Sodium salicylate Methotrexate

Some lists, reviews and books on interactions say that chloramphenicol, aminosalieylie aeid, sodium salieylate, sulfamethoxypyridazine, tetracycline or tolbutamide interact with methotrexate, apparently based largely on the preliminary findings of a study in which male mice were treated for 5 days with each of 4 doses of methotrexate (1.53 to 12.25 mg/kg intravenously) and immediately afterwards with non-toxic intraperitoneal doses of the drugs listed. These drugs were said to decrease the lethal dose and/or decrease the survival time of the mice That is to say, the toxicity of the methotrexate was increased. The reasons are not understood, but it is suggested that displacement of the methotrexate from its plasma protein binding sites could result in a rise in the levels of unbound and active methotrexate, and in the case of sodium salicylate to a decrease in renal clearance. 

A study in 4 patients found that the renal clearance of methotrexate was reduced by 35% by an infusion of sodium salicylate (2 g initially, then 33 mg/minute). A further study found that choline magnesium trisali-cylate reduced methotrexate clearance by 24 to 41%, and increased the unbound fraction by 28%, when compared with paracetamol (acetaminophen). ... 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

Animal studies suggested that the toxicity of methotrexate might be increased by the use of chloramphenicol, aminosalicylic acid, sodium saUcylate, sulfamethoxypyridazine, tetracycline or tolbutamide, but confirmation of this in man has only been seen with the salicylates, sulphonamides and possibly tetracycline. 

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