orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day). In patients with body surface area < 0.5 m2, consider using an alternative allopurinol formulation.

The dosage of ZYLOPRIM to maintain normal or near-normal serum uric acid varies with the severity of the disease. Monitor serum uric acid levels at least daily and administer ZYLOPRIM at a dose and frequency to maintain the serum uric acid within the normal range. Discontinue ZYLOPRIM when the risk of tumor lysis has abated (2 days to 3 days from start of chemotherapy). For complete dosage recommendations for patients with renal impairment, see Table 2.

Recommended Dosage for Management of Recurrent Calcium Oxalate Calculi in Hyperuricosuric Patients

The recommended dosage for the management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 mg to 300 mg orally daily in divided doses or as the single equivalent. This dose may be adjusted depending upon the resultant control of the hyperuricosuria based upon subsequent 24-hour urinary urate determinations.

Recommended Dosage in Patients with Renal Impairment

The recommended initial dosages of ZYLOPRIM in adult patients with renal impairment are shown in Tables 1 and 2.

Patients with Gout

The recommended initial dosages in adult patients with gout with impaired kidney function are shown in Table 1.
Initiate treatment with a lower dose of ZYLOPRIM and increase the dose gradually in 50 mg/day increments every 2 weeks to 4 weeks in patients with renal impairment to decrease the risk of drug induced serious adverse reactions. Use the lowest dose possible to achieve the desired effect on serum and/or urine uric acid. Monitor kidney function in gout patients with chronic kidney disease closely when initiating treatment with ZYLOPRIM and decrease or withdraw the drug if increased abnormalities in kidney function appear and persist.

Table 1. Recommended Initial Dosage in Adult Patients with Gout

The maximum dosage that should be used in patients with various levels of renal impairment is not defined at different eGFR levels.

Patients with Recurrent Calcium Oxalate Calculi
Data are insufficient to provide dosage recommendations for the treatment of recurrent calcium oxalate calculi in patients with renal impairment. Allopurinol and its metabolites are excreted by the kidney, and accumulation of the drug can occur in renal failure.

Hyperuricemia Associated with Cancer Therapy
The recommended dosage of ZYLOPRIM for the management of hyperuricemia associated with cancer therapy in adult patients with renal impairment is shown in Table 2.


Table 2. Recommended Dosage of ZYLOPRIM in Adult Patients for Management of Hyperuricemia Associated with Cancer Therapy with Renal Impairment

Treatment with ZYLOPRIM has not been studied in pediatric patients with severe renal impairment (eGFR < 20 mL/min) or on dialysis. There is insufficient information to establish dosing for ZYLOPRIM in pediatric patients with renal impairment. In these patients, consider the risks and potential benefits before initiating treatment with ZYLOPRIM.