Drug Index

Allopurinol

 
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Mechanism :

Allopurinol acts on purine catabolism. It reduces the production of uric acid, by inhibiting reactions prior to 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 of xanthine to uric acid, the end product of purine metabolism in man.


Indication :

• Tumour lysis syndrome

• Urate nephropathy

• Hyperuricemia


Contraindications :

Patients who have developed a severe reaction to allopurinol should not be restarted on the drug. A few cases of reversible hepatotoxicity have been noted in patients taking allopurinol, and in some patient’s asymptomatic rises in serum alkaline phosphatase or serum transaminase have been observed. If anorexia, weight loss or pruritus develop in patients on allopurinol, evaluation of liver function should be part of their diagnostic workup. The occurrence of hypersensitivity reactions to allopurinol may be increased in patients with decreased renal function, receiving thiazides and allopurinol concurrently.


Dosing :

10 mg/kg/day orally in divided doses every 12 hours; maximum dose: 600 mg/day.

Anti-neoplastic induced hyperuricemia: Oral

<6 years: 150 mg/day in divided doses every 8 hours.

6-10 years: 300 mg/day in single daily dose or in divided doses every 8 hours.

>10 years: 600-800 mg/day, to be started 1-2 days before chemotherapy.

IV: 200 mg/m²/day, to be started 1-2 days before chemotherapy.


Adverse Effect :

Skin rash, fever, chills, arthralgia, cholestatic jaundice, eosinophilia leucocytosis, leukopenia, diarrhea, nausea, vomiting, increase alkaline phosphatase, transaminitis, renal failure. Can precipitate acute attacks of gout.


Interaction :

Mercaptopurine/Azathioprine: Will require a reduction in dose to approximately one-third to one-fourth of the usual dose of mercaptopurine or azathioprine.
Uricosuric Agents: Increase in urinary uric acid excretion.
Thiazide Diuretics: Enhancement of allopurinol toxicity in some patients.
Dicumarol: Prolongs the half-life of the anticoagulant.
Ampicillin/Amoxicillin: Increase in the frequency of skin rash.
Cytotoxic Agents: Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease, except leukemia.
Cyclosporin: Levels may be increased.
Chlorpropamide: Plasma half-life may be prolonged by allopurinol.
Carbamazepine: Allopurinol may increase the serum concentration of Carbamazepine.



Renal Dose :

Dose in Renal Impairment GFR (mL/min)
20-50200–300 mg daily
10-20100–200 mg daily
<10100 mg daily or 100 mg on alternate days

Dose in Patients undergoing Renal Replacement Therapies
CAPDDialysed. Dose as in GFR<10 mL/ min
HDDialysed. Dose as in GFR<10 mL/ min
HDF/High fluxDialysed. Dose as in GFR<10 mL/ min
CAV/VVHDDialysed. Dose as in GFR=10– 20 mL/min

Hepatic Dose :

Allopurinol is metabolized by hepatic oxidation. Reduced doses are recommended in hepatic impairment. Monitor liver function tests on therapy.
04/11/2020 15:38:47 Allopurinol
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