Allopurinol (Page 3 of 6)
7 DRUG INTERACTIONS
7.1 Drugs Known to Affect the Occurrence of Skin Rash and Hypersensitivity
Concomitant use of the following drugs may increase the risk of skin rash, which may be severe: bendamustine, thiazide diuretics, ampicillin and amoxicillin. Renal impairment may further increase risk with concomitant use of thiazide diuretics [see Warnings and Precautions (5.1, 5.2) and Clinical Pharmacology (12.2)].
Monitor kidney function and reduce the dose of allopurinol tablets in patients with concomitant thiazide diuretic use and impaired renal function [see Dosage and Administration (2.6), Warnings and Precautions (5.1)].Discontinue allopurinol tablets at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when use concomitantly with these drugs [see Warnings and Precautions (5.1)].
7.2 Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets
Table 3: Interventions for Clinically Important Drug Interactions with Allopurinol Tablets
Capecitabine | |
Clinical Impact | Concomitant use with allopurinol may decrease concentration of capecitabine’s active metabolites, which may decrease capecitabine efficacy. |
Intervention | Avoid the use of allopurinol tablets during treatment with capecitabine |
Chlorpropamide | |
Clinical Impact | Allopurinol tablets prolongs the half-life of chlorpropamide as both compete for renal tubular excretion. In patients with renal insufficiency, the risk of hypoglycemia may be increased due to this mechanism. |
Intervention | Monitor patients with renal insufficiency for hypoglycemia when administering chlorpropamide and allopurinol tablets concomitantly. |
Cyclosporine | |
Clinical Impact | Concomitant use of allopurinol increases cyclosporine concentrations, which may increase the risk of adverse reactions. |
Intervention | Increase frequency of monitoring cyclosporine concentrations as reflected in its prescribing information and modify the dosage of cyclosporine as appropriate when used concomitantly with allopurinol tablets. |
Cyclophosphamide and Other Cytotoxic Agents | |
Clinical Impact | Concomitant use of allopurinol with cyclophosphamide and other cytotoxic agents (doxorubicin, bleomycin, procarbazine, mechloroethamine) increases bone marrow suppression among patients with neoplastic disease, except leukemia. |
Intervention | Blood count monitoring and regular physician follow-up are recommended. |
Dicumarol | |
Clinical Impact | Allopurinol tablets prolongs the half-life of the anticoagulant, dicumarol. The mechanism of this drug interaction has not been established but should be noted when allopurinol tablets are given to patients already on dicumarol therapy. |
Intervention | Monitor prothrombin time. Adjust the dosage of dicumarol accordingly when allopurinol tablets are added to anticoagulant therapy. |
Fluorouracil | |
Clinical Impact | Based on non-clinical data, allopurinol may decrease anti-tumor activity due to suppression of phosphorylation of 5-fluorouracil. |
Intervention | Concomitant administration with fluorouracil should be avoided. |
Mercaptopurine or Azathioprine | |
Clinical Impact | Allopurinol inhibits xanthine oxidase mediated metabolism of mercaptopurine and azathioprine. Concomitant use of allopurinol increases the exposure of either mercaptopurine or azathioprine which may increase the risk of their adverse reactions, including myelosuppression [see Warnings and Precautions 5.5]. |
Intervention | In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300 mg to 600 mg of allopurinol tablets per day 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. |
Pegloticase | |
Clinical Impact | Concomitant use of allopurinol tablets and pegloticase may potentially blunt the rise of serum uric acid levels and increase the risk of pegloticase related anaphylaxis in patients whose uric acid level increase to above 6 mg/dL. |
Intervention | Discontinue and do not institute allopurinol tablets therapy during treatment with pegloticase. |
Theophylline | |
Clinical Impact | Concomitant use of allopurinol doses greater than or equal to 600 mg/day may decrease the clearance of theophylline |
Intervention | Monitor and adjust theophylline doses as reflected in the prescribing information. |
Uricosuric Drugs | |
Clinical Impact | Uricosuric agents increase the excretion of the active allopurinol metabolite oxypurinol. Concomitant use with uricosuric agents decreases oxypurinol exposure which may reduce the inhibition of xanthine oxidase by oxypurinol and increases the urinary excretion of uric acid. The net effect of such combined therapy may be useful in some patients in achieving minimum serum uric acid levels provided the total urinary uric acid load does not exceed the competence of the patient’s kidney function. |
Intervention | Monitor uric acid levels due to the increased chance of hypouricemic effects. |
Warfarin | |
Clinical Impact | Allopurinol may inhibit the metabolism of warfarin, possibly enhancing its anticoagulant effect. |
Intervention | Monitor patients on concomitant therapy for excessive anticoagulation. Assess INR frequently and adjust warfarin dosage accordingly when allopurinol is added to warfarin therapy. |
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