Allopurinol

Allopurinol

[300mg tablets 4 cents, 200mg tablets 2 cents]

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

DOSAGE:

  • Gout:
    The minimal effective dosage is 100-200 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. Dosage requirements in excess of 300 mg should be administered in divided doses.
  • Prevention of hyperuricaemia in patients at risk of tumour lysis syndrome:
    For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600-800 mg daily for 2-3 days is advisable together with a high fluid intake.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    <10: 100mg daily / alternate days
    10-20: 100-200mg daily
    >20-50: 200-300mg/daily
  • Dose in renal replacement therapy
    CAPD: Dose as for GFR <10ml/min
    HD: Dose as for GFR <10ml/min
    CVVHDF: Dose as for GFR 10-20ml/min

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

DOSAGE IN PAEDIATRICS:

  • Prevention of hyperuricaemia in patients at risk of tumour lysis syndrome
    Children, 6-10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol daily while those under 6 years are generally given 150 mg daily. The response is evaluated after approximately 48 hours of therapy and a dosage adjustment is made if necessary. Weight-based dosage is 10mg/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. Therefore, 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 hyperuricemia 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 the intensive care unit.
  • Drug/Laboratory Test Interactions:
    Allopurinol is not known to alter the accuracy of laboratory tests.

IMPORTANT DRUG INTERACTIONS FOR THE 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 cyclosporine levels and possible adjustment of cyclosporine 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

Critical Care Drug Manual

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