Allopurinol

ADMINISTRATION ROUTES:

PO, NG

ALTERNATIVE NAMES:

Progout, Allohexal, Apo-Allopurinol

ICU INDICATIONS:

1. Prophylaxis against gout
2. The management of patients with leukaemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels.

PRESENTATION AND ADMINISTRATION:

PO / NG

100 mg and 300 mg tablets (white); tablets may be crushed and administered via the nasogastric tube.

DOSAGE:

Gout:

100 - 200 mg daily

Increase if required to maximum daily dosage 800 mg. Appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses.

Prevention of hyperuricaemia in patients at risk of tumour lysis syndrome during chemotherapy:

600 - 800 mg daily for 2 - 3 days with high fluid intake

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

Dose in renal replacement therapy

Note: with all grades of renal impairment, commence with 100 mg/day and increase if serum urate response is unsatisfactory. Doses of less than 100 mg/day may be required in some patients.

DOSAGE IN PAEDIATRICS:

Prevention of hyperuricaemia in patients at risk of tumour lysis syndrome

For secondary hyperuricaemia associated with malignancies in children:

Age <6 years, give 150mg once daily

Age 6-10 years, give 300 mg once daily

Evaluate response after 48 hours and adjust dosage as necessary. Weight-based dose 10 mg/kg 12-24 hrly

CLINICAL PHARMACOLOGY:

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 of xanthine to uric acid, the end product of purine metabolism in man.

Allopurinol is approximately 90% absorbed from the gastrointestinal tract.

CONTRAINDICATIONS:

1. Hypersensitivity to allopurinol

WARNINGS:

The most frequent adverse reaction to allopurinol is skin rash. Skin reactions can be severe and sometimes fatal. Treatment with allopurinol should be discontinued immediately if a rash develops.

PRECAUTIONS:

General:

An increase in acute attacks of gout has been reported during the early stages of allopurinol administration, even when normal or subnormal serum uric acid levels have been attained.

Some patients with pre-existing renal disease or poor urate clearance have shown a rise in creatinine during allopurinol administration. In patients with hyperuricaemia due to malignancy, the vast majority of changes in renal function are attributable to the underlying malignancy rather than to therapy with allopurinol. Although the mechanism responsible for this has not been established, patients with impaired renal function should be carefully observed during the early stages of allopurinol administration so that the dosage can be appropriately adjusted for renal function.

Bone marrow depression has been reported in patients receiving allopurinol, most of whom received concomitant drugs with the potential for causing this reaction. This has occurred as early as 6 weeks to as long as 6 years after the initiation of allopurinol therapy.

Laboratory Tests:

The correct dosage and schedule for maintaining the serum uric acid within the normal range is best determined by using the serum uric acid as an index. It may, on occasion, be appropriate to measure a uric acid level in a patient on allopurinol in ICU

Drug/Laboratory Test Interactions:

None known

IMPORTANT DRUG INTERACTIONS IN ICU:

Mercaptopurine/Azathioprine:

Allopurinol inhibits the enzymatic oxidation of mercaptopurine and azathioprine to 6-thiouric acid.

In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300-600 mg/day of allopurinol will require a reduction in dose to approximately one third to one fourth of the usual dose of mercaptopurine or azathioprine. Subsequent adjustment of doses of mercaptopurine or azathioprine should be made on the basis of therapeutic response and the appearance of toxic effects.

Warfarin:

Allopurinol prolongs the half-life of warfarin.

Thiazide Diuretics:

Renal function may be more likely to deteriorate with the combination of allopurinol and thiazide diuretics and, in patients on thiazide diuretics, allopurinol dosage levels should be more conservative.

Amoxicillin:

An increase in the frequency of skin rash has been reported among patients receiving amoxicillin concurrently with allopurinol compared to patients who are not receiving both drugs. The cause of the reported association has not been established.

Cyclosporin:

Cyclosporin levels may be increased during concomitant treatment with allopurinol. Monitoring of cyclosporin levels and possible adjustment of cyclosporin dosage should be considered when these drugs are co-administered.

ADVERSE REACTIONS:

Body as a Whole:

Skin rash, fever, chills

Cardiovascular System:

Vasculitis

Respiratory System:

Bronchospasm, asthma, pharyngitis, rhinitis

Digestive System:

Cholestatic jaundice, diarrhoea, nausea, LFT derangement, gastritis, dyspepsia

Nervous System:

Peripheral neuropathy, neuritis, paraesthesia, somnolence

Musculoskeletal System:

Exacerbation of gout during initial treatment, arthralgias

Haematological System:

Eosinophilia and mild leukocytosis or leukopaenia