Page 16 - RxExam's Naplex Theory Book Part 2

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A). Xanthine Oxidase Inhibitors

Dose Special Notes

Allopurinol 1. Gout 1). Allopurinol (Zyloprim) acts on purine catabolism, without
(Tablet) 200 to 800 mg per disrupting the biosynthesis of purines. It reduces the production of
(Injection) day in divided uric acid by inhibiting the biochemical reactions immediately
doses. preceding its formation. Allopurinol (Zyloprim) is a structural analogue
of the natural purine base, hypoxanthine.
It is an inhibitor of xanthine oxidase, the enzyme responsible for
the conversion of hypoxanthine to xanthine and of xanthine to uric
acid, the end product of purine metabolism in human.
Allopurinol (Zyloprim) is metabolized to the corresponding
xanthine analogue, oxypurinol (alloxanthine), which also is an inhibitor
of xanthine oxidase.

2). The action of Allopurinol (Zyloprim) differs from that of uricosuric
agents, which lower the serum uric acid level by increasing urinary
excretion of uric acid. Allopurinol (Zyloprim) reduces both the serum
and urinary uric acid levels by inhibiting the formation of uric acid.

3). Allopurinol (Zyloprim) is indicated for the following:

a). The management of patients with signs and symptoms of primary
or secondary gout (acute attacks, tophi, joint destruction, uric acid
lithiasis, and/or nephropathy).
b). The management of patients with leukemia, lymphoma and
malignancies who are receiving cancer therapy which causes elevations
of serum and urinary uric acid levels.
c). The management of patients with recurrent calcium oxalate calculi
whose daily uric acid excretion exceeds 800 mg/day in male patients
and 750 mg/day in female patients.

4). Since Allopurinol (Zyloprim) and its metabolites are primarily
eliminated only by the kidney, accumulation of the drug can occur in
renal failure, and the dose of Allopurinol (Zyloprim) should
consequently be reduced.

5). One of the pathways for inactivation of Azathioprine is inhibited by
Allopurinol (Zyloprim). Patients receiving Azathioprine and Allopurinol
(Zyloprim) concomitantly should have a dose reduction of Azathioprine,
to approximately 1/3 to 1/4 the usual dose. It is recommended that a
further dose reduction or alternative therapies be considered for
patients with low or absent enzyme thiopurine S-methyltransferase
(TPMT) activity receiving Azathioprine and Allopurinol (Zyloprim)
because both TPMT and xanthine oxidase (XO) inactivation pathways
are affected.

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