Allopurinol
Indications
Allopurinol is indicated for reducing
urate/uric acid formation in conditions where urate/uric acid deposition
has already occurred (e.g. gouty arthritis, skin tophi,
nephrolithiasis). Allopurinol is indicated for management of
2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient
activity of adenine phospho ribosyltransferase. Allopurinol is indicated
for the management of recurrent mixed calcium oxalate renal stones in
the presence of hyperuricosuria, when fluid, dietary and similar
measures have failed.
Pharmacology
Allopurinol is a xanthine oxidase inhibitor
which is administered orally. It acts on purine catabolism without
disrupting the biosynthesis of purines. It reduces the production of
uric acid by inhibiting the biochemical reactions immediately preceding
its formation. Allopurinol 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
xanthine to uric acid, the end product of purine metabolism. Allopurinol
is approximately 90% absorbed from the GI tract. Peak plasma levels
generally occur at 1.5 hours to 4.5 hours. It has a plasma half life of
about 1 to 2 hours. Approximately 20% of the ingested Allopurinol is
excreted in the faeces.
Dosage & Administration
Adults: Allopurinol should
be introduced at low dosage e.g. 100mg/day to reduce the risk of
adverse reactions and increased only if the serum urate response is
unsatisfactory. Extra caution should be exercised if renal function is
poor. The following dosage schedules are suggested: 100 to 200 mg daily
in mild conditions, 300 to 600 mg daily in moderately severe conditions,
700 to 900 mg daily in severe conditions.
Children: Children under 15 years: 10 to 20 mg/kg body weight/day up to a maximum of 400 mg daily. Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.
Elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used.
Dosage in renal impairment: In severe renal insufficiency, it may be advisable to use less than 100 mg per day or to use single doses of 100mg at longer intervals than one day.
Children: Children under 15 years: 10 to 20 mg/kg body weight/day up to a maximum of 400 mg daily. Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.
Elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used.
Dosage in renal impairment: In severe renal insufficiency, it may be advisable to use less than 100 mg per day or to use single doses of 100mg at longer intervals than one day.
Interaction
When 6-mercaptopurine or azathioprine is
given concurrently with Allopurinol, only one-quarter of the usual dose
of 6- mercaptopurine or azathioprine should be given because inhibition
of xanthine oxidase will prolong their activity. Evidence suggests that
the plasma half-life of vidarabine is increased in the presence of
allopurinol. When the two products are used concomitantly extra
vigilance is necessary, to recognise enhanced toxic effects.
Theophylline levels should be monitored in patients starting or
increasing allopurinol therapy. An increase in frequency of skin rash
has been reported among patients receiving ampicillin or amoxicillin
concurrently with allopurinol compared to patients who are not receiving
both drugs. Reports suggest that the plasma concentration of
ciclosporin may be increased during concomitant treatment with
allopurinol.
Contraindications
Allopurinol tablet is contra-indicated in patients with known hypersensitive to allopurinol.
Side Effects
Rashes, gastro intestinal disorder’s,
rearly malaise, headache, vertigo, drowsiness, visual and test
disturbances, hypertension, alopecia, hepatotoxicity, neuropathy,
gynaeconastia and blood disorders.
Pregnancy & Lactation
There is inadequate evidence of safety
of Allopurinol in human pregnancy. Use in pregnancy only when there is
no safer alternative and when the disease itself carries risk for the
mother or unborn child. There are no data concerning the effects of
allopurinol or its metabolites on the breast-feed baby.
Precautions & Warnings
Allopurinol should be withdrawn immediately
when a skin rash or other evidence of sensitivity occurs. Reduced doses
should be used in patients with hepatic or renal impairment. Patients
under treatment for hypertension or cardiac insufficiency may have some
concomitant impairment of renal function and allopurinol should be used
with care in this group.
Overdose Effects
Ingestion of up to 22.5 g allopurinol
without adverse effect has been reported. Symptoms and signs including
nausea, vomiting, diarrhoea and dizziness have been reported in a
patient who ingested 20 gm allopurinol. Adequate hydration to maintain
optimum diuresis facilitates excretion of allopurinol and its
metabolites. If considered necessary haemodialysis may be used.
Therapeutic Class
Drugs used in Gout
Storage Conditions
Store in a cool and dry place, protected from light.
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