Azathioprine is metabolized to 6-mercaptopurine which is inactivated by the action of xanthine oxidase. When 6-mercaptopurine or azathioprine is given concurrently with allopurinol, only ¼ of the usual dose of 6-mercaptopurine or azathioprine should be given because inhibition of xanthine oxidase will prolong their activity.
If allopurinol is given concomitantly with chlorpropamide when renal function is poor, there may be an increased risk of prolonged hypoglycaemic activity because allopurinol and chlorpropamide may compete for excretion in the renal tubule. There have been rare reports of increased effect of warfarin and other coumarin anticoagulants when co-administered with allopurinol; therefore, all patients receiving anticoagulants must be carefully monitored.
In animal test, there is a report that hepatic iron uptake may be increased in combination use with iron supplements.
Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease (other than leukaemia), in the presence of allopurinol.
Allopurinol may inhibit hepatic oxidation of phenytoin but the clinical significance has not been demonstrated.
Reports suggest that the plasma concentration of ciclosporin may be increased during concomitant treatment with allopurinol. The possibility of enhanced ciclosporin toxicity should be considered if the drugs are co-administered.
Inhibition of the metabolism of theophylline has been reported. The mechanism of interaction may be explained by the xanthine oxidase being involved in the biotransformation of theophylline in man. Theophylline levels should be monitored in patients starting or increasing allopurinol therapy.
Evidence suggests that the plasma half-life of vidarabine is increased in the presence of allopurinol. When the 2 products are used concomitantly, extra vigilance is necessary to recognize enhanced toxic effects.
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. The cause of the reported association has not been established. However, it is recommended that in patients receiving allopurinol an alternative to ampicillin or amoxicillin is used where available.
Oxipurinol, the major metabolite of allopurinol and itself therapeutically active, is excreted by the kidney in a similar way to urate. Hence, drugs with uricosuric activity eg, probenecid or large doses of salicylate may accelerate the excretion of oxipurinol. This may decrease the therapeutic activity of allopurinol, but the significance needs to be assessed in each case.
Allopurinol may enhance the action of salicylates.