Sulfinpyrazone, interaction with

O Reilly RA. Phenylbutazone and sulfinpyrazone interaction with oral anticoagulant phenprocoumon. Arch Intern Med 1982 142(9) 1634-7. 

Sulfinpyrazone [HP] Decreased uricosuric effect of sulfinpyrazone (interaction unlikely with less than 1.5 g of salicylate daily). 

Fig. 4 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. MDR-Modulating agents. Abbreviations CSA cyclosporin A, VERAP verapamil STAURO staurosporine, ECON econazole, PRAZ prazosine, FTC fumitremor-gin C, PROB probenecide, BBR benzbromarone, SUPYR sulfinpyrazone, INDOM in-domethacin, GENIS genistein, PGA2 prostaglandin A2, CCCP chlorocarbonyl cyanide phenylhydrazine. (Reproduced from [4])...

Sulfinpyrazone has a biphasic interaction with phenylbutazone (enhancement followed by antagonism). 

Clinically important, potentially hazardous interactions with amiodarone, anabolic steroids, antithyroid agents, barbiturates, bivalirudin, cimetidine, clofibrate, clopidogrel, cyclosporine, delavirdine, dextrothyroxine, disulfiram, fluconazole, glutethimide, imatinib, itraconazole, ketoconazole, metronidazole, miconazole, penicillins, phenylbutazones, piperacillin, quinidine, quinine, rifabutin, rifampin, rifapentine, rofecoxib, salicylates, sulfinpyrazone, sulfonamides, testosterone, thyroid, zileuton... 

Clinically important, potentially hazardous interactions with alcohol, anticoagulants, carbenicillin, dipyridamole, heparin, pentoxifylline, plicamycin, sulfinpyrazone, ticarcillin, valproic acid... 

Clinically important, potentially hazardous interactions with amiodarone, clarithromycin, clopidogrel, desirudin, dextran, fondaparinux, gpiib/iiia receptor antagonists, heparin, quinidine, rifampin, St John s wort, sulfinpyrazone, thrombolytic agents, tidopidine, verapamil, vitamin k antagonists... 

Clinically important, potentially hazardous interactions with estrogens, methotrexate, neomycin, phenindione, probenecid, sulfinpyrazone, warfarin... 

A review of the drug interactions of sulfinpyrazone identified two studies that found interactions with phenytoin. In the first, the serum phenytoin levels of 2 out of 5 patients taking phenytoin 250 to 350 mg daily were doubled from about 10 to 20 micrograms/mL within 11 days of starting to take sulfinpyrazone 800 mg daily. One of the remaining patients had a small increase in phenytoin levels, but the other two had no changes at all. When the sulfinpyrazone was withdrawn, the serum phenytoin concentrations fell to their former levels. The second study was a clinical study in epileptic patients that found that sulfinpyrazone 800 mg daily for a week increased the phenytoin half-life from 10 to 16.5 hours and reduced the metabolic clearance from 59 to 32 mL/minute. 

Information seems to be limited. If sulfinpyrazone is given to patients taking oxprenolol for hypertension, the effects should be monitored. It seems likely that this interaetion eould be aeeommodated by raising the dosage of the oxprenolol but this needs eonfirmation. The effect of this interaction on cardiac workload appears to be less important, but it would still be prudent to monitor coneurrent use if oxprenolol is used for angina. Metoprolol may be a suitable alternative to oxprenolol as it does not appear to interact with sulfinpyrazone. 

O Reilly RA, Goulart DA. Comparative interaction of sulfinpyrazone and phenylbutazone with racemic warfarin alteration in vivo of free fraction of plasma warfarin. J Pharmacol Exp Ther 1981 219(3) 691-4. 

A study of the way the kidneys handle nitrofurantoin found that intravenous sulfinpyrazone 2.5 mg/kg reduced the secretion of nitrofurantoin by the kidney tubules by about 50%. Thi s reduction would be expected to reduce its urinary antibacterial efficacy, and the higher serum levels might lead to increased systemic toxicity, but there do not seem to be any reports suggesting that this represents a real problem in practice. The same situation would also seem likely with probenecid, but there do not appear to be any reports confirming this interaction. 

The clinical importance of both of these interactions is therefore uncertain, but it would seem prudent to be alert for any evidence of reduced antibacterial efficacy and increased systemic toxicity if either sulfinpyrazone or probenecid is used with nitrofurantoin. 

Information appears to be limited to these reports but the interaction would seem to be established and clinically important. If sulfinpyrazone is added to established treatment with ciclosporin, be alert for the need to raise the ciclosporin dosage. The mean fall in trough ciclosporin levels seen in the major study cited was 39%. This study does comment on how quickly this interaction develops but the two cases of transplant rejection occurred after 4 months and 7 months, which implies that it can possibly be slow. Long-term monitoring would therefore be a prudent precaution. The authors of this report say that sulfinpyrazone is an effective alternative to al-lopurinol and no additional adverse effects occur including myelotoxicity when it is used with azathioprine. 

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